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BACKGROUND: The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. METHODS AND RESULTS: We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). CONCLUSIONS: The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI. [ABSTRACT FROM AUTHOR]

Aromatic compounds are an important source of commodity chemicals traditionally produced from fossil fuels. Aromatics derived from plant lignin can potentially be converted into commodity chemicals through depolymerization followed by microbial funneling of monomers and low molecular weight oligomers. This study investigates the catabolism of the β-5 linked aromatic dimer dehydrodiconiferyl alcohol (DC-A) by the bacterium Novosphingobium aromaticivorans . We used genome-wide screens to identify candidate genes involved in DC-A catabolism. Subsequent in vivo and in vitro analyses of these candidate genes elucidated a catabolic pathway composed of four required gene products and several partially redundant dehydrogenases that convert DC-A to aromatic monomers that can be funneled into the central aromatic metabolic pathway of N. aromaticivorans . Specifically, a newly identified γ-formaldehyde lyase, PcfL, opens the phenylcoumaran ring to form a stilbene and formaldehyde. A lignostilbene dioxygenase, LsdD, then cleaves the stilbene to generate the aromatic monomers vanillin and 5-formylferulate (5-FF). We also showed that the aldehyde dehydrogenase FerD oxidizes 5-FF before it is decarboxylated by LigW, yielding ferulic acid. We found that some enzymes involved in the β-5 catabolism pathway can act on multiple substrates and that some steps in the pathway can be mediated by multiple enzymes, providing new insights into the robust flexibility of aromatic catabolism in N. aromaticivorans . A comparative genomic analysis predicted that the newly discovered β-5 aromatic catabolic pathway is common within the order Sphingomonadales., Importance: In the transition to a circular bioeconomy, the plant polymer lignin holds promise as a renewable source of industrially important aromatic chemicals. However, since lignin contains aromatic subunits joined by various chemical linkages, producing single chemical products from this polymer can be challenging. One strategy to overcome this challenge is using microbes to funnel a mixture of lignin-derived aromatics into target chemical products. This approach requires strategies to cleave the major inter-unit linkages of lignin to release monomers for funneling into valuable products. In this study, we report newly discovered aspects of a pathway by which the Novosphingobium aromaticivorans DSM12444 catabolizes aromatics joined by the second most common inter-unit linkage in lignin, the β-5 linkage. This work advances our knowledge of aromatic catabolic pathways, laying the groundwork for future metabolic engineering of this and other microbes for optimized conversion of lignin into products., Competing Interests: The authors declare no conflict of interest.

This article proposes a more individualized approach to organizational and food safety culture development through the creation of culture change agents. The study used action research with individual therapeutic training of sensory and emotional skills as the action intervention to reveal underlying mechanisms of the culture and create long-term culture change. The study was conducted with a group of voluntary employees over a 3-year period at a department under Food Safety and Veterinary Issues in Danish Agriculture and Food Council. Data was collected using individual in-depth qualitative interviews with a novel questionnaire technique that facilitated participants to bring otherwise unconscious underlying assumptions to awareness. The study found that working intensely and therapeutically on an individual and group level, had a significant impact on the surrounding culture and social capital. Five underlying mechanisms were revealed linking individual culture change to changes in the social capital and culture of the department. Going through the five underlying mechanisms may enable individuals to get to the root causes of issues, facilitate more sharing and collaboration to learn from near-misses and failures, and take action despite facing uncomfortable situations, all important abilities to develop FSC. Based on the underlying mechanisms a 'Change Agent Model' was developed. The model illustrates the important underlying mechanisms that any individual or group can work through to become culture change agents and drivers for organizational culture and FSC development. This is the first of two articles., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Suction feeding in ray-finned fishes involves powerful buccal cavity expansion to accelerate water and food into the mouth. Previous XROMM studies in largemouth bass (Micropterus salmoides), bluegill sunfish (Lepomis macrochirus) and channel catfish (Ictalurus punctatus) have shown that more than 90% of suction power in high performance strikes comes from the axial musculature. Thus, the shape of the axial muscles and skeleton may affect suction feeding mechanics. Royal knifefish (Chitala blanci) have an unusual postcranial morphology, with a ventrally flexed vertebral column and relatively large mass of epaxial muscle. Based on their body shape, we hypothesized that royal knifefish would generate high power strikes by utilizing large neurocranial elevation, vertebral column extension and epaxial shortening. As predicted, C. blanci generated high suction expansion power compared with the other three species studied to date (up to 160 W), which was achieved by increasing both the rate of volume change and the intraoral subambient pressure. The large epaxial muscle (25% of body mass) shortened at high velocities to produce large neurocranial elevation and vertebral extension (up to 41 deg, combined), as well as high muscle mass-specific power (up to 800 W kg-1). For the highest power strikes, axial muscles generated 95% of the power, and 64% of the axial muscle mass consisted of the epaxial muscles. The epaxial-dominated suction expansion of royal knifefish supports our hypothesis that postcranial morphology may be a strong predictor of suction feeding biomechanics., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

This data paper describes a compilation of 73,075 quantitative diet data records for 759 primarily North American bird species, providing standardized information not just on the diet itself, but on the context for that diet information including the year, season, location, and habitat type of each study. The methods used for collecting and cleaning these data are described, and we present tools for summarizing and visualizing diet information by bird species or prey., (© 2021. The Author(s).)

We tested the efficacy of a stereo camera (SC) system adapted for use with a remotely operated vehicle (ROV) to estimate fish length distributions at reef sites in the northern Gulf of Mexico. A pool experiment was conducted to test the effect of distance (1, 2, 3 or 5 m), angle of incidence (AOI; 0° to 40° at 5° increments), and SC baseline distance (BD; BD1 = 406, BD2 = 610, and BD3 = 762 mm camera separation) on the accuracy and precision of fish model length (288, 552, or 890 mm fork length) estimates compared to a red laser scaler (RLS). A field experiment was then conducted at 20 reef sites with SCs positioned at BD1 to compare fish length distribution estimates between the SC and RLS systems under in situ conditions. In the pool experiment, mean percent errors were consistently within the a priori selected threshold of ±5% at AOIs ≤10° at all distances with all four systems. However, SCs produced accurate estimates at AOIs up to 30° at all distances tested; 2-3 m was optimal. During reef site surveys, SCs collected 10.4 times as many length estimates from 4.3 times as many species compared to the RLS. Study results demonstrate that, compared to laser scalers, ROV-based SC systems can substantially increase the number of available fish length estimates by producing accurate length estimates at a wider range of target orientations while also enabling measurements from a greater portion of the cameras' field of view., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19., Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender., Setting: All hospitals in Denmark., Participants: 1310 patients aged ≥18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data., Main Outcome Measures: A composite of death/ICU admission occurring within 30 days., Results: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin., Conclusion: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fish perform many complex manipulation behaviors without hands or flexible muscular tongues, instead relying on more than 20 movable skeletal elements in their highly kinetic skulls. How fish use their skulls to accomplish these behaviors, however, remains unclear. Most previous mechanical models have represented the fish skull using one or more planar four-bar linkages, which have just a single degree of freedom (DoF). In contrast, truncated-cone hydrodynamic models have assumed up to five DoFs. In this study, we introduce and validate a 3D mechanical linkage model of a fish skull that incorporates the pectoral girdle and mandibular and hyoid arches. We validate this model using an in vivo motion dataset of suction feeding in channel catfish and then use this model to quantify the DoFs in the fish skull, to categorize the motion patterns of the cranial linkage during feeding, and to evaluate the association between these patterns and food motion. We find that the channel catfish skull functions as a 17-link, five-loop parallel mechanism. Despite having 19 potential DoFs, we find that seven DoFs are sufficient to describe most of the motion of the cranial linkage, consistent with the fish skull functioning as a multi-DoF, manipulation system. Channel catfish use this linkage to generate three different motion patterns (rostrocaudal wave, caudorostral wave, and compressive wave), each with its own associated food velocity profile. These results suggest that biomechanical manipulation systems must have a minimum number of DoFs to effectively control objects, whether in water or air., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Objective: To use the small data approach of the Clinical and Laboratory Standards Institute (CLSI) to evaluate the transferability of reference intervals (RIs) for kinetic variables obtained with instrumented gait analysis (IGA) in dogs from an RI-originator laboratory to another laboratory that used the same data acquisition and analytic techniques for IGA in walking dogs., Animals: 27 adult client-owned dogs without evidence of lameness., Procedures: Dogs were individually walked at their preferred velocity on a pressure-sensing walkway for IGA at the Colorado State University Animal Gait Laboratory (CSU-AGL), and 6 valid trials were analyzed for each dog. The small data approach of the CLSI was then used to evaluate transferability of RIs previously established at the Purdue University Animal Gait Laboratory (PU-AGL). A linear model was used to establish weight-dependent RIs for peak vertical force (PVF)., Results: Results indicated that RIs of dynamic weight distribution (DWD), DWD symmetry index, DWD coefficient of variation, PVF symmetry index, and PVF coefficient of variation were transferable from PU-AGL to CSU-AGL, whereas the weight-dependent RIs for PVF were not. Regression slopes for PVF versus body weight were greater for all limbs in dogs tested at the CSU-AGL, compared with historic results for dogs tested at the PU-AGL., Conclusions and Clinical Relevance: Use of the small data approach method of the CLSI to validate transference of RIs for IGA kinetic variables in walking dogs was simple and efficient to perform and may help facilitate clinical and research collaborations on gait analysis.

