Search

Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on n=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04492-1.

The death of a husband had adverse economic effects for the majority of Victorian women, but for working-class mothers the threat of destitution was an almost inevitable feature of widowhood. Widows, with some restrictions, were entitled to outdoor relief under the Poor Law Amendment Act (1834), and they comprised the largest group of adult paupers outside of the workhouse well into the early twentieth century, outnumbered only and always by their children. Able-bodied widows therefore presented crucial opportunities for poor-law officials in the quest to minimize outdoor relief and make significant reductions in welfare spending. Focusing particularly on the 1830s, 1840s, and 1870s (the first decade of the so-called ‘crusade’ against out-relief), this article examines the competing discourses of deservingness and deception that dominated the representations and treatment of able-bodied widows in poor law legislation, orders, reports, and parliamentary debates. An uneasy combination of sympathy and suspicion shaped officials’ treatment of these women, rendering them ambiguous figures in the dominant dichotomy of the deserving and undeserving poor, potential drains on the economic prosperity of the state, threats to the nuclear family, and, by extension, a danger to the nation’s moral core. These discourses, I suggest, reflect a wider ideological unease with, and attempts to mitigate and police, the widow’s exceptional social status in Victorian Britain as a woman with sexual experience, potential economic independence, and yet no male guardian.

The widow was a much-satirized figure throughout the Victorian era, but humour has rarely featured in studies concerned with the period’s attitudes towards women and death. Widows, whose behaviour ...

We report an outbreak of coronavirus disease with 74 cases related to a nightclub in Germany in March 2020. Staff members were particularly affected (attack rate 56%) and likely caused sustained viral transmission after an event at the club. This outbreak illustrates the potential for superspreader events and corroborates current club closures.

Background Several sub-Saharan African countries use digital financial services to improve health financing, especially for maternal and child health. In cooperation with the Malagasy Ministry of Health, the NGO Doctors for Madagascar is implementing a mobile health wallet for maternal health care in public-sector health facilities in Madagascar. Our aim was to explore the enabling and limiting factors related to the usability and acceptance of the Mobile Maternal Health Wallet (MMHW) intervention during its implementation. Methods We conducted a cross-sectional, mixed methods study with mothers and pregnant women and facility- (FBHWs) and community-based (CHWs) health workers from public-sector health facilities in three districts of the Analamanga region in Madagascar. We used a convergent design in collecting and analyzing quantitative and qualitative data. We performed one-stage proportional sampling of women who had signed up for the MMHW. All FBHWs and CHWs at primary care facilities in the intervention area were eligible to participate. Results and significance 314 women, 76 FBHWs, and 52 CHWs were included in the quantitative survey. Qualitative data were extracted from in-depth interviews with 12 women and 12 FBHWs and from six focus group discussions with 39 CHWSs. The MMHW intervention was accepted and used by health workers and women from different socioeconomic backgrounds. Main motivations for women to enroll in the intervention were the opportunity to save money for health (30.6%), electronic vouchers for antenatal ultrasound (30.2%), and bonus payments upon reaching a savings goal (27.9%). Main motivation for health workers was enabling pregnant women to save for health, thus encouraging facility-based deliveries (57.9%). Performance-based payments had low motivational value for health workers. Key facilitators were community sensitization, strong women-health worker relationship, decision making at the household level, and repetitive training on the use of the MMHW. Key barriers included limited phone ownership, low level of digital literacy, disinformation concerning the effects of the intervention, and technical problems like slow payout processes.

Background Detailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic. Aim We aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany. Methods Between March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset. Results Median age was 35 years (range 18–74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7–14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively. Conclusion Our study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.

