Accelerating fishes increase propulsive efficiency by modulating vortex ring geometry.

Swimming animals need to generate propulsive force to overcome drag, regardless of whether they swim steadily or accelerate forward. While locomotion strategies for steady swimming are well characterized, far less is known about acceleration. Animals exhibit many different ways to swim steadily, but we show here that this behavioral diversity collapses into a single swimming pattern during acceleration regardless of the body size, morphology, and ecology of the animal. We draw on the fields of biomechanics, fluid dynamics, and robotics to demonstrate that there is a fundamental difference between steady swimming and forward acceleration. We provide empirical evidence that the tail of accelerating fishes can increase propulsive efficiency by enhancing thrust through the alteration of vortex ring geometry. Our study provides insight into how propulsion can be altered without increasing vortex ring size and represents a fundamental departure from our current understanding of the hydrodynamic mechanisms of acceleration. Our findings reveal a unifying hydrodynamic principle that is likely conserved in all aquatic, undulatory vertebrates.

Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for Aortic Stenosis.

BACKGROUND: After aortic valve replacement, left ventricular afterload is often characterized by the residual valve obstruction. Our objective was to determine whether higher systemic arterial afterload-as reflected in blood pressure, pulsatile and resistive load-is associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Total, pulsatile, and resistive arterial load were measured in 2141 patients with severe aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause mortality. Lower SBP at 30 days after TAVR was associated with higher mortality (20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P<0.001). This association remained significant after adjustment, was consistent across subgroups, and confirmed in sensitivity analyses. In adjusted models that included SBP, higher total and pulsatile arterial load were associated with increased mortality (P<0.001 for all), but resistive load was not. Patients with low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio, 3.62; 95% confidence interval, 2.36-5.55). CONCLUSIONS: Even after relief of valve obstruction in patients with aortic stenosis, there is an independent association between post-TAVR blood pressure, systemic arterial load, and mortality. Blood pressure goals in patients with a history of aortic stenosis may need to be redefined. Increased pulsatile arterial load, rather than blood pressure, may be a target for adjunctive medical therapy to improve outcomes after TAVR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Fish prey change strategy with the direction of a threat.

Predation is a fundamental interaction between species, yet it is unclear what escape strategies are effective for prey survival. Classical theory proposes that prey should either escape in a direction that conforms to a performance optimum or that is random and therefore unpredictable. Here, we show that larval zebrafish (Danio rerio) instead use a mixed strategy that may be either random or directed. This was determined by testing classic theory with measurements of the escape direction in response to a predator robot. We found that prey consistently escaped in a direction contralateral to the robot when approached from the side of the prey's body. At such an orientation, the predator appeared in the prey's central visual field and the contralateral response was consistent with a model of strategy that maximizes the distance from the predator. By contrast, when the robot approached the rostral or caudal ends of the body, and appeared in the prey's peripheral vision, the escape showed an equal probability of a contralateral or ipsilateral direction. At this orientation, a contralateral response offered little strategic advantage. Therefore, zebrafish larvae adopt an escape strategy that maximizes distance from the threat when strategically beneficial and that is otherwise random. This sensory-mediated mixed strategy may be employed by a diversity of animals and offers a new paradigm for understanding the factors that govern prey survival.

A non-toxic dose of cobalt chloride blocks hair cells of the zebrafish lateral line.

Experiments on the flow-sensitive lateral line system of fishes have provided important insights into the function and sensory transduction of vertebrate hair cells. A common experimental approach has been to pharmacologically block lateral line hair cells and measure how behavior changes. Cobalt chloride (CoCl2) blocks the lateral line by inhibiting calcium movement through the membrane channels of hair cells, but high concentrations can be toxic, making it unclear whether changes in behavior are due to a blocked lateral line or poor health. Here, we identify a non-toxic treatment of cobalt that completely blocks lateral line hair cells. We exposed 5-day post fertilization zebrafish larvae to CoCl2 concentrations ranging from 1 to 20 mM for 15 min and measured 1) the spiking rate of the afferent neurons contacting hair cells and 2) the larvae's health and long-term survival. Our results show that a 15-min exposure to 5 mM CoCl2 abolishes both spontaneous and evoked afferent firing. This treatment does not change swimming behavior, and results in >85% survival after 5 days. Weaker treatments of CoCl2 did not eliminate afferent activity, while stronger treatments caused close to 50% mortality. Our work provides a guideline for future zebrafish investigations where physiological confirmation of a blocked lateral line system is required.

