Exploring shear alignment of concentrated wormlike micelles using rheology coupled with small-angle neutron scattering

Wormlike micelles (WLMs) are vital components of many consumer products and industrial fluids, adding a shear-dependent viscous texture through their entanglement in solutions. It is now well accepted from experiments such as coupling rheology and scattering that, similar to many polymer solutions and dispersions of highly anisotropic particles, WLM behavior during shear arises from the alignment of the "worms"with the shear field, resulting in ordering that is rapidly lost in the cessation of shear. Most studies of such systems have been limited to dilute systems that are far below concentrations used industrially and commercially, due to the complexity of analyzing shear-induced many-body effects in high volume fraction dispersions. Here, we explore the shear alignment of concentrated WLM solutions comprising sodium laureth sulfate and cocamidopropyl betaine in 0.38 M aqueous sodium chloride. By analyzing only scattering data at high values of the scattering vector (i.e., correlations at short length scales that are dominant in such concentrated systems), we explore whether useful information can be obtained by naïvely approximating the WLMs as an ensemble of unconnected short rods representing sections of the worms. By taking this reductionist approach to analyzing the obtained two-dimensional scattering patterns from these systems under shear, we find that in this regime, such concentrated worms can be approximated as cylinders that become more aligned with the direction of shear as volume fraction and shear rate increase

Maintenance lenalidomide in newly diagnosed transplant eligible and non-eligible myeloma patients; profiling second primary malignancies in 4358 patients treated in the Myeloma XI Trial

\ua9 2023 The AuthorsBackground: Early trials of long-term lenalidomide use reported an increased incidence of second primary malignancy (SPM), including acute myeloid leukaemia and myelodysplastic syndrome. Later, meta-analysis suggested the link to be secondary to lenalidomide in combination with melphalan. Methods: Myeloma XI is a large, phase III randomised trial in-which lenalidomide was used at induction and maintenance, in transplant eligible (TE) and non-eligible (TNE) newly diagnosed patients (NCT01554852). Here we present an analysis of SPM incidence and profile the SPM type to determine the impact of autologous stem cell transplantation (ASCT) and lenalidomide exposure in 4358 patients treated on study. Data collection took place from the start of the trial in May 2010, to May 2019, as per the protocol timeline. The Median follow-up following maintenance randomisation was 54.5 and 46.1 months for TE and TNE patients, respectively. Findings: In the TE pathway, the overall SPM incidence was 7.7% in lenalidomide maintenance patients compared to 3.2% in those being observed (p = 0.006). Although the TNE lenalidomide maintenance patients had the greatest SPM incidence (15.4%), this was not statistically significant when compared to the observed patients (10%, p = 0.10). The SPM incidence was higher in patients who received lenalidomide at induction and maintenance (double exposure), when compared to those treated with lenalidomide at one time point (single exposure). Again, this was most marked in TNE patients where the overall SPM incidence was 16.9% in double exposed patients, compared to 11.7% in single exposed patients, and 11.2% in patients who did not receive lenalidomide (p = 0.04). This is likely an effect of treatment duration, with the median number of cycles being 27 in the TNE double exposed patients, vs 6 in the single exposure patients. Haematological SPMs were uncommon, diagnosed in 50 patients (incidence 1.1%). The majority of cases were diagnosed in TE patients treated with lenalidomide maintenance (n = 25, incidence 2.8%), suggesting a possible link with melphalan. Non-melanoma skin cancer incidence was highest in patients receiving lenalidomide maintenance, particularly in TNE patients, where squamous cell carcinoma and basal cell carcinoma were diagnosed in 5.5% and 2.6% of patients, respectively. The incidence of most solid tumour types was higher in lenalidomide maintenance patients. Mortality due to progressive myeloma was reduced in patients receiving lenalidomide maintenance, noted to be 16.6% compared 22.6% in those observed in TE patients and 32.7% compared to 41.5% in TNE patients. SPM related mortality was low, 1.8% and 6.1% in TE and TNE lenalidomide maintenance patients, respectively, compared to 0.4% and 2.8% in those being observed. Interpretation: This provides reassurance that long-term lenalidomide treatment is safe and associated with improved outcomes in TE and TNE populations, although monitoring for SPM development should be incorporated into clinic review processes. Funding: Primary financial support was from Cancer Research UK [ C1298/A10410]

Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients.

Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10 -7 ), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10 -14 ) and 1.68 (P=2.18 × 10 -14 ), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10 -27 ) for all patients and 3.19 (P=1.23 × 10 -18 ) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10 -15 ), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment

Orthodontics in the era of big data analytics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/1/ocr12279_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/2/ocr12279.pd