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The quantal hypothesis is central to the modern understanding of how a neurotransmitter is released from synapses. This hypothesis expresses that a neurotransmitter is packaged together in quanta that are released probabilistically. The experiments that led to the quantal hypothesis are often related in introductory neuroscience textbooks, but these experiments use advanced concepts that can be unfamiliar even to advanced students. To remedy this, the author has developed a tangible model of the concepts associated with the quantal hypothesis, suitable for an interactive classroom demonstration. These activities were designed to explain the physiology experiments of Katz (who formulated the quantal hypothesis in the 1950s) and the application of probability theory. The activities can be presented interactively in a discussion section or laboratory, or they can be streamlined and covered during a lecture. These activities will help students appreciate the trial-by-trial nature of the quantal analysis performed by del Castillo and Katz and Boyd and Martin. (Contains 3 figures and 1 footnote.)

The Association of American Medical Colleges has encouraged educators to investigate proper linkage of simulation experiences with medical curricula. The authors aimed to determine if student knowledge and satisfaction differ between participation in web-based and manikin simulations for learning shock physiology and treatment and to determine if a specific training sequencing had a differential effect on learning. All 40 second-year medical students participated in a randomized, counter-balanced study with two interventions: "group 1" (n = 20) participated in a web-based simulation followed by a manikin simulation and "group 2" (n = 20) participated in reverse order. Knowledge and attitudes were documented. Mixed-model ANOVA indicated a significant main effect of time (F[subscript 1,38] = 18.6, P less than 0.001, [[eta][subscript [rho]]][superscript 2] = 0.33). "Group 1" scored significantly higher on "quiz 2" (81.5%) than on "quiz 1" (74.3%, t[subscript 19] = 3.9, P = 0.001), for an observed difference of 7.2% (95% confidence interval: 3.3, 11.0). Mean quiz scores of "group 2" did not differ significantly ("quiz 1": 77.0% and "quiz 2": 79.7%). There was no significant main effect of group or a group by time interaction effect. Students rated the simulations as equally effective in teaching shock physiology (P = 0.88); however, the manikin simulation was regarded as more effective in teaching shock treatment (P less than 0.001). Most students (73.7%) preferred the manikin simulation. The two simulations may be of similar efficacy for educating students on the physiology of shock; however, the data suggest improved learning when web-based simulation precedes manikin use. This finding warrants further study. (Contains 4 figures and 1 table.)

Military personnel are required to complete physically demanding tasks when performing work and training, which may be quantified through the physical stress imposed (external load) or the resultant physiological strain (internal load). The aim of this narrative review is to provide an overview of the techniques used to monitor work and training load in military settings, summarise key findings, and discuss important practical, analytical, and conceptual considerations. Most investigations have focused upon measuring external and internal load in military training environments; however, limited data exist in operational settings. Accelerometry has been the primary tool used to estimate external load, with heart rate commonly used to quantify internal load. Supplemental to heart rate, psychophysiological and biochemical measures have also been investigated to elucidate aspects of internal load. Broadly, investigations have revealed that military training requires personnel to perform relatively large volumes of physical activity (e.g. averaging ∼15,000 steps·day−1) of typically low-moderate intensity activity (<6 MET), although considerable temporal and inter-individual variability is observed from these gross mean estimates. There are limitations associated with these measures and, at best, estimates of external and internal load can only be inferred. These limitations are particularly pertinent for military tasks such as load carriage and manual material handling, which often involve complex activities performed individually or in teams, in a range of operational environments, with multiple layers of protection, over a protracted duration. Comprehensively quantifying external and internal loads during these functional activities poses substantial practical and analytical challenges. [ABSTRACT FROM AUTHOR]

In an earlier article, Gordon Drummond summarized ongoing changes in how statistics are being used in experimental physiology. He described the near‐ubiquitous use of the P value, cautioning against declaring an analysis 'statistically significant'. He mentioned alternative approaches, including Bayesian and likelihood approaches. This article focuses on the latter approach, although I initially take another look at the P value. Then the likelihood approach is introduced with a very artificial example to enable the concept to be grasped easily. Next, a more realistic example is described, with associated calculations. A further example using real categorical data is explained, showing how it relates to and is superior to the oft‐used χ2 test. A final discussion reveals that the likelihood approach, although mathematically and statistically accurate, is poorly supported by literature and training. [ABSTRACT FROM AUTHOR]

