A 3D printable alloy designed for extreme environments.

Multiprincipal-element alloys are an enabling class of materials owing to their impressive mechanical and oxidation-resistant properties, especially in extreme environments1,2. Here we develop a new oxide-dispersion-strengthened NiCoCr-based alloy using a model-driven alloy design approach and laser-based additive manufacturing. This oxide-dispersion-strengthened alloy, called GRX-810, uses laser powder bed fusion to disperse nanoscale Y2O3 particles throughout the microstructure without the use of resource-intensive processing steps such as mechanical or in situ alloying3,4. We show the successful incorporation and dispersion of nanoscale oxides throughout the GRX-810 build volume via high-resolution characterization of its microstructure. The mechanical results of GRX-810 show a twofold improvement in strength, over 1,000-fold better creep performance and twofold improvement in oxidation resistance compared with the traditional polycrystalline wrought Ni-based alloys used extensively in additive manufacturing at 1,093 °C5,6. The success of this alloy highlights how model-driven alloy designs can provide superior compositions using far fewer resources compared with the 'trial-and-error' methods of the past. These results showcase how future alloy development that leverages dispersion strengthening combined with additive manufacturing processing can accelerate the discovery of revolutionary materials.

The primacy of temporal dynamics in driving spatial self-organization of soil iron redox patterns.

This study investigates mechanisms that generate regularly spaced iron-rich bands in upland soils. These striking features appear in soils worldwide, but beyond a generalized association with changing redox, their genesis is yet to be explained. Upland soils exhibit significant redox fluctuations driven by rainfall, groundwater changes, or irrigation. Pattern formation in such systems provides an opportunity to investigate the temporal aspects of spatial self-organization, which have been heretofore understudied. By comparing multiple alternative mechanisms, we found that regular iron banding in upland soils is explained by coupling two sets of scale-dependent feedbacks, the general principle of Turing morphogenesis. First, clay dispersion and coagulation in iron redox fluctuations amplify soil Fe(III) aggregation and crystal growth to a level that negatively affects root growth. Second, the activation of this negative root response to highly crystalline Fe(III) leads to the formation of rhythmic iron bands. In forming iron bands, environmental variability plays a critical role. It creates alternating anoxic and oxic conditions for required pattern-forming processes to occur in distinctly separated times and determines durations of anoxic and oxic episodes, thereby controlling relative rates of processes accompanying oxidation and reduction reactions. As Turing morphogenesis requires ratios of certain process rates to be within a specific range, environmental variability thus modifies the likelihood that pattern formation will occur. Projected changes of climatic regime could significantly alter many spatially self-organized systems, as well as the ecological functioning associated with the striking patterns they present. This temporal dimension of pattern formation merits close attention in the future.

Identification of small-molecule protein-protein interaction inhibitors for NKG2D.

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ+, and CD8+ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

Disentangling the size-dependent redox reactivity of iron oxides using thermodynamic relationships.

Nanoparticles often exhibit size-dependent redox reactivities, with smaller particles being more reactive in some cases, while less reactive in others. Predicting trends between redox reaction rates and particle sizes is often complicated because a particle's dimensions can simultaneously influence its aggregation state, reactive surface area, and thermodynamic properties. Here, we tested the hypothesis that interfacial redox reaction rates for nanoparticles with different sizes can be described with a single linear free-energy relationship (LFER) if size-dependent reactive surface areas and thermodynamic properties are properly considered. We tested this hypothesis using a well-known interfacial redox reaction: the reduction of nitrobenzene to aniline by iron-oxide-bound Fe2+. We measured the reduction potential (EH) values of nano-particulate hematite suspensions containing aqueous Fe2+ using mediated potentiometry and characterized the size and aggregation states of hematite samples at circumneutral pH values. We used the measured EH values to calculate surface energies and reactive surface areas using thermodynamic relationships. Nitrobenzene reduction rates were lower for smaller particles, despite their larger surface areas, due to their higher surface energies. When differences in surface areas and thermodynamic properties were considered, nitrobenzene reduction kinetics for all particle sizes was described with a LFER. Our results demonstrate that when Fe2+ serves as a reductant, an antagonistic effect exists, with smaller particles having larger reactive surface areas but also more positive reduction potentials. When Fe3+ serves as an oxidant, however, these two effects work in concert, which likely explains past discrepancies regarding how iron oxide particle sizes influence redox reaction rates.