Despite a free TB care policy, access to TB care in rural Madagascar is limited due to a markedly underfunded health care system. The World Health Organization estimated the yearly TB incidence in Madagascar at 238 cases per 100,000 people in 2020; only half of the patients with TB are being notified and treated. We describe the development, implementation, and lessons learned of an intervention to improve TB care services in a remote, rural district in southern Madagascar. We involved national, regional, and local stakeholders in assessing the multifaceted challenges in a remote, rural area and codesigning activities to address them. The overarching principles of the intervention were to (1) promote national TB guidelines, (2) build on best practices, and (3) prioritize low-cost activities to enable scale-up. An in-depth assessment of challenges in accessing and delivering TB care resulted in the following prioritization of activities: (1) fostering community engagement, (2) decentralizing service provision, (3) improving quality of care, (4) providing nutritional support, and (5) ensuring staff support and supervision. The intervention was launched in September 2019 and is ongoing as of October 2022. During mobile TB clinics conducted between September 2019 and December 2020, 4,982 presumptive patients were screened and 1,706 (34.2%) have been diagnosed with TB. Based on 2010-2020 official TB notification data, we calculated trend-adjusted additional TB notifications during the intervention, resulting in a 2.6-fold increase in cases in 2019-2020. The intervention district's TB notification rate increased from 178 cases per 100,000 people in 2018 to 424 cases per 100,000 people in 2020. Involving stakeholders from all levels of care was perceived as a key to success. The unexpected increase in the number of patients with TB in the intervention district overburdened the current paper-based TB notification system and emphasized the need for expanded diagnostics and social support services.

Summary Background In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. Methods A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. Findings Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3–4·3) and the median serial interval was 4·0 days (3·0–5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0–99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2–32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6–8·9; 11 of 217) among non-household, high-risk contacts. Interpretation Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. Funding All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Background: In December 2019, a newly identified coronavirus (SARS-CoV-2) emerged in Wuhan, China, causing respiratory disease (COVID-19) presenting with fever

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose-reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non-treatment-related occurrence supports the pathogenetic role of pre-existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.

Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups: community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.

Mobile savings and payment systems have been widely adopted to store money and pay for a variety of services, including health care. However, the possible implications of these technologies on financing and payment for maternal health care services-which commonly require large 1-time out-of-pocket payments-have not yet been systematically assessed in low-resource settings.The aim of this study was to determine the structural, contextual, and experiential characteristics of a mobile phone-based savings and payment platform, the Mobile Health Wallet (MHW), for skilled health care during pregnancy among women in Madagascar.We used a 2-stage cluster random sampling scheme to select a representative sample of women utilizing either routine antenatal (ANC) or routine postnatal care (PNC) in public sector health facilities in 2 of 8 urban and peri-urban districts of Antananarivo, Madagascar (Atsimondrano and Renivohitra districts). In a quantitative structured survey among 412 randomly selected women attending ANC or PNC, we identified saving habits, mobile phone use, media consumptions, and perception of an MHW with both savings and payment functions. To confirm and explain the quantitative results, we used qualitative data from 6 semistructured focus group discussions (24 participants in total) in the same population.59.3% (243/410, 95% CI 54.5-64.1) saved toward the expected costs of delivery and, out of those, 64.4% (159/247, 95% CI 58.6-70.2) used household cash savings for this purpose. A total of 80.3% (331/412, 95% CI 76.5-84.1) had access to a personal or family phone and 35.7% (147/412, 95% CI 31.1-40.3) previously used Mobile Money services. Access to skilled health care during pregnancy was primarily limited because of financial obstacles such as saving difficulties or unpredictability of costs. Another key barrier was the lack of information about health benefits or availability of services. The general concept of an MHW for saving toward and payment of pregnancy-related care, including the restriction of payments, was perceived as beneficial and practicable by the majority of participants. In the discussions, several themes pointed to opportunities for ensuring the success of an MHW through design features: (1) intuitive technical ease of use, (2) clear communication and information about benefits and restrictions, and (3) availability of personal customer support.Financial obstacles are a major cause of limited access to skilled maternal health care in Madagascar. An MHW for skilled health care during pregnancy was perceived as a useful and desirable tool to reduce financial barriers among women in urban Madagascar. The design of this tool and the communication strategy will likely be the key to success. Particularly important dimensions of design include technical user friendliness and accessible and personal customer service.