Surgical management of infective endocarditis complicated by ischemic stroke.

Embolism to the central nervous system is a frequent and important complication of infective endocarditis. While early surgery improves outcomes in many groups of patients with infective endocarditis, ischemic stroke secondary to septic embolism carries the risk of hemorrhagic transformation and neurological deterioration with heparinization and cardiopulmonary bypass. We review the literature regarding the surgical management of infective endocarditis in patients with cerebral emboli.

Anticoagulation versus antiplatelet or no therapy in patients undergoing bioprosthetic valve implantation: a systematic review and meta-analysis.

OBJECTIVE: Use of vitamin K antagonist (VKA) versus antiplatelet (AP)/no therapy following bioprosthetic valve implantation remains controversial. The aims of the current study were to (a) systematically review the published literature comparing the use of VKA versus AP/no treatment in such patients and (b) perform a meta-analysis of the risks and benefits of using a VKA compared with AP/no therapy. METHODS: Five databases were searched including PubMed, Medline, Embase, Ovid and Cochrane for randomised clinical trials and observational studies comparing VKA (group I) versus AP/no therapy (group II). Outcome was after surgical intervention. Mantel-Haenszel odds ratio (OR) was calculated using random-effects meta-analysis for the outcome. Heterogeneity was assessed by I2 statistics. A total of 14 studies were included (two randomised trials, 12 observational studies and one conference abstract, 31 740 patients). RESULTS: Between groups I (VKA) and II (AP/no therapy), there were no differences in thromboembolic events (145 (1%) vs 262 (1.5%), OR 0.96 (95% CI 0.60 to 1.52)), all-cause mortality (351 (3.5%) vs 415 (2.9%), OR 1.48 (95% CI 0.87 to 2.50)) or need for redo surgery (47 (3.3%) vs 55 (3.2%); OR 0.81 (95% CI 0.42 to 1.58)). However, there were more bleeding events in group I versus group II (292 (2.6%) vs 189 (1.1%); OR 2.26 (95% CI 1.67 to 3.05)). CONCLUSIONS: In a meta-analysis of randomised and observational studies of VKA versus AP/no treatment in patients undergoing bioprosthetic valve implantation, there was no benefit of adding a VKA regarding thromboembolism or mortality. However, use of a VKA was associated with increased risk of major bleeding.

Speciation through the lens of biomechanics: locomotion, prey capture and reproductive isolation.

Speciation is a multifaceted process that involves numerous aspects of the biological sciences and occurs for multiple reasons. Ecology plays a major role, including both abiotic and biotic factors. Whether populations experience similar or divergent ecological environments, they often adapt to local conditions through divergence in biomechanical traits. We investigate the role of biomechanics in speciation using fish predator-prey interactions, a primary driver of fitness for both predators and prey. We highlight specific groups of fishes, or specific species, that have been particularly valuable for understanding these dynamic interactions and offer the best opportunities for future studies that link genetic architecture to biomechanics and reproductive isolation (RI). In addition to emphasizing the key biomechanical techniques that will be instrumental, we also propose that the movement towards linking biomechanics and speciation will include (i) establishing the genetic basis of biomechanical traits, (ii) testing whether similar and divergent selection lead to biomechanical divergence, and (iii) testing whether/how biomechanical traits affect RI. Future investigations that examine speciation through the lens of biomechanics will propel our understanding of this key process.

Evaluation of Flow After Transcatheter Aortic Valve Replacement in Patients With Low-Flow Aortic Stenosis: A Secondary Analysis of the PARTNER Randomized Clinical Trial.

