An introduction to Elinor Glyn : her life and legacy

This special issue of Women: A Cultural Review re-evaluates an author who was once a household name, beloved by readers of romance, and whose films were distributed widely in Europe and the Americas. Elinor Glyn (1864–1943) was a British author of romantic fiction who went to Hollywood and became famous for her movies. She was a celebrity figure of the 1920s, and wrote constantly in Hearst's press. She wrote racy stories which were turned into films—most famously, Three Weeks (1924) and It (1927). These were viewed by the judiciary as scandalous, but by others—Hollywood and the Spanish Catholic Church—as acceptably conservative. Glyn has become a peripheral figure in histories of this period, marginalized in accounts of the youth-centred ‘flapper era’. Decades on, the idea of the ‘It Girl’ continues to have great pertinence in the post-feminist discourses of the twenty-first century. The 1910s and 1920s saw the development of intermodal networks between print, sound and screen cultures. This introduction to Glyn's life and legacy reviews the cross-disciplinary debate sparked by renewed interest in Glyn by film scholars and literary and feminist historians, and offers a range of views of Glyn's cultural and historical significance and areas for future research

Human resources for health challenges of public health system reform in Georgia

<p>Abstract</p> <p>Background</p> <p>Human resources (HR) are one of the most important components determining performance of public health system. The aim of this study was to assess adequacy of HR of local public health agencies to meet the needs emerging from health care reforms in Georgia.</p> <p>Methods</p> <p>We used the Human Resources for Health Action Framework, which includes six components: HR management, policy, finance, education, partnerships and leadership. The study employed: (a) quantitative methods: from September to November 2004, 30 randomly selected district Centers of Public Health (CPH) were surveyed through face-to-face interviews with the CPH director and one public health worker randomly selected from all professional staff; and (b) qualitative methods: in November 2004, Focus Group Discussions (FGD) were held among 3 groups: a) 12 district public health professionals, b) 11 directors of district public health centers, and c) 10 policy makers at central level.</p> <p>Results</p> <p>There was an unequal distribution of public health workers across selected institutions, with lack of professionals in remote rural district centers and overstaffing in urban centers. Survey respondents disagreed or were uncertain that public health workers possess adequate skills and knowledge necessary for delivery of public health programs. FGDs shed additional light on the survey findings that there is no clear vision and plans on HR development. Limited budget, poor planning, and ignorance from the local government were mentioned as main reasons for inadequate staffing. FGD participants were concerned with lack of good training institutions and training programs, lack of adequate legislation for HR issues, and lack of necessary resources for HR development from the government.</p> <p>Conclusion</p> <p>After ten years of public health system reforms in Georgia, the public health workforce still has major problems such as irrational distribution and inadequate knowledge and skills. There is an urgent need for re-training and training programs and development of conducive policy environment with sufficient resources to address these problems and assure adequate functionality of public health programs.</p

SPT-CL J0205-5829: A z = 1.32 Evolved Massive Galaxy Cluster in the South Pole Telescope Sunyaev-Zel'dovich Effect Survey

The galaxy cluster SPT-CL J0205-5829 currently has the highest spectroscopically-confirmed redshift, z=1.322, in the South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. XMM-Newton observations measure a core-excluded temperature of Tx=8.7keV producing a mass estimate that is consistent with the Sunyaev-Zel'dovich derived mass. The combined SZ and X-ray mass estimate of M500=(4.9+/-0.8)e14 h_{70}^{-1} Msun makes it the most massive known SZ-selected galaxy cluster at z>1.2 and the second most massive at z>1. Using optical and infrared observations, we find that the brightest galaxies in SPT-CL J0205-5829 are already well evolved by the time the universe was <5 Gyr old, with stellar population ages >3 Gyr, and low rates of star formation (<0.5Msun/yr). We find that, despite the high redshift and mass, the existence of SPT-CL J0205-5829 is not surprising given a flat LambdaCDM cosmology with Gaussian initial perturbations. The a priori chance of finding a cluster of similar rarity (or rarer) in a survey the size of the 2500 deg^2 SPT-SZ survey is 69%.Comment: 11 pages, 5 figures, submitted to Ap

Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer

Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34+/VEGFR-2+) as well as their progenitor cell population CD133+/CD34+ and the population of CD34+ stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy

Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications.

Methylation of cytosine deoxynucleotides generates 5-methylcytosine (m(5)dC), a well-established epigenetic mark. However, in higher eukaryotes much less is known about modifications affecting other deoxynucleotides. Here, we report the detection of N(6)-methyldeoxyadenosine (m(6)dA) in vertebrate DNA, specifically in Xenopus laevis but also in other species including mouse and human. Our methylome analysis reveals that m(6)dA is widely distributed across the eukaryotic genome and is present in different cell types but is commonly depleted from gene exons. Thus, direct DNA modifications might be more widespread than previously thought.M.J.K. was supported by the Long-Term Human Frontiers Fellowship (LT000149/2010-L), the Medical Research Council grant (G1001690), and by the Isaac Newton Trust Fellowship (R G76588). The work was sponsored by the Biotechnology and Biological Sciences Research Council grant BB/M022994/1 (J.B.G. and M.J.K.). The Gurdon laboratory is funded by the grant 101050/Z/13/Z (J.B.G.) from the Wellcome Trust, and is supported by the Gurdon Institute core grants, namely by the Wellcome Trust Core Grant (092096/Z/10/Z) and by the Cancer Research UK Grant (C6946/A14492). C.R.B. and G.E.A. are funded by the Wellcome Trust Core Grant. We are grateful to D. Simpson and R. Jones-Green for preparing X. laevis eggs and oocytes, F. Miller for providing us with M. musculus tissue, T. Dyl for X. laevis eggs and D. rerio samples, and to Gurdon laboratory members for their critical comments. We thank U. Ruether for providing us with M. musculus kidney DNA (Entwicklungs- und Molekularbiologie der Tiere, Heinrich Heine Universitaet Duesseldorf, Germany). We also thank J. Ahringer, S. Jackson, A. Bannister and T. Kouzarides for critical input and advice, M. Sciacovelli and E. Gaude for suggestions.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nsmb.314

Chitohexaose Activates Macrophages by Alternate Pathway through TLR4 and Blocks Endotoxemia

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.