BACKGROUND Mobile savings and payment systems have been widely adopted to store money and pay for a variety of services, including health care. However, the possible implications of these technologies on financing and payment for maternal health care services—which commonly require large 1-time out-of-pocket payments—have not yet been systematically assessed in low-resource settings. OBJECTIVE The aim of this study was to determine the structural, contextual, and experiential characteristics of a mobile phone–based savings and payment platform, the Mobile Health Wallet (MHW), for skilled health care during pregnancy among women in Madagascar. METHODS We used a 2-stage cluster random sampling scheme to select a representative sample of women utilizing either routine antenatal (ANC) or routine postnatal care (PNC) in public sector health facilities in 2 of 8 urban and peri-urban districts of Antananarivo, Madagascar (Atsimondrano and Renivohitra districts). In a quantitative structured survey among 412 randomly selected women attending ANC or PNC, we identified saving habits, mobile phone use, media consumptions, and perception of an MHW with both savings and payment functions. To confirm and explain the quantitative results, we used qualitative data from 6 semistructured focus group discussions (24 participants in total) in the same population. RESULTS 59.3% (243/410, 95% CI 54.5-64.1) saved toward the expected costs of delivery and, out of those, 64.4% (159/247, 95% CI 58.6-70.2) used household cash savings for this purpose. A total of 80.3% (331/412, 95% CI 76.5-84.1) had access to a personal or family phone and 35.7% (147/412, 95% CI 31.1-40.3) previously used Mobile Money services. Access to skilled health care during pregnancy was primarily limited because of financial obstacles such as saving difficulties or unpredictability of costs. Another key barrier was the lack of information about health benefits or availability of services. The general concept of an MHW for saving toward and payment of pregnancy-related care, including the restriction of payments, was perceived as beneficial and practicable by the majority of participants. In the discussions, several themes pointed to opportunities for ensuring the success of an MHW through design features: (1) intuitive technical ease of use, (2) clear communication and information about benefits and restrictions, and (3) availability of personal customer support. CONCLUSIONS Financial obstacles are a major cause of limited access to skilled maternal health care in Madagascar. An MHW for skilled health care during pregnancy was perceived as a useful and desirable tool to reduce financial barriers among women in urban Madagascar. The design of this tool and the communication strategy will likely be the key to success. Particularly important dimensions of design include technical user friendliness and accessible and personal customer service.

Multidrug-resistant organisms (MDRO) have been developing as an emerging problem in allogeneic hematopoietic cell transplantation (HCT). Since no data are available on the course of MDRO colonization after HCT, we investigated in this retrospective, single-center study, persistence and clearance of MDRO after HCT. From June 2010 to December 2015, 121 consecutive HCT patients were included. Patients received a MDRO screening before conditioning as well as surveillance cultures after HCT. In MDRO-colonized patients, surveillance specimens were taken until MDRO were no longer detectable. Thirty-three patients (27%) were found to be colonized by at least one MDRO at any time point until day 100 post HCT. Day 100 (2-year) non-relapse mortality (NRM) and overall survival (OS) of MDRO-colonized (MDRO+) versus non-colonized (MDRO−) patients were essentially the same. NRM is 15% (21%) versus 15% (24%). Two-year OS is 60 versus 55% for MDRO+ versus MDRO− patients. Out of the 33 MDRO+ patients, 21 cleared the MDRO. Median time to non-detectability of MDRO was 6 months. In 12 patients, the MDRO persisted. There was a significant (p

There exists a considerable amount of research focused on the female body in the Victorian period, from texts such as Krugovoy Silver's exploration of anorexic female bodies to Talairach-Vielmas's ...

