Статті в журналах з теми "Labour contract alteration"

The article is dedicated to the detection of the specific features of scientific work which determine the specificity of the legal regulation of the labour relations of scientists and scholars. The author provides a general characteristic of the legal status of the researcher and analyses the exceptions from general rules stipulated by Russian legislation as well as the additional rules for the conclusion, alteration and termination of the labour contract with the said category of workers, their qualifications, working conditions and salaries.

Pregnancy in insulin-dependent diabetes mellitus is associated with a greater incidence of fetal abnormality. Animal studies suggested that increased free-radical production and antioxidant depletion may contribute to this risk. The objective of this work was to evaluate oxidative stress and antioxidant capacity in hypertensive, diabetics, and healthy control women during labor. Simultaneous determination of antioxidant enzymes activities, namely glutathione peroxidase (GSH-Px), glutathione reductase (GSH-red), superoxide dismutase (SOD), total antioxidant, and lipid peroxides measured as thiobarbituric acid-reactive substances (TBARS) levels, were carried out in maternal plasma during labor. Plasma GSH-Px activity was found to be significantly increased as it doubled in hypertensive, and diabetic women when compared with healthy control women (P<0.05). In contrast, plasma SOD activity was significantly decreased in both groups when compared to the control group (P<0.05). No significant differences were detected in GSH-Red activity between diabetic, hypertensive and control groups. Alterations in antioxidant enzyme activities were accompanied by a significant increase in the levels of plasma lipid peroxides in hypertensive and diabetic women during labor. Plasma levels of total antioxidants were significantly increased in diabetic women as compared with the control group. Based on our results, it may be concluded that enhanced generation of oxidative stress causes alteration of antioxidant capacity in diabetic and hypertensive women during labor. Alterations in antioxidant and prooxidant components may result in various complications including peroxidation of vital body molecules which may be regarded as an increased risk factor for pregnant women as well as the fetus.

’’Active ageing’’ policies have been presented as a potential panacea for the conflict between generations many argue will result from demographic ageing. Indeed, as part of a new intergenerational contract, older individuals (here defined as those aged 50-64) are expected to re-engage with, and remain in, the labour market longer. However, this implies all individuals experience the same policy mix. This study uses micro-level data to address changes to work and retirement policies for older individuals from 1995 to 2005, and the resultant alterations to the degree of choice in terms of labour market participation different sub-groups within this age cohort had. The data demonstrate that the policy shift towards ’’active ageing’’ is not universally applied to all older individuals as some retain the ability to early exit from the labour market. Thus the notion of a single intergenerational contract is overly simplistic and neglects a great deal of intragenerational difference.

Extracellular Ca2+ is normally required for myometrial cells to contract. Ca2+ enters muscle cells mainly through voltage-dependent Ca2+ channels (VDCCs) that open in response to action potentials. The synthesis of myometrial VDCCs may change during pregnancy to alter excitation-contraction coupling. We investigated the mRNA levels for the alpha 1- and beta-subunits of the L-type VDCC in rat myometrium to determine whether alterations are associated with term or preterm labor. RNA isolated from myometrial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) using specific primers designed according to the published sequences of the VDCC subunits. From pregnant rat myometrium, two distinct PCR products were obtained for the alpha 1-subunit: one of the expected size at 372 bp and a smaller at 339 bp. Sequence analysis of the larger product revealed a 99.5 or 88% sequence homology between rat myometrium and rat aorta or rabbit heart, respectively, and the smaller product had an identical sequence to a 33-bp deletion. The two alpha 1-products followed the same trend throughout pregnancy. VDCC alpha 1-mRNA levels increased gradually to 6.9-fold just before labor on day 22 but decreased during labor. However, the beta-subunit mRNA level increased sharply on day 22 and then also declined during labor. Progesterone treatment from day 19 to day 22 inhibited term delivery and prevented the significant increase in alpha 1-mRNA levels. In contrast, antiprogesterone (onapristone, ZK-98.299) treatment on day 17 caused a statistically significant increase in the alpha 1- and beta-VDCC subunit mRNA after 8 and 15 h, respectively, then a decrease during preterm labor at 24 h. We conclude that mRNA levels for the VDCC subunits increase before term and preterm labor but decline during periods when VDCCs are likely at their peaks. The increase in levels of mRNA for VDCC likely reflects changes in expression of VDCCs during periods of term and preterm labor that may facilitate uterine contractility required for this process. Progesterone withdrawal or blockade appears to be responsible for regulating levels of mRNA for VDCC in the myometrium in preparation for labor.

The smooth muscle cells of the uterus contract in unison during delivery. These cells achieve coordinated activity via electrical connections called gap junctions which consist of aggregated connexin proteins such as connexin43 and connexin45. The density of gap junctions governs the excitability of the myometrium (among other factors). An increase in gap junction density occurs immediately prior to parturition. We extend a mathematical model of the myometrium by incorporating the voltage-dependence of gap junctions that has been demonstrated in the experimental literature. Two functional subtypes exist, corresponding to systems with predominantly connexin43 and predominantly connexin45, respectively. Our simulation results indicate that the gap junction protein connexin45 acts as a negative modulator of uterine excitability, and hence, activity. A network with a higher proportion of connexin45 relative to connexin43 is unable to excite every cell. Connexin45 has much more rapid gating kinetics than connexin43 which we show limits the maximum duration of a local burst of activity. We propose that this effect regulates the degree of synchronous excitation attained during a contraction. Our results support the hypothesis that as labour approaches, connexin45 is downregulated to allow action potentials to spread more readily through the myometrium.

Philosophical treatments of core value concepts often abstract from the troubled history and fractured present of the societies to which those concepts are meant to apply. In the case of the political tradition of liberal democratic thought, stretching from the social contract theories of the seventeenth and eighteenth centuries up through contemporary writers, the notion of individual freedom or liberty is central. However, often that idea, and the assumption of its foundational value for persons, is specified from the perspective of those who enjoy it rather than those struggling to attain it. Moreover, the social spaces that theories of justice that locate freedom as a central value have continue to bracket out of existence the patterns of enslavement, oppression and domination that mark all social spaces. This article attempts a reappraisal of certain dominant understandings of the idea of freedom in both historical and contemporary philosophical discourse in light of this alteration of perspective. Specifically, the current practices of coercive labor, trafficking, irregular labor migration, and other forms of “marginal” social lives are brought into focus in order to guide this reappraisal. The article argues that if we assess these conditions as modes of unfreedom then we must utilize an account of freedom that diverges significantly from those dominant notions. A sketch of this alternative, positive, conception of freedom is then offered.

Parthenocarpy, the pollination-independent fruit set, can raise the productivity of the fruit set even under adverse factors during the reproductive phase. The application of plant hormones stimulates parthenocarpy, but artificial hormones incur extra financial and labour costs to farmers and can induce the formation of deformed fruit. This study examines the performance of parthenocarpic mutants having no transcription factors of SlIAA9 and SlTAP3 and sldella that do not have the protein-coding gene, SlDELLA, in tomato (cv. Micro-Tom). At 0 day after the flowering (DAF) stage and DAFs after pollination, the sliaa9 mutant demonstrated increased pistil development compared to the other two mutants and wild type (WT). In contrast to WT and the other mutants, the sliaa9 mutant with pollination efficiently stimulated the build-up of auxin and GAs after flowering. Alterations in both transcript and metabolite profiles existed for WT with and without pollination, while the three mutants without pollination demonstrated the comparable metabolomic status of pollinated WT. Network analysis showed key modules linked to photosynthesis, sugar metabolism and cell proliferation. Equivalent modules were noticed in the famous parthenocarpic cultivars ‘Severianin’, particularly for emasculated samples. Our discovery indicates that controlling the genes and metabolites proffers future breeding policies for tomatoes.