Some fishes rely on large regions of the dorsal (epaxial) and ventral (hypaxial) body muscles to power suction feeding. Epaxial and hypaxial muscles are known to act as motors, powering rapid mouth expansion by shortening to elevate the neurocranium and retract the pectoral girdle, respectively. However, some species, like catfishes, use little cranial elevation. Are these fishes instead using the epaxial muscles to forcefully anchor the head, and if so, are they limited to lower-power strikes? We used X-ray imaging to measure epaxial and hypaxial length dynamics (fluoromicrometry) and associated skeletal motions (XROMM) during 24 suction feeding strikes from three channel catfish ( Ictalurus punctatus ). We also estimated the power required for suction feeding from oral pressure and dynamic endocast volume measurements. Cranial elevation relative to the body was small (<5 deg) and the epaxial muscles did not shorten during peak expansion power. In contrast, the hypaxial muscles consistently shortened by 4-8% to rotate the pectoral girdle 6-11 deg relative to the body. Despite only the hypaxial muscles generating power, catfish strikes were similar in power to those of other species, such as largemouth bass ( Micropterus salmoides ), that use epaxial and hypaxial muscles to power mouth expansion. These results show that the epaxial muscles are not used as motors in catfish, but suggest they position and stabilize the cranium while the hypaxial muscles power mouth expansion ventrally. Thus, axial muscles can serve fundamentally different mechanical roles in generating and controlling cranial motion during suction feeding in fishes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Most predatory ray-finned fishes swallow their food whole, which can pose a significant challenge, given that prey items can be half as large as the predators themselves. How do fish transport captured food from the mouth to the stomach? Prior work indicates that, in general, fish use the pharyngeal jaws to manipulate food into the esophagus, where peristalsis is thought to take over. We used X-Ray Reconstruction of Moving Morphology to track prey transport in channel catfish ( Ictalurus punctatus ). By reconstructing the 3D motions of both the food and the catfish, we were able to track how the catfish move food through the head and into the stomach. Food enters the oral cavity at high velocities as a continuation of suction and stops in the approximate location of the branchial basket before moving in a much slower, more complex path toward the esophagus. This slow phase coincides with little motion in the head and no substantial mouth opening or hyoid depression. Once the prey is in the esophagus, however, its transport is surprisingly tightly correlated with gulping motions (hyoid depression, girdle retraction, hypaxial shortening, and mouth opening) of the head. Although the transport mechanism itself remains unknown, to our knowledge, this is the first description of synchrony between cranial expansion and esophageal transport in a fish. Our results provide direct evidence of prey transport within the esophagus and suggest that peristalsis may not be the sole mechanism of esophageal transport in catfish., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