SummaryMyelodysplastic syndromes (MDSs) are a heterogeneous group of myeloid neoplasms with defects in hematopoietic stem and progenitor cells (HSPCs) and possibly the HSPC niche. Here, we show that patient-derived mesenchymal stromal cells (MDS MSCs) display a disturbed differentiation program and are essential for the propagation of MDS-initiating Lin−CD34+CD38− stem cells in orthotopic xenografts. Overproduction of niche factors such as CDH2 (N-Cadherin), IGFBP2, VEGFA, and LIF is associated with the ability of MDS MSCs to enhance MDS expansion. These factors represent putative therapeutic targets in order to disrupt critical hematopoietic-stromal interactions in MDS. Finally, healthy MSCs adopt MDS MSC-like molecular features when exposed to hematopoietic MDS cells, indicative of an instructive remodeling of the microenvironment. Therefore, this patient-derived xenograft model provides functional and molecular evidence that MDS is a complex disease that involves both the hematopoietic and stromal compartments. The resulting deregulated expression of niche factors may well also be a feature of other hematopoietic malignancies.

Grain non-oriented electrical steel has its main application in electrical motors and its microstructure significantly influences their efficiency. The objective of this work was to investigate whether or not magnetic field applied during annealing process affects grain growth and the development of important texture components leading to an improvement of the magnetic properties. GNO Fe-3.25%Si 75% cold rolled specimens were annealed inside magnetic field with strength of 17 T at the temperature of 800°C for 3, 10 and 30 minutes. Results of average grain size after magnetic annealing showed a microstructure formed by small grains and a few very large grains. Magnetic field did not increase orientation density of {100} oriented grains and Goss grains but was able to increase density of θ fiber and decrease the density of γ fiber.

Over the past decade, the detective widow has become a well-established character in the little-explored subgenre of neo-Victorian crime fiction. In Tasha Alexander's Lady Emily series, the author argues, the detective widow investigates the gendered characteristics and com- plexities of Victorian widowhood while detecting the artistic crimes associated with historical fiction's imitations and adaptations of the past. In outlining the scope of the academic journal Neo-Victorian Studies, Marie-Luise Kohlke describes neo-Victorianism as "the contemporary fascination with reimagining the nineteenth century and its varied literary, artistic, socio-political and historical contexts"; this fascination is "perhaps most evident in the proliferation of so-called neo-Victorian novels" ("Aims and Scopes"). Fictional revisitings of the nineteenth century by authors such as A. S. Byatt, Michel Faber, Amitav Ghosh, and Sarah Waters have topped bestseller lists and have begun to form part of a neo-Victorian canon that, since the turn of the new millennium, has begun to receive significant critical attention. 1 Despite this burgeoning aca- demic interest in literary manifestations of the neo-Victorian, however, critics have largely neglected neo-Victorian crime fiction. 2 This essay considers the significance of one partic- ularly striking feature of recent examples in the subgenre: the figure of the detective widow. A dilettante sleuth, this character strives to break, or at least occasionally transgress, the boundaries of respectable femininity, not only through her investigative association with the crimes of others but also through her own deviant (if not criminal) intellectual pur- suits (usually in the form of certain reading and/or writing activities) as well as her partial disregard for mourning customs and other matters of social etiquette. This figure, who usu

This is an introduction for the Journal of Gender Studies discussing the feminisms, sex and the body debate.