Redox Properties of Structural Fe in Clay Minerals: 4. Reinterpreting Redox Curves by Accounting for Electron Transfer and Structural Rearrangement Kinetics.

Iron-bearing smectite clay minerals can act as electron sources and sinks in the environment. Previous studies using mediated electrochemical analyses to determine the reduction potential (EH) values of smectites observed that the relationship between the structural Fe2+(s)/FeTotal ratio in the smectite and EH varied based on the redox history of the smectite. We hypothesize that this behavior, referred to as redox hysteresis, results from the smectite particles not equilibrating with the applied EH over the course of the experiment (∼30 min). To test this hypothesis, we developed a model incorporating interfacial electron transfer kinetics and charge redistribution within the particle to simulate the mediated electrochemical experiments from previous studies. The simulated redox curves accurately matched the previously reported experimental redox curves of the smectite SWa-1, demonstrating that longer equilibration periods led to a decrease in redox hysteresis. We validated this experimentally by measuring the redox curve of SWa-1 after an equilibration period of at least 12 h. Furthermore, we extended the simulations to three other smectites (NAu-1, NAu-2, and SWy-2) and extracted their respective thermodynamic and kinetic parameters. This work offers a framework for interpreting and modeling redox reactions on clay surfaces, along with key parameters for four commonly studied smectites.

The Influence of Seawater on Fe(II)-Catalyzed Ferrihydrite Transformation and Its Subsequent Consequences for C Dynamics.

Short-range-ordered minerals like ferrihydrite often bind substantial organic carbon (OC), which can be altered if the minerals transform. Such mineral transformations can be catalyzed by aqueous Fe(II) (Fe(II)aq) in redox-dynamic environments like coastal wetlands, which are inundated with seawater during storm surges or tidal events associated with sea-level rise. Yet, it is unknown how seawater salinity will impact Fe(II)-catalyzed ferrihydrite transformation or the fate of bound OC. We reacted ferrihydrite with Fe(II)aq under anoxic conditions in the absence and presence of dissolved organic matter (DOM). We compared treatments with no salts (DI water), NaCl-KCl salts, and artificial seawater mixes (containing Ca and Mg ions) with or without SO42-/HCO3-. Both XRD and Mössbauer showed that NaCl-KCl favored lepidocrocite formation, whereas Ca2+/Mg2+/SO42-/HCO3- ions in seawater overrode the effects of NaCl-KCl and facilitated goethite formation. We found that the highly unsaturated and phenolic compounds (HuPh) of DOM selectively bound to Fe minerals, promoting nanogoethite formation in seawater treatments. Regardless of salt presence, only 5-9% of Fe-bound OC was released during ferrihydrite transformation, enriching HuPh relative to aliphatics in solution. This study offers new insights into the occurrence of (nano)goethite and the role of Fe minerals in OC protection in coastal wetlands.

ECHO OEM virtual community of learning for primary care.

BACKGROUND: Health issues caused and/or exacerbated by work are common in patients seeking primary health care. Yet, primary care providers generally receive little or no training in the assessment and management of occupational injuries and illnesses. AIMS: To conduct a pilot project to develop, implement and evaluate a programme to teach occupational and environmental medicine to primary healthcare providers. METHODS: We followed the Extensions for Community Healthcare Outcomes (ECHO) model to connect primary healthcare providers with experts in Occupational and Environmental Medicine (OEM). We employed an observational pre-post study design to assess changes in self-efficacy, knowledge, attitudes and beliefs towards OEM. RESULTS: From September 2021 to June 2022, we offered two cycles of 12 sessions each. Participants came from medicine, nursing, psychology, occupational and physical therapy, chiropractic, kinesiology, social work, and pharmacy. Sixty-seven participants completed both pre- and post-ECHO questionnaires. Self-efficacy and knowledge ratings significantly increased after attendance at ECHO compared to the pre-ECHO responses. Attitudes and beliefs were unchanged in most of the items assessed. Participants rated their satisfaction with ECHO between 59% and 97%. CONCLUSIONS: Our pilot study demonstrated the challenges in implementing the first ECHO OEM in Canada. Findings show acceptability and satisfaction, improved self-efficacy, and small increases in knowledge, but not overall attitudes and beliefs. There is a need to understand barriers to participation and to target participants with less knowledge and experience in occupational and environmental medicine.

