Rationale: Mutations in the LMNA gene, which encodes the nuclear lamina proteins lamin A and lamin C, are the most common cause of familial dilated cardiomyopathy (DCM). Mechanical stress-induced apoptosis has been proposed as the mechanism underpinning DCM in lamin A/C-deficient hearts, but supporting in vivo evidence has been lacking. Objective: Our aim was to study interventions to modify mechanical stress in heterozygous Lmna knockout (Lmna ؉/؊ ) mice. Methods and Results: Cardiac structure and function were evaluated before and after exercise training, thoracic aortic constriction, and carvedilol treatment. Lmna ؉/؊ mice develop adult-onset DCM with relatively more severe disease in males. Lmna ؉/؊ cardiomyocytes show altered nuclear morphology and perinuclear desmin organization, with enhanced responses to hypo-osmotic stress indicative of cytoskeletal instability. Despite these structural defects that provide a template for mechanical stress-induced damage, young Lmna ؉/؊ mice subjected to 6 weeks of moderate or strenuous exercise training did not show induction of apoptosis or accelerated DCM. In contrast, regular moderate exercise attenuated DCM development in male Lmna ؉/؊ mice. Sustained pressure overload generated by thoracic aortic constriction depressed ventricular contraction in young wild-type and Lmna ؉/؊ mice with no sex or genotype differences in the time-course or severity of response. Treatment of male Lmna ؉/؊ mice from 12 to 40 weeks with the ␤-blocker, carvedilol, prevented the dilatation and contractile dysfunction that was observed in placebo-treated mice. Conclusions: These data suggest that factors other than mechanical stress-induced apoptosis contribute to DCM and provide the first demonstration that regular moderate exercise and carvedilol can modify disease progression in lamin A/C-deficient hearts. (Circ Res. 2010;106:573-582.)Key Words: familial dilated cardiomyopathy Ⅲ lamin A/C Ⅲ mechanical stress Ⅲ exercise Ⅲ carvedilol M utations in the LMNA gene that encodes the nuclear lamina proteins lamin A and lamin C are the most common cause of familial dilated cardiomyopathy (DCM) identified to date, 1 accounting for 5% to 10% familial DCM overall and 30% to 45% families with DCM and conduction system disease (CD). [2][3][4][5] Affected individuals frequently have a rapidly progressive downhill clinical course, requiring pacemaker implantation or heart transplantation, with an increased risk of sudden death. [2][3][4][5] Despite the clinical importance of LMNA mutations, very little is known about mechanisms of disease pathogenesis and strategies to prevent DCM have not been investigated.Because one-third of DCM-causing LMNA mutations are stop codons, splice site variants or insertions/deletions that reduce lamin A/C protein levels, 1,5 Lmna knockout mice are a useful and clinically relevant model to study DCM mechanisms. 6 We have previously reported that homozygous Lmna knockout (Lmna Ϫ/Ϫ ) mice exhibit severe DCM by 4 to 6 weeks. 7 Heterozygous Lmna knockout (Lmna ϩ/Ϫ ) mice show ...

Enhanced recovery after surgery (ERAS) protocols are designed to reduce medical complications, the length of hospital stays (LoS), and healthcare costs. ERAS is considered safe and effective for kidney transplant (KTx) surgery. KTx recipients are often frail with multiple comorbidities. As these patients follow an extensive diagnostic pathway preoperatively, the ERAS protocol can ideally be implemented at this stage. Small singular changes in a long perioperative pathway can result in significant positive outcomes. We have investigated the current evidence for an ERAS pathway related to anaesthetic considerations in renal transplant surgery for adult recipients.

This paper describes an investigation of transverse acoustic instabilities in premixed, swirl-stabilized flames. Additional measurements, beyond the scope of the current work, are described in O’Connor et al. [1]. Transverse excitation of swirling flow involves complex interactions between acoustic waves and fluid mechanic instabilities. The flame’s response to transverse acoustic excitation is a superposition of both acoustic and vortical disturbances that fluctuate in both the longitudinal and transverse direction. In the nozzle near field region, the disturbance field is a complex superposition of convecting vortical disturbances, as well as longer wavelength transverse and longitudinal acoustic disturbances. Farther downstream, the disturbance field is dominated by the transverse acoustic field. The phasing between the disturbances on the inside and outside of the burner annulus, as well as the left and right sides of the burner annulus is a strong function of the transverse disturbance field characteristics. For cases where the burner centerline is an approximate pressure node and velocity anti-node, the mass flow out of the left and right sides of the burner actually oscillates out-of-phase with respect to each other. In contrast, for cases where the centerline is a pressure anti-node, the burner responds symmetrically about the burner and annulus centerlines. These results show that the burner response characteristics strongly depend upon their location in the acoustic mode shape.

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Methods used to measure the temperature of AlxGa1−xN based ultraviolet light emitting diodes (UV LEDs) are based on optical or electrical phenomena that are sensitive to either local, surface, or average temperatures within the LED. A comparative study of the temperature rise of AlxGa1−xN UV LEDs measured by micro-Raman spectroscopy, infrared (IR) thermography, and the forward voltage method is presented. Experimental temperature measurements are provided for UV LEDs with micropixel and interdigitated contact geometries, as well as for a number of different packaging configurations. It was found that IR spectroscopy was sensitive to optical properties of the device layers, while forward voltage method provided higher temperatures, in general. Raman spectroscopy was used to measure specific layers within the LED, showing that growth substrate temperatures in the flip-chip LEDs agreed more closely to IR measurements while layers closer to the multiple quantum wells (MQWs) agreed more closely with Forward Voltage measurements.