IMPORTANCE: Low-flow (LF) severe aortic stenosis (AS) is an independent predictor of mortality in patients undergoing aortic valve replacement (AVR). Little is known about improvement in flow after AVR and its effects on survival. OBJECTIVE: To determine whether higher flow (left-ventricular stroke volume index [LVSVI]) after transcatheter AVR (TAVR) would indicate better clinical outcomes in this at-risk population. DESIGN, SETTING, AND PARTICIPANTS: A substudy analysis of data from the Placement of Aortic Transcatheter Valves (PARTNER) randomized clinical trial and continued-access registry was conducted. A total of 984 participants with evaluable echocardiograms and baseline LF AS (LVSVI ≤35 mL/m2) were included. The trial was conducted at 26 sites in the United States and Canada. Patients were stratified after TAVR into tertiles by discharge LVSVI status (severe low flow [SLF], moderate low flow [MLF], and normal flow [(NF]). The present study was conducted from May 11, 2007, to January 9, 2012, with data analysis performed from April 25, 2014, to January 21, 2016. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality at 1 year. RESULTS: Baseline characteristics of 984 patients with LF AS included mean (SD) age, 84 (7) years; 582 (59.1%) men; mean Society of Thoracic Surgeons (STS) score, 11.4% (4.0%); and mean LVSVI, 27.6 (5.0) mL/m2. The discharge LVSVI values by group were SLF, 23.1 (3.5) mL/m2; MLF, 31.7 (2.2) mL/m2; and NF, 43.1 (7.0). All-cause mortality at 1 year was SLF, 26.5%; MLF, 20.1%; and NF, 19.6% (P = .045). Mean LVSVI normalized by 6 months in the MLF (35.9 [9.3] mL/m2) and NF (38.8 [11.1] mL/m2) groups, but remained low in the SLF group at 6 months and 1 year (31.4 [8.4] and 33.0 [8.3] mL/m2], respectively) (P < .001 for all groups). Reported as multivariate hazard ratio, mortality at 1 year was higher in the SLF group compared with the other groups (1.61; 95% CI, 1.17-2.23; P = .004). In addition to SLF, sex (1.59; 95% CI, 1.18-2.13; P = .002), presence of atrial fibrillation (1.41; 95% CI, 1.06-1.87; P = .02), STS score (1.03; 95% CI, 1.01-1.06; P = .02), presence of moderate or severe mitral regurgitation at discharge (1.65; 95% CI, 1.21-2.26; P = .001), pre-TAVR mean transvalvular gradient (0.98; 95% CI, 0.97-0.99; P = .004), and effective orifice area index (1.87; 95% CI, 1.09-3.19; P = .02) were independent predictors of 1-year mortality. CONCLUSIONS AND RELEVANCE: Severe LF at discharge is associated with an increased risk of mortality following TAVR in patients with severe AS and preexisting LF. The identification of remedial causes of persistent LF after TAVR may represent an opportunity to improve the outcome of these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00530894.

Refuging rainbow trout selectively exploit flows behind tandem cylinders.

Fishes may exploit environmental vortices to save in the cost of locomotion. Previous work has investigated fish refuging behind a single cylinder in current, a behavior termed the Kármán gait. However, current-swept habitats often contain aggregations of physical objects, and it is unclear how the complex hydrodynamics shed from multiple structures affect refuging in fish. To begin to address this, we investigated how the flow fields produced by two D-shaped cylinders arranged in tandem affect the ability of rainbow trout (Oncorhynchus mykiss) to Kármán gait. We altered the spacing of the two cylinders from l/D of 0.7 to 2.7 (where l=downstream spacing of cylinders and D=cylinder diameter) and recorded the kinematics of trout swimming behind the cylinders with high-speed video at Re=10,000-55,000. Digital particle image velocimetry showed that increasing l/D decreased the strength of the vortex street by an average of 53% and decreased the frequency that vortices were shed by ∼20% for all speeds. Trout were able to Kármán gait behind all cylinder treatments despite these differences in the downstream wake; however, they Kármán gaited over twice as often behind closely spaced cylinders (l/D=0.7, 1.1, and 1.5). Computational fluid dynamics simulations show that when cylinders are widely spaced, the upstream cylinder generates a vortex street that interacts destructively with the downstream cylinder, producing weaker, more widely spaced and less-organized vortices that discourage Kármán gaiting. These findings are poised to help predict when fish may seek refuge in natural habitats based on the position and arrangement of stationary objects.

Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels.

Synaptic ribbons are structures made largely of the protein Ribeye that hold synaptic vesicles near release sites in non-spiking cells in some sensory systems. Here, we introduce frameshift mutations in the two zebrafish genes encoding for Ribeye and thus remove Ribeye protein from neuromast hair cells. Despite Ribeye depletion, vesicles collect around ribbon-like structures that lack electron density, which we term "ghost ribbons." Ghost ribbons are smaller in size but possess a similar number of smaller vesicles and are poorly localized to synapses and calcium channels. These hair cells exhibit enhanced exocytosis, as measured by capacitance, and recordings from afferent neurons post-synaptic to hair cells show no significant difference in spike rates. Our results suggest that Ribeye makes up most of the synaptic ribbon density in neuromast hair cells and is necessary for proper localization of calcium channels and synaptic ribbons.

The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis: intermediate-term efficacy and durability.

BACKGROUND: The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis (Edwards Lifesciences, Irvine, CA) is a low-profile version of the earlier Perimount valve that uses the ThermaFix process for enhanced calcium removal. The Magna valve has been in use since 2008, yet no publication, until now, has verified its intermediate-term safety and efficacy. METHODS: From 2008 through 2011 (our 4-year study period), 70 Magna valves were implanted in the mitral position at a single institution (the Cleveland Clinic). Echocardiograms were prospectively interpreted. For this study, we reviewed patients' charts; endpoints included hemodynamic measurements, in-hospital morbidity and mortality, valve-related events, resource utilization, and 5-year survival rates. RESULTS: The mean patient age was 68 years; 43 % of the patients had New York Heart Association (NYHA) class III or IV disease, and 51.4 % had moderately severe, or worse, mitral regurgitation (MR). For 43 % of the patients, the Magna valve implantation was a reoperation. For 83 %, the Magna valve implantation also included a concomitant cardiac procedure. The median survival rate was 4.7 years and 90 % of patients were free from significant structural valve degeneration at 5 years. Preoperative atrial fibrillation, ischemic MR, intraaortic balloon pump placement, cardiogenic shock, cardiac arrest, and renal failure were associated with increased mortality. Right ventricular systolic pressure decreased from 50 mmHg preoperatively to 40 mmHg postoperatively, according to our matched-pair analysis (P = 0.003). Per their final echocardiogram during our study period, 98 % of surviving patients had trivial or no MR, one patient had mild MR, and one patient had severe MR. CONCLUSIONS: Our 5-year experience indicates that the Magna valve offers excellent intermediate-term durability and substantial echocardiographic improvement; its low-profile design make it ideal for reoperations and for concomitant cardiac procedures, including valve replacement.

Turbulence, Temperature, and Turbidity: The Ecomechanics of Predator-Prey Interactions in Fishes.

Successful feeding and escape behaviors in fishes emerge from precise integration of locomotion and feeding movements. Fishes inhabit a wide range of habitats, including still ponds, turbulent rivers, and wave-pounded shorelines, and these habitats vary in several physical variables that can strongly impact both predator and prey. Temperature, the conditions of ambient flow, and light regimes all have the potential to affect predator-prey encounters, yet the integration of these factors into our understanding of fish biomechanics is presently limited. We explore existing knowledge of kinematics, muscle function, hydrodynamics, and evolutionary morphology in order to generate a framework for understanding the ecomechanics of predator-prey encounters in fishes. We expect that, in the absence of behavioral compensation, a decrease in temperature below the optimum value will reduce the muscle power available both to predator and prey, thus compromising locomotor performance, suction-feeding mechanics of predators, and the escape responses of prey. Ambient flow, particularly turbulent flow, will also challenge predator and prey, perhaps resulting in faster attacks by predators to minimize mechanical instability, and a reduced responsiveness of prey to predator-generated flow. Reductions in visibility, caused by depth, turbidity, or diel fluctuations in light, will decrease distances at which either predator or prey detect each other, and generally place a greater emphasis on the role of mechanoreception both for predator and prey. We expect attack distances to be shortened when visibility is low. Ultimately, the variation in abiotic features of a fish's environment will affect locomotion and feeding performance of predators, and the ability of the prey to escape. The nature of these effects and how they impact predator-prey encounters stands as a major challenge for future students of the biomechanics of fish during feeding. Just as fishes show adaptations for capturing specific types of prey, we anticipate they are also adapted to the physical features of their preferred habitat and show a myriad of behavioral mechanisms for dealing with abiotic factors during predator-prey encounters.

