Estimation of prediction error variances via Monte Carlo sampling methods using different formulations of the prediction error variance

Calculation of the exact prediction error variance covariance matrix is often computationally too demanding, which limits its application in REML algorithms, the calculation of accuracies of estimated breeding values and the control of variance of response to selection. Alternatively Monte Carlo sampling can be used to calculate approximations of the prediction error variance, which converge to the true values if enough samples are used. However, in practical situations the number of samples, which are computationally feasible, is limited. The objective of this study was to compare the convergence rate of different formulations of the prediction error variance calculated using Monte Carlo sampling. Four of these formulations were published, four were corresponding alternative versions, and two were derived as part of this study. The different formulations had different convergence rates and these were shown to depend on the number of samples and on the level of prediction error variance. Four formulations were competitive and these made use of information on either the variance of the estimated breeding value and on the variance of the true breeding value minus the estimated breeding value or on the covariance between the true and estimated breeding values.     

Location of rat liver iodothyronine deiodinating enzymes in the endoplasmic reticulum

The iodothyronine-deiodinating enzymes (iodothyronine-5- and 5′-deiodinase) of rat liver were found to be located in the parenchymal cells. Differential centrifugation of rat liver homogenate revealed that the deiodinases resided mainly in the microsomal fraction. The subcellular distribution pattern of these enzymes correlated best with glucose-6-phosphatase, a marker enzyme of the endoplasmic reticulum. Plasma membranes, prepared by discontinuous sucrose gradient centrifugation, were found to contain very little deiodinating activity. Analysis of fractions obtained during the course of plasma membrane isolation showed that the deiodinases correlated positively with glucose-6-phosphates (r >/ 0.98) and negatively with the plasma membrane marker 5′-nucleotidase (r ranging between ?0.88 and ?0.97). It is concluded that the iodothyronine-deiodinating enzymes of rat liver are associated with the endoplasmic reticulum.     

Linking flow and upper thermal limits of freshwater mussels to inform environmental flow benchmarks

1. Freshwater ecosystems are experiencing shifts in the natural range and variation of water temperatures due to anthropogenic activity, and these shifts can negatively affect survival, growth, and reproduction of aquatic species. Among the groups most affected are freshwater mussels of the family Unionidae. Knowledge of sublethal and lethal effects on mussels from changes in water temperature are largely unknown, especially for species from arid and semi-arid regions such as the south-western U.S.A. This limits the ability to assess, forecast, and adaptively manage this threat for those species and to understand how temperature influences population performance and community structure.
2. To determine the effects of elevated water temperature on mussels from the south-western U.S.A., we evaluated the upper thermal tolerances of adults of three species (Amblema plicata, Cyclonaias necki, and Fusconaia mitchelli) from the Guadalupe River. Mussels were acclimated to 27°C and then tested across a range of experimental temperatures (30–39°C) in standard acute (96-hr) and chronic (10-day) laboratory tests. The acute and chronic thresholds identified in thermal tolerance testing were then related to in situ water temperature and flows using a uniform continuous above-threshold analysis, which evaluates the duration and frequency of continuous events above a specified temperature threshold.
3. Median lethal temperature in 96-hr tests averaged 36.4°C and ranged from 33.7 to 37.5°C, while the chronic 10-day tests averaged 35.9°C and ranged from 32.4 to 37.5°C. Thermal tolerances of F. mitchelli were significantly lower than both A. plicata and C. necki, and the uniform continuous above-threshold analysis showed that temperature affecting 5% of the population thresholds were exceeded for F. mitchelli in the Guadalupe River at both acute (96-hr) and chronic (10-day) values (30.5 and 28.4°C, respectively).
4. Findings from this study indicate that freshwater mussels from the arid and semi-arid regions of the south-west U.S.A. are already at risk from rising environmental temperatures and altered hydrology. However, by incorporating laboratory thermal tolerance estimates with in situ temperature and discharge data, we provide a range of hydrologic thresholds to inform environmental flow recommendations and potentially mitigate thermal stress occurring during periods of low flow. In addition, this method can be readily adapted to other arid regions to guide flow recommendations or assess whether flow standards are sufficient to protect freshwater mussel populations during severe droughts and low flow periods.

     

Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Sheep are a commonly used and well-validated model for cardiovascular research, particularly for heart valve research, as blood pressure, heart rate, cardiac output, and intracardiac pressures are similar between sheep and humans. Sheep are particularly useful for heart valve research because observable changes in implanted heart valve bioprostheses that would take several years to develop in humans are apparent after only a few months in sheep.^3,11 This feature allows the ovine model to provide relevant and important information about heart valve prostheses in a relatively short time span. The first preclinical step in developing novel heart valves is to test the valve in the pulmonary position in sheep. This surgical technique is relatively easy, as the procedure can be performed on a beating heart in a low-pressure circulation. However, aortic valve surgery is the most frequently performed valvular surgical intervention in human patients.¹² Thus, an important next step is to prove the clinical applicability of a new valve by testing the valve in-vivo in the aortic position in an animal model. In contrast to pulmonary valve replacement, aortic valve replacement must be performed on an arrested heart, which makes the surgical procedure significantly more complex. The sheep is a difficult model for aortic valve replacements due to its narrow annulus, short distance between the annulus and coronary ostia, a short ascending aorta, and difficulty in de-airing of the heart prior to suturing the aortotomy.¹⁹ Consequently, high on-table mortality rates, ranging from 9% to 33%, have been reported.^1,18,21,24 Furthermore, the incidence of mortality during the first 30 d after surgery, directly related to the surgical procedure, is often high, ranging from 17% to 50%.^1,2,16,18,21 Therefore, optimizing cardioprotective strategies during surgery would improve postoperative survival. However, little is known about protective strategies in sheep. In the current series of experiments, we implanted stented, tissue engineered, aortic heart valve prostheses in 20 adult domestic sheep and developed cardioprotective techniques to increase survival rates. In this observational study, we share our experience and insights regarding cardioprotective management to potentially improve the outcome of future surgeries that require an arrested heart in sheep.