Women develop important changes in their cardiovascular and respiratory systems during pregnancy. They also have important changes in their immune system which are necessary to tolerate foreign fetal tissue. These expected alterations can increase the likelihood of poor outcomes with certain respiratory infections, especially viral infection. There is extensive literature describing COVID-19 in pregnant women, and there is evidence that this virus can infect the placenta, raising implications for maternal-fetal transmission. Women who contract COVID-19 during pregnancy are at increased risk of preterm labor and other perinatal complications when compared to non-pregnant women. Trials on the safety and efficacy of the COVID-19 vaccines during pregnancy are in progress; several reproductive societies have recommended that women who are planning to get pregnant or are pregnant should get vaccination since there are few reports of adverse events in pregnant women who have received vaccines. Healthcare providers will need to address concerns of infertility, the possibility of vertical transmission, and neonatal infection with women regarding timely vaccination against this disease and other necessary precautions. Keywords: coronavirus, COVID-19, pregnancy, placental pathology, vertical transmission

Labor and a vaginal delivery trigger changes in peripheral organs that prepare the mammalian fetus to survive ex utero. Surprisingly little attention has been given to whether birth also influences the brain, and to how alterations in birth mode affect neonatal brain development. These are important questions, given the high rates of cesarean section (C-section) delivery worldwide, many of which are elective. We examined the effect of birth mode on neuronal cell death, a widespread developmental process that occurs primarily during the first postnatal week in mice. Timed-pregnant dams were randomly assigned to C-section deliveries that were yoked to vaginal births to carefully match gestation length and circadian time of parturition. Compared with rates of cell death just before birth, vaginally-born offspring had an abrupt, transient decrease in cell death in many brain regions, suggesting that a vaginal delivery is neuroprotective. In contrast, cell death was either unchanged or increased in C-section–born mice. Effects of delivery mode on cell death were greatest for the paraventricular nucleus of the hypothalamus (PVN), which is central to the stress response and brain–immune interactions. The greater cell death in the PVN of C-section–delivered newborns was associated with a reduction in the number of PVN neurons expressing vasopressin at weaning. C-section–delivered mice also showed altered vocalizations in a maternal separation test and greater body mass at weaning. Our results suggest that vaginal birth acutely impacts brain development, and that alterations in birth mode may have lasting consequences.

We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), gamma-linolenic acid (GLA, 18:3, n-6) or arachidonic acid (AA, 20:4, n-6) in concentrations of 0 (control), 20 or 100 microM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0.1 micro g/ml) or dexamethasone (DEX, 5 microM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF(2alpha) and PGE(2). Supplementation with LA inhibited the production of PGF(2alpha) but did not alter PGE(2), whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE(2) to PGF(2alpha) (E:F ratio) two- to threefold. In control cells, OT and LPS challenges stimulated the production of PGF(2alpha) and PGE(2). In all challenge groups, the concentrations of PGF(2alpha) in response to PUFAs followed the same pattern - LA<control<;GLA<AA - but there were significant alterations in responsiveness as a result of PUFA treatment. In the cells supplemented with 100 microM AA, there was no further increase in PGF(2alpha) output in the presence of OT or LPS and when 100 microM GLA was present neither LPS nor OT stimulated PGE(2) significantly. When LPS was given to AA-supplemented cells, the E:F ratio was increased. DEX did not change PGE(2) production in control or LA-treated cells, but the cells produced significantly less PGF(2alpha), so the E:F ratio was increased. In contrast, in GLA- and AA-treated cells, DEX reduced the production of both PGF(2alpha) and PGE(2), so the E:F ratio was unaltered. In summary, the study showed altered production of PGs in the presence of different PUFAs according to their position in the n-6 metabolic pathway. The type of PUFA present affected responsiveness to OT, LPS and DEX and also changed the ratio of PGE(2) to PGF(2alpha) produced. The possible implications of this work are discussed in relation to the effect of diet on term and pre-term labour, which both require upregulation of the endometrial PG synthetic pathway.

This paper is aimed at analyzing the changing pattern of prostitution. However, the definition of the act of prostitution has been metamorphosing for centuries from acceptable to illegal and then (in some jurisdictions) to criminal again, agitations by advocates have also necessitated the nomenclatural alteration from “prostitution” to “commercial sex work”. The paper examined how development in information and communication technology allows commercial sex workers to make connections with clients through internet and sell sex on this platform. Globalization processes has also changed the pattern of this business to a transnational activity. Although there are many willing transnational commercial sex workers, but organized criminal syndicates are using this development to traffic some women and children with the false promises of getting a lucrative from overseas but ultimately subject them to sex exploitation, child prostitution and sex labor. As is the plight of some Nigerian women in Italy and other European, Middle Eastern and Asian countries, many women from developing countries are recruited into this institution through human trafficking. As a result of commercial sex many women and girls suffer sexual violence, sex exploitation, sexual abuse and contract STDs. To curtail these problems, governments and transnational institutions are therefore urged to develop mechanisms that can tackle these problems by providing women with decent employment opportunities and increase surveillance across national borders.

Background: Pregnancy is a very crucial time in a woman’s life. In this period of time, not only multiple physiological alterations effect the usual health status but also makes women more vulnerable to contract infection and face negative sequalae. Hepatitis C, a blood borne viral infection serve the similar fate when encountered by pregnant ladies. This study is based on exploring the prevalence of the Hepatitis C virus seropositivity among pregnant population. Moreover, we also evaluated the major risk factors leading to the infection in these mothers. Besides this, infected mothers were studied for their pregnancy outcomes.Methods: In this study 114 pregnant females were observed for this cross-sectional study. It was conducted in Gynecology Unit- 1, Liaquat University Hospital Hyderabad, for the period of January 2017 to July 2017. Chi square test was applied for statistical analysis on SPSS version 16. The criteria for enrollment in the study was set to be a pregnant lady belonging to age group 20-35 years; having singleton pregnancy; was a booked case at the hospital with compliant to antenatal follow ups; admitted to the labor room for delivery. All the non-pregnant ladies, whom had co morbid conditions such as hypertension or diabetes or had infected with hepatitis B or D were excluded from the study. Furthermore, pregnant ladies with multiple gestion or those who were either diagnosed of hepatitis C prior to conceive or had a previous history of hepatitis C were also excluded.Results: Present study revealed that out of 114, 10(8.8%) pregnant ladies were found seropositive for Hepatitis C virus. Prior history for transfusion of blood was the Foremost risk factor discovered, with 60.5% women reported this. History of surgery was the 2nd commonest factor and 43.9% had this in their medical records. On the other hand, only 8.8% women gave the history for previous evacuation. While observing pregnancy outcomes, we found 48.2% neonates had low birth weight, 41.2% were born preterm and 21.1% had low APGAR score.Conclusions: In a nutshell hepatitis c is prevalent in the pregnant population of this region and showing its effects in the form of compromised pregnancies. History of blood transfusion and previous surgery were found to be chief risk factors in the study.