When Optimal Strategy Matters to Prey Fish.

Predator-prey interactions are commonly studied with an interest in determining the optimal strategy for prey. However, the implications of deviating from optimal strategy are often unclear. The present study considered these consequences by studying how the direction of an escape response affects the strategy of prey fish. We simulated these interactions with numerical and analytical mathematics and compared our predictions with measurements in zebrafish larvae (Danio rerio), which are preyed upon by adults of the same species. Consistent with existing theory, we treated the minimum distance between predator and prey as the strategic payoff that prey aim to maximize. We found that these interactions may be characterized by three strategic domains that are defined by the speed of predator relative to the prey. The "fast predator" domain occurs when the predator is more than an order of magnitude faster than the prey. The escape direction of the prey had only a small effect on the minimum distance under these conditions. For the "slow predator" domain, when the prey is faster than the predator, we found that differences in direction had no effect on the minimum distance for a broad range of escape angles. This was the regime in which zebrafish were found to operate. In contrast, the optimal escape angle offers a large benefit to the minimum distance in the intermediate strategic domain. Therefore, optimal strategy is most meaningful to prey fish when predators are faster than prey by less than a factor of 10. This demonstrates that the strategy of a prey animal does not matter under certain conditions that are created by the behavior of the predator.

Outcomes of inoperable symptomatic aortic stenosis patients not undergoing aortic valve replacement: insight into the impact of balloon aortic valvuloplasty from the PARTNER trial (Placement of AoRtic TraNscathetER Valve trial).

OBJECTIVES: The aim of this report is to characterize the impact of balloon aortic valvuloplasty (BAV) in patients not undergoing aortic valve replacement in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial. BACKGROUND: The PARTNER trial is the only randomized trial with independently adjudicated data of inoperable severe symptomatic aortic stenosis patients, allowing outcome analysis of unoperated-on patients. METHODS: The design and initial results of the PARTNER trial (Cohort B) were reported previously. After excluding patients with pre-randomization BAV, we compared patients undergoing BAV within 30 days of randomization (BAV group) with those not having BAV within 30 days of randomization (no BAV group) to characterize the use and impact of BAV. RESULTS: In the PARTNER Cohort B study, 179 inoperable patients were randomized to standard treatment including 39 patients (21.8%) who had undergone a BAV before randomization (previous BAV group). Of the 140 patients who did not have BAV before enrollment in the study, 102 patients (73%) had BAV within 30 days of study randomization (BAV group). Survival at 3 months was greater in the BAV group compared with the no BAV group (88.2%; 95% confidence interval [CI]: 82.0% to 94.5% vs. 73.0%; 95% CI: 58.8% to 87.4%). However, survival was similar at 6-month follow-up (74.5%; 95% CI: 66.1% to 83.0% vs. 73.1%; 58.8% to 87.4%). There was improvement in quality of life parameters when paired comparisons were made between baseline and 30 days and 6 months between the BAV and no BAV groups, but this effect was lost at 12-month follow-up. CONCLUSIONS: BAV improves functional status and survival in the short term, but these benefits are not sustained. BAV for aortic stenosis patients who cannot undergo aortic valve replacement is a useful palliative therapy. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).