Antarctic emerald rockcod have the capacity to compensate for warming when uncoupled from CO2 -acidification.

Increases in atmospheric CO2 levels and associated ocean changes are expected to have dramatic impacts on marine ecosystems. Although the Southern Ocean is experiencing some of the fastest rates of change, few studies have explored how Antarctic fishes may be affected by co-occurring ocean changes, and even fewer have examined early life stages. To date, no studies have characterized potential trade-offs in physiology and behavior in response to projected multiple climate change stressors (ocean acidification and warming) on Antarctic fishes. We exposed juvenile emerald rockcod Trematomus bernacchii to three PCO2 treatments (~450, ~850, and ~1,200 µatm PCO2 ) at two temperatures (-1 or 2°C). After 2, 7, 14, and 28 days, metrics of physiological performance including cardiorespiratory function (heart rate [fH ] and ventilation rate [fV ]), metabolic rate (M˙O2), and cellular enzyme activity were measured. Behavioral responses, including scototaxis, activity, exploration, and escape response were assessed after 7 and 14 days. Elevated PCO2 independently had little impact on either physiology or behavior in juvenile rockcod, whereas warming resulted in significant changes across acclimation time. After 14 days, fH , fV and M˙O2 significantly increased with warming, but not with elevated PCO2 . Increased physiological costs were accompanied by behavioral alterations including increased dark zone preference up to 14%, reduced activity by 12%, as well as reduced escape time suggesting potential trade-offs in energetics. After 28 days, juvenile rockcod demonstrated a degree of temperature compensation as fV , M˙O2, and cellular metabolism significantly decreased following the peak at 14 days; however, temperature compensation was only evident in the absence of elevated PCO2 . Sustained increases in fV and M˙O2 after 28 days exposure to elevated PCO2 indicate additive (fV ) and synergistic (M˙O2) interactions occurred in combination with warming. Stressor-induced energetic trade-offs in physiology and behavior may be an important mechanism leading to vulnerability of Antarctic fishes to future ocean change.

The role of stochastic thermal environments in modulating the thermal physiology of an intertidal limpet, Lottia digitalis.

Much of our understanding of the thermal physiology of intertidal organisms comes from experiments with animals acclimated under constant conditions and exposed to a single heat stress. In nature, however, the thermal environment is more complex. Aerial exposure and the unpredictable nature of thermal stress during low tides may be critical factors in defining the thermal physiology of intertidal organisms. In the fingered limpet, Lottia digitalis, we investigated whether upper temperature tolerance and thermal sensitivity were influenced by the pattern of fluctuation with which thermal stress was applied. Specifically, we examined whether there was a differential response (measured as cardiac performance) to repeated heat stress of a constant and predictable magnitude compared with heat stress applied in a stochastic and unpredictable nature. We also investigated differences in cellular metabolism and damage following immersion for insights into biochemical mechanisms of tolerance. Upper temperature tolerance increased with aerial exposure, but no significant differences were found between predictable treatments of varying magnitudes (13°C versus 24°C versus 32°C). Significant differences in thermal tolerance were found between unpredictable trials with different heating patterns. There were no significant differences among treatments in basal citrate synthase activity, glycogen content, oxidative stress or antioxidants. Our results suggest that aerial exposure and recent thermal history, paired with relief from high low-tide temperatures, are important factors modulating the capacity of limpets to deal with thermal stress.

Juvenile Antarctic rockcod (Trematomus bernacchii) are physiologically robust to CO2-acidified seawater.

