Lead poisoning of raptors: state of the science and cross-discipline mitigation options for a global problem.

Lead poisoning is an important global conservation problem for many species of wildlife, especially raptors. Despite the increasing number of individual studies and regional reviews of lead poisoning of raptors, it has been over a decade since this information has been compiled into a comprehensive global review. Here, we summarize the state of knowledge of lead poisoning of raptors, we review developments in manufacturing of non-lead ammunition, the use of which can reduce the most pervasive source of lead these birds encounter, and we compile data on voluntary and regulatory mitigation options and their associated sociological context. We support our literature review with case studies of mitigation actions, largely provided by the conservation practitioners who study or manage these efforts. Our review illustrates the growing awareness and understanding of lead exposure of raptors, and it shows that the science underpinning this understanding has expanded considerably in recent years. We also show that the political and social appetite for managing lead ammunition appears to vary substantially across administrative regions, countries, and continents. Improved understanding of the drivers of this variation could support more effective mitigation of lead exposure of wildlife. This review also shows that mitigation strategies are likely to be most effective when they are outcome driven, consider behavioural theory, local cultures, and environmental conditions, effectively monitor participation, compliance, and levels of raptor exposure, and support both environmental and human health.

Agency, Goal-Directed Behavior, and Part-Whole Relationships in Biological Systems.

In this essay we aim to present some considerations regarding a minimal but concrete notion of agency and goal-directed behavior that are useful for characterizing biological systems at different scales. These considerations are a particular perspective, bringing together concepts from dynamical systems, combinatorial problem-solving, and connectionist learning with an emphasis on the relationship between parts and wholes. This perspective affords some ways to think about agents that are concrete and quantifiable, and relevant to some important biological issues. Instead of advocating for a strict definition of minimally agential characteristics, we focus on how (even for a modest notion of agency) the agency of a system can be more than the sum of the agency of its parts. We quantify this in terms of the problem-solving competency of a system with respect to resolution of the frustrations between its parts. This requires goal-directed behavior in the sense of delayed gratification, i.e., taking dynamical trajectories that forego short-term gains (or sustain short-term stress or frustration) in favor of long-term gains. In order for this competency to belong to the system (rather than to its parts or given by its construction or design), it can involve distributed systemic knowledge that is acquired through experience, i.e., changes in the organization of the relationships among its parts (without presupposing a system-level reward function for such changes). This conception of agency helps us think about the ways in which cells, organisms, and perhaps other biological scales, can be agential (i.e., more agential than their parts) in a quantifiable sense, without denying that the behavior of the whole depends on the behaviors of the parts in their current organization.

Enlisting Probiotics to Combat Recurrent Urinary Tract Infections in Women-A Military Strategy for Meeting the Challenge.

For decades, the potential role of probiotics in the prevention and treatment of recurrent urinary tract infections has been extensively studied. However, achieving an effective problem-solving strategy has thus far proven elusive. Perhaps adopting a military paradigm might expedite our assault on chronic, recurring bacteriuria in women. What is needed is a targeted strategy with specific attention to (1) the enemy: the case-specific uropathogen; (2) the battlefield: the extraordinarily complex interplay of factors within the bladder, unique to a given patient, which interface with profoundly important influences from the gut biome, as well as the vaginal biota; (3) the weapon: an antimicrobial probiotic with demonstrated activity against that specific uropathogen; (4) a new strategy: taking these complexities into account, we posit a key role for the instillation of case-specific lactobacilli directly into the bladder of the designated patient. This newly proposed, targeted intervention might be termed "Probiotic Intravesical Organic Therapy-PIVOT"; and (5) the long campaign: reaching clinically proven success may entail a long campaign. However, already, on many fronts, the elements necessary for victory recently seem to be falling into place.

Blood Flow Restriction Therapy: An Evidence-Based Approach to Postoperative Rehabilitation.

➢: Blood flow restriction therapy (BFRT) involves the application of a pneumatic tourniquet cuff to the proximal portion of the arm or leg. This restricts arterial blood flow while occluding venous return, which creates a hypoxic environment that induces many physiologic adaptations. ➢: BFRT is especially useful in postoperative rehabilitation because it produces muscular hypertrophy and strength gains without the need for heavy-load exercises that are contraindicated after surgery. ➢: Low-load resistance training with BFRT may be preferable to low-load or high-load training alone because it leads to comparable increases in strength and hypertrophy, without inducing muscular edema or increasing pain.

Factors That Affect Legionella Positivity in Healthcare Building Water Systems from a Large, National Environmental Surveillance Initiative.

Legionella growth in healthcare building water systems can result in legionellosis, making water management programs (WMPs) important for patient safety. However, knowledge is limited on Legionella prevalence in healthcare buildings. A dataset of quarterly water testing in Veterans Health Administration (VHA) healthcare buildings was used to examine national environmental Legionella prevalence from 2015 to 2018. Bayesian hierarchical logistic regression modeling assessed factors influencing Legionella positivity. The master dataset included 201,146 water samples from 814 buildings at 168 VHA campuses. Overall Legionella positivity over the 4 years decreased from 7.2 to 5.1%, with the odds of a Legionella-positive sample being 0.94 (0.90-0.97) times the odds of a positive sample in the previous quarter for the 16 quarters of the 4 year period. Positivity varied considerably more at the medical center campus level compared to regional levels or to the building level where controls are typically applied. We found higher odds of Legionella detection in older buildings (OR 0.92 [0.86-0.98] for each more recent decade of construction), in taller buildings (OR 1.20 [1.13-1.27] for each additional floor), in hot water samples (O.R. 1.21 [1.16-1.27]), and in samples with lower residual biocide concentrations. This comprehensive healthcare building review showed reduced Legionella detection in the VHA healthcare system over time. Insights into factors associated with Legionella positivity provide information for healthcare systems implementing WMPs and for organizations setting standards and regulations.

Human CD99L2 Regulates a Unique Step in Leukocyte Transmigration.

CD99-like 2 (CD99L2 [L2]) is a highly glycosylated 52-kDa type 1 membrane protein that is important for leukocyte transendothelial migration (TEM) in mice. Inhibiting L2 using function-blocking Ab significantly reduces the recruitment of leukocytes to sites of inflammation in vivo. Similarly, L2 knockout mice have an inherent defect in leukocyte transmigration into sites of inflammation. However, the role of L2 in inflammation has only been studied in mice. Furthermore, the mechanism by which it regulates TEM is not known. To study the relevance to human inflammation, we studied the role of L2 on primary human cells in vitro. Our data show that like PECAM and CD99, human L2 is constitutively expressed at the borders of endothelial cells and on the surface of leukocytes. Inhibiting L2 using Ab blockade or genetic knockdown significantly reduces transmigration of human neutrophils and monocytes across endothelial cells. Furthermore, our data also show that L2 regulates a specific, sequential step of TEM between PECAM and CD99, rather than operating in parallel or redundantly with these molecules. Similar to PECAM and CD99, L2 promotes transmigration by recruiting the lateral border recycling compartment to sites of TEM, specifically downstream of PECAM initiation. Collectively, our data identify a novel functional role for human L2 in TEM and elucidate a mechanism that is distinct from PECAM and CD99.

Lateral Patellar Dislocation: A Critical Review and Update of Evidence-Based Rehabilitation Practice Guidelines and Expected Outcomes.

¼: Nonoperative treatment of a lateral patellar dislocation produces favorable functional results, but as high as 35% of individuals experience recurrent dislocations. ¼: Medial patellofemoral ligament reconstruction is an effective treatment to prevent recurrent dislocations and yield excellent outcomes with a high rate of return to sport. ¼: Both nonoperative and postoperative rehabilitation should center on resolving pain and edema, restoring motion, and incorporating isolated and multijoint progressive strengthening exercises targeting the hip and knee. ¼: Prior to return to sports, both functional and isolated knee strength measurements should be used to determine leg symmetry strength and to utilize patient-reported outcome measures to assess the patient's perceived physical abilities and patellofemoral joint stability.

Optimised polymer trapped-air lenses for ultrasound focusing in water exploiting Fabry-Pérot resonance.

The concept of employing air volumes trapped inside polymer shells to make a lens for ultrasound focusing in water is investigated. The proposed lenses use evenly-spaced concentric rings, each having an air-filled polymer shell construction, defining concentric water-filled channels. Numerical simulations and experiments have shown that a plane wave can be focused, and that the amplification can be boosted by Fabry-Pérot resonances within the water channels with an appropriate choice of the lens thickness. The effect of the polymer shell thickness and the depth of the channels is discussed, as these factors can affect the geometry and hence the frequency of operation. The result was a lens with a Full Width at Half Maximum value of 0.65 of a wavelength at the focus. Results obtained on a metal-based counterpart are also shown for comparison. An advantage of this polymeric design is that it is easily constructed via additive manufacturing. This study shows that trapped-air lenses made of polymer are suitable for ultrasound focusing in water near 500 kHz.

Secondary structure prediction for RNA sequences including N6-methyladenosine.

There is increasing interest in the roles of covalently modified nucleotides in RNA. There has been, however, an inability to account for modifications in secondary structure prediction because of a lack of software and thermodynamic parameters. We report the solution for these issues for N6-methyladenosine (m6A), allowing secondary structure prediction for an alphabet of A, C, G, U, and m6A. The RNAstructure software now works with user-defined nucleotide alphabets of any size. We also report a set of nearest neighbor parameters for helices and loops containing m6A, using experiments. Interestingly, N6-methylation decreases folding stability for adenosines in the middle of a helix, has little effect on folding stability for adenosines at the ends of helices, and increases folding stability for unpaired adenosines stacked on a helix. We demonstrate predictions for an N6-methylation-activated protein recognition site from MALAT1 and human transcriptome-wide effects of N6-methylation on the probability of adenosine being buried in a helix.

Development and selective grain make plasticity 'take the lead' in adaptive evolution.

BACKGROUND: Biological evolution exhibits an extraordinary capability to adapt organisms to their environments. The explanation for this often takes for granted that random genetic variation produces at least some beneficial phenotypic variation in which natural selection can act. Such genetic evolvability could itself be a product of evolution, but it is widely acknowledged that the immediate selective gains of evolvability are small on short timescales. So how do biological systems come to exhibit such extraordinary capacity to evolve? One suggestion is that adaptive phenotypic plasticity makes genetic evolution find adaptations faster. However, the need to explain the origin of adaptive plasticity puts genetic evolution back in the driving seat, and genetic evolvability remains unexplained. RESULTS: To better understand the interaction between plasticity and genetic evolvability, we simulate the evolution of phenotypes produced by gene-regulation network-based models of development. First, we show that the phenotypic variation resulting from genetic and environmental perturbation are highly concordant. This is because phenotypic variation, regardless of its cause, occurs within the relatively specific space of possibilities allowed by development. Second, we show that selection for genetic evolvability results in the evolution of adaptive plasticity and vice versa. This linkage is essentially symmetric but, unlike genetic evolvability, the selective gains of plasticity are often substantial on short, including within-lifetime, timescales. Accordingly, we show that selection for phenotypic plasticity can be effective in promoting the evolution of high genetic evolvability. CONCLUSIONS: Without overlooking the fact that adaptive plasticity is itself a product of genetic evolution, we show how past selection for plasticity can exercise a disproportionate effect on genetic evolvability and, in turn, influence the course of adaptive evolution.

Holey-structured tungsten metamaterials for broadband ultrasonic sub-wavelength imaging in water.

Metamaterials exhibiting Fabry-Pérot resonances are shown to achieve ultrasonic imaging of a sub-wavelength aperture in water immersion across a broad bandwidth. Holey-structured metamaterials of different thickness were additively manufactured using a tungsten substrate and selective laser melting, tungsten being chosen so as to create a significant acoustic impedance mismatch with water. Both broadband metamaterial behavior and sub-wavelength imaging in water are demonstrated experimentally and validated with finite element simulations over the 200-300 kHz range.

Humans rely more on algorithms than social influence as a task becomes more difficult.

Algorithms have begun to encroach on tasks traditionally reserved for human judgment and are increasingly capable of performing well in novel, difficult tasks. At the same time, social influence, through social media, online reviews, or personal networks, is one of the most potent forces affecting individual decision-making. In three preregistered online experiments, we found that people rely more on algorithmic advice relative to social influence as tasks become more difficult. All three experiments focused on an intellective task with a correct answer and found that subjects relied more on algorithmic advice as difficulty increased. This effect persisted even after controlling for the quality of the advice, the numeracy and accuracy of the subjects, and whether subjects were exposed to only one source of advice, or both sources. Subjects also tended to more strongly disregard inaccurate advice labeled as algorithmic compared to equally inaccurate advice labeled as coming from a crowd of peers.

