A pilot study of the Mistletoe and Breast Cancer (MAB) trial:a protocol for a randomised double-blind controlled trial

BACKGROUND: A Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim is to add to this evidence base by initially testing the feasibility of a UK pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy. METHODS/DESIGN: A mixed phase pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer (EudraCT number: 2018-000279-34). There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the mistletoe and breast cancer (MAB) therapies subcutaneously. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and 1 month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff. DISCUSSION: This trial is the first of its kind in the UK. Currently, mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy

Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription

The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome “remodeler” rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4′s action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription—one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not—clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here—that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform—contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field

Exploring the impact of skin tone on family dynamics and race-related outcomes.

Racism has historically been a primary source of discrimination against African Americans but there has been little research on the role that skin tone plays in explaining experiences with racism. Similarly, colorism within African American families and the ways in which skin tone influences family processes is an understudied area of research. Utilizing data from a longitudinal sample of African American families (N= 767), we assessed whether skin tone impacted experiences with discrimination or was related to differences in quality of parenting and racial socialization within families. Findings indicated no link between skin tone and racial discrimination, which suggests that lightness or darkness of skin does not either protect African Americans from or exacerbate the experiences of discrimination. On the other hand, families displayed preferential treatment toward offspring based on skin tone and these differences varied by gender of child. Specifically, darker skin sons received higher quality parenting and more racial socialization promoting mistrust compared to their counterparts with lighter skin. Lighter skin daughters received higher quality parenting compared to those with darker skin. In addition, gender of child moderated the association between primary caregiver skin tone and racial socialization promoting mistrust. These results suggest that colorism remains a salient issue within African American families. Implications for future research, prevention and intervention are discussed

A study exploring learners' informal learning space behaviors, attitudes, and preferences

What makes a successful informal learning space is a topic in need of further research. The body of discourse on informal space design is drawn from learning theory, placemaking and architecture, with a need for understanding of the synergy between the three. Findings from a longitudinal, quantitative and qualitative study at Sheffield Hallam University, explore learners' behaviours, attitudes and preferences towards informal learning spaces in higher education, within and outside of the context of the academic library. The learning spaces study contributes to the discourse on informal learning spaces design by producing a typology of nine learning space preference attributes which address aspects of learning theory, placemaking and architecture. The typology can be used to evaluate existing spaces and inform redevelopment of informal learning spaces in higher education institutions. Implementing the typology will be subject to localised conditions, but at Sheffield Hallam University the key conclusions have included developing a portfolio of discrete, interrelated learning environments, offering spaces with a clear identity and encouraging students to translate their learning preferences into space selection

The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia

yesRecent studies portend a rising global spread and adaptation of human- or healthcare- associated pathogens. Here, we analyse an international collection of the emerging, multi-drug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals

Performance and characterization of the SPT-3G digital frequency-domain multiplexed readout system using an improved noise and crosstalk model

The third-generation South Pole Telescope camera (SPT-3G) improves upon its predecessor (SPTpol) by an order of magnitude increase in detectors on the focal plane. The technology used to read out and control these detectors, digital frequency-domain multiplexing (DfMUX), is conceptually the same as used for SPTpol, but extended to accommodate more detectors. A nearly 5× expansion in the readout operating bandwidth has enabled the use of this large focal plane, and SPT-3G performance meets the forecasting targets relevant to its science objectives. However, the electrical dynamics of the higher-bandwidth readout differ from predictions based on models of the SPTpol system due to the higher frequencies used and parasitic impedances associated with new cryogenic electronic architecture. To address this, we present an updated derivation for electrical crosstalk in higher-bandwidth DfMUX systems and identify two previously uncharacterized contributions to readout noise, which become dominant at high bias frequency. The updated crosstalk and noise models successfully describe the measured crosstalk and readout noise performance of SPT-3G. These results also suggest specific changes to warm electronics component values, wire-harness properties, and SQUID parameters, to improve the readout system for future experiments using DfMUX, such as the LiteBIRD space telescope

Letter to the editor from Gene Bryant of Hallowell, in response to The Betrayal

Letter to the editor from Gene Bryant of Hallowell, in response to The Betrayal of Local 14, which appeared in the June 30 issue about the 1987-88 strike at International Paper Co. in Jay

Design of a Constant Angle Arch Dam at Devil's Gate in Connection with the Flood Control of Los Angeles County

No abstract