Vector boson fusion searches for dark matter at the LHC

The vector boson fusion (VBF) event topology at the Large Hadron Collider (LHC) allows efficient suppression of dijet backgrounds and is therefore a promising target for new physics searches. We consider dark matter models which interact with the Standard Model through the electroweak sector: either through new scalar and pseudoscalar mediators which can be embedded into the Higgs sector, or via effective operators suppressed by some higher scale, and therefore have significant VBF production cross-sections. Using realistic simulations of the ATLAS and CMS analysis chain, including estimates of major error sources, we project the discovery and exclusion potential of the LHC for these models over the next decade.Comment: 16 pages, 2 tables, 12 figure

Lessons Learned Study Final Report for the Exploration Systems Mission Directorate

This report is the final product of a 90-day study performed for the Exploration Systems Mission Directorate. The study was to assemble lessons NASA has learned from previous programs that could help the Exploration Systems Mission Directorate pursue the Exploration vision. It focuses on those lessons that should have the greatest significance to the Directorate during the formulation of program and mission plans. The study team reviewed a large number of lessons learned reports and data bases, including the Columbia Accident Investigation Board and Rogers Commission reports on the Shuttle accidents, accident reports from robotic space flight systems, and a number of management reviews by the Defense Sciences Board, Government Accountability Office, and others. The consistency of the lessons, findings, and recommendations validate the adequacy of the data set. In addition to reviewing existing databases, a series of workshops was held at each of the NASA centers and headquarters that included senior managers from the current workforce as well as retirees. The full text of the workshop reports is included in Appendix A. A lessons learned website was opened up to permit current and retired NASA personnel and on-site contractors to input additional lessons as they arise. These new lessons, when of appropriate quality and relevance, will be brought to the attention of managers. The report consists of four parts: Part 1 provides a small set of lessons, called the Executive Lessons Learned, that represent critical lessons that the Exploration Systems Mission Directorate should act on immediately. This set of Executive Lessons and their supporting rationale have been reviewed at length and fully endorsed by a team of distinguished NASA alumni; Part 2 contains a larger set of lessons, called the Selected Lessons Learned, which have been chosen from the lessons database and center workshop reports on the basis of their specific significance and relevance to the near-term work of the Exploration Directorate. These lessons frequently support the Executive lessons but are more general in nature; Part 3 consists of the reports of the center workshops that were conducted as part of this activity. These reports are included in their entirety (approximately 200 pages) in Appendix G and have significance for specific managers; Part 4 consists of the remainder of the lessons that have been selected by this effort and assembled into a database for the use of the Explorations Directorate. The database is archived and hosted in the Lessons Learned Knowledge Network, which provides a flexible search capability using a wide variety of search terms. Finally, a spreadsheet lists databases searched and a bibliography identifies reports that have been reviewed as sources of lessons for this task. NASA has been presented with many learning opportunities. We have conducted numerous programs, some extremely successful and others total failures. Most have been documented with a formal lessons learned activity, but we have not always incorporated these learning opportunities into our normal modes of business. For example, the Robbins Report of 2001 clearly indicates that many project failures of the past two decades were the result of violating well documented best practices, often in direct violation of management instructions and directives. An overarching lesson emerges: that disciplined execution in accordance with proven best practices is the greatest single contributor to a successful program. The Lessons Learned task team offers a sincere hope that the lessons presented herein will be helpful to the Exploration Systems Directorate in charting and executing their course. The success of the Directorate and of NASA in general depends on our collective ability to move forward without having to relearn the lessons of those who have gone before

A Letter of Intent to Install a milli-charged Particle Detector at LHC P5

In this LOI we propose a dedicated experiment that would detect "milli-charged" particles produced by pp collisions at LHC Point 5. The experiment would be installed during LS2 in the vestigial drainage gallery above UXC and would not interfere with CMS operations. With 300 fb$^{-1}$ of integrated luminosity, sensitivity to a particle with charge $\mathcal{O}(10^{-3})~e$ can be achieved for masses of $\mathcal{O}(1)$ GeV, and charge $\mathcal{O}(10^{-2})~e$ for masses of $\mathcal{O}(10)$ GeV, greatly extending the parameter space explored for particles with small charge and masses above 100 MeV.Comment: 19 pages, 7 figure

