Unfinished Decolonisation and Globalisation

This article locates John Darwin’s work on decolonisation within an Oxbridge tradition which portrays a British world system, of which formal empire was but one part, emerging to increasing global dominance from the early nineteenth century. In this mental universe, decolonisation was the mirror image of that expanding global power. According to this point of view, it was not the sloughing off of individual territories, but rather the shrinking away of the system and of the international norms that supported it, until only its ghost remained by the end of the 1960s. The article then asks, echoing the title of Darwin’s Unfinished Empire, whether the decolonisation project is all but complete, or still ongoing. In addition, what is the responsibility of the imperial historian to engage with, inform, or indeed refrain from, contemporary debates that relate to some of these issues? The answer is twofold. On the one hand, the toolkit that the Oxbridge tradition and Darwin provide remains relevant, and also useful in thinking about contemporary issues such as China’s move towards being a global power, the United States’ declining hegemony, and some states and groups desires to rearticulate their relationship with the global. On the other hand, the decline of world systems of power needs to be recognised as just one of several types of, and approaches to, analysing ‘decolonisation’. One which cannot be allowed to ignore or marginalise the study of others, such as experience, first nations issues, the shaping of the postcolonial state, and empire legacies. The article concludes by placing the Oxbridge tradition into a broader typology of types and methodologies of decolonisation, and by asking what a new historiography of decolonisation might look like. It suggests that it would address the Oxbridge concern with the lifecycles of systems of power and their relationship to global changes, but also place them alongside, and in dialogue with, a much broader set of perspectives and analytical approaches

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Families, children, and memories: Britons in India, 1857-1947.

This dissertation explores how British middle-class families residing in India between the mid-nineteenth and mid-twentieth centuries raised their children and conducted private life. The sanctity of the domestic sphere and the importance of family intimacy that symbolized the ideal bourgeois household in Britain were complicated by the perceived need to send young children away from this setting in India. Most parents believed India's hot climate and racially inferior population posed cultural and physical threats to white children. In addition, education in the metropole was considered essential if children were to possess a high cultural, social, and racial status as adults, and many therefore left India when their schooling began. Some parents could not afford to send their children back to Britain for their entire education, however, and temporarily had them taught at home or enrolled them at schools in India established for European and mixed-race pupils. Because of their clientele's racial and social diversity, these Indian schools lacked prestige and limited the opportunities of children attending them. Children who went to school in Britain often returned overseas as adults to embark upon colonial careers or marriages resembling those of their parents. Both preexisting family connections with India as well as the British schools they attended helped perpetuate traditions of Indian work and residence. Multigenerational colonial life in turn contributed to the way members and descendants of such families have glorified lengthy associations with India after it became independent in 1947, contributing extensive oral and written commentary featuring prominently in media productions of imperial nostalgia popular in the late twentieth century. Source materials consulted for this analysis include published manuals on raising British children in a colonial setting, case studies of schooling options in both Britain and India, and personal narratives such as letters, diaries, and retrospective oral and written renditions of childhood and family life. This project contrasts these modes of representation and reviews the claims and valuable material offered by each.Ph.D.Asian historyEuropean historyIndividual and family studiesModern historySocial SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131173/2/9840509.pd

Effectiveness of community-based nonpharmacological interventions for early-stage dementia: conclusions and recommendations

In 2007, a comprehensive review of the extant research on nonpharmacological interventions for persons with early-stage dementia was conducted. More than 150 research reports, centered on six major domains, were included: early-stage support groups, cognitive training and enhancement programs, exercise programs, exemplar programs, health promotion programs, and “other” programs not fitting into previous categories. Theories of neural regeneration and plasticity were most often used to support the tested interventions. Recommendations for practice, research, and health policy are outlined, including evidence-based, nonpharmacological treatment protocols for persons with mild cognitive impairment and early-stage dementia. A tested, community-based, multimodal treatment program is also described. Overall, findings identify well-supported nonpharmacological treatments for persons with early-stage dementia and implications for a national health care agenda to optimize outcomes for this growing population of older adults