To date, numerous studies have shown negative impacts of CO2-acidified seawater (i.e. ocean acidification, OA) on marine organisms, including calcifying invertebrates and fishes; however, limited research has been conducted on the physiological effects of OA on polar fishes and even less on the impact of OA on early developmental stages of polar fishes. We evaluated aspects of aerobic metabolism and cardiorespiratory physiology of juvenile emerald rockcod, ITALIC! Trematomus bernacchii, an abundant fish in the Ross Sea, Antarctica, to elevated partial pressure of carbon dioxide ( ITALIC! PCO2 ) [420 (ambient), 650 (moderate) and 1050 (high) µatm ITALIC! PCO2 ] over a 1 month period. We examined cardiorespiratory physiology, including heart rate, stroke volume, cardiac output and ventilation rate, whole organism metabolism via oxygen consumption rate and sub-organismal aerobic capacity by citrate synthase enzyme activity. Juvenile fish showed an increase in ventilation rate under high ITALIC! PCO2 compared with ambient ITALIC! PCO2 , whereas cardiac performance, oxygen consumption and citrate synthase activity were not significantly affected by elevated ITALIC! PCO2 Acclimation time had a significant effect on ventilation rate, stroke volume, cardiac output and citrate synthase activity, such that all metrics increased over the 4 week exposure period. These results suggest that juvenile emerald rockcod are robust to near-future increases in OA and may have the capacity to adjust for future increases in ITALIC! PCO2  by increasing acid-base compensation through increased ventilation.

Temperature and acidification variability reduce physiological performance in the intertidal zone porcelain crab Petrolisthes cinctipes.

We show here that increased variability of temperature and pH synergistically negatively affects the energetics of intertidal zone crabs. Under future climate scenarios, coastal ecosystems are projected to have increased extremes of low tide-associated thermal stress and ocean acidification-associated low pH, the individual or interactive effects of which have yet to be determined. To characterize energetic consequences of exposure to increased variability of pH and temperature, we exposed porcelain crabs, Petrolisthes cinctipes, to conditions that simulated current and future intertidal zone thermal and pH environments. During the daily low tide, specimens were exposed to no, moderate or extreme heating, and during the daily high tide experienced no, moderate or extreme acidification. Respiration rate and cardiac thermal limits were assessed following 2.5 weeks of acclimation. Thermal variation had a larger overall effect than pH variation, though there was an interactive effect between the two environmental drivers. Under the most extreme temperature and pH combination, respiration rate decreased while heat tolerance increased, indicating a smaller overall aerobic energy budget (i.e. a reduced O2 consumption rate) of which a larger portion is devoted to basal maintenance (i.e. greater thermal tolerance indicating induction of the cellular stress response). These results suggest the potential for negative long-term ecological consequences for intertidal ectotherms exposed to increased extremes in pH and temperature due to reduced energy for behavior and reproduction.

Effects of ocean acidification on early life-history stages of the intertidal porcelain crab Petrolisthes cinctipes.

Intertidal zone organisms naturally experience daily fluctuations in pH, presently reaching values beyond what is predicted for open ocean surface waters from ocean acidification (OA) by the year 2100, and thus present an opportunity to study the pH sensitivity of organisms that are presumably adapted to an acidified environment. The intertidal zone porcelain crab, Petrolisthes cinctipes, was used to study physiological responses to low pH in embryonic, larval and newly recruited juvenile life-history stages. In these crabs, embryonic development occurs in the pH-variable intertidal zone (pH 6.9-9.5), larvae mature in the more stable pelagic environment (pH 7.9-8.2), and juvenile crabs settle back into the pH-variable intertidal zone. We examined survival, cardiac performance, energetics and morphology in embryonic, larval and juvenile crabs exposed to two pH conditions (pH 7.9 and 7.6). Embryos and larvae were split by brood between the pH treatments for 9 days to examine brood-specific responses to low pH. Hatching success did not differ between pH conditions, but ranged from 30% to 95% among broods. Larval survival was not affected by acidification, but juvenile survival was reduced by ~30% after longer (40 days) exposure to low pH. Embryonic and larval heart rates were 37% and 20% lower at low pH, and there was a brood-specific response in embryos. Embryos did not increase in volume under acidified conditions, compared with a 15% increase in ambient conditions. We conclude that sustained exposure to low pH could be detrimental to P. cinctipes embryos and larvae despite the fact that embryos are regularly exposed to naturally fluctuating hypercapnic water in the intertidal zone. Importantly, our results indicate that early life-history stage responses to OA may be brood specific through as yet undetermined mechanisms.

