107 research outputs found

    Consecutive Misdemeanor Sentencing: Curing The Inequity

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    Trophodynamics of krill and its potential role in blue whale feeding in the Perth Canyon, south-east Indian Ocean

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    Migrating blue whales along the Western Australian coast exhibit feeding behaviour within the Perth Canyon, which is an area of high krill abundance, particularly for Euphausia recurva. The importance of krill in marine food webs has led to a number of trophodynamic studies investigating their fatty acid and stable isotope compositions. In the south-east Indian Ocean, the suppression of upwelling by the dominant Leeuwin Current results in relatively oligotrophic waters, particularly during autumn and winter. Oligotrophic waters tend to be dominated by small autotrophic flagellates (i. e. dinoflagellates) and cyanobacteria. We relate biochemical data obtained for E. recurva, as well as Stylocheiron carinatum and Pseudeuphausia latifrons with their potential food source, phytoplankton, and one of their potential predators, the endangered pygmy blue whale (Balaenoptera musculus brevicauda) sampled in the Perth Canyon. Fatty acids of all three krill species were dominated by polyunsaturated fatty acids (PUFA; ~50%) largely comprised of omega-3 PUFA, which is typical for krill. The high docosahexaenoic acid (DHA) to eicosapentaenoic acid (EPA) ratio reflects a dinoflagellate, rather than a diatom diet, and the high oleic acid (18: 1 9) to vaccenic acid (18: 1 7) ratio is indicative of an omnivorous diet. Stable isotope analysis positions E. recurva as a first, possibly second order consumer (5. 8 - 8. 4 15N)and phytoplankton as the likely source of carbon (-18 to -24 13C) .The fatty acid composition of krill did not match that of the surface phytoplankton sampled, which was low in PUFA and more reflective of degraded and detrital material. This suggests that krill are not feeding at the surface, and may feed closer to the deep chlorophyll maximum. The outer blubber layer sampled from the pygmy blue whale was high in monounsaturated fatty acids (MUFA, 58%) rather than PUFA, and did not reflect the krill fatty acid composition. However, the high DHA to EPA ratio in the blubber indicated a diet originating from dinoflagellates, as found for krill. Stratification of fatty acids across blubber layers is common for marine mammals and the outer blubber layer for some species has been found to not accurately reflect the diet of the animal

    Social Work Theories and Practice with Battered Women: A Conflict-of-Values Analysis

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    In the 1970s, wife abuse became a concern of sociologists, feminists, and family theorists. The new perspectives they brought to the problem, which focused more on social factors than on individual pathology, challenged social workers to examine how their practice and assumptions perpetuated the problem. This article investigates how the social work literature has been affected by new theories of domestic violence and analyzes the impact that these theories have had on practice with battered women.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67024/2/10.1177_088610998700200205.pd

    Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa

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    Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy

    Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

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    BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease

    Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

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    BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≄100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≀0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.
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