Statistical Equilibrium Principles in 2D Fluid Flow: From Geophysical Fluids to the Solar Tachocline.

An overview is presented of several diverse branches of work in the area of effectively 2D fluid equilibria which have in common that they are constrained by an infinite number of conservation laws. Broad concepts, and the enormous variety of physical phenomena that can be explored, are highlighted. These span, roughly in order of increasing complexity, Euler flow, nonlinear Rossby waves, 3D axisymmetric flow, shallow water dynamics, and 2D magnetohydrodynamics. The classical field theories describing these systems bear some resemblance to perhaps more familiar fluctuating membrane and continuous spin models, but the fluid physics drives these models into unconventional regimes exhibiting large scale jet and eddy structures. From a dynamical point of view these structures are the end result of various conserved variable forward and inverse cascades. The resulting balance between large scale structure and small scale fluctuations is controlled by the competition between energy and entropy in the system free energy, in turn highly tunable through setting the values of the conserved integrals. Although the statistical mechanical description of such systems is fully self-consistent, with remarkable mathematical structure and diversity of solutions, great care must be taken because the underlying assumptions, especially ergodicity, can be violated or at minimum lead to exceedingly long equilibration times. Generalization of the theory to include weak driving and dissipation (e.g., non-equilibrium statistical mechanics and associated linear response formalism) could provide additional insights, but has yet to be properly explored.

Panitumumab-IRDye800CW for Fluorescence-Guided Surgical Resection of Colorectal Cancer.

BACKGROUND: Fluorescence-guided surgery (FGS) is a rapidly advancing field that may improve outcomes in several cancer types. Although screening has decreased colorectal cancer (CRC) mortality, it remains a common and often fatal malignancy. In this study, we sought to identify an optical imaging agent for the application of FGS technology to CRC. METHODS: We compared a panitumumab-IRDye800CW conjugate to an IgG-IRDye800CW isotype control. Mice were implanted with one of three CRC cell lines (LS174T, Colo205, and SW948) and imaged with open- and closed-filed fluorescence imaging systems. Fluorescent contrast was quantified by calculating the ratio between tumor and background fluorescence. After 10 d, the mice were sacrificed, and their tumors stained for microscopic imaging. RESULTS: Panitumumab-IRDye800CW produced significantly greater (P < 0.05) fluorescent contrast in all three cell lines. Average tumor to background ratio was 6.00 versus 2.60 for LS174T, 5.78 versus 2.52 for Colo205, and 4.31 versus 1.70 for SW948. A 1-mg tumor fragment produced significantly greater fluorescent contrast in the Colo205 and SW948 cell lines in the panitumumab-IRDye800CW group. Western blotting for epidermal growth factor receptor (EGFR) and a semiquantitative analysis of EGFR expression noted strong expression in all three cell lines; however, EGFR expression did not directly correlate to tumor to background ratio. CONCLUSIONS: Panitumumab-IRDye800CW produces significantly greater fluorescent contrast than IgG-IRDye800CW in a murine model of CRC and is a suitable agent for the application of FGS technology to CRC.

Modeling the role of fire and cooking in the competitive exclusion of Neanderthals.

The Neanderthal body was more robust and energetically costly than the bodies of anatomically modern humans (AMH). Different metabolic budgets between competing populations of Neanderthals and AMH may have been a factor in the varied ranges of behavior and timelines for Neanderthal extinction that we see in the Paleolithic archaeological record. This paper uses an adaptation of the Lotka-Volterra model to determine whether metabolic differences alone could have accounted for Neanderthal extinction. In addition, we use a modeling approach to investigate Neanderthal fire use, evidence for which is much debated and is variable throughout different climatic phases of the Middle Paleolithic. The increased caloric yield from a cooked versus a raw diet may have played an important role in population competition between Neanderthals and AMH. We arrive at two key conclusions. First, given differences in metabolic budget between Neanderthals and AMH and their dependence on similar or overlapping food resources, Neanderthal extinction is likely inevitable over the long term. Second, the rate of Neanderthal extinction increases as the frequency of AMH fire use increases. Results highlight the importance of understanding the variable behaviors at play on a regional scale in order to understand global Neanderthal extinction. We also emphasize the importance of understanding the role of fire use in the Middle to Upper Paleolithic transition.

MapMySmoke: feasibility of a new quit cigarette smoking mobile phone application using integrated geo-positioning technology, and motivational messaging within a primary care setting.

BACKGROUND: Approximately 11,000 people die in Scotland each year as a result of smoking-related causes. Quitting smoking is relatively easy; maintaining a quit attempt is a very difficult task with success rates for unaided quit attempts stubbornly remaining in the single digits. Pharmaceutical treatment can improve these rates by lowering the overall reward factor of nicotine. However, these and related nicotine replacement therapies do not operate on, or address, the spatial and contextual aspects of smoking behaviour. With the ubiquity of smartphones that can log spatial, quantitative and qualitative data related to smoking behaviour, there exists a person-centred clinical opportunity to support smokers attempting to quit by first understanding their smoking behaviour and subsequently sending them dynamic messages to encourage health behaviour change within a situational context. METHODS: We have built a smartphone app-MapMySmoke-that works on Android and iOS platforms. The deployment of this app within a clinical National Health Service (NHS) setting has two distinct phases: (1) a 2-week logging phase where pre-quit patients log all of their smoking and craving events; and (2) a post-quit phase where users receive dynamic support messages and can continue to log craving events, and should they occur, relapse events. Following the initial logging phase, patients consult with their general practitioner (GP) or healthcare provider to review their smoking patterns and to outline a precise, individualised quit attempt plan. Our feasibility study consists of assessment of an initial app version during and after use by eight patients recruited from an NHS Fife GP practice. In addition to evaluation of the app as a potential smoking cessation aid, we have assessed the user experience, technological requirements and security of the data flow. RESULTS: In an initial feasibility study, we have deployed the app for a small number of patients within one GP practice in NHS Fife. We recruited eight patients within one surgery, four of whom actively logged information about their smoking behaviour. Initial feedback was very positive, and users indicated a willingness to log their craving and smoking events. In addition, two out of three patients who completed follow-up interviews noted that the app helped them reduce the number of cigarettes they smoked per day, while the third indicated that it had helped them quit. The study highlighted the use of pushed notifications as a potential technology for maintaining quit attempts, and the security of collection of data was audited. These initial results influenced the design of a planned second larger study, comprised of 100 patients, the primary objectives of which are to use statistical modelling to identify times and places of probable switches into smoking states, and to target these times with dynamic health behaviour messaging. CONCLUSIONS: While the health benefits of quitting smoking are unequivocal, such behaviour change is very difficult to achieve. Many factors are likely to contribute to maintaining smoking behaviour, yet the precise role of cues derived from the spatial environment remains unclear. The rise of smartphones, therefore, allows clinicians the opportunity to better understand the spatial aspects of smoking behaviour and affords them the opportunity to push targeted individualised health support messages at vulnerable times and places. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02932917.

Effect of diet on the survival and phenotype of a mouse model for spinal muscular atrophy.

Proximal spinal muscular atrophy (SMA) is a leading genetic cause of infant death. Patients with SMA lose alpha-motor neurons in the ventral horn of the spinal cord which leads to skeletal muscle weakness and atrophy. SMA is the result of reduction in Survival Motor Neuron (SMN) expression. Transgenic mouse models of SMA have been generated and are extremely useful in understanding the mechanisms of motor neuron degeneration in SMA and in developing new therapeutic candidates for SMA patients. Several research groups have reported varying average lifespans of SMNDelta7 SMA mice (SMN2(+/+);SMNDelta7(+/+);mSmn(-/-)), the most commonly used mouse model for preclinical therapeutic candidate testing. One environmental factor that varied between research groups was maternal diet. In this study, we compared the effects of two different commercially available rodent chows (PicoLab20 Mouse diet and Harlan-Teklad 22/5 diet) on the survival and motor phenotype of the SMNDelta7 mouse model of SMA. Specifically, the PicoLab20 diet significantly extends the average lifespan of the SMNDelta7 SMA mice by approximately 25% and improved the motor phenotype as compared to the Harlan diet. These findings indicate that maternal diet alone can have considerable impact on the SMA phenotype.