For many fish species, rhythmic movement of the pectoral fins, or forelimbs, drives locomotion. In terrestrial vertebrates, normal limb-based rhythmic gaits require ongoing modulation with limb mechanosensors. Given the complexity of the fluid environment and dexterity of fish swimming through it, we hypothesize that mechanosensory modulation is also critical to normal fin-based swimming. Here, we examined the role of sensory feedback from the pectoral fin rays and membrane on the neuromuscular control and kinematics of pectoral fin-based locomotion. Pectoral fin kinematics and electromyograms of the six major fin muscles of the parrotfish, Scarus quoyi , a high-performance pectoral fin swimmer, were recorded during steady swimming before and after bilateral transection of the sensory nerves extending into the rays and surrounding membrane. Alternating activity of antagonistic muscles was observed and drove the fin in a figure-of-eight fin stroke trajectory before and after nerve transection. After bilateral transections, pectoral fin rhythmicity remained the same or increased. Differences in fin kinematics with the loss of sensory feedback also included fin kinematics with a significantly more inclined stroke plane angle, an increased angular velocity and fin beat frequency, and a transition to the body-caudal fin gait at lower speeds. After transection, muscles were active over a larger proportion of the fin stroke, with overlapping activation of antagonistic muscles rarely observed in the trials of intact fish. The increased overlap of antagonistic muscle activity might stiffen the fin system in order to enhance control and stability in the absence of sensory feedback from the fin rays. These results indicate that fin ray sensation is not necessary to generate the underlying rhythm of fin movement, but contributes to the specification of pectoral fin motor pattern and movement during rhythmic swimming., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Closed kinematic chains (CKCs), links connected to form one or more closed loops, are used as simple models of musculoskeletal systems (e.g. the four-bar linkage). Previous applications of CKCs have primarily focused on biomechanical systems with rigid links and permanently closed chains, which results in constant mobility (the total degrees of freedom of a system). However, systems with non-rigid elements (e.g. ligaments and muscles) and that alternate between open and closed chains (e.g. standing on one foot versus two) can also be treated as CKCs with changing mobility. Given that, in general, systems that have fewer degrees of freedom are easier to control, what implications might such dynamic changes in mobility have for motor control? Here, I propose a CKC classification to explain the different ways in which mobility of musculoskeletal systems can change dynamically during behavior. This classification is based on the mobility formula, taking into account the number of loops in the CKC and the nature of the constituent joint mobilities. I apply this mobility-based classification to five biomechanical systems: the human lower limbs, the operculum-lower jaw mechanism of fishes, the upper beak rotation mechanism of birds, antagonistic muscles at the human ankle joint and the human jaw processing a food item. I discuss the implications of this classification, including that mobility itself may be dynamically manipulated to simplify motor control. The principal aim of this Commentary is to provide a framework for quantifying mobility across diverse musculoskeletal systems to evaluate its potentially key role in motor control., Competing Interests: Competing interestsThe author declares no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

High-performance suction feeding is often presented as a classic innovation of ray-finned fishes, likely contributing to their remarkable evolutionary success, whereas sharks, with seemingly less sophisticated jaws, are generally portrayed as morphologically conservative throughout their history. Here, using a combination of computational modeling, physical modeling, and quantitative three-dimensional motion simulation, we analyze the cranial skeleton of one of the earliest known stem elasmobranchs, Tristychius arcuatus from the Middle Mississippian of Scotland. The feeding apparatus is revealed as highly derived, capable of substantial oral expansion, and with clear potential for high-performance suction feeding some 50 million years before the earliest osteichthyan equivalent. This exceptional jaw performance is not apparent from standard measures of ecomorphospace using two-dimensional data. Tristychius signals the emergence of entirely new chondrichthyan ecomorphologies in the aftermath of the end-Devonian extinction and highlights sharks as significant innovators in the early radiation of the modern vertebrate biota.

