Quark Masses: An Environmental Impact Statement

We investigate worlds that lie on a slice through the parameter space of the Standard Model over which quark masses vary. We allow as many as three quarks to participate in nuclei, while fixing the mass of the electron and the average mass of the lightest baryon flavor multiplet. We classify as "congenial" worlds that satisfy the environmental constraint that the quark masses allow for stable nuclei with charges one, six, and eight, making organic chemistry possible. Whether a congenial world actually produces observers depends on a multitude of historical contingencies, beginning with primordial nucleosynthesis, which we do not explore. Such constraints may be independently superimposed on our results. Environmental constraints such as the ones we study may be combined with information about the a priori distribution of quark masses over the landscape of possible universes to determine whether the measured values of the quark masses are determined environmentally, but our analysis is independent of such an anthropic approach. We estimate baryon masses as functions of quark masses and nuclear masses as functions of baryon masses. We check for the stability of nuclei against fission, strong particle emission, and weak nucleon emission. For two light quarks with charges 2/3 and -1/3, we find a band of congeniality roughly 29 MeV wide in their mass difference. We also find another, less robust region of congeniality with one light, charge -1/3 quark, and two heavier, approximately degenerate charge -1/3 and 2/3 quarks. No other assignment of light quark charges yields congenial worlds with two baryons participating in nuclei. We identify and discuss the region in quark-mass space where nuclei would be made from three or more baryon species.Comment: 40 pages, 16 figures (in color), 4 tables. See paper for a more detailed abstract. v4: Cleaning up minor typo

In Whose Backyard?: Concern About Sitting a Nuclear Waste Facility

Proponents of hazardous and nuclear waste depositories label opponents to local siting of such facilities NIMBYs (Not In My Backyard). This study assesses the extent to which the NIMBY label and the strategies of industry proponents to reduce opposition function on a reasonable set of assumptions. Using survey data and multiple regression techniques, the levels of concern of residents living in the county selected as the site of a low level radioactive wane disposal facility (imminent threat condition) are compared with a statewide sample (hypothetical threat condition). Consistent with proponents\u27 theoretical assumptions, the levels of concern are greater for respondents under conditions of imminent threat than of hypothetical threat. However, within the host county, levels of concern are lowest, albeit most polarized, in the community closest to the proposed site. A conflict theory approach enhances an understanding of these findings by suggesting that within the most proximate community levels of concern are lowest for citizens who stand to gain the most economic benefits from the facility but highest for those citizens who are least likely to derive tangible gains

In Whose Backyard?: Concern About Sitting a Nuclear Waste Facility

Proponents of hazardous and nuclear waste depositories label opponents to local siting of such facilities NIMBYs (Not In My Backyard). This study assesses the extent to which the NIMBY label and the strategies of industry proponents to reduce opposition function on a reasonable set of assumptions. Using survey data and multiple regression techniques, the levels of concern of residents living in the county selected as the site of a low level radioactive wane disposal facility (imminent threat condition) are compared with a statewide sample (hypothetical threat condition). Consistent with proponents\u27 theoretical assumptions, the levels of concern are greater for respondents under conditions of imminent threat than of hypothetical threat. However, within the host county, levels of concern are lowest, albeit most polarized, in the community closest to the proposed site. A conflict theory approach enhances an understanding of these findings by suggesting that within the most proximate community levels of concern are lowest for citizens who stand to gain the most economic benefits from the facility but highest for those citizens who are least likely to derive tangible gains

Anti-tumour activity of bisphosphonates in preclinical models of breast cancer

There is increasing evidence of anti-tumour effects of bisphosphonates from pre-clinical studies, supporting a role for these drugs beyond their traditional use in treatment of cancer-induced bone disease. A range of model systems have been used to investigate the effects of different bisphosphonates on tumour growth, both in bone and at peripheral sites. Most of these studies conclude that bisphosphonates cause a reduction in tumour burden, but that early intervention and the use of high and/or repeated dosing is required. Successful eradication of cancer may only be achievable by targeting the tumour cells directly whilst also modifying the tumour microenvironment. In line with this, bisphosphonates are demonstrated to be particularly effective at reducing breast tumour growth when used in combination with agents that directly target cancer cells. Recent studies have shown that the effects of bisphosphonates on breast tumours are not limited to bone, and that prolonged anti-tumour effects may be achieved following their inclusion in combination therapy. This has opened the field to a new strand of bisphosphonate research, focussed on elucidating their effects on cells and components of the local, regional and distal tumour microenvironment. This review highlights the recent developments in relation to proposed anti-tumour effects of bisphosphonates reported from in vitro and in vivo models, and summarises the data from key breast cancer studies. Evidence for effects on different processes and cell types involved in cancer development and progression is discussed, and the main outstanding issues identified

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice