Annexin A8 identifies a subpopulation of transiently quiescent c-kit positive luminal progenitor cells of the ductal mammary epithelium

We have previously shown that Annexin A8 (ANXA8) is strongly associated with the basal-like subgroup of breast cancers, including BRCA1-associated breast cancers, and poor prognosis; while in the mouse mammary gland AnxA8 mRNA is expressed in low-proliferative isolated pubertal mouse mammary ductal epithelium and after enforced involution, but not in isolated highly proliferative terminal end buds (TEB) or during pregnancy. To better understand ANXA8’s association with this breast cancer subgroup we established ANXA8’s cellular distribution in the mammary gland and ANXA8’s effect on cell proliferation. We show that ANXA8 expression in the mouse mammary gland was strong during pre-puberty before the expansion of the rudimentary ductal network and was limited to a distinct subpopulation of ductal luminal epithelial cells but was not detected in TEB or in alveoli during pregnancy. Similarly, during late involution its expression was found in the surviving ductal epithelium, but not in the apoptotic alveoli. Double-immunofluorescence (IF) showed that ANXA8 positive (+ve) cells were ER-alpha negative (−ve) and mostly quiescent, as defined by lack of Ki67 expression during puberty and mid-pregnancy, but not terminally differentiated with ~15% of ANXA8 +ve cells re-entering the cell cycle at the start of pregnancy (day 4.5). RT-PCR on RNA from FACS-sorted cells and double-IF showed that ANXA8+ve cells were a subpopulation of c-kit +ve luminal progenitor cells, which have recently been identified as the cells of origin of basal-like breast cancers. Over expression of ANXA8 in the mammary epithelial cell line Kim-2 led to a G0/G1 arrest and suppressed Ki67 expression, indicating cell cycle exit. Our data therefore identify ANXA8 as a potential mediator of quiescence in the normal mouse mammary ductal epithelium, while its expression in basal-like breast cancers may be linked to ANXA8’s association with their specific cells of origin

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Symmetry breaking, conformal geometry and gauge invariance

When the electroweak action is rewritten in terms of SU(2) gauge invariant variables, the Higgs can be interpreted as a conformal metric factor. We show that asymptotic flatness of the metric is required to avoid a Gribov problem: without it, the new variables fail to be nonperturbatively gauge invariant. We also clarify the relations between this approach and unitary gauge fixing, and the existence of similar transformations in other gauge theories.Comment: 11 pages. Version 2: typos corrected, discussion of Elitzur's theorem added. Version to appear in J.Phys.

Long-lived charged Higgs at LHC as a probe of scalar Dark Matter

We study inert charged Higgs boson $H^\pm$ production and decays at LHC experiments in the context of constrained scalar dark matter model (CSDMM). In the CSDMM the inert doublet and singlet scalar's mass spectrum is predicted from the GUT scale initial conditions via RGE evolution. We compute the cross sections of processes $pp\to H^+H^-,\, H^\pm S_i^0$ at the LHC and show that for light $H^\pm$ the first one is dominated by top quark mediated 1-loop diagram with Higgs boson in s-channel. In a significant fraction of the parameter space $H^\pm$ are long-lived because their decays to predominantly singlet scalar dark matter (DM) and next-to-lightest (NL) scalar, $H^\pm\to S_{\text{DM, NL}} ff',$ are suppressed by the small singlet-doublet mixing angle and by the moderate mass difference $\Delta M=M_{H^+}-M_{\text{DM}} .$ The experimentally measurable displaced vertex in $H^\pm$ decays to leptons and/or jets and missing energy allows one to discover the $H^+H^-$ signal over the huge $W^+W^-$ background. We propose benchmark points for studies of this scenario at the LHC. If, however, $H^\pm$ are short-lived, the subsequent decays $S_{\text{NL}}\to S_{\text{DM}} f\bar f$ necessarily produce additional displaced vertices that allow to reconstruct the full $H^\pm$ decay chain.Comment: 15 pages, 5 figure

Turfgrass research report 1995

Postemergence herbicide efficacy on crabgrass / John R. Street and Renee M. Stewart -- Preemergence herbicide efficacy on crabgrass / John R. Street and Renee M. Stewart --Preemergent common chickweed weed control evaluation / William Pound -- Preemergent purple dead nettle weed control evaluation / William Pound -- General turfgrass broadleaf weed control evaluation / William Pound -- Finale/Roundup herbicide demonstration evaluation / William Pound -- Ground ivy control evaluation / William Pound -- Manage yellow nutsedge control evaluation / William Pound -- Alternative Turflon solvent tolerance evaluation / William Pound -- Wild violet control evaluation / William Pound --Leaf spot study, 1995 / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Leaf spot control study - Galena, Ohio / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Red thread control study, 1995 / Joe Rimelspach, Karl Danneberger -- Brown patch study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Brown patch (Rhizoctonia solani) curative study / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Preventive dollar spot (Sclerotinia homoeocarpa) control study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Take-All control study / Joe Rimelspach and Karl Danneberger -- Yellow tuft study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Summer patch control study / Rob Golembiewski, Joe Rimelspach and Karl Danneberger -- Sentinel and Daconil Ultrex gallonage study: influence on dollar spot control / Karl Danneberger and Jill Taylor -- Pink snow mold control study, 1994-1995 / Jill Taylor, Joe Rimelspach and Karl Danneberger -- Control of black cutworm, Agrotis ipsilon (Hufnagel), and sod webworms (Pyralidae: Crambinae) on short cut bentgrass, Agrostis palustris Hudson-1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Control of black cutworm, Agrotis ipsilon (Hufnagel), and sod webworms (Pyralidae: Crambinae) on short cut bentgrass, Agrostis palustris Hudson using spinosad formulations -1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Applications of insecticides for control of second generation hairy chinch bugs in turfgrass -1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Preventive application of insecticides for control of black turfgrass Ataenius larvae on golf course fairways, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Spring application of chemical and biological insecticides for control of overwintered white grubs in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Influence of post-treatment irrigation on the efficacy of RH 0345 and Merit applied at the time of egg hatch for control of Japanese beetle larvae in turf, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Application of various insecticides for preventive control of Japanese Beetle larvae in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Chemical and biological insecticides applied for control of white grubs in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Nitrogen source, rate, and timing effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- Natural organic source evaluation on a Kentucky bluegrass-perennial ryegrass mixture / John R. Street and Renee M. Stewart -- Nitrogen source, rate, and timing effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- Polymer-coated nitrogen source effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- 1993 NTEP bentgrass test (fairway/tee) / Jill A. Taylor -- 1993 NTEP fineleaf fescue test / Jill Taylor -- 1994 NTEP perennial ryegrass test / Jill Taylor -- 'Primo' growth regulator evaluation on creeping bentgrass / William Pound -- Bermudagrass management study / John Street and Jill Taylor -- Electrophoretic evaluation of esterase isozymes from turfgrass seed blends and mixtures / G. E. Bell, M. B. McDonald Jr. and T. K. Danneberger -- Computer Imaging of Electrophoretic Gels / G. E. Bell, M. B. McDonald Jr., T. K. Danneberger and S. K. St. Martin -- Evaluation of Kentucky bluegrass blends using isoelectric focusing and computer imaging / G. E. Bell, M. B. McDonald Jr. and T. K. Danneberger -- Identification of RAFLP markers in perennial ryegrass / Patricia M. Sweeney and Karl Danneberger -- RAPD analysis of dry turfgrass seed / Patricia Sweeney, Robert Golembiewski and Karl Danneberge

Week 48 outcomes from the BRAAVE 2020 study: a randomised switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in African American adults with HIV

Background: Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines- recommended single- tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Method: Adults with HIV self- identifying as Black or African American and virologically suppressed on 2 NRTIs plus a 3rd agent were randomised (2:1) to switch to open- label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69- insertions. Primary INSTI- resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at W24 (Primary endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV- 1 RNA ≥50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results: 495 were randomised and treated (B/F/TAF n = 330, SBR n = 165): 32% cis women, 2% transgender women, median age 49 years (range 18– 79) and 10% had pre- existing M184V/I mutation. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV- 1 RNA ≥50 c/mL (difference - 1.2%; 95% CI - 4.8% to 0.9%) demonstrating non-inferiority of B/F/TAF; 2 with pre- existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomised to B/F/TAF and 0 SBR to B/F/TAF had HIV- 1 RNA ≥50 c/mL. Baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. Median (IQR) weight increased 0.9 kg (- 1.5, 4.1) and 0.6 kg (- 1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug- related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Conclusion: Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre- existing NRTI resistance and was associated with few treatment re-lated AEs or discontinuations

A gauge-mediated supersymmetry breaking model with an extra singlet Higgs field

We study in some detail the next-to-minimal supersymmetric standard model with gauge mediation of supersymmetry breaking. We find that it is feasible to spontaneously generate values of the Higgs mass parameters $\mu$ and $B_\mu$ consistent with radiative electroweak symmetry breaking. The model has a phenomenologically viable particle spectrum. Messenger sneutrinos with mass in the range 6 to 25 TeV can serve as cold dark matter. It is also possible to evade the cosmological domain wall problem in this scenario.Comment: revised version to appear in PR

‘You’re just chopped off at the end’: Retired servicemen’s identity work struggles in the military to civilian transition

Promoting positive transition to retirement and cultural adaption for ex-service personnel has been identified as a priority for both social-science research and for public health policy in the UK. The Royal British Legion (RBL) aims to provide support to service and retired service personnel, but to date the transition to retirement experiences of older (60-plus) ex- service personnel remain under-researched. In this article, we employ a symbolic interactionist theoretical framework to examine older servicemen’s experiences and identity challenges post-retirement from the British armed forces. Data were collected primarily through semi-structured, focus-group interviews with 20 former servicemen. Here, we focus specifically upon the challenges encountered by these ex-servicemen in the retirement transition from military to civilian life, a time of identity flux of sociological interest. To navigate this period of identity change and challenge, many participants constructed a ‘modified military self’ through involvement with the RBL as a key social support network. For many retired personnel the RBL offered a form of identification and group identity that resonated strongly with earlier experiences of comradeship in the military