Impact of ocean acidification on metabolism and energetics during early life stages of the intertidal porcelain crab Petrolisthes cinctipes.

Absorption of elevated atmospheric CO2 is causing surface ocean pH to decline, a process known as ocean acidification (OA). To date, few studies have assessed the physiological impacts of OA on early life-history stages of intertidal organisms, which transition from habitats with fluctuating pH (intertidal zone) to relatively stable (pelagic zone) pH environments. We used the intertidal crab Petrolisthes cinctipes to determine whether metabolic responses to year 2300 predictions for OA vary among early developmental stages and to examine whether the effects were more pronounced in larval stages developing in the open ocean. Oxygen consumption rate, total protein, dry mass, total lipids and C/N were determined in late-stage embryos, zoea I larvae and newly settled juveniles reared in ambient pH (7.93 ± 0.06) or low pH (7.58 ± 0.06). After short-term exposure to low pH, embryos displayed 11% and 6% lower metabolism and dry mass, respectively, which may have an associated bioenergetic cost of delayed development to hatching. However, metabolic responses appeared to vary among broods, suggesting significant parental effects among the offspring of six females, possibly a consequence of maternal state during egg deposition and genetic differences among broods. Larval and juvenile metabolism were not affected by acute exposure to elevated CO2. Larvae contained 7% less nitrogen and C/N was 6% higher in individuals reared at pH 7.58 for 6 days, representing a possible switch from lipid to protein metabolism under low pH; the metabolic switch appears to fully cover the energetic cost of responding to elevated CO2. Juvenile dry mass was unaffected after 33 days exposure to low pH seawater. Increased tolerance to low pH in zoea I larvae and juvenile stages may be a consequence of enhanced acid-base regulatory mechanisms, allowing greater compensation of extracellular pH changes and thus preventing decreases in metabolism after exposure to elevated PCO2. The observed variation in responses of P. cinctipes to decreased pH in the present study suggests the potential for this species to adapt to future declines in near-shore pH.

Fishing through the cracks: The unregulated nature of global squid fisheries.

While most research has focused on the legality of global industrial fishing, unregulated fishing has largely escaped scrutiny. Here, we evaluate the unregulated nature of global squid fisheries using AIS data and nighttime imagery of the globalized fleet of light-luring squid vessels. We find that this fishery is extensive, fishing 149,000 to 251,000 vessel days annually, and that effort increased 68% over the study period 2017-2020. Most vessels are highly mobile and fish in multiple regions, largely (86%) in unregulated areas. While scientists and policymakers express concerns over the declining abundance of squid stocks globally and regionally, we find a net increase in vessels fishing squid globally and spatial expansion of effort to novel areas. Since fishing effort is static in areas with increasing management, and rising in unmanaged areas, we suggest actors may take advantage of fragmented regulations to maximize resource extraction. Our findings highlight a profitable, but largely unregulated fishery, with strong potential for improved management.

Tracking elusive and shifting identities of the global fishing fleet.

Illegal, unreported, and unregulated (IUU) fishing costs billions of dollars per year and is enabled by vessels obfuscating their identity. Here, we combine identities of ~35,000 vessels with a decade of GPS data to provide a global assessment of fishing compliance, reflagging patterns, and fishing by foreign-owned vessels. About 17% of high seas fishing is by potentially unauthorized or internationally unregulated vessels, with hot spots of this activity in the west Indian and the southwest Atlantic Oceans. In addition, reflagging, a tactic often used to obscure oversight, occurs in just a few ports primarily by fleets with high foreign ownership. Fishing by foreign-owned vessels is concentrated in parts of high seas and certain national waters, often flying flags of convenience. These findings can address the global scope of potential IUU fishing and enable authorities to improve oversight.

Comparison of osteotomy level with three different canine total hip replacement systems.