Environmental oestrogens, class of endocrine-disrupting chemicals, are defined as compounds that bind the oestrogen receptors and elicit or modulate an ER-mediated response. Examples of suspected environmental oestrogenic chemicals include plastic components such as bisphenol A (BPA) and some components of detergents and their biodegradation products, 4-octylphenol (OP). The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed endometrial waves or contractile waves. The balanced contractile waves play an important role in regulating oestrus or menstrual cycles, implantation, maintaining pregnancy, and parturition. The uterine contraction has been known to be regulated by contraction-associated proteins such as oxytocin, oxytocin receptor (OTR), connexin 43, prostaglandin F2 alpha receptor (FP), and 15-hydroxy prostaglandin dehydrogenase (PDGH). Endogenous steroid hormones including oestrogen and progesterone have been shown to regulate contraction-associated proteins and, thereby, modify uterine contraction. Forty female immature rats were divided into 8 groups, each group composed of 5 rats. They were injected subcutaneously daily for 3 days with BPA and OP at doses of 20, 100, and 500 mg kg–1 of BW per day; 17β-estradiol (E2, 40 µg kg–1 per day) was a positive control. After 24 h of the final treatment, the rats were euthanized and the uteri were collected for further experiments. Total RNA and protein were extracted from uteri. The mRNA expressions for CaBP-9k, oxytocin, OTR, FP, and PDGH were determined by real-time PCR with specific primers, and the protein levels were examined by Western blot assay. The data were analyzed using a one-way ANOVA. The P-values <0.05 were considered statistically significant. The treatment of oestrogenic compounds significantly regulated the contraction-associated proteins. First, the mRNA levels of CaBP-9k that is a biomarker for evaluating oestrogenicity in the rats were significantly induced by positive control, E2. Chemicals OP and BPA at doses of 100 and 500 mg kg–1 also induced the gene expression of CaBP-9k. Oxytocin and OTR were highly augmented by OP (40 fold) and BPA (6-fold) at a dose of 500 mg kg–1 compared with control, whereas PDGH was moderately upregulated by the chemicals. Interestingly, FP was decreased by E2 and high doses of OP and BPA. These results showed that exposure of immature rats to BPA and OP regulated expression of oxytocin, OTR, PDGH, and FP genes in the rat uterus. Taken together, uterine contraction and physiological conformational change of the uterus were affected by exposure to oestrogenic endocrine-disrupting chemicals. Because balanced contractile activity of the uterus maintains regular menstrual cycles, pregnancy, and labor, alteration of the contractility raised by oestrogenic compounds may cause severe adverse effects on the female reproductive system.

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks three major drug-targetable receptors, ER, PR, and HER2. TNBC patients have much worse 5-year survival rates (60%) in contrast to 90% for other breast cancer subtypes and display highly heterogeneous molecular profiles, cellular phenotypes, and drug responses, which poses major challenges in patient treatments. The tumor suppressor gene TP53 is mutated in 30% of breast tumors overall and but highly prevalent (~80%) in TNBC. Unlike mutations in other tumor suppressor genes that are predominantly loss-of-function deletions or truncations, TP53 mutations occur mostly as &gt;100 different missense mutations within the DNA binding domain, implying that the mutant proteins may exert both loss-of-function activities and gain of distinct neomorphic functions, thus contributing to phenotypic heterogeneity of TNBC. When we characterized systematically a panel of MCF10A cell lines expressing 10 most prevalent missense mutant p53 proteins, the cell lines indeed displayed highly diverse neomorphic cellular phenotypes distinct from those of p53-knockdown cells. To investigate molecular mechanisms underlying the heterogeneity, we then performed RNA-Seq and pathway analysis and identified the key pathways, such as the Hippo/YAP pathway, that were dysregulated correlatively with phenotypic aggressiveness of the mutant p53 cell lines. In addition, ChIP-Seq analysis revealed that promoter binding capacity and preference of mutant p53 proteins associated with more aggressive phenotypes were more severely affected, especially for the genes in the dysregulated pathways identified from RNA-Seq analysis. These demonstrated collectively that different missense p53 mutations lead to heterogeneous phenotypes by exerting distinct neomorphic molecular functions. Further, given that TP53 mutations by themselves cannot drive full cancer progression, these imply that cells with different p53 missense mutations need distinct sets of additional “co-driver” mutations and alteration of cellular programs specific to each mutation for full cancer progression, representing potential molecular targets for personalized therapies. Supporting this hypothesis, when we performed genome-wide in vitro CRISPR screens in search of co-driver mutations specific to different p53 mutations, a unique set of hits was identified for each mutant p53-expressing cell lines. However, in in vivo mouse xenograft models, even the cells expressing aggressive p53 mutants such R273C failed to develop tumors upon transducing gene-deleting CRISPR gRNA libraries at high MOI. Based on reasoning that development of tumor requires mutations in both tumor suppressors and oncogenes, we then performed CRISPR screens on the p53-R273C cells overexpressing MYC, a known oncogene for TNBC, and observed tumor formation within 9 weeks, only after the CRISPR library transduction. By next-generation sequencing of the gRNA cassettes amplified from the tumors, &gt;20 novel co-driver candidates in addition to known tumor suppressors such as NF2 and PTEN were identified. Interestingly, ARAF, a proto-oncogene, was one of the top candidates found in multiple tumors, and the targeted sequencing confirmed out-of-frame deletions resulting in truncated proteins with only the N-term Ras-binding domain. We are currently validating the functional relevance of these findings in conjunction with the dysregulated pathways identified from RNA-Seq and ChIP-Seq analysis. Taken together, our integrated approach of utilizing phenotyping, multi-omics bioinformatics analysis, and screening has revealed the molecular mechanisms underlying phenotypic and molecular heterogeneity and potential molecular targets of TNBC. Citation Format: Dustin Grief, Anasuya Pal, Laura Gonzalez-Malerva, Seron Eaton, Chenxi Xu, Grant Christensen, Joy Blain, Nicholas Mellor, Jason Steel, Chitrak Gupta, Ellen Streitwieser, Abhishek Singharoy, Jin Park, Joshua LaBaer. A genome-wide functional genomics screen reveals unique co-driver mutations of mutant TP53 promoting cellular heterogeneity during breast cancer progression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-05.

