On Multiphase-Linear Ranking Functions

Multiphase ranking functions ($\mathit{M{\Phi}RFs}$) were proposed as a means to prove the termination of a loop in which the computation progresses through a number of "phases", and the progress of each phase is described by a different linear ranking function. Our work provides new insights regarding such functions for loops described by a conjunction of linear constraints (single-path loops). We provide a complete polynomial-time solution to the problem of existence and of synthesis of $\mathit{M{\Phi}RF}$ of bounded depth (number of phases), when variables range over rational or real numbers; a complete solution for the (harder) case that variables are integer, with a matching lower-bound proof, showing that the problem is coNP-complete; and a new theorem which bounds the number of iterations for loops with $\mathit{M{\Phi}RFs}$. Surprisingly, the bound is linear, even when the variables involved change in non-linear way. We also consider a type of lexicographic ranking functions, $\mathit{LLRFs}$, more expressive than types of lexicographic functions for which complete solutions have been given so far. We prove that for the above type of loops, lexicographic functions can be reduced to $\mathit{M{\Phi}RFs}$, and thus the questions of complexity of detection and synthesis, and of resulting iteration bounds, are also answered for this class.Comment: typos correcte

Signatures of Reductive Magnetic Mineral Diagenesis From Unmixing of First-Order Reversal Curves

Diagenetic alteration of magnetic minerals occurs in all sedimentary environments and tends to be severe in reducing environments. Magnetic minerals provide useful information about sedimentary diagenetic processes, which makes it valuable to use magnetic properties to identify the diagenetic environment in which the magnetic minerals occur and to inform interpretations of paleomagnetic recording or environmental processes. We use a newly developed first-order reversal curve (FORC) unmixing method on well-studied samples to illustrate how magnetic properties can be used to assess diagenetic processes in reducing sedimentary environments. From our analysis of multiple data sets, consistent magnetic components are identified for each stage of reductive diagenesis. Relatively unaltered detrital and biogenic magnetic mineral assemblages in surficial oxic to manganous diagenetic environments undergo progressive dissolution with burial into ferruginous and sulfidic environments, and largely disappear at the sulfate-methane transition (SMT). Below the SMT, a weak superparamagnetic to largely non-interacting stable single domain (SD) greigite component is observed in all studied data sets. Moderately interacting stable SD authigenic pyrrhotite and strongly interacting stable SD greigite are observed commonly in methanic environments. Recognition of these characteristic magnetic components enables identification of key diagenetic processes and should help to constrain interpretation of magnetic mineral assemblages in future studies. A key question for future studies concerns whether stable SD greigite forms in the sulfidic or methanic zones, where formation in deeper methanic sediments will cause greater delays in paleomagnetic signal recording. Authigenic pyrrhotite forms in methanic environments, so it will usually record a delayed paleomagnetic signal.European Research Council (320750) Australian Research Council (DP160100805

Domain State Diagnosis in Rock Magnetism: Evaluation of Potential Alternatives to the Day Diagram

The Day diagram is used extensively in rock magnetism for domain state diagnosis. It has been shown recently to be fundamentally ambiguous for ten sets of reasons. This ambiguity highlights the urgency for adopting suitable alternative approaches to identify the domain state of magnetic mineral components in rock magnetic studies. We evaluate ten potential alternative approaches here and conclude that four have value for identifying data trends, but, like the Day diagram, they are affected by use of bulk parameters that compromise domain state diagnosis in complex samples. Three approaches based on remanence curve and hysteresis loop unmixing, when “supervised” by independent data to avoid non-uniqueness of solutions provide valuable component-specific information that can be linked by inference to domain state. Three further approaches based on first-order reversal curve (FORC) diagrams provide direct domain state diagnosis with varying effectiveness. Environmentally important high coercivity hematite and goethite are represented with variable effectiveness in the evaluated candidate approaches. These minerals occur predominantly in non-interacting single domain particle assemblages in paleomagnetic contexts, so domain state diagnosis is more critical for ferrimagnetic minerals. Treating the high-coercivity component separately following normal rock magnetic procedures allows focus on the more vexing problem of diagnosing domain state in ferrimagnetic mineral assemblages. We suggest a move away from non-diagnostic methods based on bulk parameters and adoption of approaches that provide unambiguous component-specific domain state identification, among which various FORC-based approaches provide diagnostic information.European Research Council (ERC) Australian Research Council (ARC