Background: Numerous cementless total hip replacement (THR) systems are available for application in dogs and one of the potential differences among these systems is the technique for performing a femoral osteotomy and the amount of bone preserved in the calcar region. However, no quantitative comparison of osteotomy level has been performed for canine THRs to date. Aims: To develop and validate a method for quantifying the level of the osteotomy at its most distomedial aspect in conjunction with canine THR and to compare osteotomy level between multiple different THRs. Methods: Immediate post-operative cranial-caudal or caudal-cranial radiographs of 33 dogs treated with 17 Helica and 17 BFX THR were assessed and osteotomy level was quantified using a novel radiographic assessment by 3 independent observers. Correlation among observers was quantified using a Spearman rank order correlation. Osteotomy location was subsequently quantified for an additional 10 Zurich THRs. The osteotomy level for each THR was subsequently compared between Helica, BFX, and Zurich THRs using one-way non-parametric Mann-Whitney rank sum tests and significance set at p < 0.05. Results: R-values assessing correlation between observers were 0.87, 0.72, and 0.60. Osteotomy location was significantly more proximal in conjunction with the Helica (0.75 ± 0.22) versus the BFX (0.97 ± 0.13; p < 0.001) and Zurich (1.1 ± 0.15; p < 0.001) femoral prostheses. Osteotomy location was also significantly more proximal with the BFX prosthesis in comparison to the Zurich THR (p < 0.05). Conclusion: The strong correlations among three different observers indicate that the technique for measuring the location of the distomedial aspect of the osteotomy was acceptably precise. The osteotomies made in conjunction with the short-stemmed Helica implants were significantly more proximal than those made with both of the long-stemmed (BFX and Zurich) femoral prostheses. The distomedial aspect of the osteotomy with the BFX system was significantly more proximal than that with the Zurich THR, indicating that between these two long-stemmed systems the osteotomy level is unique.

Revealing global risks of labor abuse and illegal, unreported, and unregulated fishing.

Labor abuse on fishing vessels and illegal, unreported and unregulated (IUU) fishing violate human rights, jeopardize food security, and deprive governments of revenues. We applied a multi-method approach, combining new empirical data with satellite information on fishing activities and vessel characteristics to map risks of labor abuse and IUU fishing, understand their relationships, and identify major drivers. Port risks were globally pervasive and often coupled, with 57% of assessed ports associated with labor abuse or IUU fishing. For trips ending in assessed ports, 82% were linked to labor abuse or IUU fishing risks. At-sea risk areas were primarily driven by fishing vessel flags linked to poor control of corruption by the flag state, high ownership by countries other than the flag state, and Chinese-flagged vessels. Transshipment risk areas were related to the gear type of fishing vessels engaged in potential transshipment and carrier vessel flags. Measures at port offer promise for mitigating risks, through the Port State Measures Agreement for IUU fishing, and ensuring sufficient vessel time at port to detect and respond to labor abuse. Our results highlight the need for coordinated action across actors to avoid risk displacement and make progress towards eliminating these socially, environmentally and economically unsustainable practices.

Complications with the Zurich Canine Total Hip Replacement System in an Initial Series of Cases Performed by a Single Surgeon.

OBJECTIVE: The aim of this study was to quantify the complications using the Zurich total hip replacement system in an initial series of cases performed by a single surgeon who had experience with other total hip replacement systems. MATERIALS AND METHODS: This was a retrospective study in which complications were classified as major if any treatment was needed or if the outcome was less than near-normal function. Complications that did not warrant treatment and that did not result in function that was inferior to near-normal were considered minor. Outcomes were assessed by radiographic review, physical examination, subjective gait evaluation or, in one case, by objective gait analysis. Bilateral total hip replacements were considered separate procedures. RESULTS: The first 21 procedures in 19 dogs performed by a single surgeon were included. The mean time to follow-up was 48 weeks (range: 8-120 weeks; standard deviation: 36 weeks). Two cases (of 21) experienced major complications including one dog with excess internal femoral rotation during weight bearing and one dog having luxation. One case (of 21) had a minor complication; femoral fracture in the presence of an intact bone plate that maintained alignment and healed without treatment. CLINICAL SIGNIFICANCE: A high rate of successful outcomes with few major complications can be obtained in the initial cases treated using the Zurich total hip replacement system for surgeons with prior experience with other total hip replacement systems.