Overreporting has always been a concern within psychological evaluations. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (Ben-Porath & Tellegen, 2008/2011 ) contains validity scales designed for detecting noncredible responses. In this study, 270 undergraduates were instructed to feign either schizophrenia, posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD); some participants were coached on symptoms and validity scales. Results at both the individual protocol and mean validity scale score levels suggest that each feigned disorder moderates the effectiveness of coaching on validity scale detection. One finding of this study suggests that schizophrenia is generally more difficult to successfully feign than PTSD or GAD. Another finding suggests that the majority of individuals able to avoid detection as symptom overreporters are able to successfully endorse at least some disorder-relevant symptoms. We suggest that future research focus on the systematic exploration of other factors influencing the effectiveness of validity scales as well as the development of validity scales designed to detect the overreporting of internalizing forms of psychopathology.

When animals move they must coordinate motion among multiple parts of the musculoskeletal system. Different behaviours exhibit different patterns of coordination, however, it remains unclear what general principles determine the coordination pattern for a particular behaviour. One hypothesis is that speed determines coordination patterns as a result of differences in voluntary versus involuntary control. An alternative hypothesis is that the nature of the behavioural task determines patterns of coordination. Suction-feeding fishes have highly kinetic skulls and must coordinate the motions of over a dozen skeletal elements to draw fluid and prey into the mouth. We used a dataset of intracranial motions at five cranial joints in channel catfish ( Ictalurus punctatus), collected using X-ray reconstruction of moving morphology, to test whether speed or task best explained patterns of coordination. We found that motions were significantly more coordinated (by 20-29%) during prey capture than during prey transport, supporting the hypothesis that the nature of the task determines coordination patterns. We found no significant difference in coordination between low- and high-speed motions. We speculate that capture is more coordinated to create a single fluid flow into the mouth while transport is less coordinated so that the cranial elements can independently generate multiple flows to reposition prey. Our results demonstrate the benefits of both higher and lower coordination in animal behaviours and the potential of motion analysis to elucidate motor tasks.

The organization of tissues in appendages often affects their mechanical properties and function. In the fish family Labridae, swimming behavior is associated with pectoral fin flexural stiffness and morphology, where fins range on a continuum from stiff to relatively flexible fins. Across this diversity, pectoral fin flexural stiffness decreases exponentially along the length of any given fin ray, and ray stiffness decreases along the chord of the fin from the leading to trailing edge. In this study, we examine the morphological properties of fin rays, including the effective modulus in bending (E), second moment of area (I), segmentation, and branching patterns, and their impact on fin ray stiffness. We quantify intrinsic pectoral fin ray stiffness in similarly sized fins of two closely related species that employ fins of divergent mechanics, the flapping Gomphosus varius and the rowing Halichoeres bivittatus. While segmentation patterns and E were similar between species, measurements of I and the number of fin ray branch nodes were greater in G. varius than in H. bivittatus. A multiple regression model found that of these variables, I was always significantly correlated with fin ray flexural stiffness and that variation in I always explained the majority of the variation in flexural stiffness. Thus, while most of the morphological variables quantified in this study correlate with fin ray flexural stiffness, second moment of area is the greatest factor contributing to variation in flexural stiffness. Further, interspecific variation in fin ray branching pattern could be used as a means of tuning the effective stiffness of the fin webbing to differences in swimming behavior and hydrodynamics. The comparison of these results to other systems begins to unveil fundamental morphological features of biological beams and yields insight into the role of mechanical properties in fin deformation for aquatic locomotion., (© 2018 Wiley Periodicals, Inc.)