Chromosomal abnormalities have been shown to play a major role in disease evolution of multiple myeloma. Specific changes in interphase cells can be detected by fluorescent in situ hybridization, which overcomes the problem of the lack of dividing cells required for conventional cytogenetics.We analyzed the prognostic value of 12 frequent chromosomal abnormalities detected by fluorescent in situ hybridization in a series of patients (n=315) with newly diagnosed, symptomatic multiple myeloma. All patients underwent frontline autologous stem cell transplantation according to the GMMG-HD3- or GMMG-HD4-trial protocols or analogous protocols.Univariate statistical analyses revealed that the presence of del(13q14), del(17p13), t(4;14), +1q21 and non-hyperdiploidy was associated with adverse progression-free and overall survival rates independently of the International Staging System (ISS) classification. Multivariate analyses showed that only t(4;14) and del(17p13) retained prognostic value for both progression-free and overall survival. According to the presence or absence of t(4;14) and del(17p13) and the patients' International Staging System classification, the cohort could be stratified into three distinct groups: a group with a favorable prognosis [absence of t(4;14)/del(17p13) and ISS I], a group with a poor prognosis [presence of t(4;14)/del(17p13) and ISS II/III] and a group with an intermediate prognosis (all remaining patients). The probabilities of overall survival at 5 years decreased from 72% in the favorable prognostic group to 62% (hazard ratio 2.4; P=0.01) in the intermediate and 41% (hazard ratio 5.6; P0.001) in the poor prognostic groups.These results have implications for risk-adapted management for patients with multiple myeloma undergoing high-dose chemotherapy followed by autologous stem cell transplantation and suggest that new treatment concepts are urgently needed for patients who belong to the poor prognosis group. As targeted therapies evolve, different treatment options might have variable success, depending on the underlying genetic nature of the clone.

Systemic mastocytosis (SM) is characterized by abnormal proliferation and accumulation of mast cells (MC) in various tissues and organs, predominantly skin, bone marrow (BM) and visceral organs. The extent of organ infiltration and subsequent organ damage is the basis for the classification of SM into indolent SM (ISM), smoldering SM (SSM), SM with associated clonal hematologic non-MC lineage disease (SM-AHNMD), aggressive SM (ASM) and MC leukemia (MCL). Depending on the subtype of SM, cell source (BM or peripheral blood) and assay sensitivity, an acquired mutation in the receptor tyrosine kinase KIT, usually KIT D816V, is detectable in 80-90% of patients. Next-Generation Deep Amplicon Sequencing (NGS) was performed to investigate 18 candidate genes at known mutational hotspot regions as previously described. Additional mutations in genes encoding for signaling molecules (JAK2, CBL, KRAS, NRAS), transcription factors (RUNX1), epigenetic regulators (ASXL1, DNMT3A, EZH2, TET2) or splicing factors (SRSF2, SF3B1, U2AF1) are detectable in the vast majority of patients KIT D816V+ advanced SM. In order to gain more insight into clonal evolution of myeloid progenitors in indolent and advanced SM with or without AHNMD, we explored the mutation profile of single-cell-derived CFU-GM colonies - by using Sanger sequencing - in 19 KIT D816V+ SM patients (investigated colonies, n=285; median per patient, n=15; range 10-30). The study included 7 patients with ISM/SSM/ASM (0 additional mutations), 4 patients with SM-AHNMD (median 1 additional mutation, range 1-4) and 8 patients with ASM-AHNMD (median 3 additional mutations, range 1-4). KIT D816V+ CFU-GM could be identified in all 8 patients with ASM ± AHNMD but in only 20% (1/5) of patients with SM-AHNMD, while all CFU-GM colonies derived from ISM patients were completely KIT D816V negative. On the other hand, CFU-GM colonies from individual ASM ± AHNMD patients were never entirely KIT D816V+ (median 60%, range 0-95). In contrast to KIT D816V, additional mutations were identified in CFU-GM colonies from all 12 multi-mutated (A)SM-AHNMD patients and many of these mutations were present in 100% of the CFU-GM-derived colonies analyzed. In 8 patients, different subclones with variable proportions of the number of mutated genes were identified and allowed to generate putative evolutionary trees. These mutations included TET2 and SRSF2 mutations in 6/6 and 4/4 patients with (A)SM-AHNMD. In contrast, ASXL1 mutations were not identified in all TET2/SRSF2 positive CFU-GM colonies suggesting that they are likely to occur later than TET2 and SRSF2. When additional mutations and KIT D816V were detected concomitantly in individual single-cell-derived CFU-GM colonies, the overall frequency of CFU-GM colonies positive for additional mutations was always higher than those that were KIT D816V positive, indicating that the KIT D816V mutation was a secondary event. In contrast to advanced SM, all ISM patients were negative for additional mutations. CFU-GM colonies and also microdissected CD15+ cells derived from BM biopsies were entirely KIT D816V negative in these patients, highlighting that the KIT D816V mutation may be restricted to other (probably later) stages of stem cell development and possibly only to the MC lineage. In general, the relative proportion of KIT D816V+ progenitors correlated well with established parameters for quantification of disease burden, e.g. BM MC infiltration, serum tryptase levels and KIT D816V allele burden in individual patients. In conclusion, the presence of multi-mutated myeloid non-MC lineage progenitors of the CFU-GM-type suggests an initial clonal expansion at an early stage of hematopoietic development due to mutations other than KIT D816V with a subsequent phenotype modification towards SM due to a later acquisition of KIT D816V. In contrast, ISM/SSM is not affected by mutations at the CFU-GM level which may at least in part explain its excellent prognosis. Disclosures Schnittger: MLL Munich Leukemia Laboratory: Other. Horny:Novartis: Consultancy, Honoraria. Haferlach:MLL: Equity Ownership. Valent:Novartis: Consultancy. Reiter:Novartis: Consultancy, Honoraria.