Understanding the Unmet Accommodation Needs of People Working with Mental or Cognitive Conditions: The Importance of Gender, Gendered Work, and Employment Factors.

PURPOSE: Workplace support needs for women and men living with mental health conditions are not well understood. This study examined workplace accommodation and support needs among women and men with and without mental health or cognitive conditions and individual and workplace factors associated with having unmet needs. METHODS: A cross-sectional survey of 3068 Canadian workers collected information on disability, gender, gendered occupations, job conditions, work contexts, and workplace accommodations. Multivariable logistic regression analyses examined gender- and disability-based differences in unmet needs for workplace flexibility, work modifications, and health benefits, and the association of work context (i.e., work schedule, job sector) and job conditions (i.e., precarious work) on the likelihood of unmet accommodation needs. The additive (i.e., super- or sub-additive) and multiplicative effects of disability, gender, and occupational gender distribution on the probability of unmet accommodation needs were also assessed. RESULTS: The most common unmet workplace accommodation was work modifications reported by 35.9% of respondents with mental/cognitive disability and workplace flexibility reported by 19.6% of individuals without a mental/cognitive disability. Women, employees in female dominant occupations, and participants with mental/cognitive disabilities were more likely to report unmet needs compared with men, employees in non-female dominant occupations, and participants without disabilities but these findings were largely explained by differences in job conditions and work contexts. No interacting effects on the likelihood of reporting unmet needs for workplace accommodations were observed. CONCLUSIONS: To support employee mental health, attention is needed to address work contexts and job conditions, especially for people working with mental/cognitive disabilities, women, and workers in female-dominated occupations where unmet accommodation needs are greatest.

The Job Demands and Accommodation Planning Tool (JDAPT): A Nine-Month Evaluation of Use, Changes in Self-efficacy, Presenteeism, and Absenteeism in Workers with Chronic and Episodic Disabilities.

PURPOSE: Enhancing workplace communication and support processes to enable individuals living with disabilities to sustain employment and return to work is a priority for workers, employers, and community stakeholders. The objective of this study was to evaluate a new resource that addresses support challenges, the Job Demands and Accommodation Planning Tool (JDAPT), and assess its use, relevance, and outcomes over a nine-month follow-up period. METHODS: Workers with physical and mental health/cognitive conditions causing limitations at work were recruited using purposive sampling. Online surveys were administered at baseline (prior to using the JDAPT), and at three and nine months post-baseline. Information was collected on demographics (e.g., age, gender) and work characteristics (e.g., job sector, organization size). Outcomes included assessing JDAPT use and relevance, and changes in self-efficacy, work productivity difficulties, employment concerns, difficulties with job demands, and absenteeism. RESULTS: Baseline participants were 269 workers (66% women; mean age 41 years) of whom 188 (69.9%) completed all three waves of data collection. Many workers reported using JDAPT strategies at and outside of work, and held positive perceptions of the tool's usability, relevance, and helpfulness. There were significant improvements (Time 1-2; Time 1-3) in self-efficacy, perceived work productivity, and absenteeism with moderate to large effect sizes in self-efficacy and productivity (0.46 to 0.78). Findings were consistent across gender, age, health condition, and work context variables. CONCLUSIONS: The JDAPT can enhance support provision and provide greater transparency and consistency to workplace disability practices, which is critical to creating more inclusive and accessible employment opportunities.

Development of small molecule inhibitors of natural killer group 2D receptor (NKG2D).

Natural killer group 2D (NKG2D) is a homodimeric activating immunoreceptor whose function is to detect and eliminate compromised cells upon binding to the NKG2D ligands (NKG2DL) major histocompatibility complex (MHC) molecules class I-related chain A (MICA) and B (MICB) and UL16 binding proteins (ULBP1-6). While typically present at low levels in healthy cells and tissue, NKG2DL expression can be induced by viral infection, cellular stress or transformation. Aberrant activity along the NKG2D/NKG2DL axis has been associated with autoimmune diseases due to the increased expression of NKG2D ligands in human disease tissue, making NKG2D inhibitors an attractive target for immunomodulation. Herein we describe the discovery and optimization of small molecule PPI (protein-protein interaction) inhibitors of NKG2D/NKG2DL. Rapid SAR was guided by structure-based drug design and accomplished by iterative singleton and parallel medicinal chemistry synthesis. These efforts resulted in the identification of several potent analogs (14, 21, 30, 45) with functional activity and improved LLE.

Electron Transfer, Atom Exchange, and Transformation of Iron Minerals in Soils: The Influence of Soil Organic Matter.

Despite substantial experimental evidence of electron transfer, atom exchange, and mineralogical transformation during the reaction of Fe(II)aq with synthetic Fe(III) minerals, these processes are rarely investigated in natural soils. Here, we used an enriched Fe isotope approach and Mössbauer spectroscopy to evaluate how soil organic matter (OM) influences Fe(II)/Fe(III) electron transfer and atom exchange in surface soils collected from Luquillo and Calhoun Experimental Forests and how this reaction might affect Fe mineral composition. Following the reaction of 57Fe-enriched Fe(II)aq with soils for 33 days, Mössbauer spectra demonstrated marked electron transfer between sorbed Fe(II) and the underlying Fe(III) oxides in soils. Comparing the untreated and OM-removed soils indicates that soil OM largely attenuated Fe(II)/Fe(III) electron transfer in goethite, whereas electron transfer to ferrihydrite was unaffected. Soil OM also reduced the extent of Fe atom exchange. Following reaction with Fe(II)aq for 33 days, no measurable mineralogical changes were found for the Calhoun soils enriched with high-crystallinity goethite, while Fe(II) did drive an increase in Fe oxide crystallinity in OM-removed LCZO soils having low-crystallinity ferrihydrite and goethite. However, the presence of soil OM largely inhibited Fe(II)-catalyzed increases in Fe mineral crystallinity in the LCZO soil. Fe atom exchange appears to be commonplace in soils exposed to anoxic conditions, but its resulting Fe(II)-induced recrystallization and mineral transformation depend strongly on soil OM content and the existing soil Fe phases.

A Sensibility Assessment of the Job Demands and Accommodation Planning Tool (JDAPT): A Tool to Help Workers with an Episodic Disability Plan Workplace Support.

Purpose Sensibility refers to a tool's comprehensiveness, understandability, relevance, feasibility, and length. It is used in the early development phase to begin assessing a new tool or intervention. This study examined the sensibility of the job demands and accommodation planning tool (JDAPT). The JDAPT identifies job demands related to physical, cognitive, interpersonal, and working conditions to better target strategies for workplace supports and accommodations aimed at assisting individuals with chronic health conditions. Methods Workers with a chronic health condition and workplace representatives were recruited from health charities, workplaces, and newsletters using convenience sampling. Cognitive interviews assessed the JDAPT's sensibility. A 70% endorsement rate was the minimum level of acceptability for sensibility concepts. A short screening tool also was administered, and answers compared to the complete JDAPT. Results Participants were 46 workers and 23 organizational representatives (n = 69). Endorsements highly exceeded the 70% cut-off for understandability, relevance, and length. Congruence between screening questions and the complete JDAPT suggested both workers and organizational representatives overlooked job demands when completing the screener. Participants provided additional examples and three new items to improve comprehensiveness. The JDAPT was rated highly relevant and useful, although not always easy to complete for someone with an episodic condition. Conclusions This study highlights the need for tools that facilitate accommodations for workers with episodic disabilities and provides early evidence for the sensibility of the JDAPT.

Beyond bulk: Density fractions explain heterogeneity in global soil carbon abundance and persistence.

