Bottom-quark Fusion Processes at the LHC for Probing Z′Z^{\prime} Models and B-meson Decay Anomalies

We investigate models of a heavy neutral gauge boson Z' which could explain anomalies in B meson decays reported by the LHCb experiment. In these models, the Z' boson couples mostly to third generation fermions. We show that bottom quarks arising from gluon splitting can fuse into Z' as an essential production mechanism at the LHC, thereby allowing to probe these models. The study is performed within a generic framework for explaining the B anomalies that can be accommodated in well motivated models. The flavor violating b s coupling associated with Z' in such models produces lower bound on the production cross-section which gives rise to a cross-section range for such scenarios for the LHC to probe. Results are presented in Z' -> $\mu \mu$ decays with at least one bottom-tagged jet in its final state. Some parts of the model parameter space become constrained by the existing dimuon-resonance searches by the ATLAS and CMS collaborations. However, the requirement of one or two additional bottom-tagged jets in the final state would allow for probing a larger region of the parameter space of the models at the ongoing LHC program.Comment: 7 pages, 3 figures, v3: added discussion with updated figures, conclusions unchanged, published version in PR

Transforming innovation for sustainability

The urgency of charting pathways to sustainability that keep human societies within a "safe operating space" has now been clarified. Crises in climate, food, biodiversity, and energy are already playing out across local and global scales and are set to increase as we approach critical thresholds. Drawing together recent work from the Stockholm Resilience Centre, the Tellus Institute, and the STEPS Centre, this commentary article argues that ambitious Sustainable Development Goals are now required along with major transformation, not only in policies and technologies, but in modes of innovation themselves, to meet them. As examples of dryland agriculture in East Africa and rural energy in Latin America illustrate, such "transformative innovation" needs to give far greater recognition and power to grassroots innovation actors and processes, involving them within an inclusive, multi-scale innovation politics. The three dimensions of direction, diversity, and distribution along with new forms of "sustainability brokering" can help guide the kinds of analysis and decision making now needed to safeguard our planet for current and future generations

Open-Label Taste-Testing Study to Evaluate the Acceptability of Both Strawberry-Flavored and Orange-Flavored Amylmetacresol/2,4-Dichlorobenzyl Alcohol Throat Lozenges in Healthy Children

BACKGROUND: Acute sore throat (pharyngitis) is one of the most common illnesses for which children are seen by primary care physicians. Most cases are caused by viruses and are benign and self-limiting. Clinically proven, over-the-counter throat lozenges provide rapid and effective relief of acute sore throat symptoms, and are increasingly important in self-management of this condition. OBJECTIVE: The purpose of this study (International Standard Randomized Controlled Trial Number: ISRCTN34958871) was to evaluate the acceptability of two licensed, commercially available sore throat lozenges containing amylmetacresol and 2,4-dichlorobenzyl (AMC/DCBA)—one strawberry flavored and the other orange flavored—in healthy children. STUDY DESIGN: This was an open-label, single-dose, crossover, taste-testing study in children recruited via a clinical database and advertisements over a 3.5-week period. SETTING: Potentially eligible participants were invited to attend the taste-testing session at a clinic. PARTICIPANTS: At the screening session, which took place either before or on the day of taste testing, details of relevant medical history, medication, and demographics were recorded. Of the 108 screened subjects, 102 were recruited. These were healthy male and female children aged 6–12 years. INTERVENTION: Each child cleansed their palate with water and water biscuits before tasting a strawberry-flavored lozenge (Strepsils(®) strawberry sugar free, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 00063/0395), which was sucked for 1 minute and then expelled. The orange-flavored lozenge (Strepsils(®) orange with vitamin C, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 016242152) was tasted at least 15 minutes later following further cleansing of the palate. The spontaneous reaction of the child on tasting each lozenge was observed and recorded. Subjects were asked to indicate their liking for each lozenge, using a 7-point hedonic facial scale, and were required to answer a series of questions relating to what they liked and disliked about the taste and the feel of the lozenge in the mouth and throat. The primary endpoint was the proportion of subjects with a hedonic facial score of >4. Secondary endpoints included the spontaneous reaction of the child on tasting the lozenge and responses to questions related to taste. RESULTS: The taste of the lozenge was scored >4 (i.e. ‘good’, ‘really good’, or ‘super good’) by 85.3 % of subjects for the strawberry flavor and 49.0 % for the orange flavor (p < 0.0001). The mean (standard deviation) score was 5.72 (1) for the strawberry-flavored lozenge and 4.35 (2) for the orange-flavored lozenge. The proportion of subjects willing to take the lozenge again was 94 % for the strawberry flavor and 56 % for the orange flavor. CONCLUSIONS: Strawberry-flavored AMC/DCBA lozenges were liked by, and acceptable to, the majority of the children. AMC/DCBA orange-flavored lozenges were also liked by, and acceptable to, approximately half the children. Overall, both strawberry and orange would be suitable flavors for lozenges intended for children when they suffer from sore throat

A complete rethink is needed on how greenhouse gas emissions are quantified for national reporting

The 2015 Conference of the Parties (COP21) in Paris has for the first time agreed that both developed and developing countries need to reduce greenhouse gas (GHG) emissions to maintain a global average temperature ‘well below’ 2°C and aim to limit the increase to less than 1.5°C above pre-industrial temperatures. This requires more ambitious emission reduction targets and an increased level of cooperation and transparency between countries. With the start of the second Kyoto Commitment period in 2013, and the 2015 Paris Agreement, it is, therefore, timely to reconsider how GHG emissions are determined and verified

Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age &lt;50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses