A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m−2 DL), combined with cisplatin (standard dose 75 mg m−2). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m−2 DL; at the 110 mg m−2 DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m−2, but not through the 150 mg m−2 DL. The mean±SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317±60 ml min−1 m−2, 258±96 l m−2 and 30.8±7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m−2 (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m−2

Pegfilgrastim ± ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study

Background: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. Patients and methods: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 μg/kg/day or lenograstim 150 μg/m2/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). Results: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. Conclusion: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxaci

Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer.

The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity and specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and lobular epithelia. Nipple aspirate fluid proteins are breast specific and generally more concentrated than corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13 with nondiseased breasts identified five differentially expressed proteins. The most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of samples from women with cancer but in only 0-9% of samples from normal women. These findings suggest that (1) differential expression of nipple aspirate fluid proteins exists between women with normal and diseased breasts, and (2) analysis of these proteins may predict the presence of breast cancer

Transcribing screen-capture data : the process of developing a transcription system for multi-modal text-based data

Transcription of audio data is widespread in qualitative research, with transcription of video data also becoming common. Online data is now being collected using screen-capture or video software, which then needs transcribing. This paper draws together literature on transcription of spoken interaction and highlights key transcription principles, namely reflecting the methodological approach, readability, accessibility, and usability. These principles provide a framework for developing a transcription system for multi-modal text-based data. The process of developing a transcription system for data from Facebook chat is described and reflected on. Key issues in the transcription of multi-modal text-based data are discussed, and examples provided of how these were overcome when developing the transcription system

The wages of whiteness in the absence of wages: racial capitalism, reactionary intercommunalism and the rise of Trumpism

In November 1970, Black Panther Party leader Huey P. Newton gave a lecture at Boston College where he introduced his theory of intercommunalism. Newton re-articulated Marxist theories of imperialism through the lens of the Black liberation struggle and argued that imperialism had entered a new phase called ‘reactionary intercommunalism’. Newton’s theory of intercommunalism o ers nothing less than a proto-theorisation of what we have come to call neo-liberal globalisation and its e ects on what W. E. B. Du Bois had seen as the racialisation of modern imperialism. Due to the initial historical dismissal of the Black Panther Party’s political legacy, Newton’s thought has largely been neglected for the past 40 years. This paper revisits Newton’s theory of intercommunalism, with the aim of achieving some form of epistemic justice for his thought, but also to highlight how Newton’s recasting of imperialism as reactionary intercommunalism provides critical insight into the rise of Trumpism in the US

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt

Stochastic dynamics of correlations in quantum field theory: From Schwinger-Dyson to Boltzmann-Langevin equation

The aim of this paper is two-fold: in probing the statistical mechanical properties of interacting quantum fields, and in providing a field theoretical justification for a stochastic source term in the Boltzmann equation. We start with the formulation of quantum field theory in terms of the Schwinger - Dyson equations for the correlation functions, which we describe by a closed-time-path master ($n = \infty PI$) effective action. When the hierarchy is truncated, one obtains the ordinary closed-system of correlation functions up to a certain order, and from the nPI effective action, a set of time-reversal invariant equations of motion. But when the effect of the higher order correlation functions is included (through e.g., causal factorization-- molecular chaos -- conditions, which we call 'slaving'), in the form of a correlation noise, the dynamics of the lower order correlations shows dissipative features, as familiar in the field-theory version of Boltzmann equation. We show that fluctuation-dissipation relations exist for such effectively open systems, and use them to show that such a stochastic term, which explicitly introduces quantum fluctuations on the lower order correlation functions, necessarily accompanies the dissipative term, thus leading to a Boltzmann-Langevin equation which depicts both the dissipative and stochastic dynamics of correlation functions in quantum field theory.Comment: LATEX, 30 pages, no figure

Conviviality and Parallax in David Olusoga’s Black and British: A Forgotten History

Through examining the BBC television series, Black and British: A Forgotten History, written and presented by the historian David Olusoga, and in extending Paul Gilroy’s assertion that the everyday, banality of living with difference is now an ordinary part of British life, this article considers how Olusoga’s historicization of the black British experience reflects a convivial rendering of UK multiculture. In particular, when used alongside Žižek’s notion of parallax, it is argued that understandings of convivial culture can be supported by a historical importance that deliberately ‘shocks’ and, subsequently dislodges, popular interpretations of the UK’s ‘white past’. Notably, it is parallax which puts antagonism, strangeness and ambivalence at the heart of contemporary depictions of convivial Britain, with the UK’s cultural differences located in the ‘gaps’ and tensions which characterize both its past and present. These differences should not be feared but, as a characteristic part of our convivial culture, should be supplemented with historical analyses that highlight but, also, undermine, the significance of cultural differences in the present. Consequently, it is suggested that if the spontaneity of conviviality is to encourage openness, then, understandings of multiculturalism need to go beyond reification in order to challenge our understandings of the past. Here, examples of ‘alterity’ are neither ‘new’ nor ‘contemporary’ but, instead, constitute a fundamental part of the nation’s history: of the ‘gap’ made visible in transiting past and present

Unsettling planning theory

Recent political developments in many parts of the world seem likely to exacerbate rather than ameliorate the planetary-scale challenges of social polarization, inequality and environmental change societies face. In this unconventional multi-authored essay, we therefore seek to explore some of the ways in which planning theory might respond to the deeply unsettling times we live in. Taking the multiple, suggestive possibilities of the theme of unsettlement as a starting point, we aim to create space for reflection and debate about the state of the discipline and practice of planning theory, questioning what it means to produce knowledge capable of acting on the world today. Drawing on exchanges at a workshop attended by a group of emerging scholars in Portland, Oregon in late 2016, the essay begins with an introduction section exploring the contemporary resonances of ‘unsettling’ in, of and for planning theory. This is followed by four, individually authored responses which each connect the idea of unsettlement to key challenges and possible future directions. We end by calling for a reflective practice of theorizing that accepts unsettlement but seeks to act knowingly and compassionately on the uneven terrain that it creates

Perceptions of mixed-race

The psychology of race is in its infancy, particularly in the United Kingdom and especially regarding mixed-race. Most use untimed explicit indexes and qualitative/self-report measures. Here, we used not only explicit responses (participants’ choice of response categories) but also implicit data (participants’ response times, RT). In a Stroop task, 92 Black, White, and mixed-race participants classified photographs of mixed-race persons. Photos were accompanied by a word, such as Black or White. Participants ignored the word, simply deciding whether to categorize photos as White or Black. Averaged across three different instructional sets, White participants categorized mixed-race slightly to the White side of the center point, with Black participants doing the converse. Intriguingly, mixed-race participants placed mixed-race photos further toward Black than did the Black group. But for RT, they now indicated midway between White and Black participants. We conclude that at the conscious (key-press) level, mixed-race persons see being mixed-race as Black, but at the unconscious (RT) level, their perception is a perfect balance between Black and White. Findings are discussed in terms of two recent theories of racial identity