Illuminating dark fishing fleets in North Korea.

Illegal, unreported, and unregulated fishing threatens resource sustainability and equity. A major challenge with such activity is that most fishing vessels do not broadcast their positions and are "dark" in public monitoring systems. Combining four satellite technologies, we identify widespread illegal fishing by dark fleets in the waters between the Koreas, Japan, and Russia. We find >900 vessels of Chinese origin in 2017 and >700 in 2018 fished illegally in North Korean waters, catching an estimated amount of Todarodes pacificus approximating that of Japan and South Korea combined (>164,000 metric tons worth >$440 million). We further find ~3000 small-scale North Korean vessels fished, mostly illegally, in Russian waters. These results can inform independent oversight of transboundary fisheries and foreshadow a new era in satellite monitoring of fisheries.

Studies for the synthesis of xenicane diterpenes. A stereocontrolled total synthesis of 4-hydroxydictyolactone.

The stereocontrolled total synthesis of 4-hydroxydictyolactone (4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C(2), C(3), C(10) stereotriad of 4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols 22. In addition, an internally directed S(E)' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C(4) alcohol in 27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield 30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from 43 leads to the desired syn-oxidative elimination to yield the natural product 4.

Assessing Client Progress Session by Session in the Treatment of Social Anxiety Disorder: The Social Anxiety Session Change Index.

Frequent assessment during therapy can improve treatments and provide accountability. However, clinicians often do not monitor progress because of the time it takes to administer and score assessments. In response, the Social Anxiety Session Change Index (SASCI) was developed. The SASCI is a short, easily administered rating of subjective improvement that asks clients with social anxiety disorder how much they have changed since the beginning of therapy. Change on the SASCI was related to change in fear of negative evaluation, a core aspect of social anxiety, and to clinician-rated improvement, but not to ratings of anxiety sensitivity or depression. Because it is brief and easily interpretable, the SASCI can be used in a variety of clinical settings to monitor change across therapy. The SASCI is presented along with examples of how the information gathered from frequent administration can inform clinical practice.

Global hot spots of transshipment of fish catch at sea.

A major challenge in global fisheries is posed by transshipment of catch at sea from fishing vessels to refrigerated cargo vessels, which can obscure the origin of the catch and mask illicit practices. Transshipment remains poorly quantified at a global scale, as much of it is thought to occur outside of national waters. We used Automatic Identification System (AIS) vessel tracking data to quantify spatial patterns of transshipment for major fisheries and gear types. From 2012 to 2017, we observed 10,510 likely transshipment events, with trawlers (53%) and longliners (21%) involved in a majority of cases. Trawlers tended to transship in national waters, whereas longliners did so predominantly on the high seas. Spatial hot spots were seen off the coasts of Russia and West Africa, in the South Indian Ocean, and in the equatorial Pacific Ocean. Our study highlights novel ways to trace seafood supply chains and identifies priority areas for improved trade regulation and fisheries management at the global scale.

Juvenile rockfish show resilience to CO2-acidification and hypoxia across multiple biological scales.

