82 research outputs found

    Committing to Justice: The Case for Impact of Race and Culture Assessments in Sentencing African Canadian Offenders

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    Canadian judges have made notable, although too limited, strides to recognize the unique conditions of Black Canadians in sentencing processes and decisionmaking. The use of Impact of Race and Culture Assessments in sentencing people of African descent has gradually gained popularity since they were first introduced in R v “X.” These reports provide the court with the necessary information about the effect of systemic anti-Black racism on people of African descent and how the experience of racism has informed the circumstances of the offence, the offender, and how it might inform the offender’s experience of the carceral state. This paper lays out the legislative authority for considering systemic and background factors in sentencing African Canadian offenders; analyzes and classifies the relevant case law with a view to establishing a framework for sentencing African Canadian offenders and clarifying our thinking about how impact assessments may advance sentencing goals; and flags some of the outstanding issues that require further study. Les juges canadiens ont fait des progrès notables, bien que trop limités, pour reconnaître les conditions uniques des Canadiens noirs dans les processus de détermination de la peine et de prise de décision. L’utilisation des évaluations de l’impact de la race et de la culture dans la détermination de la peine des personnes d’origine africaine a progressivement gagné en popularité depuis qu’elles ont été introduites dans l’affaire R c. « X .» Ces rapports fournissent au tribunal les informations nécessaires sur l’effet du racisme anti-Noir systémique sur les personnes d’origine africaine et sur la manière dont l’expérience du racisme a influencé les circonstances de la perpétration de l’infraction, le délinquant, et comment elle pourrait influencer l’expérience de l’état carcéral du délinquant. Dans le présent article, nous présentons l’autorité législative permettant de prendre en compte des facteurs systémiques et contextuels dans la condamnation des délinquants afro-canadiens; nous analysons et classons la jurisprudence pertinente en vue d’établir un cadre pour la condamnation des délinquants afro-canadiens et de clarifier notre réflexion sur la manière dont les évaluations d’impact peuvent faire progresser les objectifs de condamnation; enfin, nous signalons certaines des questions en suspens qui nécessiteraient une étude plus approfondie

    Molecular Blocking of CD23 Supports Its Role in the Pathogenesis of Arthritis

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    BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23

    The Death Throes of a Stripped Massive Star: An Eruptive Mass-Loss History Encoded in Pre-Explosion Emission, a Rapidly Rising Luminous Transient, and a Broad-Lined Ic Supernova SN2018gep

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    We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.3 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The rapid rise to peak bolometric luminosity and blue colors at peak (t_(rise)∼0.5-3 days, L_(bol)≳3×10^(44) erg sec^(−1), g−r = −0.3) resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) < 4.9×10^(48) erg, a limit on X-ray emission L_X < 10^(40) erg sec^(−1), and a limit on radio emission νL_ν ≲ 10^(37) erg sec^(−1). Taken together, we find that the data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3×10^(14)cm) that was ejected in eruptive pre-explosion mass-loss episodes

    Genome-Wide Search Reveals the Existence of a Limited Number of Thyroid Hormone Receptor Alpha Target Genes in Cerebellar Neurons

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    Thyroid hormone (T3) has a major influence on cerebellum post-natal development. The major phenotypic landmark of exposure to low levels of T3 during development (hypothyroidism) in the cerebellum is the retarded inward migration of the most numerous cell type, granular neurons. In order to identify the direct genetic regulation exerted by T3 on cerebellar neurons and their precursors, we used microarray RNA hybridization to perform a time course analysis of T3 induced gene expression in primary cultures of cerebellar neuronal cell. These experiments suggest that we identified a small set of genes which are directly regulated, both in vivo and in vitro, during cerebellum post-natal development. These modest changes suggest that T3 does not acts directly on granular neurons and mainly indirectly influences the cellular interactions taking place during development

    Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova: Pre-explosion Emission and a Rapidly Rising Luminous Transient

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    We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 ± 0.1 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L_(bol) ≳ 3×10^(44) erg sec^(−1)), the short rise time (t_(rise) = 3 days in g-band), and the blue colors at peak (g−r ∼ −0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56

    The Death Throes of a Stripped Massive Star: An Eruptive Mass-Loss History Encoded in Pre-Explosion Emission, a Rapidly Rising Luminous Transient, and a Broad-Lined Ic Supernova SN2018gep

    Get PDF
    We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.3 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The rapid rise to peak bolometric luminosity and blue colors at peak (t_(rise)∼0.5-3 days, L_(bol)≳3×10^(44) erg sec^(−1), g−r = −0.3) resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) < 4.9×10^(48) erg, a limit on X-ray emission L_X < 10^(40) erg sec^(−1), and a limit on radio emission νL_ν ≲ 10^(37) erg sec^(−1). Taken together, we find that the data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3×10^(14)cm) that was ejected in eruptive pre-explosion mass-loss episodes

    Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

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    Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
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