Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis

Citation: Hanzlicek, G. A., Raghavan, R. K., Ganta, R. R., & Anderson, G. A. (2016). Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis. Plos One, 11(3), 13. doi:10.1371/journal.pone.0151924The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (>0.7). The relevance of climatological factors for bovine anaplasmosis is discussed

An in vitro study comparing a peripherally inserted central catheter to a conventional central venous catheter: no difference in static and dynamic pressure transmission

<p>Abstract</p> <p>Background</p> <p>Early goal directed therapy improves survival in patients with septic shock. Central venous pressure (CVP) monitoring is essential to guide adequate resuscitation. Use of peripherally inserted central catheters (PICC) is increasing, but little data exists comparing a PICC to a conventional CVP catheter. We studied the accuracy of a novel PICC to transmit static and dynamic pressures <it>in vitro</it>.</p> <p>Methods</p> <p>We designed a device to generate controlled pressures via a column of water allowing simultaneous measurements from a PICC and a standard triple lumen catheter. Digital transducers were used to obtain all pressure readings. Measurements of static pressures over a physiologic range were recorded using 5Fr and 6Fr dual lumen PICCs. Additionally, random repetitive pressure pulses were applied to the column of water to simulate physiologic intravascular pressure variations. The resultant PICC and control waveforms were recorded simultaneously.</p> <p>Results</p> <p>Six-hundred thirty measurements were made using the 5 Fr and 6 Fr PICCs. The average bias determined by Bland-Altman plot was 0.043 mmHg for 5 Fr PICC and 0.023 mmHg for 6 Fr PICC with a difference range of 1.0 to -1.0. The correlation coefficient for both catheters was 1.0 (p-value < 0.001). Dynamic pressure waveforms plotted simultaneously between PICC and control revealed equal peaks and troughs.</p> <p>Conclusion</p> <p><it>In vitro</it>, no static or dynamic pressure differences were found between the PICC and a conventional CVP catheter. Clinical studies are required to assess whether the novel PICC has bedside equivalence to conventional catheters when measuring central venous pressures.</p

Is there a U-shaped association between physical activity and falling in older persons?

Summary: This study tests whether the relationship between physical activity and (recurrent) falling is U-shaped. Among 1,337 community-dwelling older persons, no evidence for a nonlinear association was found. If all older persons increase their physical activity level with 100 units, 4% may be prevented to become recurrent fallers. Introduction: Previous studies suggest a U-shaped relationship between physical activity and falling. This study tests this hypothesis and examines whether this relationship is modified by level of physical functioning. Methods: Community-dwelling persons (65+) from the Longitudinal Aging Study Amsterdam (LASA) were prospectively followed on falls for 3 years after baseline assessment in 1995/1996 (n=1,337). Outcome measures were time to first fall and time to recurrent falling. The LASA Physical Activity Questionnaire was used to calculate physical activity in minutes per day weighted for intensity (range 0-2000). Physical functioning was measured with physical performance tests and self reported functional limitations. Confounders were age, sex, body mass index, chronic diseases, psychotropic medication, cognitive functioning, depressive symptoms, and fear of falling. Results: No evidence for a nonlinear association was found (p for physical activity > 0.20). No significant association was found between physical activity and time to first fall. An increase in physical activity of 100 units led to a 4% decrease in risk of recurrent falling (adjusted hazard ratio 0.96, 95% confidence interval 0.92, 0.99). No interactions with physical performance or functional limitations were found (p>0.50). Conclusions: The hypothesized U-shaped relationship between physical activity and falling could not be confirmed. At higher levels of physical activity, the risk of recurrent falling decreased, while no association was found with fall risk

Lentiviral gene therapy for X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

Operant Sensation Seeking Requires Metabotropic Glutamate Receptor 5 (mGluR5)

Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior

Educational disparities in health behaviors among patients with diabetes: the Translating Research Into Action for Diabetes (TRIAD) Study

<p>Abstract</p> <p>Background</p> <p>Our understanding of social disparities in diabetes-related health behaviors is incomplete. The purpose of this study was to determine if having less education is associated with poorer diabetes-related health behaviors.</p> <p>Methods</p> <p>This observational study was based on a cohort of 8,763 survey respondents drawn from ~180,000 patients with diabetes receiving care from 68 provider groups in ten managed care health plans across the United States. Self-reported survey data included individual educational attainment ("education") and five diabetes self-care behaviors among individuals for whom the behavior would clearly be indicated: foot exams (among those with symptoms of peripheral neuropathy or a history of foot ulcers); self-monitoring of blood glucose (SMBG; among insulin users only); smoking; exercise; and certain diabetes-related health seeking behaviors (use of diabetes health education, website, or support group in last 12 months). Predicted probabilities were modeled at each level of self-reported educational attainment using hierarchical logistic regression models with random effects for clustering within health plans.</p> <p>Results</p> <p>Patients with less education had significantly lower predicted probabilities of being a non-smoker and engaging in regular exercise and health-seeking behaviors, while SMBG and foot self-examination did not vary by education. Extensive adjustment for patient factors revealed no discernable confounding effect on the estimates or their significance, and most education-behavior relationships were similar across sex, race and other patient characteristics. The relationship between education and smoking varied significantly across age, with a strong inverse relationship in those aged 25–44, modest for those ages 45–64, but non-evident for those over 65. Intensity of disease management by the health plan and provider communication did not alter the examined education-behavior relationships. Other measures of socioeconomic position yielded similar findings.</p> <p>Conclusion</p> <p>The relationship between educational attainment and health behaviors was modest in strength for most behaviors. Over the life course, the cumulative effect of reduced practice of multiple self-care behaviors among less educated patients may play an important part in shaping the social health gradient.</p