Recent years have seen rapid growth in data-driven distributed systems, such as Hadoop MapReduce, Spark, and Dryad. However, the counterparts for high-performance or compute-intensive applications including large-scale optimizations, modeling, and simulations are still nascent. In this paper, we introduce DtCraft, a modern C++ based distributed execution engine to streamline the development of high-performance parallel applications. Users need no understanding of distributed computing and can focus on high-level developments, leaving difficult details, such as concurrency controls, workload distribution, and fault tolerance handled by our system transparently. We have evaluated DtCraft on both micro-benchmarks and large-scale optimization problems, and shown the promising performance from single multicore machines to clusters of computers. In a particular semiconductor design problem, we achieved ${30\times }$ speedup with 40 nodes and ${15\times }$ less development efforts over hand-crafted implementation. [ABSTRACT FROM AUTHOR]

Local and spontaneous calcium signals play important roles in neurons and neuronal networks. Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites. We developed an open source bioinformatics tool for an unbiased assessment of calcium signals in x,y-t imaging series. The tool bases its algorithm on a continuous wavelet transform-guided peak detection to identify calcium signal candidates. The highly sensitive calcium event definition is based on identification of peaks in 1D data through analysis of a 2D wavelet transform surface. For spatial analysis, the tool uses a grid to separate the x,y-image field in independently analyzed grid windows. A document containing a graphical summary of the data is automatically created and displays the loci of activity for a wide range of signal intensities. Furthermore, the number of activity events is summed up to create an estimated total activity value, which can be used to compare different experimental situations, such as calcium activity before or after an experimental treatment. All traces and data of active loci become documented. The tool can also compute the signal variance in a sliding window to visualize activity-dependent signal fluctuations. We applied the calcium signal detector to monitor activity states of cultured mouse neurons. Our data show that both the total activity value and the variance area created by a sliding window can distinguish experimental manipulations of neuronal activity states. Notably, the tool is powerful enough to compute local calcium events and ‘signal-close-to-noise’ activity in small loci of distal neurites of neurons, which remain during pharmacological blockade of neuronal activity with inhibitors such as tetrodotoxin, to block action potential firing, or inhibitors of ionotropic glutamate receptors. The tool can also offer information about local homeostatic calcium activity events in neurites. [ABSTRACT FROM AUTHOR]

Kerala is the most advanced Indian state in epidemiological transition and has the highest type 2 diabetes prevalence. However, data on incidence of diabetes in Kerala are limited. We studied the incidence of diabetes and pre-diabetes among industrial workers. We measured fasting plasma glucose (FPG) among 326 workers (mean age 51 years, men 76 %) from two major industries in Kerala in the years 2009 and 2011 using standard protocol. Individuals with FPG ≥126 mg/dl or on medications for diabetes were considered to have diabetes mellitus, FPG ≥100 mg/dl and ≤125/dl mg as pre-diabetic, and FPG <100 mg/dl as normal. Among the 326 workers, 26.1 % (95 % CI 21.6-31.1) were diabetic, 32.8 % (CI 28.7-37.2) were pre-diabetic, and the remaining 41.1 % were having normal FPG at baseline. At year two, 13.3 % of the 241 workers who were either normal or had pre-diabetes at baseline developed diabetes providing an incidence rate of 6.65 % per year. Among the 134 workers with normal FPG at baseline 28.4 % progressed to pre-diabetes, 5.2 % developed diabetes, and among the 107 pre-diabetics, 23.4 % developed diabetes at year two. The odds of progressing to diabetes from pre-diabetes were five times higher compared to those from normal FPG (OR 5.53; CI 2.28-13.37). Progression to pre-diabetes and diabetes occurred at a very fast rate in this population indicating the need for preventive measures to slow down this fast progression. [ABSTRACT FROM AUTHOR]

Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA. [ABSTRACT FROM AUTHOR]

The article focuses on the mathematical problem presented by the mathematician David Freedman and colleagues in a text titled "Statistics." It says that Freedman and colleagues expected the readers to conclude that male data is analogous to a subset of combined set of data by controlling the variables of height and weight. It discusses pairs of bivariate data sets to prove that two data sets has a correlation that is lesser than the common correlation of two data sets.

The physiology analysis system (PAS) was developed as a resource to support the efficient warehousing, management, and analysis of physiology data, particularly, continuous time-series data that may be extensive, of variable quality, and distributed across many files. The PAS incorporates time-series data collected by many types of data-acquisition devices, and it is designed to free users from data management burdens. This Web-based system allows both discrete (attribute) and time-series (ordered) data to be manipulated, visualized, and analyzed via a client's Web browser. All processes occur on a server, so that the client does not have to download data or any application programs, and the PAS is independent of the client''s computer operating system. The PAS contains a library of functions, written in different computer languages that the client can add to and use to perform specific data operations. Functions from the library are sequentially inserted into a function chain-based logical structure to construct sophisticated data operators from simple function building blocks, affording ad hoc query and analysis of time-series data. These features support advanced mining of physiology data. [Copyright &y& Elsevier]