Systems Medicine 2.0: Potential Benefits of Combining Electronic Health Care Records With Systems Science Models

Background: The global burden of disease is increasingly dominated by non-communicable diseases.These diseases are less amenable to curative and preventative interventions than communicable disease. This presents a challenge to medical practice and medical research, both of which are experiencing diminishing returns from increasing investment. / Objective: Our aim was to (1) review how medical knowledge is generated, and its limitations, (2) assess the potential for emerging technologies and ideas to improve medical research, and (3) suggest solutions and recommendations to increase medical research efficiency on non-communicable diseases. / Methods: We undertook an unsystematic review of peer-reviewed literature and technology websites. / Results: Our review generated the following conclusions and recommendations. (1) Medical knowledge continues to be generated in a reductionist paradigm. This oversimplifies our models of disease, rendering them ineffective to sufficiently understand the complex nature of non-communicable diseases. (2) Some of these failings may be overcome by adopting a “Systems Medicine” paradigm, where the human body is modeled as a complex adaptive system. That is, a system with multiple components and levels interacting in complex ways, wherein disease emerges from slow changes to the system set-up. Pursuing systems medicine research will require larger datasets. (3) Increased data sharing between researchers, patients, and clinicians could provide this unmet need for data. The recent emergence of electronic health care records (EHR) could potentially facilitate this in real-time and at a global level. (4) Efforts should continue to aggregate anonymous EHR data into large interoperable data silos and release this to researchers. However, international collaboration, data linkage, and obtaining additional information from patients will remain challenging. (5) Efforts should also continue towards “Medicine 2.0”. Patients should be given access to their personal EHR data. Subsequently, online communities can give researchers the opportunity to ask patients for direct access to the patient’s EHR data and request additional study-specific information. However, selection bias towards patients who use Web 2.0 technology may be difficult to overcome. / Conclusions: Systems medicine, when combined with large-scale data sharing, has the potential to raise our understanding of non-communicable diseases, foster personalized medicine, and make substantial progress towards halting, curing, and preventing non-communicable diseases. Large-scale data amalgamation remains a core challenge and needs to be supported. A synthesis of “Medicine 2.0” and “Systems Science” concepts into “Systems Medicine 2.0” could take decades to materialize but holds much promise

Impact of calcium on salivary α-amylase activity, starch paste apparent viscosity and thickness perception

Thickness perception of starch-thickened products during eating has been linked to starch viscosity and salivary amylase activity. Calcium is an essential cofactor for α-amylase and there is anecdotal evidence that adding extra calcium affects amylase activity in processes like mashing of beer. The aims of this paper were to (1) investigate the role of salivary calcium on α-amylase activity and (2) to measure the effect of calcium concentration on apparent viscosity and thickness perception when interacting with salivary α-amylase in starch-based samples. α-Amylase activity in saliva samples from 28 people was assessed using a typical starch pasting cycle (up to 95 °C). The activity of the enzyme (as measured by the change in starch apparent viscosity) was maintained by the presence of calcium, probably by protecting the enzyme from heat denaturation. Enhancement of α-amylase activity by calcium at 37 °C was also observed although to a smaller extent. Sensory analysis showed a general trend of decreased thickness perception in the presence of calcium, but the result was only significant for one pair of samples, suggesting a limited impact of calcium enhanced enzyme activity on perceived thickness

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Potential of a cyclone prototype spacer to improve in vitro dry powder delivery

Copyright The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPurpose: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrierbased DPIs was investigated. Methods: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30-60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Results: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51 % at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. Conclusion: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.Peer reviewe

From quantum fusiliers to high-performance networks

Our objective was to design a quantum repeater capable of achieving one million entangled pairs per second over a distance of 1000km. We failed, but not by much. In this letter we will describe the series of developments that permitted us to approach our goal. We will describe a mechanism that permits the creation of entanglement between two qubits, connected by fibre, with probability arbitrarily close to one and in constant time. This mechanism may be extended to ensure that the entanglement has high fidelity without compromising these properties. Finally, we describe how this may be used to construct a quantum repeater that is capable of creating a linear quantum network connecting two distant qubits with high fidelity. The creation rate is shown to be a function of the maximum distance between two adjacent quantum repeaters.Comment: 2 figures, Comments welcom

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets