Magnetic oxides exhibit rich fundamental physics
and technologically desirable properties for spin-based memory, logic and signal transmission
. Recently, spin-orbit-induced spin transport phenomena ...have been realized in insulating magnetic oxides by using proximate heavy metal layers such as platinum
. In their metallic ferromagnet counterparts, such interfaces also give rise to a Dzyaloshinskii-Moriya interaction
that can stabilize homochiral domain walls and skyrmions with efficient current-driven dynamics. However, chiral magnetism in centrosymmetric oxides has not yet been observed. Here we discover chiral magnetism that allows for pure spin-current-driven domain wall motion in the most ubiquitous class of magnetic oxides, ferrimagnetic iron garnets. We show that epitaxial rare-earth iron garnet films with perpendicular magnetic anisotropy exhibit homochiral Néel domain walls that can be propelled faster than 800 m s
by spin current from an adjacent platinum layer. We find that, despite the relatively small interfacial Dzyaloshinskii-Moriya interaction, very high velocities can be attained due to the antiferromagnetic spin dynamics associated with ferrimagnetic order.
The development of novel antivirals is crucial not only for managing current COVID‐19 infections but for addressing potential future zoonotic outbreaks. SARS‐CoV‐2 main protease (Mpro) is vital for ...viral replication and viability and therefore serves as an attractive target for antiviral intervention. Herein, we report the optimization of a cyclic peptide inhibitor that emerged from an mRNA display selection against the SARS‐CoV‐2 Mpro to enhance its cell permeability and in vitro antiviral activity. By identifying mutation‐tolerant amino acid residues within the peptide sequence, we describe the development of a second‐generation Mpro inhibitor bearing five cyclohexylalanine residues. This cyclic peptide analogue exhibited significantly improved cell permeability and antiviral activity compared to the parent peptide. This approach highlights the importance of optimizing cyclic peptide hits for activity against intracellular targets such as the SARS‐CoV‐2 Mpro.
The urgent need for novel antivirals extends beyond managing current COVID‐19 infections to preparing for future zoonotic outbreaks. The SARS‐CoV‐2 main protease (Mpro) is essential for viral replication and a validated antiviral target. Through optimization of a peptide inhibitor identified via mRNA display, a cyclic peptide with enhanced cell permeability and antiviral activity was developed.
Extensor mechanism disruption is a devastating complication after TKA. Extensor mechanism reconstruction can be performed using an allograft or synthetic mesh. Recent studies have disagreed about the ...durability of these reconstructions. Evaluating a larger series of reconstructions that use current popular techniques and principles provides information to guide patient and surgeon expectations while bringing to light the potential fate of patients who experience an infection postoperatively.
(1) What was the 5-year survival free of repeat revision surgery or persistent extensor lag of more than 30° after allograft or synthetic mesh reconstruction of extensor mechanism disruptions after TKA, and did this differ between techniques? (2) What was the 5-year survival free of infection after allograft or mesh reconstruction, and what proportion of those patients experienced a secondary severe complication (arthrodesis or amputation)?
Between April 2008 and December 2020, 123 patients underwent extensor mechanism reconstruction after TKA at one center. Of those, 37% (45) were lost to follow-up before 2 years, had not been seen in the past 5 years, did not reach a study endpoint (repeat revision or extensor lag > 30°) before that time, or underwent primary repair and thus could not be analyzed, leaving 63% (78) for analysis here. During the study period, we considered extensor mechanism surgery when acute or chronic disruption of the patellar or quadriceps tendon was present or there was a fracture of the patella resulting in extensor lag. The decision to use either mesh or an allograft largely depended on surgeon experience and familiarity with either technique. We collected patient demographics, operative details (location of disruption and presence of a hinged prosthesis), subsequent periprosthetic joint infection (PJI), and postoperative SF-12 and Knee Injury and Osteoarthritis Outcome Score, Joint Replacement, scores. We used Kaplan-Meier survivorship analysis, with endpoints of extensor lag more than 30° or revision of the reconstruction and PJI. The mean follow-up duration was 5.3 ± 3.2 years.
Survivorship free from revision or recurrent extensor lag was 54% (95% CI 44% to 66%) at 5 years. There was no difference between those undergoing reconstruction with allografts and those with mesh in terms of survivorship free from those endpoints at that timepoint (52% 95% CI 40% to 68% versus 57% 95 CI% 41 to 78%; p = 0.99). Survivorship free from PJI was 81% (95% CI 73% to 90%) at 2 years. There was no difference between those with allografts and those with mesh in terms of survivorship free from PJI at that timepoint (79% 95% CI 69% to 92% versus 83% 95% CI 71% to 98%; p = 0.75). Of the 17 patients who experienced PJI, four ultimately underwent arthrodesis and three more underwent transfemoral amputation.
Allograft and synthetic mesh reconstructions commonly left patients with persistent limb dysfunction, while several patients had PJI and some underwent salvage procedures. Although improvements have been made with regard to treating extensor mechanism disruptions, patients and surgeons should be well aware of the potential adverse outcomes when determining management and use these findings to conduct risk-benefit analyses. There is a need for future studies to identify protocols that improve the durability of reconstructions and to determine whether interventions such as prolonged prophylactic antibiotic therapy have a role in minimizing the risk of PJI.
Level III, therapeutic study.
Social liberals tend to be less pathogen-avoidant than social conservatives, a pattern consistent with a model wherein ideological differences stem from differences in threat reactivity. Here we ...investigate if and how individual responses to a shared threat reflect those patterns of ideological difference. In seeming contradiction to the general association between social conservatism and pathogen avoidance, the more socially conservative political party in the United States has more consistently downplayed the dangers of COVID-19 during the ongoing pandemic. This puzzle offers an opportunity to examine the contributions of multiple factors to disease avoidance. We investigated the relationship between social conservatism and COVID-19 precautionary behavior in light of the partisan landscape of the United States. We explored whether consumption of, and attitudes toward, different sources of information, as well as differential evaluation of various threats caused by the pandemic-such as direct health costs versus indirect harms to the economy and individual liberties-shape partisan differences in responses to the pandemic in ways that overwhelm the contributions of social conservatism. In two pre-registered studies, socially conservative attitudes correlate with self-reported COVID-19 prophylactic behaviors, but only among Democrats. Reflecting larger societal divisions, among Republicans and Independents, the absence of a positive relationship between social conservatism and COVID-19 precautions appears driven by lower trust in scientists, lower trust in liberal and moderate sources, lesser consumption of liberal news media, and greater economic conservatism.
While Medicare requires patient-reported outcome measures (PROMs) for many quality programs, some commercial insurers are requiring preoperative PROMs when determining eligibility for total knee ...arthroplasty (TKA). Concerns exist that these data may be used to deny TKA to patients above a specific PROM score, but the optimal threshold is unknown. We aimed to evaluate TKA outcomes based on theoretical PROM thresholds.
We retrospectively analyzed 25,246 consecutive primary TKA patients from 2016 to 2019. Hypothesized preoperative knee injury and osteoarthritis outcome score for joint replacement cutoffs of 40, 50, 60, and 70 points were used. Preoperative scores below each threshold were considered “approved” surgery. Preoperative scores above each threshold were considered “denied” surgery. In-hospital complications, 90-day readmissions, and discharge disposition were evaluated. One-year minimum clinically important difference (MCID) achievement was calculated using previously validated anchor-based methods.
For “denied” patients below thresholds 40, 50, 60, and 70 points, 1-year MCID achievement was 88.3%, 85.9%, 79.6%, and 77%, respectively. In-hospital complication rates for approved patients were 2.2%, 2.3%, 2.1%, and 2.1%, while 90-day readmission rates were 4.6%, 4.5%, 4.3%, and 4.3%, respectively. Approved patients had higher MCID achievement rates (P < .001) for all thresholds but higher nonhome discharge rates than denied patients for thresholds 40 (P < .001), 50 (P = .002), and 60 (P = .024). Approved and denied patients had similar in-hospital complication and 90-day readmission rates.
Most patients achieved MCID at all theoretical PROMs thresholds with low complication and readmission rates. Setting preoperative PROM thresholds for TKA eligibility can help optimize patient improvement, but such a policy can create access to care barriers for some patients who would otherwise benefit from a TKA.
The effects of mountain pine beetle (MPB)‐induced tree mortality on a headwater hydrologic system were investigated using an integrated physical modeling framework with a high‐resolution ...computational grid. Simulations of MPB‐affected and unaffected conditions, each with identical atmospheric forcing for a normal water year, were compared at multiple scales to evaluate the effects of scale on MPB‐affected hydrologic systems. Individual locations within the larger model were shown to maintain hillslope‐scale processes affecting snowpack dynamics, total evapotranspiration, and soil moisture that are comparable to several field‐based studies and previous modeling work. Hillslope‐scale analyses also highlight the influence of compensating changes in evapotranspiration and snow processes. Reduced transpiration in the Grey Phase of MPB‐induced tree mortality was offset by increased late‐summer evaporation, while overall snowpack dynamics were more dependent on elevation effects than MPB‐induced tree mortality. At the watershed scale, unaffected areas obscured the magnitude of MPB effects. Annual water yield from the watershed increased during Grey Phase simulations by 11 percent; a difference that would be difficult to diagnose with long‐term gage observations that are complicated by inter‐annual climate variability. The effects on hydrology observed and simulated at the hillslope scale can be further damped at the watershed scale, which spans more life zones and a broader range of landscape properties. These scaling effects may change under extreme conditions, e.g., increased total MPB‐affected area or a water year with above average snowpack.
Key Points:
Hydrologic simulations show decreasing influence of MPB as scale increases
Ground evaporation and groundwater recharge emerge as compensating factors
Increase in annual water yield caused by tree mortality is small
The science of the host-virus network Albery, Gregory F; Becker, Daniel J; Brierley, Liam ...
Nature microbiology,
12/2021, Letnik:
6, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Better methods to predict and prevent the emergence of zoonotic viruses could support future efforts to reduce the risk of epidemics. We propose a network science framework for understanding and ...predicting human and animal susceptibility to viral infections. Related approaches have so far helped to identify basic biological rules that govern cross-species transmission and structure the global virome. We highlight ways to make modelling both accurate and actionable, and discuss the barriers that prevent researchers from translating viral ecology into public health policies that could prevent future pandemics.
The SARS‐CoV‐2 pandemic has led to increased concern over transmission of pathogens from humans to animals, and its potential to threaten conservation and public health. To assess this threat, we ...reviewed published evidence of human‐to‐wildlife transmission events, with a focus on how such events could threaten animal and human health. We identified 97 verified examples, involving a wide range of pathogens; however, reported hosts were mostly non‐human primates or large, long‐lived captive animals. Relatively few documented examples resulted in morbidity and mortality, and very few led to maintenance of a human pathogen in a new reservoir or subsequent “secondary spillover” back into humans. We discuss limitations in the literature surrounding these phenomena, including strong evidence of sampling bias towards non‐human primates and human‐proximate mammals and the possibility of systematic bias against reporting human parasites in wildlife, both of which limit our ability to assess the risk of human‐to‐wildlife pathogen transmission. We outline how researchers can collect experimental and observational evidence that will expand our capacity for risk assessment for human‐to‐wildlife pathogen transmission.
Human‐to‐wildlife pathogen transmission has played an important role in the epidemiology of a number of pathogens in the past, and is likely continuing to play an important role in the Anthropocene. Despite much concern surrounding the transmission of human pathogens into animal populations, particularly during the SARS‐CoV‐2 pandemic, there has been little critical assessment of the evidence base and the threat of these pathogens for conservation and public health. Here, we compile an evidence base of 97 published human‐to‐wildlife pathogen transmission events, and we discuss the sampling biases that have likely played an important role in producing the observed patterns, discussing how to collect further data to aid in risk assessment in the near future.
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