Bed particle dynamics at entrainment

The reported work was partly supported by Engineering and Physical Sciences Research Council [EPSRC(UK)], Grant EP/G056404/1 “High resolution numerical and experimental studies of turbulence-induced sediment erosion and near-bed transport” and Grant EP/K041088/1 “Bed friction in rough-bed free-surface flows: a theoretical framework, roughness regimes, and quantification”.Peer reviewedPublisher PD

An excess Ra-226 chronology for deep-sea sediments from Saanich Inlet, British Columbia

To further explore the efficacy of 226Ra(excess) dating for deep-sea sediments, previously dated varve sediments from Saanich Inlet were investigated. Ages obtained using 226Ra(excess) are comparable to the varve ages in the upper 20-25 m of the sedimentary record, but radiometric ages for those sediments older than c. 4000 yr BP are significant underestimates. This results from major changes in sedimentation within Saanich Inlet around 4000 yr BP linked to rising sea levels, with younger sediments characterised by a higher biogenic contribution resulting from the establishment of an anoxic fjord environment. The older sediments were deposited in a shallow water inlet characterised by variable Ra mass balance and non-radiogenic losses. Therefore, while 226Ra(excess) can produce reliable dates, its application may be limited where the relative significance of authigenic and allogenic input and bottom water anoxia have been variable and where closed-system behaviour is compromised

Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer

Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient‐, tumor‐, and treatment‐related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence‐free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23–39 years) with a median follow‐up of 47 months (8–138 months). Breast‐conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty‐two percent of patients had triple negative tumors (TN, ER‐/PR‐/HER2 nonamplified). Four‐year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis

Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for lynch syndrome

We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister’s colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified

Improved exclusion limit for light dark matter from e+e− annihilation in NA64

The current most stringent constraints for the existence of sub-GeV dark matter coupling to Standard Model via a massive vector boson A′ were set by the NA64 experiment for the mass region mA′≲250  MeV, by analyzing data from the interaction of 2.84×1011 100-GeV electrons with an active thick target and searching for missing-energy events. In this work, by including A′ production via secondary positron annihilation with atomic electrons, we extend these limits in the 200-300 MeV region by almost an order of magnitude, touching for the first time the dark matter relic density constrained parameter combinations. Our new results demonstrate the power of the resonant annihilation process in missing energy dark-matter searches, paving the road to future dedicated e+ beam efforts