Fecal glucocorticoids and anthropogenic injury and mortality in North Atlantic right whales Eubalaena glacialis

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Endangered Species Research 34 (2017): 417-429, doi:10.3354/esr00866.As human impacts on marine ecosystems escalate, there is increasing interest in quantifying sub-lethal physiological and pathological responses of marine mammals. Glucocorticoid hormones are commonly used to assess stress responses to anthropogenic factors in wildlife. While obtaining blood samples to measure circulating hormones is not currently feasible for free-swimming large whales, immunoassay of fecal glucocorticoid metabolites (fGCs) has been validated for North Atlantic right whales Eubalaena glacialis (NARW). Using a general linear model, we compared fGC concentrations in right whales chronically entangled in fishing gear (n = 6) or live-stranded (n = 1), with right whales quickly killed by vessels (n = 5) and healthy right whales (n = 113) to characterize fGC responses to acute vs. chronic stressors. fGCs in entangled whales (mean ± SE: 1856.4 ± 1644.9 ng g-1) and the stranded whale (5740.7 ng g-1) were significantly higher than in whales killed by vessels (46.2 ± 19.2 ng g-1) and healthy whales (51.7 ± 8.7 ng g-1). Paired feces and serum collected from the live-stranded right whale provided comparison of fGCs in 2 matrices in a chronically stressed whale. Serum cortisol and corticosterone in this whale (50.0 and 29.0 ng ml-1, respectively) were much higher than values reported in other cetaceans, in concordance with extremely elevated fGCs. Meaningful patterns in fGC concentration related to acute vs. chronic impacts persisted despite potential for bacterial degradation of hormone metabolites in dead whales. These results provide biological validation for using fGCs as a biomarker of chronic stress in NARWs.This research was funded by the NOAA/NMFS, Office of Naval Research Marine Mammals and Biology Program, Northeast Consortium, Island Foundation, Irving Oil, NEAq Internal Research Fund, Prescott Grant NA08NMF4390590, and NOAA CINAR Cooperative Agreement NA09OAR4320129

Hematologic, Hepatic, Renal, and Lipid Laboratory Monitoring After Initiation of Combination Antiretroviral Therapy in the United States, 2000–2010

We assessed laboratory monitoring following combination antiretroviral therapy (cART) initiation among 3,678 patients in a large US multi-site clinical cohort, censoring participants at last clinic visit, cART change, or three years. Median days (interquartile range) to first hematologic, hepatic, renal and lipid tests were 30 (18–53), 31 (19–56), 33 (20–59) and 350 (96–1106), respectively. At one year, approximately 80% received more than two hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received one or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities

Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence

To estimate the association between immunologic response to antiretroviral therapy (ART) and non-AIDS-defining cancer (NADC) incidence in HIV-infected patients

Incidence and Timing of Cancer in HIV-Infected Individuals Following Initiation of Combination Antiretroviral Therapy

Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Measurement as relational, intensive and inclusive: Towards a ‘minor’ mathematics

Minor mathematics refers to the mathematical practices that are often erased by state-sanctioned curricular images of mathematics. We use the idea of a minor mathematics to explore alternative measurement practices. We argue that minor measurement practices have been buried by a ‘major’ settler mathematics, a process of erasure that distributes ‘sensibility’ and formulates conditions of mathematics dis/ability. We emphasize how measuring involves the making and mixing of analogies, and that this involves attending to intensive relationships rather than extensive properties. Our philosophical and historical approach moves from the archeological origins of human measurement activity, to pivotal developments in modern mathematics, to configurations of curriculum. We argue that the project of proliferating multiple mathematics is required in order to disturb narrow (and perhaps white, western, male) images of mathematics—and to open up opportunities for a more pluralist and inclusive school mathematics