Understanding the controls on the amount and persistence of soil organic carbon (C) is essential for predicting its sensitivity to global change. The response may depend on whether C is unprotected, isolated within aggregates, or protected from decomposition by mineral associations. Here, we present a global synthesis of the relative influence of environmental factors on soil organic C partitioning among pools, abundance in each pool (mg C g-1  soil), and persistence (as approximated by radiocarbon abundance) in relatively unprotected particulate and protected mineral-bound pools. We show that C within particulate and mineral-associated pools consistently differed from one another in degree of persistence and relationship to environmental factors. Soil depth was the best predictor of C abundance and persistence, though it accounted for more variance in persistence. Persistence of all C pools decreased with increasing mean annual temperature (MAT) throughout the soil profile, whereas persistence increased with increasing wetness index (MAP/PET) in subsurface soils (30-176 cm). The relationship of C abundance (mg C g-1  soil) to climate varied among pools and with depth. Mineral-associated C in surface soils (<30 cm) increased more strongly with increasing wetness index than the free particulate C, but both pools showed attenuated responses to the wetness index at depth. Overall, these relationships suggest a strong influence of climate on soil C properties, and a potential loss of soil C from protected pools in areas with decreasing wetness. Relative persistence and abundance of C pools varied significantly among land cover types and soil parent material lithologies. This variability in each pool's relationship to environmental factors suggests that not all soil organic C is equally vulnerable to global change. Therefore, projections of future soil organic C based on patterns and responses of bulk soil organic C may be misleading.

Redox Properties of Solid Phase Electron Acceptors Affect Anaerobic Microbial Respiration under Oxygen-Limited Conditions in Floodplain Soils.

Mountain floodplain soils often show spatiotemporal variations in redox conditions that arise due to changing hydrology and resulting biogeochemistry. Under oxygen-depleted conditions, solid phase terminal electron acceptors (TEAs) can be used in anaerobic respiration. However, it remains unclear to what degree the redox properties of solid phases limit respiration rates and hence organic matter degradation. Here, we assess such limitations in soils collected across a gradient in native redox states from the Slate River floodplain (Colorado, U.S.A.). We incubated soils under anoxic conditions and quantified CO2 production and microbial Fe(III) reduction, the main microbial metabolic pathway, as well as the reactivity of whole-soil solid phase TEAs toward mediated electrochemical reduction. Fe(III) reduction occurred together with CO2 production in native oxic soils, while neither Fe(II) nor CO2 production was observed in native anoxic soils. Initial CO2 production rates increased with increasing TEA redox reactivity toward mediated electrochemical reduction across all soil depths. Low TEA redox reactivity appears to be caused by elevated Fe(II) concentrations rather than crystallinity of Fe(III) phases. Our findings illustrate that the buildup of Fe(II) in systems with long residence times limits the thermodynamic viability of dissimilatory Fe(III) reduction and thereby limits the mineralization of organic carbon.

Biological Oxidation of Fe(II)-Bearing Smectite by Microaerophilic Iron Oxidizer Sideroxydans lithotrophicus Using Dual Mto and Cyc2 Iron Oxidation Pathways.

Fe(II) clays are common across many environments, making them a potentially significant microbial substrate, yet clays are not well established as an electron donor. Therefore, we explored whether Fe(II)-smectite supports the growth of Sideroxydans lithotrophicus ES-1, a microaerophilic Fe(II)-oxidizing bacterium (FeOB), using synthesized trioctahedral Fe(II)-smectite and 2% oxygen. S. lithotrophicus grew substantially and can oxidize Fe(II)-smectite to a higher extent than abiotic oxidation, based on X-ray near-edge spectroscopy (XANES). Sequential extraction showed that edge-Fe(II) is oxidized before interior-Fe(II) in both biotic and abiotic experiments. The resulting Fe(III) remains in smectite, as secondary minerals were not detected in biotic and abiotic oxidation products by XANES and Mössbauer spectroscopy. To determine the genes involved, we compared S. lithotrophicus grown on smectite versus Fe(II)-citrate using reverse-transcription quantitative PCR and found that cyc2 genes were highly expressed on both substrates, while mtoA was upregulated on smectite. Proteomics confirmed that Mto proteins were only expressed on smectite, indicating that ES-1 uses the Mto pathway to access solid Fe(II). We integrate our results into a biochemical and mineralogical model of microbial smectite oxidation. This work increases the known substrates for FeOB growth and expands the mechanisms of Fe(II)-smectite alteration in the environment.

Secondary Mineral Formation and Carbon Dynamics during FeS Oxidation in the Presence of Dissolved Organic Matter.

Iron (Fe) minerals constitute a major control on organic carbon (OC) storage in soils and sediments. While previous research has mainly targeted Fe (oxyhydr)oxides, the impact of Fe sulfides and their subsequent oxidation on OC dynamics remains unresolved in redox-fluctuating environments. Here, we investigated the impact of dissolved organic matter (DOM) on FeS oxidation and how FeS and its oxidation may alter the retention and nature of DOM. After the anoxic reaction of DOM with FeS, FeS preferentially removed high-molecular-weight and nitrogen-rich compounds and promoted the formation of aqueous sulfurized organic molecules, according to Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS) analysis. When exposed to O2, FeS oxidized to nanocrystalline lepidocrocite and additional aqueous sulfurized organic compounds were generated. The presence of DOM decreased the particle size of the resulting nano-lepidocrocite based on Mössbauer spectroscopy. Following FeS oxidation, most solid-phase OC remained associated with the newly formed lepidocrocite via a monodentate chelating mechanism (based on FTIR analysis), and FeS oxidation caused only a slight increase in the solubilization of solid-phase OC. Collectively, this work highlights the under-appreciated role of Fe sulfides and their oxidation in driving OC transformation and preservation.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Effect of Daily Teacher Feedback on Subsequent Motivation and Mental Health Outcomes in Fifth Grade Students: a Person-Centered Analysis.

Prevention scientists recognize that implementing effective prevention practices and programs responsive to the needs of individuals but based solely upon the findings from variable-centered methods presents several limitations due to numerous risk factors, pathways, and unobserved influences. One such understudied influence that is masked by variable-centered methods, motivation, is a person-level characteristic that influences treatment outcomes. The purpose of this paper is to demonstrate the use of an alternative person-centered approach, group iterative multiple model estimation (GIMME), to model change over time that focuses on the interdependence of daily student motivation levels and teacher feedback and their relations to student outcomes over time. Specifically, we used GIMME to model person level responses to negative teacher feedback regarding students' next day motivational ratings using data from 58 5th grade students participating in a study of the impact of the self-monitoring and regulation training strategy (SMARTS). Results identified a set of SMARTS students whose daily readiness aligned with high rates of self and teacher agreement regarding ongoing performance ratings. However, results identified a group of students whose daily motivation and readiness for change was adversely impacted by negative teacher feedback the day before. For these students, they were more likely than their peers to experience high levels of depression and internalization scores. Motivationally oriented practice suggestions for providing feedback to students who may be sensitive to this type of feedback and research implications of these findings are discussed.

Disclosure, Privacy and Workplace Accommodation of Episodic Disabilities: Organizational Perspectives on Disability Communication-Support Processes to Sustain Employment.

Purpose Employers increasingly are asked to accommodate workers living with physical and mental health conditions that cause episodic disability, where periods of wellness are punctuated by intermittent and often unpredictable activity limitations (e.g., depression, anxiety, arthritis, colitis). Episodic disabilities may be challenging for workplaces which must comply with legislation protecting the privacy of health information while believing they would benefit from personal health details to meet a worker's accommodation needs. This research aimed to understand organizational perspectives on disability communication-support processes. Methods Twenty-seven participants from diverse employment sectors and who had responsibilities for supporting workers living with episodic disabilities (e.g., supervisors, disability managers, union representatives, occupational health representatives, labour lawyers) were interviewed. Five participants also had lived experience of a physical or mental health episodic disability. Participants were recruited through organizational associations, community networks and advertising. Semi-structured interviews and qualitative content analysis framed data collection and analyses, and mapped communication-support processes. Results Seven themes underpinned communication-support process: (1) similarities and differences among physical and mental health episodic disabilities; (2) cultures of workplace support, including contrasting medical and biopsychosocial perspectives; (3) misgivings about others and their role in communication-support processes; (4) that subjective perceptions matter; (5) the inherent complexity of the response process; (6) challenges arising when a worker denies a disability; and (7) casting disability as a performance problem. Conclusions This study identifies a conceptual framework and areas where workplace disability support processes could be enhanced to improve inclusion and the sustainability of employment among workers living with episodic disabilities.

Molecular control of δ-opioid receptor signalling.

Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 Å high-resolution crystal structure of the human δ-opioid receptor (δ-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive δ-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive ß-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical δ-opioid antagonists such as naltrindole into potent ß-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.