Introduction: Inherited predisposition to myeloid malignancies in adults may be more common than previously suggested with recent studies suggesting a prevalence of candidate predisposition alleles in 15-20% of patients. An inherited predisposition may not be considered in older AML patients despite significant clinical implications for family members as potential stem cell transplant donors. To better define the role of inherited genetic alterations in older AML patients , we analyzed a unique cohort of newly diagnosed older (&gt;60 years) patients enrolled in) Beat AML® Master Trial(BAMT) for candidate genes associated with a known or putative inherited cancer predisposition. Methods: We analyzed extracted DNA from skin and/or saliva samples compared to paired leukemia samples of 176 AML patients enrolled in the BAMT. All samples underwent genomic profiling using a modified FoundationOne®Heme platform (capture-based) and/or the Oregon Health Sciences University panel (amplicon-based), evaluating 477 and 220 genes respectively, with a known role in hematologic malignancies. Germline(GL) variants were identified by the haplotype-based Bayesian genetic variant detector FreeBayes and using variant allele frequency(VAF) values. The pathogenicity and clinical significance of the variants was interpreted according to the 2015 ACMG/AMP guidelines while the AMP/CAP/ASCO guidelines and various disease databases were used in the somatic variant calls. Results: -The mutational landscape of the 176 newly diagnosed older AML patients is detailed in Table 1. Our cohort has a higher proportion of adverse risk patients, consistent with an older AML patient population. 27 pathogenic or likely pathogenic GL variants were detected in 24 AML patients, with a germline mutation prevalence of 14% in this cohort. Deleterious GL mutations were found in the gene DDX41 (5), followed by SBDS (4), CHEK2 (4), MPL (3), BRCA2 (2), HAX1 (2), DNAH9 (2), FANCA (1), FANCL (1), SAMD9 (1), BLM (1), and ATM (1) (Table 2). The types of mutations included missense mutations (9), nonsense mutations (8), frameshift mutations (7), splice site mutations (2), and an exonic deletion (1). Family history of leukemia was available on 129 patients from this cohort. 12 patients have at least one family member with AML. Of these 12 patients, 2 had a deleterious GL alteration identified. Along with the 14% prevalence of pathogenic/likely pathogenic GL mutations , there were an additional 181 GL variants of unknown significance (VUS) in 102 patients, seen in genes implicated in inherited predisposition to hematologic malignancies, most commonly variants in DOCK8 and CREBBP(&gt;5% VUS) with both genes being implicated in leukemogenesis . As skin and/or saliva samples were collected at the time of AML diagnosis, tumor-in-normal presence was expectedly observed. The median VAF for somatic mutations was significantly lower (p &lt; 0.0001) in skin (median 6%; mean 9%; standard deviation (SD) 10%; N=562 variants) than in saliva (median 17%; mean 21%; SD 16%; N=368 variants). In 37 patients who had both saliva and skin tissue concomitantly ,skin had a significantly lower tumor-in-normal presence (median VAF 5%, mean 8%, SD 8%;) than saliva (median 15%, mean 20%, SD 16%)(p &lt; 0.0001). Conclusions: We found a prevalence of 14% pathogenic/ likely pathogenic GL mutations in cancer predisposition genes in this unique cohort of newly diagnosed older AML patients. This finding has potential clinical implications for patients and family members. We also found a large number of VUS in genes implicated in hematological malignancies. Additional studies linking candidate VUS' to familial predisposition to understand contribution to AML predisposition are needed. We are in the process of comparing the manual curation of ACMG classification of pathogenicity with a computational curation algorithm to assess the potential for automated classification of GL variants. Our study suggests the choice of source for germline DNA in patients with AML is variably impacted by leukemic contamination. Cultured skin fibroblasts are the current standard for tumor-normal paired genotyping, with the caveat of being labor intensive and not routinely performed in clinical diagnostic laboratories. This is a critical consideration for rapid GL screening of patients and family members with hematologic malignancies and suspected cancer predisposition. Disclosures Borate: Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Stein:Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Patel:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dava Oncology: Honoraria; France Foundation: Honoraria. Baer:Astellas: Research Funding; Abbvie: Research Funding; AI Therapeutics: Research Funding; Forma: Research Funding; Incyte: Research Funding; Kite: Research Funding; Takeda: Research Funding. Stock:Agios: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Daiichi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria. Schiller:Bristol Myer Squibb: Research Funding; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Agios: Research Funding, Speakers Bureau; Amgen: Other, Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding. Blum:AmerisourceBergen: Consultancy; Forma: Research Funding; Xencor: Research Funding; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas,: Research Funding. Shami:JSK Therapeutics: Employment, Equity Ownership; Amgen: Research Funding; Pfizer: Research Funding; Cantex: Research Funding; Aptevo: Research Funding; Jazz: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Lone Star Thiotherapies: Equity Ownership. Foran:Agios: Honoraria, Research Funding. Byrd:Acerta: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; BeiGene: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau. Druker:OHSU (licensing fees): Patents & Royalties: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees ; Bristol-Myers Squibb: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Novartis: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Patents & Royalties: Patent 6958335, Treatment of Gastrointestinal Stromal Tumors, exclusively licensed to Novartis, Research Funding; Monojul: Other: former consultant; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Beat AML LLC: Other: Service on joint steering committee; Merck & Co: Patents & Royalties: Dana-Farber Cancer Institute license #2063, Monoclonal antiphosphotyrosine antibody 4G10, exclusive commercial license to Merck & Co; Dana-Farber Cancer Institute (antibody royalty): Patents & Royalties: #2524, antibody royalty; Aileron Therapeutics: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees , Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Patents & Royalties, Research Funding; Pfizer: Research Funding; ALLCRON: Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Patient True Talk: Consultancy; GRAIL: Equity Ownership, Other: former member of Scientific Advisory Board; Cepheid: Consultancy, Honoraria; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Pfizer: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; ICON: Other: Scientific Founder of Molecular MD, which was acquired by ICON in Feb. 2019; CureOne: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Other: former member of Scientific Advisory Board. Vergilio:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Levine:Imago Biosciences: Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Research Funding; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Honoraria; Gilead: Consultancy; Lilly: Honoraria; Qiagen: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Loxo: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.

Alterations in maternal physiology and pathological changes in kyphoscoliosis results in anaesthetic complications for caesarean section with potential risk for both mother and fetus. Safe and skilled anaesthetic management to minimize risk to mother and fetus is required. We report a case of 25-year-old female, with G2P1L1, with 28 weeks of period of gestation, with history of previous caesarean section, with pre-eclampsia, with kyphoscoliosis in labour with contracted pelvis, managed by general anaesthesia for caesarean section.

This article discusses the main changes introduced to the Portuguese labour market following the adoption of the Memorandum of Understanding of 2011. The intent behind the Memorandum's demands was to reduce the costs related to employment contracts, to expand both internal and external flexibility, and to relaunch collective bargaining under a new and more decentralised framework. However, several measures ended up being at odds not only with the Portuguese Constitution, but also with ILO Conventions and the (Revised) European Social Charter. We address the changes to wage policies, working time, employment protection legislation, and collective bargaining, which gave way to a new ‘flexibility-oriented’ labour relations model, characterised by a global reduction of labour protection levels. We argue that not only were these measures unable to fix the problems of the Portuguese labour market, but they also had crippling effects on social rights in general and, most particularly, on workers’ rights. Moreover, despite the overcoming of the economic crisis, as well as the changes to the political scene, the most significant alterations were maintained. This demonstrates that bailout reforms leave their mark, particularly when they correspond to measures previously under discussion and when their implementation is supported by external pressures.

This article discusses the main changes introduced to the Portuguese labour market following the adoption of the Memorandum of Understanding of 2011. The intent behind the Memorandum's demands was to reduce the costs related to employment contracts, to expand both internal and external flexibility, and to relaunch collective bargaining under a new and more decentralised framework. However, several measures ended up being at odds not only with the Portuguese Constitution, but also with ILO Conventions and the (Revised) European Social Charter. We address the changes to wage policies, working time, employment protection legislation, and collective bargaining, which gave way to a new ‘flexibility-oriented’ labour relations model, characterised by a global reduction of labour protection levels. We argue that not only were these measures unable to fix the problems of the Portuguese labour market, but they also had crippling effects on social rights in general and, most particularly, on workers’ rights. Moreover, despite the overcoming of the economic crisis, as well as the changes to the political scene, the most significant alterations were maintained. This demonstrates that bailout reforms leave their mark, particularly when they correspond to measures previously under discussion and when their implementation is supported by external pressures.

