Kenneth Lewis Roberts Correspondence

Entries include brief biographical information, a typed biography, typed and handwritten correspondence on personal stationery from Kennebunk Beach, Maine, including a humorous letter in 1933 concerning the Society for Helping Maine Literature, his belief that the author collection was in need of Arnoldiana such as a donated pike head handmade by Arnold\u27s blacksmiths for the attack on Quebec, the manuscript of Arundel sent to be opened after publication and loaned to Leonard for Doubleday Doran and Company and a surprising Western Union telegram requesting permanent loan of the manuscript for MIT, handwritten and typed correspondence from Roberts in Italy including a handwritten artistic postcard from his wife, numerous biographical newspaper review clippings with photographic images, book synopses, and a poem for Theodore Roosevelt who could remember neither the author nor title of the book he was reading, a research question concerning Maine people on cookery, notes through the years concerning his friends, the staff at Doubleday, historians, libraries, and librarians as well as transition at the Maine Development Commission, correspondence with Mary A. Benjamin on Walter R. Benjamin, Autographs, stationery and a postcard concerning the possible sale of a copy of a Maine land grant document, a gift instead from Roberts of his vellum copy of the Trelawny-Goodyear grant of 1631, and the reply of Stubbs from the Maine State Library on receipt of this copy of the Casco Bay land grant

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

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

Kenneth Lewis Roberts Correspondence

Entries include brief biographical information, a typed biography, typed and handwritten correspondence on personal stationery from Kennebunk Beach, Maine, including a humorous letter in 1933 concerning the Society for Helping Maine Literature, his belief that the author collection was in need of Arnoldiana such as a donated pike head handmade by Arnold\u27s blacksmiths for the attack on Quebec, the manuscript of Arundel sent to be opened after publication and loaned to Leonard for Doubleday Doran and Company and a surprising Western Union telegram requesting permanent loan of the manuscript for MIT, handwritten and typed correspondence from Roberts in Italy including a handwritten artistic postcard from his wife, numerous biographical newspaper review clippings with photographic images, book synopses, and a poem for Theodore Roosevelt who could remember neither the author nor title of the book he was reading, a research question concerning Maine people on cookery, notes through the years concerning his friends, the staff at Doubleday, historians, libraries, and librarians as well as transition at the Maine Development Commission, correspondence with Mary A. Benjamin on Walter R. Benjamin, Autographs, stationery and a postcard concerning the possible sale of a copy of a Maine land grant document, a gift instead from Roberts of his vellum copy of the Trelawny-Goodyear grant of 1631, and the reply of Stubbs from the Maine State Library on receipt of this copy of the Casco Bay land grant

Kenneth Lewis Roberts Correspondence

Entries include brief biographical information, a typed biography, typed and handwritten correspondence on personal stationery from Kennebunk Beach, Maine, including a humorous letter in 1933 concerning the Society for Helping Maine Literature, his belief that the author collection was in need of Arnoldiana such as a donated pike head handmade by Arnold\u27s blacksmiths for the attack on Quebec, the manuscript of Arundel sent to be opened after publication and loaned to Leonard for Doubleday Doran and Company and a surprising Western Union telegram requesting permanent loan of the manuscript for MIT, handwritten and typed correspondence from Roberts in Italy including a handwritten artistic postcard from his wife, numerous biographical newspaper review clippings with photographic images, book synopses, and a poem for Theodore Roosevelt who could remember neither the author nor title of the book he was reading, a research question concerning Maine people on cookery, notes through the years concerning his friends, the staff at Doubleday, historians, libraries, and librarians as well as transition at the Maine Development Commission, correspondence with Mary A. Benjamin on Walter R. Benjamin, Autographs, stationery and a postcard concerning the possible sale of a copy of a Maine land grant document, a gift instead from Roberts of his vellum copy of the Trelawny-Goodyear grant of 1631, and the reply of Stubbs from the Maine State Library on receipt of this copy of the Casco Bay land grant

Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome

Noonan syndrome (MIM 163950) is an autosomal dominant disorder characterized by dysmorphic facial features, proportionate short stature and heart disease (most commonly pulmonic stenosis and hypertrophic cardiomyopathy). Webbed neck, chest deformity, cryptorchidism, mental retardation and bleeding diatheses also are frequently associated with this disease. This syndrome is relatively common, with an estimated incidence of 1 in 1,000-2,500 live births. It has been mapped to a 5-cM region (NS1) [corrected] on chromosome 12q24.1, and genetic heterogeneity has also been documented. Here we show that missense mutations in PTPN11 (MIM 176876)-a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2, which contains two Src homology 2 (SH2) domains-cause Noonan syndrome and account for more than 50% of the cases that we examined. All PTPN11 missense mutations cluster in interacting portions of the amino N-SH2 domain and the phosphotyrosine phosphatase domains, which are involved in switching the protein between its inactive and active conformations. An energetics-based structural analysis of two N-SH2 mutants indicates that in these mutants there may be a significant shift of the equilibrium favoring the active conformation. This implies that they are gain-of-function changes and that the pathogenesis of Noonan syndrome arises from excessive SHP-2 activity

Samuel Stouffer and Relative Deprivation

This paper first offers a tribute to Samuel Stouffer (1900–1960), a major contributor to social psychology. He helped to establish probability surveys as a useful method for social science, led three major studies at midcentury, and introduced important new concepts and statistical methods. Thus, both conceptually and methodologically, he shaped modern social psychology. Second, the paper revitalizes Stouffer’s most famous concept—relative deprivation. A new meta-analysis demonstrates that relative deprivation predicts a wide range of important outcomes, so long as it measures resentment with data from individuals and is paired with dependent variables of similar scope. Unfortunately, sociology largely abandoned the concept because it failed to meet the overstated early claims made for it in the collective protest domain. The history of this use and disuse of relative deprivation is summarized and critiqued