Cross‐link stabilization does not affect the response of collagen molecules,fibrils, or tendons to tensile overload

We investigated whether immature allysine‐derived cross‐links provide mechanically labile linkages by exploring the effects of immature cross‐link stabilization at three levels of collagen hierarchy: damaged fibril morphology, whole tendon mechanics, and molecular stability. Tendons from the tails of young adult steers were either treated with sodium borohydride (NaBH₄) to stabilize labile cross‐links, exposed only to the buffer used during stabilization treatment, or maintained as untreated controls. One‐half of each tendon was then subjected to five cycles of subrupture overload. Morphologic changes to collagen fibrils resulting from overload were investigated using scanning electron microscopy, and changes in the hydrothermal stability of collagen molecules were assessed using hydrothermal isometric tension testing. NaBH₄ cross‐link stabilization did not affect the response of tendon collagen to tensile overload at any of the three levels of hierarchy studied. Cross‐link stabilization did not prevent the characteristic overload‐induced mode of fibril damage that we term discrete plasticity. Similarly, stabilization did not alter the mechanical response of whole tendons to overload, and did not prevent an overload‐induced thermal destabilization of collagen molecules. Our results indicate that hydrothermally labile cross‐links may not be as mechanically labile as was previously thought. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1907–1913, 2013     

Variable selection for discrete survival model with frailty in presence of left truncation and right censoring: Studying association of environmental toxicants on time-to-pregnancy

Understanding the association between mixtures of environmental toxicants and time-to-pregnancy (TTP) is an important scientific question as sufficient evidence has emerged about the impact of individual toxicants on reproductive health and that individuals are exposed to a whole host of toxicants rather than an individual toxicant. Assessing mixtures of chemical effects on TTP poses significant statistical challenges, namely (i) TTP being a discrete survival outcome, typically subject to left truncation and right censoring, (ii) chemical exposures being strongly correlated, (iii) appropriate transformation to account for some lipid-binding chemicals, (iv) non-linear effects of some chemicals, and (v) high percentage of concentration below the limit of detection (LOD) for some chemicals. We propose a discrete frailty modeling framework (named Discnet) that allows selection of correlated covariates while appropriately addressing the methodological issues mentioned above. Discnet is shown to have better and stable false negative and false positive rates compared to alternative methods in various simulation settings. We did a detailed analysis of the pre-conception endocrine disrupting chemicals and TTP from the LIFE study and found that older females, female exposure to cotinine (smoking), DDT conferred a delay in getting pregnant, which was consistent across various approaches to account for LOD as well as non-linear associations.     

Electrical and optical study of nerve impulse-evoked ATP-induced, P2X-receptor-mediated sympathetic neurotransmission at single smooth muscle cells in mouse isolated VAS deferens

Simultaneous electrophysiology and confocal microscopy were used to investigate purinergic neurotransmission at single smooth muscle cells (SMCs) in mouse isolated vas deferens, and to explore the relationship between two high-resolution P2X-receptor-mediated measures of per pulse ATP release: transient peaks in the first time derivative of the rising phase of excitatory junction potentials (EJPs) recorded in single SMCs ('discrete events'; DEs) and neuroeffector Ca(2+) transients (NCTs) in the impaled SMCs. This study shows that discrete events represent neurotransmitter release onto the impaled cell. First, the median amplitude of the first derivative of the EJP was larger when there was a coincident NCT in the impaled cell, compared with instances when no coincident NCT occurred. Second, the time-to-peak amplitude of the first derivative was shorter if there was a coincident NCT in the impaled cell, compared with when no coincident NCT was observed within the field. Surprisingly, first derivative amplitude increased with the distance (of the corresponding NCT) from the microelectrode. The microelectrode did not locally inhibit the functional quantal size as there was no effect of distance on the normalized NCT amplitude. When the significant effect of distance (between the microelectrode and NCTs) on the first derivative amplitude was removed, there was no correlation between the unstandardized residual (of distance vs. first derivative amplitude) and NCT amplitude. The absence of a correlation between DE and NCT amplitudes suggests that the NCT amplitude is a poor measure of quantal size. The usefulness of NCTs hence lies primarily in locating neurotransmitter release and measuring changes in local release probability.     

Preferences for symmetry in faces change across the menstrual cycle

Symmetry in human male faces may be a cue to heritable fitness benefits and is found attractive. Preferences for facial masculinity, another proposed marker of genetic quality, have been found to vary in ways that may maximise evolutionary relevant benefits and masculinity is found to be of increased attractiveness at peak fertility across the menstrual cycle. Here we show that women prefer more symmetric faces at peak fertility (Study 1) and that such shifting preferences may be potentially strategic preferences as we found them to occur only for judgements concerning short-term relations and when women already had a partner (Study 2). Such preferences potentially indicate a strategy that maximises the quality of extra-pair/short-term partners or a quality dependent response to hormones. Such strategic preferences for symmetry may support the role of symmetry in signalling potential good-gene benefits.     

Potential users’ preferences towards cardiac telemedicine: A discrete choice experiment investigation in Sardinia

Background

Potential users’ preferences for telemedicine services directed to cardio-vascular diseases are investigated applying a discrete choice experiment (DCE). Given the potential of telemedicine to minimize costs without reducing overall efficiency, assessing preferences for these types of services represents a priority for policy makers. This is especially true for those pathologies that absorb a relatively high quota of total health expenditure. The empirical setting is Sardinia (Italy) because of its insularity and the underdeveloped internal transport network. Telemedicine is likely to mitigate distance between healthcare providers and final users.

Modeling Clinical Outcomes in Prostate Cancer: Application and Validation of the Discrete Event Simulation Approach

Objectives

Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer.

Dissociable Contributions of Anterior Cingulate Cortex and Basolateral Amygdala on a Rodent Cost/Benefit Decision-Making Task of Cognitive Effort

Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen–muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to ‘slack off'' and ‘slacker'' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.