In July 2001, New York couple Jason Black and Francis Schroeder opened bidding on the internet for corporate sponsorship of their newborn son. Naming rights started at $US5000 000. For Black, the logic was simple: given the inescapable prevalence of commercial sponsorship in contemporary life, this was a valid way of working with corporate America. Black and Schroeder already had two daughters and lived in a small two-bedroom apartment. In exchange for their son’s financial security, they risked branding him ‘Big Mac’ or ‘Nike’ – literally. If nothing else, the case exemplified the amazing reach of brand consciousness. The couple had internalised its values and rationale with such ease and comfort, the notion of forfeiting their child’s name was not abhorrent, but a lucrative marketing opportunity. Then again, the story was not without precedent. In 2000, teenagers Chris Barrett and Luke McCabe, both from New Jersey, became ‘spokesguys’ for First USA, one of America’s top credit-card companies. By sporting the company logo on their surfboards and all their clothes, the pair receives an annual $US40 000 each in tuition, board and books for their four-year university contract. They do not just advertise the brand; they are its living embodiment. For critics of consumer culture, such stories exemplify the extent to which corporatism has become a complete and closed system, with the panoramic presence of brands and logos and the commodification of life itself. They demonstrate the alarming readiness of some people to encode and enact the consumerist impulse. At its most malignant, this impulse appears as a crass consumerism that eats up every aspect of a culture, so much so that consumerism becomes the culture – all meaning is both anchored in and governed by the capitalist creed. For many, mass-produced contemporary culture provides a seemingly empty substitute, what Fredric Jameson (1991) termed “a new kind of flatness or depthlessness, a new kind of superficiality in the most literal sense” (9), for genuine experience and emotion. In turn, the contemporary consumer has been reduced to a mere imitation of mediated expectations, a functionary cog in the corporatist machine. As this sign system infects and invades more and more space, a certain cultural literacy is inevitably called for, an intimate knowledge of symbol and significance, logo and logic. However, like all living language, this one is open to some resistance, albeit a somewhat piecemeal one. Part appropriation, part antithesis, it is a resistance that hijacks form in order to subvert content. To explain how this type of activism might work, one could consider the highly effective activist operation, ®TMark (http://rtmark.com). ®TMark is an online centre that organizes and directs funding for the ‘information alteration’ of corporate products (otherwise known as ‘sabotage’). In 1993, ®TMark was involved in its first high-profile act of sabotage when it channelled $US 8000 to the Barbie Liberation Organization (BLO), a group that switched the voice boxes of 300 GI Joe and Barbie dolls. As befits a project affiliated with ®TMark, the critical content of BLO’s act was an alchemic stroke of humour and commentary. The protest lies within the ‘information alteration’ of commodities that usually rely on their supposed virtues. The BLO offensive drew attention to the questionable labour practices of Mattel, manufacturers of Barbie, thereby undermining the perceptions on which Barbie’s popularity rests. From the outset, ®TMark’s key feature is its corporate status. As a brokerage, ®TMark benefits from ‘limited liability’, just like any other corporation. It exploits this principle (that is, corporate protection, thereby bypassing legal responsibility) to sabotage other corporate products. Unlike other corporations, though, its bottom-line is cultural profit. As spokesperson Ray Thomas explains, the corporate model is both the object of ®TMark’s criticism, and the method by which that criticism is being facilitated: “Projects can be seen as stocks, and when you support a project you’re investing in it. When you contribute, say, $100 to a project that you would like to see accomplished, you are sort of investing in the accomplishment of the project. What you want to see out of that project is cultural dividends; you want to see a beneficial cultural event take place because of your money, as a reward. What you’re doing is investing in the improvement of the culture.” As with almost all ®TMark literature and material, the tone here is one of clipped civility, similar to the tense restraint characteristic of almost any corporation. Perhaps the closest the site gets to a ‘straightforward’ philosophy is in this piece of advice to dispirited students, fearful that, one day, they too will be sucked into the corporate void: “We believe that performing an ®TMark project can help you, psychologically at least, at such a difficult juncture; but more importantly, we urge you to at all costs remember that laws should defend human people, not corporate people like the one of which you will be a part. If you keep this in mind and work towards making it a reality, you may find your life much more bearable.” While this pseudo mission statement might be read as yet another appendage to ®TMark’s corporate veneer, it also points to some of the goals of the site. The depiction of ®TMark projects as morale boosters for disenchanted cynics goes some way in illustrating the ambitions and limits of the site. Rather than prescribe a far-reaching, holistic approach to social change (what might be termed a ‘revolutionary’ vision), ®TMark marshals ideas and initiatives a little more subtly. This is not to belittle or dispute its utility or significance; on the contrary, it is an approach that effectively (in)corporates a diverse range of people and programs. For example, rather than unifying its adherents to a common agenda, ®TMark operates as a coalition of interests. As such, the followings funds collectively serve the ®TMark project: the Labor Fund; the Frontier Fund (which challenges naïve visions of the ‘global village’); the Education Fund; the Health Fund; the Alternative Markets Fund (which considers overlooked demographics, such as poor gays); the Media Fund; the Intellectual Property Fund; the Biological Property Fund; the Corporate Law Fund; and the Environment Fund, among others. In turn, the ®TMark spectrum canvasses a plethora of pertinent, interconnected themes. This includes: the plight of workers in developing countries; censorship; institutionalised racism; the nominal triumph of consumer culture; techno-utopianism and the ‘digerati’; copyright law; and the increasing opacity of corporate activities. Underlying all these issues is ®TMark’s intention to publicise corporate abuses of