Policy Solutions to Address Mass Shootings

In the past decade, mass shootings, particularly those that take place in public areas, have increasingly become part of the national conversation in the United States. Mass public shootings instill widespread fear, in part because of their seeming randomness and unpredictability. Yet when these incidents occur, which has been with somewhat greater frequency and lethality as of late, public calls for policy responses are immediate. In this policy brief, we review efforts to evaluate the effect of gun control measures on mass public shootings, including a discussion of our recently published study on the relationship between state gun laws and the incidence and severity of these shootings. The findings of this work point to gun permits and bans on large-capacity magazines as having promise in reducing (a) mass public shooting rates and (b) mass public shooting victimization, respectively. Interestingly, however, most gun laws that we examined, including assault weapon bans, do not appear to be causally related to the rate of mass public shootings

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial

BACKGROUND Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers

RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina

SummaryA fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression

Identification of intermediates of in vivo trichloroethylene oxidation by the membrane-associated methane monooxygenase

The rate and products of trichloroethylene (TCE) oxidation by Methylomicrobium album BG8 expressing membrane-associated methane monooxygenase (pMMO) were determined using 14 C radiotracer techniques. [ 14 C]TCE was degraded at a rate of 1.24 nmol (min mg protein) −1 with the initial production of glyoxylate and then formate. Radiolabeled CO 2 was also found after incubating M. album BG8 for 5 h with [ 14 C]TCE. Experiments with purified pMMO from Methylococcus capsulatus Bath showed that TCE could be mineralized to CO 2 by pMMO. Oxygen uptake studies verified that M. album BG8 could oxidize glyoxylate and that pMMO was responsible for the oxidation based on acetylene inactivation studies. Here we propose a pathway of TCE oxidation by pMMO-expressing cells in which TCE is first converted to TCE-epoxide. The epoxide then spontaneously undergoes HCl elimination to form glyoxylate which can be further oxidized by pMMO to formate and CO 2 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74667/1/j.1574-6968.2000.tb09090.x.pd

In-situ fluorescence spectroscopy indicates total bacterial abundance and dissolved organic carbon

We explore in-situ fluorescence spectroscopy as an instantaneous indicator of total bacterial abundance and faecal contamination in drinking water. Eighty-four samples were collected outside of the recharge season from groundwater-derived water sources in Dakar, Senegal. Samples were analysed for tryptophan-like (TLF) and humic-like (HLF) fluorescence in-situ, total bacterial cells by flow cytometry, and potential indicators of faecal contamination such as thermotolerant coliforms (TTCs), nitrate, and in a subset of 22 samples, dissolved organic carbon (DOC). Significant single-predictor linear regression models demonstrated that total bacterial cells were the most effective predictor of TLF, followed by on-site sanitation density; TTCs were not a significant predictor. An optimum multiple-predictor model of TLF incorporated total bacterial cells, nitrate, nitrite, on-site sanitation density, and sulphate (r2 0.68). HLF was similarly related to the same parameters as TLF, with total bacterial cells being the best correlated (ρs 0.64). In the subset of 22 sources, DOC clustered with TLF, HLF, and total bacterial cells, and a linear regression model demonstrated HLF was the best predictor of DOC (r2 0.84). The intergranular nature of the aquifer, timing of the study, and/or non-uniqueness of the signal to TTCs can explain the significant associations between TLF/HLF and indicators of faecal contamination such as on-site sanitation density and nutrients but not TTCs. The bacterial population that relates to TLF/HLF is likely to be a subsurface community that develops in-situ based on the availability of organic matter originating from faecal sources. In-situ fluorescence spectroscopy instantly indicates a drinking water source is impacted by faecal contamination but it remains unclear how that relates specifically to microbial risk in this setting

The higher education impact agenda, scientific realism and policy change: the case of electoral integrity in Britain

Pressures have increasingly been put upon social scientists to prove their economic, cultural and social value through ‘impact agendas’ in higher education. There has been little conceptual and empirical discussion of the challenges involved in achieving impact and the dangers of evaluating it, however. This article argues that a critical realist approach to social science can help to identify some of these key challenges and the institutional incompatibilities between impact regimes and university research in free societies. These incompatibilities are brought out through an autobiographical ‘insider-account’ of trying to achieve impact in the field of electoral integrity in Britain. The article argues that there is a more complex relationship between research and the real world which means that the nature of knowledge might change as it becomes known by reflexive agents. Secondly, the researchers are joined into social relations with a variety of actors, including those who might be the object of study in their research. Researchers are often weakly positioned in these relations. Some forms of impact, such as achieving policy change, are therefore exceptionally difficult as they are dependent on other actors. Strategies for trying to achieve impact are drawn out such as collaborating with civil society groups and parliamentarians to lobby for policy change

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV

Comparing ocean surface boundary vertical mixing schemes including langmuir turbulence

Six recent Langmuir turbulence parameterization schemes and five traditional schemes are implemented in a common single‐column modeling framework and consistently compared. These schemes are tested in scenarios versus matched large eddy simulations, across the globe with realistic forcing (JRA55‐do, WAVEWATCH‐III simulated waves) and initial conditions (Argo), and under realistic conditions as observed at ocean moorings. Traditional non‐Langmuir schemes systematically underpredict large eddy simulation vertical mixing under weak convective forcing, while Langmuir schemes vary in accuracy. Under global, realistic forcing Langmuir schemes produce 6% (−1% to 14% for 90% confidence) or 5.2 m (−0.2 m to 17.4 m for 90% confidence) deeper monthly mean mixed layer depths than their non‐Langmuir counterparts, with the greatest differences in extratropical regions, especially the Southern Ocean in austral summer. Discrepancies among Langmuir schemes are large (15% in mixed layer depth standard deviation over the mean): largest under wave‐driven turbulence with stabilizing buoyancy forcing, next largest under strongly wave‐driven conditions with weak buoyancy forcing, and agreeing during strong convective forcing. Non‐Langmuir schemes disagree with each other to a lesser extent, with a similar ordering. Langmuir discrepancies obscure a cross‐scheme estimate of the Langmuir effect magnitude under realistic forcing, highlighting limited understanding and numerical deficiencies. Maps of the regions and seasons where the greatest discrepancies occur are provided to guide further studies and observations

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo