The Computer for Charting and Monitoring

book chapterBiomedical Informatic

Bayesian time series analysis of terrestrial impact cratering

Giant impacts by comets and asteroids have probably had an important influence on terrestrial biological evolution. We know of around 180 high velocity impact craters on the Earth with ages up to 2400Myr and diameters up to 300km. Some studies have identified a periodicity in their age distribution, with periods ranging from 13 to 50Myr. It has further been claimed that such periods may be causally linked to a periodic motion of the solar system through the Galactic plane. However, many of these studies suffer from methodological problems, for example misinterpretation of p-values, overestimation of significance in the periodogram or a failure to consider plausible alternative models. Here I develop a Bayesian method for this problem in which impacts are treated as a stochastic phenomenon. Models for the time variation of the impact probability are defined and the evidence for them in the geological record is compared using Bayes factors. This probabilistic approach obviates the need for ad hoc statistics, and also makes explicit use of the age uncertainties. I find strong evidence for a monotonic decrease in the recorded impact rate going back in time over the past 250Myr for craters larger than 5km. The same is found for the past 150Myr when craters with upper age limits are included. This is consistent with a crater preservation/discovery bias modulating an otherwise constant impact rate. The set of craters larger than 35km (so less affected by erosion and infilling) and younger than 400Myr are best explained by a constant impact probability model. A periodic variation in the cratering rate is strongly disfavoured in all data sets. There is also no evidence for a periodicity superimposed on a constant rate or trend, although this more complex signal would be harder to distinguish.Comment: Minor typos corrected in arXiv v2. Erratum (minor notation corrections) corrected in arXiv v3. (Erratum available from http://www.mpia-hd.mpg.de/~calj/craterTS_erratum.pdf

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7+/-11.7 and 42.4+/-12.2, respectively. Significant (P \u3c 0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P \u3c 0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses

Multilayered feed forward Artificial Neural Network model to predict the average summer-monsoon rainfall in India

In the present research, possibility of predicting average summer-monsoon rainfall over India has been analyzed through Artificial Neural Network models. In formulating the Artificial Neural Network based predictive model, three layered networks have been constructed with sigmoid non-linearity. The models under study are different in the number of hidden neurons. After a thorough training and test procedure, neural net with three nodes in the hidden layer is found to be the best predictive model.Comment: 19 pages, 1 table, 3 figure

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.Fil: LaRusch, Jessica. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Jung, Jinsei. Yonsei University College of Medicine; Corea del SurFil: General, Ignacio. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lewis, Michele D.. Mayo Clinic. Division of Gastroenterology and Hepatology; Estados UnidosFil: Park, Hyun Woo. Yonsei University College of Medicine; Corea del SurFil: Brand, Randall E.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Gelrud, Andres. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Anderson, Michelle A.. University of Michigan; Estados UnidosFil: Banks, Peter A.. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Conwell, Darwin. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Lawrence, Christopher. Medical University of South Carolina; Estados UnidosFil: Romagnuolo, Joseph. Medical University of South Carolina; Estados UnidosFil: Baillie, John. University of Duke; Estados UnidosFil: Alkaade, Samer. St. Louis University. School of Medicine; Estados UnidosFil: Cote, Gregory. Indiana University; Estados UnidosFil: Gardner, Timothy B.. Dartmouth-Hitchcock Medical Center; Estados UnidosFil: Amann, Stephen T.. North Mississippi Medical Center; Estados UnidosFil: Slivka, Adam. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Sandhu, Bimaljit. Virginia Commonwealth University Medical Center; Estados UnidosFil: Aloe, Amy. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Kienholz, Michelle L.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Yadav, Dhiraj. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Barmada, M. Michael. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Bahar, Ivet. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Lee, Min Goo. Yonsei University College of Medicine; Corea del SurFil: Whitcomb, David C.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: North American Pancreatitis Study Group. No especifica

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1–2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes

The evolution of the urinary bladder as a storage organ: scent trails and selective pressure of the first land animals in a computational simulation

The function of waste control in all living organisms is one of the vital importance. Almost universally, terrestrial tetrapods have a urinary bladder with a storage function. It is well documented that many marine and aerial species do not have an organ of such a function, or have one with very depressed storage functionality. Bladder morphology indicates it has evolved from a thin-walled structure used for osmoregulatory purposes, as it is currently used in many marine animals. It is hypothesised that the storage function of the urinary bladder allows for an evolutionary selective advantage in reducing the likelihood of successful predation. Random walks simulating predator and prey movements with simplified scent trails were utilised to represent various stages of the hunt: Detection and pursuit. A final evolutionary model is proposed in order to display the advantages over inter-generational time scales and illustrates how a bladder may evolve from an osmoregulatory organ to one of the storage. Data sets were generated for each case and analysed indicating the viability of such advantages. From the highly consistent results, three distinct characteristics of having a storage function in the urinary bladder are suggested: reduced scent trail detection rate; increased prey–predator separation (upon scent trail detection); and a reduced probability of successful capture upon scent detection by the predator. Furthered by the evolutionary model indicating such characteristics are conserved and augmented over many generations, it is concluded that prey–predator interactions provide a large selective pressure in the evolution of the urinary bladder and its storage function

Charisma and the Clinic

Here we argue that ‘charisma’, a concept widely taken up within geography and the environmental humanities, is of utility to the social studies of medicine. Charisma, we suggest, draws attention to the affective dimensions of medical work, the ways in which these affective relations are structured, and the manner in which they are intimately tied to particular material-discursive contexts. The paper differentiates this notion of charisma from Weber’s analyses of the ‘charismatic leader’ before detailing three forms of charisma - ecological (which relates to the affordances an entity has), corporeal (related to bodily interaction) and aesthetic (pertaining to an entity’s initial visual and emotional impact). Drawing on interview data we then show how this framework can be used to understand the manner in which psychologists and neuroscientists have come to see and act on autism. We conclude the article by suggesting that examining charisma within healthcare settings furthers the concept, in particular by drawing attention to the discursive features of ecologies and the ‘non-innocence’ of charisma

Predicting the Effects of Supplemental EPA and DHA on the Omega-3 Index

Background: Supplemental long-chain omega-3 (n–3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. Objective: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. Methods: Deidentified data from 1422 individuals from 14 published n–3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. Results: Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P \u3c 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P \u3c 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products. Conclusions: Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form

Catching the future : Applying Bayesian belief networks to exploratory scenario storylines to assess long‐term changes in Baltic herring (Clupea harengus membras, Clupeidae) and salmon (Salmo salar, Salmonidae) fisheries

Fisheries management aims to ensure that the fishing activities are environmentally sustainable in the long term, while also achieving the economic, social and food security related management objectives. To facilitate this, both the ecological and human dimensions of sustainability need to be included in fisheries assessment. In addition, assessing long-term sustainability calls for taking into account plausible changes in the surrounding societal conditions that shape the characteristics of the fisheries governance system, as well as the ecological conditions. The paper uses a combination of qualitative exploratory scenario storylines (ESS) and Bayesian belief networks (BBN) to integrate the environmental, economic, social and food security dimensions in an interdisciplinary assessment of the future sustainability of Baltic herring (Clupea harengus membras, Clupeidae) and salmon (Salmo salar, Salmonidae) fisheries. First, four alternative ESS were created based on plausible changes in societal drivers. The ESS were then formulated into a BBN to (a) visualize the assumed causalities, and (b) examine quantitatively how changes in the societal drivers affect the social-ecological fisheries system and ultimately the fisheries management objectives. This type of probabilistic scenario synthesis can help in thinking qualitative scenarios in a quantitative way. Moreover, it can increase understanding on the causal links between societal driving forces and the complex fisheries system and on how the management objectives can be achieved, thereby providing valuable information for strategic decision-making under uncertainty.Peer reviewe