OBJECTIVE To quantitatively measure the amount of pressure induced at the calcaneus and cranial tibial surface of dogs by use of 2 cast configurations. ANIMALS 13 client- or student-owned dogs. PROCEDURES Pressure sensors were placed over the calcaneus and cranial tibial surface. Dogs then were fitted with a fiberglass cast on a pelvic limb extending from the digits to the stifle joint (tall cast). Pressure induced over the calcaneus and proximal edge of the cast at the level of the cranial tibial surface was simultaneously recorded during ambulation. Subsequently, the cast was shortened to end immediately proximal to the calcaneus (short cast), and data acquisition was repeated. Pressure at the level of the calcaneus and cranial tibial surface for both cast configurations was compared by use of paired t tests. RESULTS The short cast created significantly greater peak pressure at the level of the calcaneus (mean ± SD, 0.2 ± 0.07 MPa), compared with peak pressure created by the tall cast (0.1 ± 0.06 MPa). Mean pressure at the proximal cranial edge of the cast was significantly greater for the short cast (0.2 ± 0.06 MPa) than for the tall cast (0.04 ± 0.03 MPa). CONCLUSIONS AND CLINICAL RELEVANCE A cast extended to the level of the proximal portion of the tibia caused less pressure at the level of the calcaneus and the proximal cranial edge of the cast. Reducing the amount of pressure at these locations may minimize the potential for pressure sores and other soft tissue injuries.

The functional capabilities of flexible, propulsive appendages are directly influenced by their mechanical properties. The fins of fishes have undergone extraordinary evolutionary diversification in structure and function, which raises questions of how fin mechanics relate to swimming behavior. In the fish family Labridae, pectoral fin swimming behavior ranges from rowing to flapping. Rowers are more maneuverable than flappers, but flappers generate greater thrust at high speeds and achieve greater mechanical efficiency at all speeds. Interspecific differences in hydrodynamic capability are largely dependent on fin kinematics and deformation, and are expected to correlate with fin stiffness. Here we examine fin ray stiffness in two closely related species that employ divergent swimming behaviors, the flapping Gomphosus varius and the rowing Halichoeres bivittatus To determine the spatial distribution of flexural stiffness across the fin, we performed three-point bending tests at the center of the proximal, middle and distal regions of four equally spaced fin rays. Pectoral fin ray flexural stiffness ranged from 0.0001 to 1.5109 µN m 2 , and the proximal regions of G. varius fin rays were nearly an order of magnitude stiffer than those of H. bivittatus In both species, fin ray flexural stiffness decreased exponentially along the proximodistal span of fin rays, and flexural stiffness decreased along the fin chord from the leading to the trailing edge. Furthermore, the proportion of fin area occupied by fin rays was significantly greater in G. varius than in H. bivittatus , suggesting that the proportion of fin ray to fin area contributes to differences in fin mechanics., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Aim: Long-term prognostic impact of coronary artery disease (CAD) severity in stable post-myocardial infarction (MI) patients is not well known. We examined the impact of CAD severity and co-morbidity on the long-term (1 year and beyond) risk of cardiovascular events post-MI., Methods and Results: From nationwide administrative and clinical registers, we identified 55 747 MI patients, during 2004-2010, who had not experienced subsequent MI, stroke, or death within 7 days post-discharge. The risk for primary composite endpoint (MI, stroke, or cardiovascular death) was estimated for the first 365 days after MI (index MI) and from day 366 to study completion (stable post-MI population), corresponding to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative incidence, multivariable adjusted logistic regression and Cox proportional-hazards models. The 1-year cumulative incidence for primary endpoint was 20.0% [95% confidence interval (CI), (19.6-20.3)]. Correspondingly, the 4-year cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6-21.4) in patients without events on the first year. In multivariable models with no significant stenosis as reference, CAD severity was the most important risk factor for cardiovascular events the first 365 days [left main stenosis (LMS): odds ratio and 95% CI, 4.37, 3.69-5.17; 3-vessel disease (VD), 4.18, 3.66-4.77; 2-VD, 3.23, 2.81-3.72; 1-VD, 2.12,-1.85-2.43] and remained from day 366 to study completion [LMS: hazard ratio and 95% CI, 1.91, 1.64-2.22; 3-VD, 1.85,1.65-2.07; 2-VD, 1.55, 1.38-1.74; 1-VD, 1.30, 1.16-1.45]., Conclusion: Despite contemporary treatment at baseline, stable post-MI patients' 4-year outcome was similar to 1-year outcome after MI, and CAD severity remained a critical risk factor the first year and thereafter., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The planar, one degree of freedom (1-DoF) four-bar linkage is an important model for understanding the function, performance and evolution of numerous biomechanical systems. One such system is the opercular mechanism in fishes, which is thought to function like a four-bar linkage to depress the lower jaw. While anatomical and behavioral observations suggest some form of mechanical coupling, previous attempts to model the opercular mechanism as a planar four-bar have consistently produced poor model fits relative to observed kinematics. Using newly developed, open source mechanism fitting software, we fitted multiple three-dimensional (3D) four-bar models with varying DoF to in vivo kinematics in largemouth bass to test whether the opercular mechanism functions instead as a 3D four-bar with one or more DoF. We examined link position error, link rotation error and the ratio of output to input link rotation to identify a best-fit model at two different levels of variation: for each feeding strike and across all strikes from the same individual. A 3D, 3-DoF four-bar linkage was the best-fit model for the opercular mechanism, achieving link rotational errors of less than 5%. We also found that the opercular mechanism moves with multiple degrees of freedom at the level of each strike and across multiple strikes. These results suggest that active motor control may be needed to direct the force input to the mechanism by the axial muscles and achieve a particular mouth-opening trajectory. Our results also expand the versatility of four-bar models in simulating biomechanical systems and extend their utility beyond planar or single-DoF systems., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

