Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts

Background: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-αβ/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition. Methods: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 ‘poor mobilizers’ (PM) failing to attain ≥40 CD34+ HSCs/μL after 4 daily G-CSF doses and/or with predicted apheresis yields ≤12.0x106 CD34+ cells/kg recipient’s body weight. Results: MZ significantly increased CD34+ counts in PM. Naïve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16+ monocytes and the down-regulation of IFN-γ production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs. Conclusions: MZ facilitates the collection of mega-doses of CD34+ HSCs for haploidentical HSCT, while affecting graft composition

Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis.

BACKGROUND: Mammography is less effective in detecting cancer in dense than in fatty breasts. METHODS: We undertook a systematic search in PubMed to identify studies on women with dense breasts who underwent screening with mammography supplemented with ultrasound. A meta-analysis was undertaken on the proportion of cancers detected only by ultrasound, out of all screen-detected cancers, and the proportion of women with negative mammography who were referred for assessment following ultrasound screening. RESULTS: Twenty-nine studies satisfied our inclusion criteria. The proportion of total cancers detected only by ultrasound was 0.29 (95% CI: 0.27-0.31), consistent with an approximately 40% increase in the detection of cancers compared to mammography. In the studied populations, this translated into an additional 3.8 (95% CI: 3.4-4.2) screen-detected cases per 1000 mammography-negative women. About 13% (32/248) of cancers were in situ from 17 studies with information on this subgroup. Ultrasound approximately doubled the referral for assessment in three studies with these data. CONCLUSIONS: Studies have consistently shown an increased detection of breast cancer by supplementary ultrasound screening. An inclusion of supplementary ultrasound into routine screening will need to consider the availability of ultrasound and diagnostic assessment capacities.Department of Health Policy Research Programme (106/0001). Cancer Research UK (grants C8162/A16892 and C569/A16891)

Correlating molecular precursor interactions with device performance in solution-processed Cu2ZnSn(S,Se)4 thin-film solar cells

Research efforts aimed at improving the crystal quality of solution-processed Cu2ZnSn(S,Se)4 (CZTSSe) absorbers have largely employed delicate pre- and post-processing strategies, such as multi-step selenization, heat treatment in mixed chalcogen atmospheres, and multinary extrinsic doping that are often complex and difficult to reproduce. On the other hand, understanding and tunning chemical interactions in precursor inks prior to the thin-film deposition have received significant less attention. Herein, we show for the first time how the complexation of metallic and chalcogen precursors in solution have a stark influence on the crystallization and optoelectronic quality of CZTSSe absorbers. By varying thiourea to metal cation ratios (TU/M) in dimethylformamide (DMF) and isopropyl alcohol (IPA) based inks, we observed the formation of nanoscale metal-organic complexes and sub-micron size aggregates which play a key role in the morphology of the precursor layers obtained by spin-coating and drying steps. We also identify the primary cations in the complexation and assembling processes in solution. The morphology of the precursor film, in turn, has an important effect on grain growth and film absorber structure after the reactive annealing in the presence of Se. Finally, we establish a link between metal complexes in precursor solutions and device performance, with power conversion efficiency increasing from approximately 2% to 8% depending on the TU/M and Cu/(Zn+Sn) ratios

Clinical and epidemiological issues in mammographic density

High mammographic density is associated with an increased risk of breast cancer, and of all known breast cancer risk factors has the greatest attributable fraction. Mammographic density is estimated to account for 16% of all breast cancers, but can be altered by endogenous and exogenous hormonal factors, and generally declines with age. Confounding factors such as age, parity, menopausal status and BMI make the interpretation of mammographic density particularly challenging. Furthermore, none of the established means of measuring mammographic density are entirely satisfactory because they are time consuming or subjective. It is hoped that by adding information regarding mammographic density to existing models of breast cancer risk assessment, the accuracy of individual risk assessments can be improved. Although mammographic density has clearly been shown to be a powerful factor for predicting the risk of developing breast cancer, its potential role in assessing hormonal preventive regimens and helping to tailor screening algorithms cannot be fully realized until we have more-precise, simple and reproducible density measures