Advanced primary care is a team-based approach to providing higher-quality primary care. The association of advanced primary care and COVID-19 outcomes is unknown.
To evaluate the association of ...advanced primary care with COVID-19 outcomes, including vaccination, case, hospitalization, and death rates during the first 2 years of the COVID-19 pandemic.
This retrospective cohort study used Medicare claims data from January 1, 2020, through January 31, 2022, and Maryland state vaccination data. All Part A and B Medicare claims for Maryland Medicare beneficiaries were included. The study population was divided into beneficiaries attributed to Maryland Primary Care Program (MDPCP) practices and a matched cohort of beneficiaries not attributed to MDPCP practices but who met the eligibility criteria for study participation from January 1, 2020, through December 31, 2021. Eligibility criteria for both groups included fee-for-service Medicare beneficiaries who were eligible for attribution to the MDPCP. A forced-match design was used to match both groups in the study population by age category, sex, race and ethnicity, Medicare-Medicaid dual eligibility status, COVID-19 Vulnerability Index score, Maryland county of residence, and primary care practice participation.
Primary care practice participation in the MDPCP.
Primary outcome variables included rate of vaccination, monoclonal antibody infusion uptake, and telehealth claims. Secondary outcomes included rates of COVID-19 diagnosis, COVID-19 inpatient claims, COVID-19 emergency department claims, COVID-19 deaths, and median COVID-19 inpatient admission length of stay. Claims measures were assessed from January 1, 2020, through October 31, 2021. Vaccination measures were assessed from January 1, 2020, through March 31, 2022.
After matching, a total of 208 146 beneficiaries in the MDPCP group and 37 203 beneficiaries in the non-MDPCP group were included in this study, comprising 60.10% women and 39.90% men with a median age of 76 (IQR, 71-82) years. Most participants (78.40% and 78.38%, respectively) were White. There were no significant demographic nor risk measure baseline differences between the 2 groups. The MDPCP beneficiaries had more favorable primary COVID-related outcomes than non-MDPCP beneficiaries: 84.47% of MDPCP beneficiaries were fully vaccinated, compared with 77.93% of nonparticipating beneficiaries (P < .001). COVID-19-positive beneficiaries in MDPCP also received monoclonal antibody treatment more often (8.45% vs 6.11%; P < .001) and received more care via telehealth (62.95% vs 54.53%; P < .001) compared with nonparticipating counterparts. In terms of secondary outcomes, beneficiaries in the MDPCP had lower rates of COVID-19 cases (6.55% vs 7.09%; P < .001), lower rates of COVID-19 inpatient admissions (1.81% vs 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs 0.77%; P < .001) compared with nonparticipating beneficiaries.
These findings suggest that participation in the MDPCP was associated with lower COVID-19 case, hospitalization, and death rates, and advanced primary care and COVID-19 response strategies within the MDPCP were associated with improved COVID-19 outcomes for attributed beneficiaries.
Approximately 20% of acute myeloid leukemia (AML) patients carry mutations in IDH1 or IDH2 that result in over-production of the oncometabolite D-2-hydroxyglutarate (2-HG). Small molecule inhibitors ...that block 2-HG synthesis can induce complete morphological remission; however, almost all patients eventually acquire drug resistance and relapse. Using a multi-allelic mouse model of IDH1-mutant AML, we demonstrate that the clinical IDH1 inhibitor AG-120 (ivosidenib) exerts cell-type-dependent effects on leukemic cells, promoting delayed disease regression. Although single-agent AG-120 treatment does not fully eradicate the disease, it increases cycling of rare leukemia stem cells and triggers transcriptional upregulation of the pyrimidine salvage pathway. Accordingly, AG-120 sensitizes IDH1-mutant AML to azacitidine, with the combination of AG-120 and azacitidine showing vastly improved efficacy in vivo. Our data highlight the impact of non-genetic heterogeneity on treatment response and provide a mechanistic rationale for the observed combinatorial effect of AG-120 and azacitidine in patients.
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•Inhibition of mutant IDH1 promotes exhaustion of the leukemic hierarchy•Resistance to the IDH1 inhibitor AG-120 can arise through transcriptional reprogramming•The differentiation state of AML cells affects their response to IDH1 inhibition•The response of LSCs to AG-120 sensitizes them to azacitidine
IDH1-mutant acute myeloid leukemia cells accumulate the oncometabolite D-2-hydroxyglutarate (2-HG). Gruber et al. demonstrate that pharmacological 2-HG blockade sensitizes rare leukemia stem cells to the cytosine analogue azacitidine by promoting cycling and upregulating pyrimidine salvage.