In 2013, the Centers for Disease Control highlighted Clostridium difficile as an urgent threat for antibiotic-resistant infections, in part due to the emergence of highly virulent fluoroquinolone-resistant strains. Limited therapeutic options currently exist, many of which result in disease relapse. We sought to identify molecules specifically targeting C. difficile in high-throughput screens of our diversity-oriented synthesis compound collection. We identified two scaffolds with apparently novel mechanisms of action that selectively target C. difficile while having little to no activity against other intestinal anaerobes; preliminary evidence suggests that compounds from one of these scaffolds target the glutamate racemase. In vivo efficacy data suggest that both compound series may provide lead optimization candidates.

Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been associated with increased cardiovascular risk. Nonetheless, it remains unknown whether use of NSAIDs is associated with out-of-hospital cardiac arrest (OHCA)., Methods and Results: From the nationwide Danish Cardiac Arrest Registry, all persons with OHCA during 2001-10 were identified. NSAID use 30 days before OHCA was categorized as follows: diclofenac, naproxen, ibuprofen, rofecoxib, celecoxib, and other. Risk of OHCA associated with use of NSAIDs was analysed by conditional logistic regression in case-time-control models matching four controls on sex and age per case to account for variation in drug utilization over time. We identified 28 947 persons with OHCA of whom 3376 were treated with an NSAID up to 30 days before OHCA. Ibuprofen and diclofenac were the most commonly used NSAIDs and represented 51.0% and 21.8% of total NSAID use, respectively. Use of diclofenac (odds ratio [OR], 1.50 [95% confidence interval (CI) 1.23-1.82]) and ibuprofen [OR, 1.31 (95% CI 1.14-1.51)] was associated with a significantly increased risk of OHCA. Use of naproxen [OR, 1.29 (95% CI 0.77-2.16)], celecoxib [OR, 1.13 (95% CI 0.74-1.70)], and rofecoxib (OR, 1.28 [95% CI 0.74-1.70)] was not significantly associated with increased risk of OHCA; however, these groups were characterized by few events., Conclusion: Use of non-selective NSAIDs was associated with an increased early risk of OHCA. The result was driven by an increased risk of OHCA in ibuprofen and diclofenac users., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Morphological changes in U 3 O 8 based on calcination temperature have been quantified enabling a morphological feature to serve as a signature of processing history in nuclear forensics. Five separate calcination temperatures were used to synthesize α-U 3 O 8 , and each sample was characterized using powder X-ray diffraction (p-XRD) and scanning electron microscopy (SEM). The p-XRD spectra were used to evaluate the purity of the synthesized U-oxide; the morphological analysis for materials (MAMA) software was utilized to quantitatively characterize the particle shape and size as indicated by the SEM images. Analysis comparing the particle attributes, such as particle area at each of the temperatures, was completed using the Kolmogorov-Smirnov two sample test (K-S test). These results illustrate a distinct statistical difference between each calcination temperature. To provide a framework for forensic analysis of an unknown sample, the sample distributions at each temperature were compared to randomly selected distributions (100, 250, 500, and 750 particles) from each synthesized temperature to determine if they were statistically different. It was found that 750 particles were required to differentiate between all of the synthesized temperatures with a confidence interval of 99.0%. Results from this study provide the first quantitative morphological study of U-oxides, and reveals the potential strength of morphological particle analysis in nuclear forensics by providing a framework for a more rapid characterization of interdicted uranium oxide samples.

Background: Accelerometer-based activity monitoring is a promising new tool in veterinary medicine used to objectively assess activity levels in dogs. To date, it is unknown how device orientation, attachment method, and attachment of a leash to the collar holding an accelerometer affect canine activity data. It was our goal to evaluate whether attachment methods of accelerometers affect activity counts. Eight healthy, client-owned dogs were fitted with two identical neck collars to which two identical activity monitors were attached using six different methods of attachment. These methods of attachment evaluated the use of a protective case, positioning of the activity monitor and the tightness of attachment of the accelerometer. Lastly, the effect of leash attachment to the collar was evaluated. For trials where the effect of leash attachment to the collar was not being studied, the leash was attached to a harness. Activity data obtained from separate monitors within a given experiment were compared using Pearson correlation coefficients and across all experiments using the Kruskal-Wallis Test., Results: There was excellent correlation and low variability between activity monitors on separate collars when the leash was attached to a harness, regardless of their relative positions. There was good correlation when activity monitors were placed on the same collar regardless of orientation. There were poor correlations between activity monitors in three experiments: when the leash was fastened to the collar that held an activity monitor, when one activity monitor was housed in the protective casing, and when one activity monitor was loosely zip-tied to the collar rather than threaded on using the provided metal loop. Follow-up, pair-wise comparisons identified the correlation associated with these three methods of attachment to be statistically different from the level of correlation when monitors were placed on separate collars., Conclusions: While accelerometer-based activity monitors are useful tools to objectively assess physical activity in dogs, care must be taken when choosing a method to attach the device. The attachment of the activity monitor to the collar should utilize a second, dedicated collar that is not used for leash attachment and the attachment method should remain consistent throughout a study period.

Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing geometries and configurations, enabling novel interpretations of the mechanics of force transmission across a diversity of vertebrate feeding mechanisms and enhancing our understanding of musculoskeletal function and evolution. J. Morphol. 277:1570-1583, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: To describe the use of hemiepiphysiodesis for the treatment of proximal tibial deformities in immature dogs and evaluate the effect on the mechanical medial proximal tibial angle (mMPTA)., Methods: Skeletally immature dogs with proximal tibial deformities from three institutions treated with hemiepiphysiodesis between March 2006 and January 2015 were included. All dogs were required to have an mMPTA outside the previously published reference range (93.3 ± 1.78°) preoperatively. Dogs were required to have radiographs or computed tomography performed preoperatively and at least eight weeks postoperatively., Results: A total of 19 dogs (n = 31 limbs) fulfilled the inclusion criteria. The mean mMPTA was 102.5° ± 5.3° preoperatively and 92.4° ± 7.2° at the final re-evaluation. The mean difference in mMPTA was -10 ± 5.1° (range, -1 to -19°; p <0.001). Overcorrection was observed in 16 limbs and mMPTA remained above the reference range in nine limbs. Rebound growth was observed in eight limbs where implant removal was performed., Clinical Significance: Hemiepiphysiodesis for the treatment of proximal tibial valgus is a technique that allows for reduction in mMPTA and should be considered as an early treatment for immature animals that are presented with proximal tibial deformities. Serial radiographs to monitor for overcorrection should be performed. Implant removal should be considered if overcorrection occurs, taking into consideration that rebound growth may be observed.

Study Question: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?, Methods: This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models., Study Answer and Limitations: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding., What This Study Adds: In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used., Funding, Competing Interests, Data Sharing: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation., (© Schjerning Olsen et al 2015.)