The synthesis of a polycyclic heterocyclic ring system compound, ethyl 7-hydroxy-4-oxo-2-phenyl-4,5-dihydro-3H-benzo[6,7]cyclohepta[1,2-d]pyrimidine-6-carboxylate was carried out by condensation of benzamidine on diethyl 5,9-dihydroxy-7H-benzo[a]cycloheptene-6,8-dicarboxylate, after opening and then closure of the seven membered ring.

Introduction: Postfeminism and Contemporary Hollywood Cinema Joel Gwynne and Nadine Muller PART I: POSTFEMINIST FEMININITIES 1. Neo-Feminism In-Between: Female Cosmopolitan Subjects in Contemporary American Film Ana Moya 2. Querying Postfeminism in Lisa Cholodenko's The Kids Are All Right Clara Bradbury-Rance 3. The Slut that Wasn't: Virginity, (Post)Feminism and Representation in Easy A Katherine Farrimond 4. The Girls of Zeta: Sororities, Ideal Femininity and the Makeover Paradigm in The House Bunny Joel Gwynne 5. Ageing Appropriately: Postfeminist Discourses of Ageing in Contemporary Hollywood Imelda Whelehan PART II: POSTFEMINIST MASCULINITIES 6. 'Chuck Flick': A Genealogy of the Postfeminist Male Singleton Benjamin A. Brabon 7. The Chick's 'New Hero': (Re)Constructing Masculinity in the Postfeminist 'Chick Flick' Amy Burns 8. Hollywood Fatherhood: Paternal Postfeminism in Contemporary Popular Cinema Hannah Hamad 9. Mancaves and Cushions: Marking Masculine and Feminine Domestic Space in Postfeminist Romantic Comedy Lauren Jade Thompson 10. 'We're not making forward progress': Postfeminist Hypermasculinity in Heat Vincent M. Gaine PART III: POSTFEMINISM AND GENRE 11. Towards a New Sexual Conservatism in Postfeminist Romantic Comedy Alexia Bowler 12. Hell is a Teenage Girl? Postfeminism and Contemporary Teen Horror Martin Fradley 13. 'A New Feminist Revolution in Hollywood Comedy'?: Postfeminist Discourses and the Critical Reception of Bridesmaids Helen Warner 14. Blood, Sweat and Tears: Women, Sport and Hollywood Katharina Lindner