Sandwich assays are among the most powerful tools in molecular detection. These assays use “pairs” of affinity reagents so that the detection signal is generated only when both reagents bind ...simultaneously to different sites on the target molecule, enabling highly sensitive and specific measurements in complex samples. Thus, the capability to efficiently screen affinity reagent pairs at a high throughput is critical. In this work, we describe an experimental strategy for screening “aptamer pairs” at a throughput of 106 aptamer pairs per hourwhich is many orders of magnitude higher than the current state of the art. The key step in our process is the conversion of solution-phase aptamers into “aptamer particles” such that we can directly measure the simultaneous binding of multiple aptamers to a target protein based on fluorescence signals and sort individual particles harboring aptamer pairs via the fluorescence-activated cell-sorter instrument. As proof of principle, we successfully isolated a high-quality DNA aptamer pair for plasminogen activator inhibitor 1 (PAI-1). Within only two rounds of screening, we discovered DNA aptamer pairs with low-nanomolar sensitivity in dilute serum and excellent specificity with minimal off-target binding even to closely related proteins such as PAI-2.
This dissertation explores how early modern playwrights articulated complaint and critique through a dramaturgy of hunger. During the sixteenth and seventeenth centuries England faced poor harvests, ...changes in land use, and ineffectual government action leading to repeated subsistence crises both actual and perceived. Employing the anthropological concept of “foodways,” which recognizes food’s entanglement in multiple imaginative and material systems of meaning, the dissertation offers a corrective to contemporary literary and cultural scholarship in accounting for the sociopolitical implications of consumption in the context of these crises. Playwrights addressed the inequities of feasting and hunger in England from a range of competing ideological perspectives, engaging with the cultural dilemmas posed by scarcity through the interplay of plenty and want onstage. Chapter One explores the poor harvest of 1586 and the drama produced in its wake, in which hungry tyrants call attention to imaginative tensions within religious framings of hunger as a punishment. Shakespeare’s 2 Henry VI simultaneously presents the rebel Cade as an ambitious glutton and draws attention to the consuming violence of the encloser Alexander Iden. Chapter Two focuses on two historical duologies influenced by the scarcity of the 1590s that re-evaluated governmental discourses condemning specific economic agents for exacerbating dearth. Shakespeare’s Henry IV plays suggest the corruption of Justices Shallow and Silence in tandem with Falstaff, while Thomas Heywood’s Edward IV plays highlight the king’s failures of traditional hospitality. Chapter Three first analyzes how Shakespeare drew on images of James-as-father and Elizabeth-as-nurturing-mother to address the 1607 Midlands Revolt in Coriolanus and Timon of Athens, then explores Thomas Middleton and Thomas Dekker’s The Bloody Banquet, which links the Queen’s starved infants with the appetites of the father-Tyrant’s court and implicitly interrogates the material value of patriarchal political theory. Chapter Four argues that representations of hungry soldiers in early Caroline drama echo Continental military humiliations to indict the royal favorite Buckingham. In The Unnatural Combat, Philip Massinger subverts this paradigm to blame the captain Belgarde’s hunger on the governor’s neglect, condemning Charles I for subsistence failures and suggesting the threat posed by an unchecked royal will.
This dissertation explores how early modern playwrights articulated complaint and critique through a dramaturgy of hunger. During the sixteenth and seventeenth centuries England faced poor harvests, ...changes in land use, and ineffectual government action leading to repeated subsistence crises both actual and perceived. Employing the anthropological concept of “foodways,” which recognizes food’s entanglement in multiple imaginative and material systems of meaning, the dissertation offers a corrective to contemporary literary and cultural scholarship in accounting for the sociopolitical implications of consumption in the context of these crises. Playwrights addressed the inequities of feasting and hunger in England from a range of competing ideological perspectives, engaging with the cultural dilemmas posed by scarcity through the interplay of plenty and want onstage.;
Chapter One explores the poor harvest of 1586 and the drama produced in its wake, in which hungry tyrants call attention to imaginative tensions within religious framings of hunger as a punishment. Shakespeare’s 2 Henry VI simultaneously presents the rebel Cade as an ambitious glutton and draws attention to the consuming violence of the encloser Alexander Iden. Chapter Two focuses on two historical duologies influenced by the scarcity of the 1590s that re-evaluated governmental discourses condemning specific economic agents for exacerbating dearth. Shakespeare’s Henry IV plays suggest the corruption of Justices Shallow and Silence in tandem with Falstaff, while Thomas Heywood’s Edward IV plays highlight the king’s failures of traditional hospitality. Chapter Three first analyzes how Shakespeare drew on images of James-as-father and Elizabeth-as-nurturing-mother to address the 1607 Midlands Revolt in Coriolanus and Timon of Athens, then explores Thomas Middleton and Thomas Dekker’s The Bloody Banquet, which links the Queen’s starved infants with the appetites of the father-Tyrant’s court and implicitly interrogates the material value of patriarchal political theory. Chapter Four argues that representations of hungry soldiers in early Caroline drama echo Continental military humiliations to indict the royal favorite Buckingham. In The Unnatural Combat, Philip Massinger subverts this paradigm to blame the captain Belgarde’s hunger on the governor’s neglect, condemning Charles I for subsistence failures and suggesting the threat posed by an unchecked royal will.
2019-03-04T00:00:00Z
How can a democratic polity reconcile the growth of decision making in large bureaucracies with popular control of government action? The classic answer of the impersonal and politically neutral ...bureaucrat and the neat dichotomy of policy and administration have long been recognized as illusions, but the search for democratic control of bureaucracy has resulted in confusion as much as solutions due to the concentration of attention on particular methods and schemes of control. This dissertation seeks to help remedy this situation by (i) creating an analytic framework within which to compare and evaluate the costs and normative assumptions involved in various control strategies and (ii) analyzing the attitudes of bureaucrats themselves--the objects of control--toward their jobs, control, and their role in the policy process. The task of creating an analytic framework begins with a map of proposed methods of constraining bureaucratic behavior. The axes of the map are two kinds of constraint, procedural and substantive, each of which may vary from low to high. The map is then used to locate various extant proposals for control. Different areas of the map are examined for their association with effectiveness and enforcement costs attendant to constraint and with normative assumptions concerning popular ability to govern and the proper role of government. The impact of policy area variation is examined by considering the impact of the technology employed by a given bureaucracy and the environment within which it operates on the likelihood that constraint will incur enforcement or effectiveness costs and on the validity of the normative assumptions concerning popular ability and the role of government. The success of democratically imposed constraint, however, is not only related to an understanding of such abstract relationships but also to the reaction of the bureaucrats whom one would constrain. In an effort to explore the bureaucrats' world and attitudes, I conducted 39 open-ended interviews with urban bureaucrats in the fields of education, fire protection, and public housing. These included all major central office administrators and randomly selected field administrators in each agency. The analysis of these interviews reveals bureaucrats who are only faintly aware of their policy making role and highly resistant to external efforts to control their behavior. They are so, however, not because of defects in their democratic values but because their work lives are not conducive to putting these values into practice and because norms are subtly redefined so that resistance is brought into congruence with democratic beliefs. Further analysis of bureaucratic attitudes reveals "perceptual filters" through which bureaucrats see efforts to control their behavior. These filters cause bureaucrats to perceive control that threatens their "core identity" as worthy of vigorous resistance but also to see certain kinds of control as legitimate or as useful or both. Thus filters encourage bureaucrats to resist some controls and to accept others. The nature of these filters varies, however, with technological and environmental differences among policy areas; and the bureaucrats' responses to control show corresponding variation. The dissertation concludes that analysts and would-be controllers of bureaucratic behavior have restricted but nonetheless real opportunities to exercise constraint. Their efforts, however, must take into account the attitudes of the bureaucrats themselves, other values controllers might seek, and the direct and indirect costs of exercising control for the bureaucrats and the controllers. Finally, this study indicates ways in which the prospects of control may be improved by altering the ability of the controllers or by restructuring the technology or the environment of the bureaucrats to encourage the coincidence of bureaucratic interest with democratic control.
Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as ...pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (μg/d) were significantly associated with natural log-transformed total urinary arsenic (Formula , Formula , both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 μg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of >2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States.
Wasps of the genus
are social insects that have become major pests and predators in their introduced range. Viruses present in these wasps have been studied in the context of spillover from honey ...bees, yet we lack an understanding of the endogenous virome of wasps as potential reservoirs of novel emerging infectious diseases. We describe the characterization of 68 novel and nine previously identified virus sequences found in transcriptomes of
in colonies sampled from their native range (Belgium) and an invasive range (New Zealand). Many viruses present in the samples were from the Picorna-like virus family (38%). We identified one Luteo-like virus, Vespula vulgaris Luteo-like virus 1, present in the three life stages examined in all colonies from both locations, suggesting this virus is a highly prevalent and persistent infection in wasp colonies. Additionally, we identified a novel Iflavirus with similarity to a recently identified Moku virus, a known wasp and honey bee pathogen. Experimental infection of honey bees with this novel Vespula vulgaris Moku-like virus resulted in an active infection. The high viral diversity present in these invasive wasps is a likely indication that their polyphagous diet is a rich source of viral infections.
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