B, Bs, K and pi weak matrix elements with physical light quarks

Calculations of pseudoscalar decay constants of B, Bs, K and pi mesons with physical light quarks are presented. We use HISQ ensembles that include u,d,s and c sea quarks at three lattice spacings. HISQ is used for the valence light quarks and a radiatively improved NRQCD action for the heavy quarks. The key results are f_{B^+}=0.184(4)$ GeV, f_{B_s}=0.224(4) GeV, f_{B_s}/f_{B^+}=1.217(8), f_{K^+}/f_{pi^+}=1.1916(21), f_{K^+}=155.37(34) MeV, giving a significant improvement over previous results that required chiral extrapolation. We also calculate the Wilson flow scale w_0, finding w_0=0.1715(9) fm

Neutral B-meson mixing from full lattice QCD at the physical point

We calculate the bag parameters for neutral $B$-meson mixing in and beyond the Standard Model, in full four-flavour lattice QCD for the first time. We work on gluon field configurations that include the effect of $u$, $d$, $s$ and $c$ sea quarks with the Highly Improved Staggered Quark (HISQ) action at three values of the lattice spacing and with three $u/d$ quark masses going down to the physical value. The valence $b$ quarks use the improved NRQCD action and the valence light quarks, the HISQ action. Our analysis was blinded. Our results for the bag parameters for all five operators are the most accurate to date. For the Standard Model operator between $B_s$ and $B_d$ mesons we find: $\hat{B}_{B_s}=1.232(53)$, $\hat{B}_{B_d}=1.222(61)$. Combining our results with lattice QCD calculations of the decay constants using HISQ quarks from the Fermilab/MILC collaboration and with experimental values for $B_s$ and $B_d$ oscillation frequencies allows determination of the CKM elements $V_{ts}$ and $V_{td}$. We find $V_{ts} = 0.04189(93)$, $V_{td} = 0.00867(23)$ and $V_{ts}/V_{td} = 0.2071(27)$. Our results agree well (within $2\sigma$) with values determined from CKM unitarity constraints based on tree-level processes (only). Using a ratio to $\Delta M$ in which CKM elements cancel in the Standard Model, we determine the branching fractions ${\text{Br}}(B_s\rightarrow \mu^+\mu^-) = 3.81(18) \times 10^{-9}$ and ${\text{Br}}(B_d\rightarrow \mu^+\mu^-) = 1.031(54) \times 10^{-10}$. We also give results for matrix elements of the operators $R_0$, $R_1$ and $\tilde{R}_1$ that contribute to neutral $B$-meson width differences.This work was funded by STFC, the Royal Society, the Wolfson Foundation and the US DOE and National Science Foundation

Fractures are common within 18 months following first-line R-CHOP in older patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if <18 months; or at progression or death. Of 877 patients identified, 148 were excluded: 121 had progression or died before 6 months; 23 had follow-up <6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk

The provision of NHS health checks in a community setting: an ethnographic account

Background: The UK National Health Service Health Checks programme aims to reduce avoidable cardiovascular deaths, disability and health inequalities in England. However, due to the reported lower uptake of screening in specific black and minority ethnic communities who are recognised as being more at risk of cardiovascular disease, there are concerns that NHS Health Checks may increase inequalities in health. This study aimed to examine the feasibility and acceptability of community outreach NHS Health Checks targeted at the Afro-Caribbean community. Methods: This paper reports findings from an ethnographic study including direct observation of four outreach events in four different community venues in inner-city Bristol, England and follow up semi-structured interviews with attendees (n = 16) and staff (n = 4). Interviews and field notes were transcribed, anonymized and analysed thematically using a process of constant comparison. Results: Analysis revealed the value of community assets (community engagement workers, churches, and community centres) to publicise the event and engage community members. People were motivated to attend for preventative reasons, often prompted by familial experience of cardiovascular disease. Attendees valued outreach NHS Health Checks, reinforcing or prompting some to make healthy lifestyle changes. The NHS Health Check provided an opportunity for attendees to raise other health concerns with health staff and to discuss their test results with peers. For some participants, the communication of test results, risk and lifestyle information was confusing and unwelcome. The findings additionally highlight the need to ensure community venues are fit for purpose in terms of assuring confidentiality. Conclusions: Outreach events provide evidence of how local health partnerships (family practice staff and health trainers) and community assets, including informal networks, can enhance the delivery of outreach NHS Health Checks and in promoting the health of targeted communities. To deliver NHS Health Checks effectively, the location and timing of events needs to be carefully considered and staff need to be provided with the appropriate training to ensure patients are supported and enabled to make lifestyle changes

The relationship between patient physiology, the systemic inflammatory response and survival in patients undergoing curative resection of colorectal cancer

&lt;p&gt;Background: It is increasingly recognised that host-related factors may be important in determining cancer outcome. The aim was to examine the relationship between patient physiology, the systemic inflammatory response and survival after colorectal cancer resection.&lt;/p&gt; &lt;p&gt;Methods: Patients undergoing potentially curative resection of colorectal cancer were identified from a prospectively maintained database. Patient physiology was assessed using the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) criteria. The systemic inflammatory response was assessed using the modified Glasgow Prognostic Score (mGPS). Multivariate 5-year survival analysis was carried out with calculation of hazard ratios (HR).&lt;/p&gt; &lt;p&gt;Results: A total of 320 patients were included. During follow-up (median 74 months), there were 136 deaths: 83 colorectal cancer related and 53 non-cancer related. Independent predictors of cancer-specific survival were age (HR: 1.46, P&#60;0.01), Dukes stage (HR: 2.39, P&#60;0.001), mGPS (HR: 1.78, P&#60;0.001) and POSSUM physiology score (HR: 1.38, P=0.02). Predictors of overall survival were age (HR: 1.64, P&#60;0.001), smoking (HR: 1.52, P=0.02), Dukes stage (HR: 1.64, P&#60;0.001), mGPS (HR: 1.60, P&#60;0.001) and POSSUM physiology score (HR: 1.27, P=0.03). A relationship between mGPS and POSSUM physiology score was also established (P&#60;0.006).&lt;/p&gt; &lt;p&gt;Conclusion: The POSSUM physiology score and the systemic inflammatory response are strongly associated and both are independent predictors of cancer specific and overall survival in patients undergoing potentially curative resection of colorectal cancer.&lt;/p&gt

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

Peer reviewedPublisher PD

Comparative Genomics of Gardnerella vaginalis Strains Reveals Substantial Differences in Metabolic and Virulence Potential

Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9.Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species.Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe