Balancing Independence and Accountability: Proposals to Reform Special Counsel Investigations

Investigations of the president and other high-ranking officials must be free from political interference yet cannot devolve into “runaway” inquiries. This report recommends reforms to the rules for every stage of special counsel investigations. Among the proposals is a requirement that federal judges oversee the attorney general’s appointment and removal of special counsels. Additionally, a special counsel should be mandatory when the president is suspected of a crime and reports on investigations should go directly to Congress

Dark Matter Halo Profiles of Massive Clusters: Theory vs. Observations

Dark matter-dominated cluster-scale halos act as an important cosmological probe and provide a key testing ground for structure formation theory. Focusing on their mass profiles, we have carried out (gravity-only) simulations of the concordance LCDM cosmology, covering a mass range of 2.10^{12}-2.10^{15} solar mass/h and a redshift range of z=0-2, while satisfying the associated requirements of resolution and statistical control. When fitting to the Navarro-Frenk-White profile, our concentration-mass (c-M) relation differs in normalization and shape in comparison to previous studies that have limited statistics in the upper end of the mass range. We show that the flattening of the c-M relation with redshift is naturally expressed if c is viewed as a function of the peak height parameter, \nu. Unlike the c-M relation, the slope of the c-\nu relation is effectively constant over the redshift range z=0-2, while the amplitude varies by ~30% for massive clusters. This relation is, however, not universal: Using a simulation suite covering the allowed wCDM parameter space, we show that the c-\nu relation varies by about +/- 20% as cosmological parameters are varied. At fixed mass, the c(M) distribution is well-fit by a Gaussian with \sigma_c/c = 0.33, independent of the radius at which the concentration is defined, the halo dynamical state, and the underlying cosmology. We compare the LCDM predictions with observations of halo concentrations from strong lensing, weak lensing, galaxy kinematics, and X-ray data, finding good agreement for massive clusters (M > 4.10^{14} solar mass/h), but with some disagreements at lower masses. Because of uncertainty in observational systematics and modeling of baryonic physics, the significance of these discrepancies remains unclear.Comment: 18 pages; 13 figures, new observational data included, minor revisions and extended discussions, improved fitting formula, results unchange

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable

BACKGROUND: Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. SUMMARY OF REVIEW: The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. CONCLUSIONS: The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies

Towards a functional model of mental disorders incorporating the laws of thermodynamics

The current paper presents the hypothesis that the understanding of mental disorders can be advanced by incorporating the laws of thermodynamics, specifically relating to energy conservation and energy transfer. These ideas, along with the introduction of the notion that entropic activities are symptomatic of inefficient energy transfer or disorder, were used to propose a model of understanding mental ill health as resulting from the interaction of entropy, capacity and work (environmental demands). The model was applied to Attention Deficit Hyperactivity Disorder, and was shown to be compatible with current thinking about this condition, as well as emerging models of mental disorders as complex networks. A key implication of the proposed model is that it argues that all mental disorders require a systemic functional approach, with the advantage that it offers a number of routes into the assessment, formulation and treatment for mental health problems

To swim or not to swim: an interpretation of farmed mink's motivation for a water bath

How an animal’s behavioural (ethological) needs can be met is a pivotal issue in the assessment of welfare for captive animals. The value of swimming water for farmed mink is an example how scientific and societal questions relating to animal welfare can be answered. A number of studies have addressed the issue of the indispensability of swimming water for mink; however, so far with inconclusive evidence. In this paper, the results of these studies and related literature are reviewed. First, the biological definition of need is discussed. Subsequently, attention is paid to the effects of the presence, absence and the removal of swimming water on behavioural and physiological correlates of well-being including stereotypic and anticipatory behaviour and urinary cortisol. Thereafter we discuss individual differences in the use of swimming water, the price animals pay for access to a water bath, and the effect of access to swimming water on juvenile play. The main conclusions of the literature review are that 1) the use of a water bath for mink is most likely related to foraging behaviour (foraging areas: land and water); 2) absence of swimming water, without prior experience, does not lead to consistent changes in level of stereotypic behaviour, or anticipatory responses; 3) removal of a previously experienced water bath may induce short-term stress as indicated by behavioural parameters and elevated cortisol responses; 4) mink work hard for access to a swimming bath and running wheel in consumer demand studies. Other cage modifications such as tunnels and biting objects, may also provide environmental enrichment, if they are added to otherwise impoverished conditions; 5) There are individual differences in the use of swimming water: these are related in part to variation in prior experience of aquatic resources.; 6) As prior experience is important both with respect to individual use of swimming water and the response to deprivation, swimming water can not be described as biological need in the sense of a fixed requirement for survival. As swimming water appears to act as an incentive that induces its own motivation a more accurate term may be an “incentive induced or environmentally facilitated need”. Given the available evidence, it is not possible to conclude whether mink that have never experienced swimming water, suffer as a consequence of its absence. However, it is possible to predict that mink with access to water have improved quality of life, due to increased behavioural opportunities, in comparison to farmed mink without access to swimming water. In practical terms, it is still open to debate whether mink should be provided with swimming water, or if alternative, less valued, but easier to install and maintain forms of environmental enrichment, should be provided in mink housing. To clarify these issues a number of future studies would be valuable. These include; 1) whether specific environmental cues affect motivation to swim, such as the form of drinking water delivery systems ; 2) whether prior experience of swimming water affects its incentive value; in other words “can you miss what you never experienced?”; 3) do behavioural parameters such as stereotypic behaviour; rebound effects and vacuum activity have any general utility in assessing the value of absent resources; 4) what are preferences for and the value of alternative resources which may act as substitutes for swimming water. In addition we would recommend further work investigating: relationship between access to swimming water and positive indicators of welfare such as play and/or anticipatory behaviour; the effects of preventing the performance of rewarding behaviours and deprivation of a previous experienced resource; and health and hygeine issues related to provision of a water bath. In future work, it would be desirable to present be the actual percentages of animals using a water bath during the experiment and the use of power analyses, to aid their interpretation

Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials.

Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George's Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n=121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.113

Mnemonic function in small vessel disease and associations with white matter tract microstructure.

Cerebral small vessel disease (SVD) is associated with deficits in working memory, with a relative sparing of long-term memory; function may be influenced by white matter microstructure. Working and long-term memory were examined in 106 patients with SVD and 35 healthy controls. Microstructure was measured in the uncinate fasciculi and cingula. Working memory was more impaired than long-term memory in SVD, but both abilities were reduced compared to controls. Regression analyses found that having SVD explained the variance in memory functions, with additional variance explained by the cingula (working memory) and uncinate (long-term memory). Performance can be explained in terms of integrity loss in specific white matter tract associated with mnemonic functions