Since the first decades of the twentieth century and the publication of Lytton Strachey’s Eminent Victorians (1918), through to the 1960s and Steven Marcus’s The Other Victorians: A Study of Sexuality and Pornography in Mid-Nineteenth-Century Victorian England (1964), the nineteenth century has been (re)defined according to its sexual politics, not least in order to contrast perceived Victorian conservativeness with later generations’ sense of their own modernity. At the turn of the new millennium, neo-Victorian fiction, through its compulsive return to matters of sex and gender, continues this sexualization of the past, a phenomenon which Marie-Luise Kohlke has termed the ‘neo-Victorian sexsation’, and which, as in previous decades, still frequently serves to ‘conveniently reassert our own supposedly enlightened stance towards sexuality and social progress’ by sexually ‘liberating’ the past and its fictional heroines.1

The synthesis of a polycyclic heterocyclic ring system compound, ethyl 7-hydroxy-4-oxo-2-phenyl-4,5-dihydro-3H-benzo[6,7]cyclohepta[1,2-d]pyrimidine-6-carboxylate was carried out by condensation of benzamidine on diethyl 5,9-dihydroxy-7H-benzo[a]cycloheptene-6,8-dicarboxylate, after opening and then closure of the seven membered ring.

Background: The soluble transferrin receptor (sTfR) is established as a test for iron deficiency (ID). In chronic lymphocytic leukemia (CLL), sTfR is not reliable for screening for ID as the latter is strongly dependent on tumor burden. Methods: We investigated whether the influence of the tumor load can be excluded or minimized using the sTfR/log ferritin ratio (TfR-F-Index) and the C-reactive protein (CRP)-adjusted TfR-F-Index in 87 patients with CLL. sTfR was measured nephelometrically (normal: 0.81–1.75 mg/L). A cut-off value of 1.5 for the TfR-F-Index and 0.8 for the CRP-adjusted TfR-F-Index, in patients with a CRP >5 mg/L, was used. Results: All Binet A patients had normal sTfR values (1.34±0.2 mg/L), TfR-F-Index (0.67±0.2) and a CRP-adjusted TfR-F-Index. In Binet B and C, sTfR and the TfR-F-Index were significantly increased compared to Binet A patients (p

AIM. Expression changes of D-type cyclins are thought to be an early event in the genesis of Multiple Myeloma and are associated with distinct cytogenetic aberrations. These aberrations appear with different percentages (“clonal” or “subclonal”) in a given patient. We assessed whether the height of CCND expression assessed by gene expression profiling and quantitative RT-PCR (qRT-PCR) correlates with the presence of clonal or subclonal aberrations of 11q13, t(11;14) and t(4;14). PATIENTS AND METHODS. 128 newly diagnosed MM-patients (65 training (TG)/63 independent validation group (VG)) and 14 normal donors (ND) were included. Bone marrow aspirates were CD138-purified by activated magnetic cell sorting. RNA was in-vitro transcribed and hybridised to Affymetrix HG U133 A+B GeneChip (TG) and HG U133 2.0 plus array (VG). CCND1 and CCND2 expression was verified by real time RT-PCR and western blotting. iFISH was performed on purified MM-cells using probesets for chromosomes 1q21, 9q34, 11q23, 11q13, 13q14, 15q22, 17p13, 19q13, 22q11 and the translocations t(4;14) and t(11;14). Clonal aberrations were defined as being present in >60%, subclonal aberrations in 20 to 60% of MMC in a given patient. Expression data were gcrma normalised and a Kruskal-Wallis rank sum test used (Bioconductor). RESULTS. 11q13+. CCND1 (208711_s_at, 208712_at) is significantly higher (p CONCLUSION. An additional copy of 11q13 or t(11;14) correlates with increased CCND1 and decreased CCND2 expression, a t(4;14) is associated with an increase of CCND2 and a decrease of CCND1 expression. In each case, the height of the CCND-expression is significantly different whether the respective aberration is clonal or subclonal. Thus, when interpreting expression data in the context of cytogenetic aberrations, it is important to consider if plasma cells carry a respective aberration in a subclonal/clonal pattern.