democratic processes. Importantly, this multiplicity of interests is considered a suitable counterpart to the dispersed nature of corporate power. So, no one enemy is identified and targeted, since such reductionism belies the degree to which capitalism, corporatism and consumerism are irredeemably entwined in contemporary culture. In turn, these funds are often ‘managed’ by public figures whose association with certain causes lend their celebrity well to particular campaigns. For example, San Francisco band Negativeland manages the Intellectual Property Fund. This is most appropriate. Their 1991 legal battle with major label Island, on account of their ‘deceptive’ use of U2 material, cemented their place as champions of ‘creative appropriation’ and the right to create ‘with mirrors’ (as Negativeland describes it on their eponymous website). Similarly, the desire to create ‘with mirrors’ propels much of ®TMark’s work. It imbues all ®TMark projects with the same sense of calculated mischief. This suggests a mode of activism that is both opportunistic and ingenious, fashioning criticism from the very resources it is attacking. Financial reward aside (which, in any case, is negligible, at best) the real pay-off for ®TMark saboteurs comes via media coverage of their projects. As such, it straddles an interesting divide, between public infamy and necessary stealth. ®TMark requires media attention to render its projects effective, yet must maintain the critical distance necessary for any activist potency. Indeed, the need to bolster ®TMark’s profile was one of the reasons it went from being a dial-in system to a website in 1997. Within its first eight months the site had received almost 20 000 visits. In this schema, the activism in question is assigned a somewhat smaller purpose than has been hitherto associated with protest movements generally. Rather than provide a grand panacea for all the world’s ills, ®TMark’s scale is, by its own admission, modest: “The value of ®TMark is, and has always been, not in any real pressure it can possibly bear, but rather in its ability to quickly and cheaply attract widespread interest to important issues. ®TMark is thus essentially a public relations agency for anti-corporate activism”. In this way, ®TMark is firmly positioned within that strand of activism often referred to as ‘culture jamming’. This type of protest relies on a distinct degree of media and cultural literacy, one that is consonant with, and a product of, the Information Age. As Mark Dery explains, these activists “introduce noise into the signal as it passes from transmitter to receiver, encouraging idiosyncratic, unintended interpretations. Intruding on the intruders, they invest ads, newscasts, and other media artefacts with subversive meanings; simultaneously, they decrypt them, rendering their seductions impotent”(http://levity.com/markdery/culturejam.html). Culture jamming draws on (and contributes to) critiques of contemporary consumer capitalism. Its premise is that too much public space has already been ceded to Hollywood, Madison Avenue et al, and that activists must seize whatever opportunities allow this space to be reclaimed, however fleetingly. Trading on publicity and shock value, jammers manipulate those icons, slogans and trademarks that will register immediate recognition, thereby rendering their efforts meaningful. It constitutes a politicised refusal to submit to the cheerful passivity scripted by the corporate class. As jammers resist this role, reclaiming rather than forfeiting public space, they create what Naomi Klein (2000) calls “a climate of semiotic Robin Hoodism” (280). This term aptly captures the spirit of moralistic idealism that is, almost inevitably, a part of the milieu. This is not to dismiss or deride the progressive agenda of most culture jammers; if anything, it is a positive endorsement of their activism, and a response to those that would deem the postmodern zeitgeist politically barren or overwhelmingly cynical. What it reveals, then, is a somewhat unexpected distribution of power, as expressions of criticism and opposition emerge at seemingly incongruous junctures. They are at once engaged and complicit, finding cracks in ‘the system’ (that is, corporate society) and co-opting them, what Linda Hutcheon (1990) calls “subversion from within” (157). Eschewing ‘big picture’ solutions, culture jammers prioritise temporary connections and hybrid forms over ideological certainties and operational rigidity. Tactical thinking, and the malleability and mobility it relies on, clearly informs and animates ®TMark’s work. As Graham Meikle (2002) explains, “Different actions and campaigns use whichever media are most appropriate at any given time for any given purpose. An event might call for making a documentary, making a website, making an A4 newsletter, or making a phone call” (120). ®TMark stops short of overstating its purpose or exaggerating its success. There is no lofty manifesto or ironclad strategy; without departing too far from its anti-corporatist stance, ®TMark encourages an almost playful combination of comedy and critique, with a thick ironic overlay. At its most ambitious, then, ®TMark can hope to alter the everyday behaviour of ordinary citizens, making inroads at the expense of powerful corporations. At the very least, it can prompt bemused surfers to rethink certain things – such as Nike’s labour practices or Shell’s environmental record. In a sense, though, the degree to which such perceptual jolts can ‘make a difference’ is almost immaterial: the fact that the status quo has been questioned is a minor triumph. Where some commentators bemoan the virtual stupor they deem characteristic of contemporary Western politics, projects like ®TMark prove that there are spaces and opportunities left for meaningful debate and dissent. Works Cited Dery, Mark. “Culture Jamming: Hacking, Slashing and Sniping in the Empire of Signs”. (http://levity.com/markdery/culturejam.html). Hutcheon, Linda. The Politics of Postmodernity. London: Routledge, 1990. Jameson, Fredric. Postmodernism, or, The Cultural Logic of Late Capitalism. Durham: Duke University Press, 1991. Klein, Naomi. No Logo. London: Flamingo, 2000. Meikle, Graham. Future Active: Media Activism and the Internet. New York and London: Routledge, and Annandale, Pluto Press, 2002. Rtmark. (http://rtmark.com). Links http://levity.com/markdery/culturejam.html http://rtmark.com Citation reference for this article Substitute your date of access for Dn Month Year etc... MLA Style Khamis, Susie. "Jamming at Work " M/C: A Journal of Media and Culture< http://www.media-culture.org.au/0306/04-jamming.php>. APA Style Khamis, S. (2003, Jun 19). Jamming at Work . M/C: A Journal of Media and Culture, 6,< http://www.media-culture.org.au/0306/04-jamming.php>

