Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

Use of mixed methods designs in substance research: a methodological necessity in Nigeria

The utility of mixed methods (qualitative and quantitative) is becoming increasingly accepted in health sciences, but substance studies are yet to substantially benefit from such utilities. While there is a growing number of mixed methods alcohol articles concerning developed countries, developing nations are yet to embrace this method. In the Nigerian context, the importance of mixed methods research is yet to be acknowledged. This article therefore, draws on alcohol studies to argue that mixed methods designs will better equip scholars to understand, explore, describe and explain why alcohol consumption and its related problems are increasing in Nigeria. It argues that as motives for consuming alcohol in contemporary Nigeria are multiple, complex and evolving, mixed method approaches that provide multiple pathways for proffering solutions to problems should be embraced

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Explaining the human resource management preferences of employees: A study of Chinese workers

The forces of globalization, technology and the differences or similarities in institutional systems place substantial pressure on convergence and divergence in HRM practices. Moreover, local customs and the responses from employees also pose serious constraints on the degree of convergence or divergence (Rowley and Benson 2002). In other words, there is what might be termed an upward influence coming from the employees. Although companies may benchmark HRM ‘best practices’, the actual adoption and success of these practices depends, to a large extent, on perceptions and acceptance from employees. However, the opinions of non-managerial employees have been largely neglected in the studies of HRM (Cooke 2009; Legge 1995; Guest 2002; Edgar and Geare 2005; Qiao, Khilji and Wang 2009). Cooke (2009), after reviewing studies on HRM in China published between 1998 and 2007 in major business and management journals, reported that two-thirds of the studies had collected data from managers and most of them relied on managers as the sole source for information. Since the information has mainly been provided by managers, there is the potential for bias because feedback from the managers probably reflects the ideal or ‘best practices’ of HRM that those managers want to implement, rather than the actual HR policies or practices being used in the organization. Thus Cooke (2009, p.19) argued that ‘unless we can broaden our research catchment to include views from the widest range of stakeholders, particularly the employees, our understanding of HRM in China remains partial, from management’s lens’. This study explores the HR preferences of Chinese employees, both non-managerial and managerial ones, based on a sample of 2852 questionnaires from companies in China. A number of questions are explored. For example, what do they think of a ‘promotion-from-within’ policy? Do they prefer an individual-based bonus or a group-based bonus? Do they prefer a ‘downward performance appraisal method’ or a ‘multi-source performance appraisal method’? The research findings shows a strong ‘group orientation’ and a great emphasis on ‘soft factors’ such as seniority, loyalty and connections in many HRM areas. The debate on whether Chinese HRM will converge or diverge towards the Western models is still ongoing. Many argue that there could be further convergence towards the Western practices because globalization may place substantial pressure on firms to standardize practices and policies (see Chen, Lawler and Bae 2005). Others argue that HRM is highly context specific in which institutional and cultural forces have enduring influences (see Rowley and Cooke 2010), which indicates a divergent perspective. The third group supports a ‘cross-vergence’ view which argues that there will be signs of convergence in certain areas but Chinese HRM will keep its ‘Chinese characteristics’ (Cooke 2005, 2010; Yeung, Warner and Rowley 2008; Warner 2009a, b). This study supports the ‘cross-vergence’ perspective. It is argued that certain areas of Chinese HRM are converging to the Western model, but the influence of traditional Chinese personnel practices remains strong. A ‘group orientation’, a major emphasis on ‘soft factors’ and a trade union presence is likely to remain as the three main features of Chinese HRM in the long-term

Harnessing Polyhydroxyalkanoates and Pressurized Gyration for Hard and Soft Tissue Engineering

Organ dysfunction is a major cause of morbidity and mortality. Transplantation is typically the only definitive cure, challenged by the lack of sufficient donor organs. Tissue engineering encompasses the development of biomaterial scaffolds to support cell attachment, proliferation, and differentiation, leading to tissue regeneration. For efficient clinical translation, the forming technology utilized must be suitable for mass production. Herein, uniaxial polyhydroxyalkanoate scaffolds manufactured by pressurized gyration, a hybrid scalable spinning technique, are successfully used in bone, nerve, and cardiovascular applications. Chorioallantoic membrane and in vivo studies provided evidence of vascularization, collagen deposition, and cellular invasion for bone tissue engineering. Highly efficient axonal outgrowth was observed in dorsal root ganglion-based 3D ex vivo models. Human induced pluripotent stem cell derived cardiomyocytes exhibited a mature cardiomyocyte phenotype with optimal calcium handling. This study confirms that engineered polyhydroxyalkanoate-based gyrospun fibers provide an exciting and unique toolbox for the development of scalable scaffolds for both hard and soft tissue regeneration

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Renal Athersosclerotic reVascularization Evaluation (RAVE Study): Study protocol of a randomized trial [NCT00127738]

BACKGROUND: It is uncertain whether patients with renal vascular disease will have renal or mortality benefit from re-establishing renal blood flow with renal revascularization procedures. The RAVE study will compare renal revascularization to medical management for people with atherosclerotic renal vascular disease (ARVD) and the indication for revascularization. Patients will be assessed for the standard nephrology research outcomes of progression to doubling of creatinine, need for dialysis, and death, as well as other cardiovascular outcomes. We will also establish whether the use of a new inexpensive, simple and available ultrasound test, the renal resistance index (RRI), can identify patients with renal vascular disease who will not benefit from renal revascularization procedures[1]. METHODS/DESIGN: This single center randomized, parallel group, pilot study comparing renal revascularization with medical therapy alone will help establish an infrastructure and test the feasibility of answering this important question in clinical nephrology. The main outcome will be a composite of death, dialysis and doubling of creatinine. Knowledge from this study will be used to better understand the natural history of patients diagnosed with renal vascular disease in anticipation of a Canadian multicenter trial. Data collected from this study will also inform the Canadian Hypertension Education Program (CHEP) Clinical Practice Guidelines for the management of Renal and Renal Vascular Disease. The expectation is that this program for ARVD, will enable community based programs to implement a comprehensive guidelines based diagnostic and treatment program, help create an evidence based approach for the management of patients with this condition, and possibly reduce or halt the progression of kidney disease in these patients. DISCUSSION: Results from this study will determine the feasibility of a multicentered study for the management of renovascular disease