High Incidence of Barotrauma in Patients With Severe Coronavirus Disease 2019.

OBJECTIVE.: To report the high incidence of barotrauma in critically ill patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) and to discuss its implications. DESIGN.: Retrospective cohort study. SETTING.: ICU of an academic county hospital in Los Angeles, CA admitted from March 15-June 20, 2020. PATIENTS.: 77 patients with COVID-19 pneumonia. 75 patients met inclusion criteria. RESULTS.: 21% of patients with severe COVID-19 sustained barotrauma (33% of patients receiving IMV, 8% of patients receiving (NIV). There were no differences between the barotrauma and non-barotrauma groups regarding demographics, illness severity, or medications received, nor tidal volume or average/peak airway pressures in those receiving IMV. In the barotrauma group there was a greater proportion of patients receiving therapeutic anticoagulation (81% vs. 47%, p = 0.023) and ventilated using airway pressure release ventilation mode (13% vs. 0%, p = 0.043). Barotrauma was associated with increased likelihood of receiving a tracheostomy (OR 2.58 [0.23-4.9], p = 0.018]), longer median ICU length of stay (17 days vs. 7 days, p = 0.03), and longer median length of hospitalization (26 days vs. 14 days, p < 0.001). There was also a trend toward prolonged median duration of IMV (12.5 days vs 7 days, p = 0.13) and higher average mortality (56% vs 37%, p = 0.25). CONCLUSIONS.: Barotrauma is seen in 5-12% of patients with ARDS receiving IMV and is exceedingly rare in patients receiving NIV. We report a high incidence of barotrauma observed in critically ill patients with COVID-19 requiring either NIV or IMV. While there was a trend toward increased mortality in patients with barotrauma, this did not reach statistical significance. The increased incidence of barotrauma with COVID-19 may be a product of the pathophysiology of this disease state and a heightened inflammatory response causing rampant acute lung injury. Evidence-based medicine and lung-protective ventilation should remain the mainstay of treatment.

High moon brightness and low ambient temperatures affect sloth predation by harpy eagles.

BACKGROUND: Climate plays a key role in the life histories of tropical vertebrates. However, tropical forests are only weakly seasonal compared with temperate and boreal regions. For species with limited ability to control core body temperature, even mild climatic variation can determine major behavioural outcomes, such as foraging and predator avoidance. In tropical forests, sloths are the arboreal vertebrate attaining the greatest biomass density, but their capacity to regulate body temperature is limited, relying on behavioural adaptations to thermoregulate. Sloths are largely or strictly nocturnal, and depend on crypsis to avoid predation. The harpy eagle (Harpia harpyja) is a sloth-specialist and exerts strong top-down control over its prey species. Yet the role of environmental variables on the regulation of predator-prey interactions between sloths and harpy eagles are unknown. The harpy eagle is considered Near Threatened. This motivated a comprehensive effort to reintroduce this species into parts of Mesoamerica. This effort incidentally enabled us to understand the prey profile of harpy eagles over multiple seasons. METHODS: Our study was conducted between 2003 and 2009 at Soberanía National Park, Panamá. Telemetered harpy eagles were seen hunting and feeding on individual prey species. For each predation event, field assistants systematically recorded the species killed. We analysed the effects of climatic conditions and vegetation phenology on the prey species profile of harpy eagles using generalised linear mixed models. RESULTS: Here we show that sloth predation by harpy eagles was negatively affected by nocturnal ambient light (i.e. bright moonshine) and positively affected by seasonally cool temperatures. We suggest that the first ensured low detectability conditions for sloths foraging at night and the second posed a thermally unsuitable climate that forced sloths to forage under riskier daylight. We showed that even moderate seasonal variation in temperature can influence the relationship between a keystone tropical forest predator and a dominant prey item. Therefore, predator-prey ecology in the tropics can be modulated by subtle changes in environmental conditions. The seasonal effects shown here suggest important demographic consequences for sloths, which are under top-down regulation from harpy eagle predation, perhaps limiting their geographic distribution at higher latitudes.