IntroductionOver three days in November 2017, 400 people gathered for a conference at the Sam’s Town Hotel and Gambling Hall in Las Vegas, Nevada. The majority of attendees were fiction authors but the conference program looked like no ordinary writer’s festival; there were no in-conversation interviews with celebrity authors, no panels on the politics of the book industry and no books launched or promoted. Instead, this was a gathering called 20Books2017, a self-publishing conference about the business of fiction ebooks and there was expertise in the room.Among those attending, 50 reportedly earned over $100,000 US per annum, with four said to be earning in excess of $1,000,000 US year. Yet none of these authors are household names. Their work is not adapted to film or television. Their books cannot be found on the shelves of brick-and-mortar bookstores. For the most part, these authors go unrepresented by the publishing industry and literary agencies, and further to which, only a fraction have ever actively pursued traditional publishing. Instead, they write for and sell into a commercial fiction market dominated by a single retailer and publisher: online retailer Amazon.While the online ebook market can be dynamic and lucrative, it can also be chaotic. Unlike the traditional publishing industry—an industry almost stoically adherent to various gatekeeping processes: an influential agent-class, formalized education pathways, geographic demarcations of curatorial power (see Thompson)—the nascent ebook market is unmapped and still somewhat ungoverned. As will be discussed below, even the markets directly engineered by Amazon are subject to rapid change and upheaval. It can be a space with shifting boundaries and thus, for many in the traditional industry both Amazon and self-publishing come to represent a type of encroaching northern dread.In the eyes of the traditional industry, digital self-publishing certainly conforms to the barbarous north of European literary metaphor: Orwell’s ‘real ugliness of industrialism’ (94) governed by the abject lawlessness of David Peace’s Yorkshire noir (Fowler). But for adherents within the day-to-day of self-publishing, this unruly space also provides the frontiers and gold-rushes of American West mythology.What remains uncertain is the future of both the traditional and the self-publishing sectors and the degree to which they will eventually merge, overlap and/or co-exist. So-called ‘hybrid-authors’ (those self-publishing and involved in traditional publication) are becoming increasingly common—especially in genre fiction—but the disruption brought about by self-publishing and ebooks appears far from complete.To the contrary, the Amazon-led ebook iteration of this market is relatively new. While self-publishing and independent publishing have long histories as modes of production, Amazon launched both its Kindle e-reader device and its marketplace Kindle Direct Publishing (KDP) a little over a decade ago. In the years subsequent, the integration of KDP within the Amazon retail environment dramatically altered the digital self-publishing landscape, effectively paving the way for competing platforms (Kobo, Nook, iBooks, GooglePlay) and today’s vibrant—and, at times, crassly commercial—self-published fiction communities.As a result, the self-publishing market has experienced rapid growth: self-publishers now collectively hold the largest share of fiction sales within Amazon’s ebook categories, as much as 35% of the total market (Howey). Contrary to popular belief they do not reside entirely at the bottom of Amazon’s expansive catalogue either: at the time of writing, 11 of Amazon’s Top 50 Bestsellers were self-published and the median estimated monthly revenue generated by these ‘indie’ books was $43,000 USD / month (per author) on the American site alone (KindleSpy).This international publishing market now proffers authors running the gamut of commercial uptake, from millionaire successes like romance writer H.M. Ward and thriller author Mark Dawson, through to the 19% of self-published authors who listed their annual royalty income as $0 per annum (Weinberg). Their overall market share remains small—as little as 1.8% of trade publishing in the US as a whole (McIlroy 4)—but the high end of this lucrative slice is particularly dynamic: science fiction author Michael Anderle (and 20Books2017 keynote) is on-track to become a seven-figure author in his second year of publishing (based on Amazon sales ranking data), thriller author Mark Dawson has sold over 300,000 copies of his self-published Milton series in 3 years (McGregor), and a slew of similar authors have recently attained New York Times and US Today bestseller status.To date, there is not a broad range of scholarship investigating the operational logics of self-published fiction. Timothy Laquintano’s recent Mass Authorship and the Rise of Self-Publishing (2016) is a notable exception, drawing self-publishing into historical debates surrounding intellectual property, the future of the book and digital abundance. The more empirical portions of Mass Authorship—taken from activity between 2011 to 2015—directly informs this research and his chapter on Amazon (Chapter 4) could be read as a more macro companion to my findings below; taken together and compared they illustrate just how fast-moving the market is. Nick Levey’s work on ‘post-press’ literature and its inherent risks (and discourses of cultural capitol) also informs my thesis here.In addition to which, there is scholarship centred on publishing more generally that also touches on self-published writers as a category of practitioner (see Baverstock and Steinitz, Haughland, Thomlinson and Bélanger). Most of this later work focuses almost entirely on the finished product, usually situating self-publishing as directly oppositional to traditional publishing, and thus subordinating it.In this paper, I hope to outline how the self-publishers I’ve observed have enacted various tactical approaches that specifically strive to tame their chaotic marketplace, and to indicate—through one case study (Amazon exclusivity)—a site of production and resistance where they have occasionally succeeded. Their approach is one that values information sharing and an open-source approach to book-selling and writing craft, ideologies drawn more from the tech / start-up world than commercial book industry described by Thompson (10). It is a space deeply informed by the virtual nature of its major platforms and as such, I argue its relation to the world of traditional publishing—and its representation within the traditional book industry—are tenuous, despite the central role of authorship and books.Making the Virtual Self-Publishing SceneWithin the study of popular music, the use of Barry Shank and Will Straw’s ‘scene’ concept has been an essential tool for uncovering and mapping independent/DIY creative practice. The term scene, defined by Straw as cultural space, is primarily interested in how cultural phenomena articulates or announces itself. A step beyond community, scene theorists are less concerned with examining an evolving history of practice (deemed essentialist) than they are concerned with focusing on the “making and remaking of alliances” as the crucial process whereby communal culture is formed, expressed and distributed (370).A scene’s spatial dimension—often categorized as local, translocal or virtual (see Bennett and Peterson)—demands attention be paid to hybridization, as a diversity of actors approach the same terrain from differing vantage points, with distinct motivations. As a research tool, scene can map action as the material existence of ideology. Thus, its particular usefulness is its ability to draw findings from diverse communities of practice.Drawing methodologies and approaches from Bourdieu’s field theory—a particularly resonant lens for examining cultural work—and de Certeau’s philosophies of space and circumstantial moves (“failed and successful attempts at redirection within a given terrain,” 375), scene focuses on articulation, the process whereby individual and communal activity becomes an observable or relatable or recordable phenomena.Within my previous work (see Bennett and Rogers, Rogers), I’ve used scene to map a variety of independent music-making practices and can see clear resemblances between independent music-making and the growing assemblage of writers within ebook self-publishing. The democratizing impulses espoused by self-publishers (the removal of gatekeepers as married to visions of a fiction/labour meritocracy) marry up quite neatly with the heady mix of separatism and entrepreneurialism inherent in Australian underground music.Self-publishers are typically older and typically more upfront about profit, but the communal interaction—the trade and gifting of support, resources and information—looks decidedly similar. Instead, the self-publishers appear different in one key regard: their scene-making is virtual in ways that far outstrip empirical examples drawn from popular music. 20Books2017 is only one of two conferences for this community thus far and represents one of the few occasions in which the community has met in any sort of organized way offline. For the most part, and in the day-to-day, self-publishing is a virtual scene.At present, the virtual space of self-published fiction is centralized around two digital platforms. Firstly, there is the online message board, of which two specific online destinations are key: the first is Kboards, a PHP-coded forum “devoted to all things Kindle” (Kboards) but including a huge author sub-board of self-published writers. The archive of this board amounts to almost two million posts spanning back to 2009. The second message board site is a collection of Facebook groups, of which the 10,000-strong membership of 20BooksTo50K is the most dominant; it is the originating home of 20Books2017.The other platform constituting the virtual scene of self-publishing is that of podcasting. While there are a number of high-profile static websites and blogs related to self-publishing (and an emerging community of vloggers), these pale in breadth and interaction when compared to podcasts such as The Creative Penn, The Self-Publishing Podcast, The Sell More Books Show, Rocking Self-Publishing (now defunct but archived) and The Self-Publishing Formula podcast. Statistical information on the distribution of these podcasts is unavailable but the circulation and online discussion of their content and the interrelation between the different shows and their hosts and guests all point to their currency within the scene.In short, if one is to learn about the business and craft production modes of self-publishing, one tends to discover and interact with one of these two platforms. The consensus best practice espoused on these boards and podcasts is the data set in which the remainder of this paper draws findings. I have spent the last two years embedded in these communities but for the purposes of this paper I will be drawing data exclusively from the public-facing Kboards, namely because it is the oldest, most established site, but also because all of the issues and discussion presented within this data have been cross-referenced across the different podcasts and boards. In fact, for a long period Kboards was so central to the scene that itself was often the topic of conversation elsewhere.Sticking in the Algorithm: The Best Practice of Fiction Self-PublishingSelf-publishing is a virtual scene because its “constellation of divergent interests and forces” (Shank, Preface, x) occur almost entirely online. This is not just a case of discussion, collaboration and discovery occurring online—as with the virtual layer of local and translocal music scenes—rather, the self-publishing community produces into the online space, almost exclusively. Its venues and distribution pathways are online and while its production mechanisms (writing) are still physical, there is an almost instantaneous and continuous interface with the online. These writers type and, increasingly dictate, their work into the virtual cloud, have it edited there (via in-text annotation) and from there the work is often designed, formatted, published, sold, marketed, reviewed and discussed online.In addition to which, a significant portion of these writers produce collaborative works, co-writing novels and co-editing them via cooperative apps. Teams of beta-readers (often fans) work on manuscripts pre-launch. Covers, blurbs, log lines, ad copy and novel openings are tested and reconfigured via crowd-sourced opinion. Seen here, the writing of the self-publishing scene is often explicitly commercial. But more to the fact, it never denies its direct co-relation with the mandates of online publishing. It is not traditional writing (it moves beyond authorship) and viewing these writers as emerging or unpublished or indeed, using the existing vernacular of literary writing practices, often fails to capture what it is they do.As the self-publishers write for the online space, Amazon forms a huge part of their thinking and working. The site sits at the heart of the practices under consideration here. Many of the authors drawn into this research are ‘wide’ in their online retail distribution, meaning they have books placed with Amazon’s online retail competitors. Yet the decision to go ‘wide’ or stay exclusive to Amazon — and the volume of discussion around this choice — is illustrative of how dominant the company remains in the scene. In fact, the example of Amazon exclusivity provides a valuable case-study.For self-publishers, Amazon exclusivity brings two stated and tangible benefits. The first relates to revenue diversification within Amazon, with exclusivity delivering an additional revenue stream in the form of Kindle Unlimited royalties. Kindle Unlimited (KU) is a subscription service for ebooks. Consumers pay a flat monthly fee ($13.99 AUD) for unlimited access to over a million Kindle titles. For a 300-page book, a full read-through of a novel under KU pays roughly the same royalty to authors as the sale of a $2.99 ebook, but only to Amazon-exclusive authors. If an exclusive book is particularly well suited to the KU audience, this can present authors with a very serious return.The second benefit of Amazon exclusivity is access to internal site merchandising; namely ‘Free Days’ where the book is given away (and can chart on the various ‘Top 100 Free’ leaderboards) and ‘Countdown Deals’ where a decreasing discount is staggered across a period (thus creating a type of scarcity).These two perks can prove particularly lucrative to individual authors. On Kboards, user Annie Jocoby (also writing as Rachel Sinclair) details her experiences with exclusivity:I have a legal thriller series that is all-in with KU [Kindle Unlimited], and I can honestly say that KU has been fantastic for visibility for that particular series. I put the books into KU in the first part of August, and I watched my rankings rise like crazy after I did that. They've stuck, too. If I weren't in KU, I doubt that they would still be sticking as well as they have. (anniejocoby)This is fairly typical of the positive responses to exclusivity, yet it incorporates a number of the more opaque benefits entangled with going exclusive to Amazon.First, there is ‘visibility.’ In self-publishing terms, ‘visibility’ refers almost exclusively to chart positions within Amazon. The myriad of charts — and how they function — is beyond the scope of this paper but they absolutely indicate — often dictate — the discoverability of a book online. These charts are the ‘front windows’ of Amazon, to use an analogy to brick-and-mortar bookstores. Books that chart well are actively being bought by customers and they are very often those benefiting from Amazon’s powerful recommendation algorithm, something that expands beyond the site into the company’s expansive customer email list. This brings us to the second point Jocoby mentions, the ‘sticking’ within the charts.There is a widely held belief that once a good book (read: free of errors, broadly entertaining, on genre) finds its way into the Amazon recommendation algorithm, it can remain there for long periods of time leading to a building success as sales beget sales, further boosting the book’s chart performance and reviews. There is also the belief among some authors that Kindle Unlimited books are actively favoured by this algorithm. The high-selling Amanda M. Lee noted a direct correlation:Rank is affected when people borrow your book [under KU]. Page reads don't play into it all. (Amanda M. Lee)Within the same thread, USA Today bestseller Annie Bellet elaborated:We tested this a bunch when KU 2.0 hit. A page read does zip for rank. A borrow, even with no pages read, is what prompts the rank change. Borrows are weighted exactly like sales from what we could tell, it doesn't matter if nobody opens the book ever. All borrows now are ghost borrows, of course, since we can't see them anymore, so it might look like pages are coming in and your rank is changing, but what is probably happening is someone borrowed your book around the same time, causing the rank jump. (Annie B)Whether this advantage is built into the algorithm in a (likely) attempt to favour exclusive authors, or by nature of KU books presenting at a lower price point, is unknown but there is anecdotal evidence that once a KU book gains traction, it can ‘stick’ within the charts for longer periods of time compared to non-exclusive titles.At the entrepreneurial end of the fiction self-publishing scene, Amazon is positioned at the very centre. To go wide—to follow vectors through the scene adjacent to Amazon — is to go around the commercial centre and its profits. Yet no one in this community remains unaffected by the strategic position of this site and the market it has either created or captured. Amazon’s institutional practices can be adopted by competitors (Kobo Plus is a version of KU) and the multitude of tactics authors use to promote their work all, in one shape or another, lead back to ‘circumstantial moves’ learned from Amazon or services that are aimed at promoting work sold there. Further to which, the sense of instability and risk engendered by such a dominant market player is felt everywhere.Some Closing Ideas on the Ideology of Self-PublishingSelf-publishing fiction remains tactical in the de Certeau sense of the term. It is responsive and ever-shifting, with a touch of communal complicity and what he calls la perruque (‘the wig’), a shorthand for resistance that presents itself as submission (25). The entrepreneurialism of self-published fiction trades off this sense of the tactical.Within the scene, Amazon bestseller charts aren’t as much markers of prestige as systems to be hacked. The choice between ‘wide’ and exclusive is only ever short-term; it is carefully scrutinised and the trade-offs and opportunities are monitored week-to-week and debated constantly online. Over time, the self-publishing scene has become expert at decoding Amazon’s monolithic Terms of Service, ever eager to find both advantage and risk as they attempt to lever the affordances of digital publishing against their own desire for profit and expression.This sense of mischief and slippage forms a big part of what self-publishing is. In contrast to traditional publishing—with its long lead times and physical real estate—self-publishing can’t help but appear fragile, wild and coarse. There is no other comparison possible.To survive in self-publishing is to survive outside the established book industry and to thrive within a new and far more uncertain market/space, one almost entirely without a mapped topology. Unlike the traditional publishing industry—very much a legacy, a “relatively stable” population group (Straw 373)—self-publishing cannot escape its otherness, not in the short term. Both its spatial coordinates and its pathways remain too fast-evolving in comparison to the referent of traditional publishing. In the short-to-medium term, I imagine it will remain at some cultural remove from traditional publishing, be it perceived as a threatening northern force or a speculative west.To see self-publishing in the present, I encourage scholars to step away from traditional publishing industry protocols and frameworks, to strive to see this new arena as the self-published authors themselves understand it (what Muggleton has referred to a “indigenous meaning” 13).Straw and Shank’s scene concept provides one possible conceptual framework for this shift in understanding as scene’s reliance on spatial considerations harbours an often underemphazised asset: it is a theory of orientation. At heart, it draws as much from de Certeau as Bourdieu and as such, the scene presented in this work is never complete or fixed. It is de Certeau’s city “shaped out of fragments of trajectories and alterations of spaces” (93). These scenes—be they musicians or authors—are only ever glimpsed and from a vantage point of close proximity. In short, it is one way out of the essentialisms that currently shroud self-published fiction as a craft, business and community of authors. The cultural space of self-publishing, to return Straw’s scene definition, is one that mirrors its own porous, online infrastructure, its own predominance in virtuality. Its pathways are coded together inside fast-moving media companies and these pathways are increasingly entwined within algorithmic processes of curation that promise meritocratization and disintermediation yet delivery systems that can be learned and manipulated.The agility to publish within these systems is the true skill-set required to self-publish fiction online. It traverses specific platforms and short-term eras. It is the core attribute of success in the scene. Everything else is secondary, including the content of the books produced. It is not the case that these books are of lesser literary quality or that their ever-growing abundance is threatening—this is the counter-argument so often presented by the traditional book industry—but more so that without entrepreneurial agility, the quality of the ebook goes undetermined as it sinks lower and lower into a distribution system that is so open it appears endless.ReferencesAmanda M. 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