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

<b>Objective</b> <i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p> <b>Methods</b> The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p> <b>Result</b> Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p> <b>Conclusion</b> Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p&gt

Too Much Medicine in older people? Deprescribing through Shared Decision Making

Too much medicine is an increasingly recognised problem,1 2 and one manifestation is inappropriate polypharmacy in older people. Polypharmacy is usually defined as taking more than five regular prescribed medicines.3 It can be appropriate (when potential benefits outweigh potential harms)4 but increases the risk of older people experiencing adverse drug reactions, impaired physical and cognitive function, and hospital admission.5 6 7 There is limited evidence to inform polypharmacy in older people, especially those with multimorbidity, cognitive impairment, or frailty.8 Systematic reviews of medication withdrawal trials (deprescribing) show that reducing specific classes of medicines may decrease adverse events and improve quality of life.9 10 11 Two recent reviews of the literature on deprescribing stressed the importance of patient involvement and shared decision making.12 13 Patients and clinicians typically overestimate the benefits of treatments and underestimate their harms.14 When they engage in shared decision making they become better informed about potential outcomes and as a result patients tend to choose more conservative options (eg, fewer medicines), facilitating deprescribing.15 However, shared decision making in this context is not easy, and there is little guidance on how to do it.16 We draw together evidence from the psychology, communication, and decision making literature (see appendix on thebmj.com). For each step of the shared decision making process we describe the unique tasks required for deprescribing decisions; identify challenges for older adults, their companions, and clinicians (figure); give practical advice on how challenges may be overcome; highlight where more work is needed; and identify priorities for future research (table). Key messages Deprescribing is a process of planned and supervised tapering or ceasing of inappropriate medicines Shared decision making should be an integral part of the deprescribing process Many factors affect this process, including trust in clinicians’ advice, contradictory patient attitudes about medication, cognitive biases that lead to a preference for the status quo and positive information, and information processing difficulties There is uncertainty about the effect of risk communication and preference elicitation tools in older people Older people’s preferences for discussing life expectancy and quality of life vary widely, but even those who wish to delegate their decisions still appreciate discussion of optionsJJ is supported by a National Health and Medical Research Council (NHMRC) early career fellowship (1037028) and KM is supported by an NHMRC career development fellowship (1029241

Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk

Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). Conclusion These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes

Building from patient experiences to deliver patient-focused healthcare systems in collaboration with patients: A call to action

Patients’ experiences of their diagnosis, condition, and treatment (including the impact on their lives), and their experiences surrounding expectations of care, are becoming increasingly important in shaping healthcare systems that meet the evolving needs and priorities of different patient communities over time; this is an ongoing goal of all healthcare stakeholders. Current approaches that capture patient experiences with data are fragmented, resulting in duplication of effort, numerous requests for information, and increased patient burden. Application of patient experience data to inform healthcare decisions is still emerging and there remains an opportunity to align diverse stakeholders on the value of these data to strengthen healthcare systems. Given the collective value of understanding patient experiences across multiple stakeholder groups, we propose a more aligned approach to the collection of patient experience data. This approach is built on the principle that the patients’ experiences are the starting point, and not just something to be considered at the end of the process. It must also be based on meaningful patient engagement, where patients are collaborators and decision makers at each step, thereby ensuring their needs and priorities are accurately reflected. The resulting data and evidence should be made available for all stakeholders, to inform their decision making and healthcare strategies in ways that meet patient priorities. We call for multi-stakeholder collaboration that will deliver healthcare systems and interventions that are better centered around and tailored to patient experiences, and that will help address patients’ unmet needs

Interplay and Characterization of Dark Matter Searches at Colliders and in Direct Detection Experiments

In this White Paper we present and discuss a concrete proposal for the consistent interpretation of Dark Matter searches at colliders and in direct detection experiments. Based on a specific implementation of simplified models of vector and axial-vector mediator exchanges, this proposal demonstrates how the two search strategies can be compared on an equal footing

National Astronomy Meeting 2019 Abstract Book

The National Astronomy Meeting 2019 Abstract Book. Abstracts accepted and presented, including both oral and poster presentations, at the Royal Astronomical Society's NAM2019 conference, held at Lancaster University between 30 June and 4 July 2019