California's coastal ecosystems are forecasted to undergo shifting ocean conditions due to climate change, some of which may negatively impact recreational and commercial fish populations. To understand if fish populations have the capacity to respond to multiple stressors, it is critical to examine interactive effects across multiple biological scales, from cellular metabolism to species interactions. This study examined the effects of CO2-acidification and hypoxia on two naturally co-occurring species, juvenile rockfish (genus Sebastes) and a known predator, cabezon (Scorpaenichthys marmoratus). Fishes were exposed to two PCO2 levels at two dissolved oxygen (DO) levels: ~600 (ambient) and ~1600 (high) µatm PCO2 and 8.0 (normoxic) and 4.5 mg l-1 DO (hypoxic) and assessments of cellular metabolism, prey behavior and predation mortality rates were quantified after 1 and 3 weeks. Physiologically, rockfish showed acute alterations in cellular metabolic enzyme activity after 1 week of acclimation to elevated PCO2 and hypoxia that were not evident in cabezon. Alterations in rockfish energy metabolism were driven by increases in anaerobic LDH activity, and adjustments in enzyme activity ratios of cytochrome c oxidase and citrate synthase and LDH:CS. Correlated changes in rockfish behavior were also apparent after 1 week of acclimation to elevated PCO2 and hypoxia. Exploration behavior increased in rockfish exposed to elevated PCO2 and spatial analysis of activity indicated short-term interference with anti-predator responses. Predation rate after 1 week increased with elevated PCO2; however, no mortality was observed under the multiple-stressor treatment suggesting negative effects on cabezon predators. Most noteworthy, metabolic and behavioral changes were moderately compensated after 3 weeks of acclimation, and predation mortality rates also decreased suggesting that these rockfish may be resilient to changes in environmental stressors predicted by climate models. Linking physiological and behavioral responses to multiple stressors is vital to understand impacts on populations and community dynamics.

Response to Comment on "Tracking the global footprint of fisheries".

Amoroso et al demonstrate the power of our data by estimating the high-resolution trawling footprint on seafloor habitat. Yet we argue that a coarser grid is required to understand full ecosystem impacts. Vessel tracking data allow us to estimate the footprint of human activities across a variety of scales, and the proper scale depends on the specific impact being investigated.

Tracking the global footprint of fisheries.

Although fishing is one of the most widespread activities by which humans harvest natural resources, its global footprint is poorly understood and has never been directly quantified. We processed 22 billion automatic identification system messages and tracked >70,000 industrial fishing vessels from 2012 to 2016, creating a global dynamic footprint of fishing effort with spatial and temporal resolution two to three orders of magnitude higher than for previous data sets. Our data show that industrial fishing occurs in >55% of ocean area and has a spatial extent more than four times that of agriculture. We find that global patterns of fishing have surprisingly low sensitivity to short-term economic and environmental variation and a strong response to cultural and political events such as holidays and closures.

Tibial tuberosity advancement for stabilization of the canine cranial cruciate ligament-deficient stifle joint: surgical technique, early results, and complications in 101 dogs.

OBJECTIVE: To describe the surgical technique, early results and complications of tibial tuberosity advancement (TTA) for treatment for cranial cruciate ligament (CrCL)-deficient stifle joints in dogs. STUDY DESIGN: Retrospective clinical study. ANIMALS: Dogs (n=101) with CrCL-deficient stifles (114). METHODS: Medical records of 101 dogs that had TTA were reviewed. Complications were recorded and separated into either major or minor complications based on the need for additional surgery. In-hospital re-evaluation of limb function and time to radiographic healing were reviewed. Further follow-up was obtained by telephone interview of owners. RESULTS: Complications occurred in 31.5% of the dogs (12.3% major, 19.3% minor). Major complications included subsequent meniscal tear, tibial fracture, implant failure, infection, lick granuloma, incisional trauma, and medial patellar luxation; all major complications were treated with successful outcomes. All but 2 minor complications resolved. The mean time to documented radiographic healing was 11.3 weeks. Final in-hospital re-evaluation of limb function (mean, 13.5 weeks), was recorded for 93 dogs with lameness categorized as none (74.5%), mild (23.5%), moderate (2%), and severe (1%). All but 2 owners interviewed were satisfied with outcome and 83.1% reported a marked improvement or a return to pre-injury status. CONCLUSIONS: TTA is a procedure comparable with alternate methods of CrCL repair with expected good to excellent functional outcome. CLINICAL RELEVANCE: TTA procedure can be successfully used to obtain the dynamic stability of a CrCL-deficient stifle joint in dogs.

Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases.

RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.