Geochemical and textural investigations of the Eoarchean Ukaliq supracrustals, Northern Québec (Canada)

co-auteur étrangerInternational audienceStructural, geochronological and geochemical studies of pre-3.75 Ga rocks of volcano-sedimentary protoliths in the Inukjuak domain in the Superior Province in Québec have been mostly focused on the Nuvvuagittuq Supracrustal Belt (NSB). The Porpoise Cove outcrops – at the southwestern limit of the NSB – are the de-facto “type locality” for the supracrustals of the Inukjuak Complex. Yet, it remains unclear whether the NSB rocks are geochemically distinct from, or are in fact common to, a host of other supracrustal enclaves locked in the dominantly gneissic Inukjuak domain. Here, we report detailed textural and geochemical studies for a suite of rocks from the Ukaliq Supracrustal Belt (USB), located approximately 3 km northeast of the NSB. We find that the USB and NSB have a similar protracted metamorphic history; both experienced amphibolite grade metamorphism and contain granitoid gneiss sheets, quartz-magnetite rocks (banded iron-formation s.l.) and quartz-biotite schists within amphibolitized rocks of basaltic affinity with local retrogressions. If the various Inukjuak supracrustal belts were once a part of a larger coherent (now dismembered) terrane, they should show similar emplacement ages and source chemistry. New zircon Usingle bondPb geochronology from five gneissic units and two quartz-biotite (metasedimentary) schists reveal the oldest emplacement ages across all units of each individual rock type to be 3.68 ± 0.07 Ga (granitoid gneisses) and 3.65 ± 0.06 Ga (quartz-biotite schists). These new ages are similar to those documented as likely minimum emplacement ages of the NSB determined by Usingle bondPb geochronology. Zircons from the quartz-biotite schist were also analyzed by ion microprobe for their Usingle bondPb geochronology and were found to yield statistically identical, albeit more precise, ages than those obtained by LA-ICP-MS. Possible detrital zircons from the USB quartz-biotite schists were analyzed by ion microprobe for their coupled δ30SiNBS28 and δ18OVSMOW values with respective values between −0.75 and − 0.07‰ (δ30SiNBS28), and + 5.61 and + 6.59‰ (δ18OVSMOW). The δ18OVSMOW values, which are on average above mantle-derived zircon, indicate contribution of altered, non-mantle, derived material into the source of the rocks that weathered to form the quartz-biotite schists. Zircon mineral inclusions (quartz, feldspar, apatite, biotite, muscovite and other unrecognized Fe/Al/Si rich phases), along with the major- and trace element contents for the rocks were analyzed to substantiate this interpretation. Together with δ30SiNBS28, δ18OVSMOW, our results suggest that lithologies like authigenic silica and serpentinized rocks re-melted to form the parent melts that gave rise to zircons found in the USB quartz-biotite schists. Additional Lusingle bondHf studies reported here on the same zircons also show similarities with NSB zircons. The εHf values showed a positive correlation with the measured Usingle bondPb age from −22.7 ± 0.8 to +1.9 ± 1.1. The Lusingle bondHf system also reveals that the USB, extracted at ca. 3.8 Ga, carries isotopic signatures of an older Hadean reservoir, having been formed from an Eoarchean mafic melt that incorporated them. Taken together, this supports a co-genetic origin for the NSB and the USB

Evidence supporting exercise interventions for persons in early-stage Alzheimer's disease

The purpose of this article is to grade research evidence supporting exercise-based interventions for persons with early-stage dementias and to report the recommendations of a consensus panel. The search produced 11 databased articles testing the effects of exercise interventions in a variety of outcomes. The body of evidence to support exercise interventions in the prevention and treatment of Alzheimer's disease is growing and has potential as a treatment modality following translational studies in recreation therapy and other fields