Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the ...clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones, although the underlying mechanisms remain unclear. Here we show that alterations in granulocyte mechanical properties are the driving force behind glucocorticoid- and catecholamine-induced demargination. First, we found that the proportions of granulocytes from healthy human subjects that traversed and demarginated from microfluidic models of capillary beds and veins, respectively, increased after the subjects ingested glucocorticoids. Also, we show that glucocorticoid and catecholamine exposure reorganizes cellular cortical actin, significantly reducing granulocyte stiffness, as measured with atomic force microscopy. Furthermore, using simple kinetic theory computational modeling, we found that this reduction in stiffness alone is sufficient to cause granulocyte demargination. Taken together, our findings reveal a biomechanical answer to an old hematologic question regarding how glucocorticoids and catecholamines cause leukocyte demargination. In addition, in a broader sense, we have discovered a temporally and energetically efficient mechanism in which the innate immune system can simply alter leukocyte stiffness to fine tune margination/demargination and therefore leukocyte trafficking in general. These observations have broad clinically relevant implications for the inflammatory process overall as well as hematopoietic stem cell mobilization and homing.
Smartphone use has quickly become a fixture of everyday life, including during church services. Drawing from the Theory of Reasoned Action and the Technology Acceptance Model, we develop a model to ...identify key drivers of smartphone use during church services. Smartphone Playfulness was included in the model to reflect a more intrinsic motivation to use one's smartphone during church services. Study 1 surveys 329 US adults and finds that our newly developed model explains 66 percent of the variation in intentions to use one's smartphone during church services. A second study conducted six weeks later with 164 of the original respondents finds that behavioral intentions explains 44 percent of the variation in actual smartphone use. Findings suggest that the newly developed model presented herein is a valuable tool in explaining smartphone use in church and may prove helpful in explaining acceptance decisions across a wide variety of computer-based media technologies.
Clinical reasoning is at the core of health professionals' practice. A mapping of what constitutes clinical reasoning could support the teaching, development, and assessment of clinical reasoning ...across the health professions.
We conducted a scoping study to map the literature on clinical reasoning across health professions literature in the context of a larger Best Evidence Medical Education (BEME) review on clinical reasoning assessment. Seven databases were searched using subheadings and terms relating to clinical reasoning, assessment, and Health Professions. Data analysis focused on a comprehensive analysis of bibliometric characteristics and the use of varied terminology to refer to clinical reasoning.
Literature identified: 625 papers spanning 47 years (1968-2014), in 155 journals, from 544 first authors, across eighteen Health Professions. Thirty-seven percent of papers used the term clinical reasoning; and 110 other terms referring to the concept of clinical reasoning were identified. Consensus on the categorization of terms was reached for 65 terms across six different categories: reasoning skills, reasoning performance, reasoning process, outcome of reasoning, context of reasoning, and purpose/goal of reasoning. Categories of terminology used differed across Health Professions and publication types.
Many diverse terms were present and were used differently across literature contexts. These terms likely reflect different operationalisations, or conceptualizations, of clinical reasoning as well as the complex, multi-dimensional nature of this concept. We advise authors to make the intended meaning of 'clinical reasoning' and associated terms in their work explicit in order to facilitate teaching, assessment, and research communication.
Purpose
Attachment theory is emerging as an important theoretical foundation in marketing because of the relational nature of consumption, but little guidance exists as to which of many attachment ...style measures is most suitable for use by researchers. As a result, many measures are being used with little justification, and frequently, these scales are being adapted due to poor measurement fit, length or wording unrelated to the focal attachment figure. This paper aims to evaluate seven existing attachment style measures and provides recommendations regarding which measure is the most suitable for assessing the impact of chronic attachment styles on marketing outcomes.
Design/methodology/approach
A literature review identified seven measures of attachment style for analysis. Two studies examine the psychometric properties, susceptibility to response bias and predictive validity of the seven measures (Study 1n = 325 and Study 2n = 205).
Findings
Among the seven scales evaluated, the Johnson et al. (2012) Johnson, Whelan, and Thomson (JWT) measure exhibited the best psychometric properties and predictive validity for general (i.e. not relationship-specific) attachment styles. In addition, two relationship-specific measures, also with strong psychometric properties, were better able to capture their respective relationships or relationship types than general attachment styles, as expected.
Research limitations/implications
This research provides guidance to researchers on which measure to use when examining the impact of attachment style in marketing.
Practical implications
This research provides marketing researchers guidance on which measure to use when examining the impact of general attachment styles. Because the JWT scale is brief, psychometrically sound and demonstrates strong predictive validity, it can be used for academic and managerial purposes. The authors also confirm previous research suggesting that relationship-specific measures of attachment style may act differently than general interpersonal attachment style measures and vary in their ability to predict marketing outcomes.
Originality/value
This research is the first to provide guidance regarding which measure of attachment style to use in marketing and consumer research. This research can serve as a reference point for future researchers in selecting measures of attachment style and may allow for convergence on a narrow set of measures to advance research in marketing.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 COVID-19), and current evidence suggests that severe ...disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon-stimulated genes. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45
cells into the lung parenchyma that is dominated by monocyte-derived cells. Single-cell RNA sequencing (scRNA-Seq) analysis of lung homogenates identified a hyperinflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a potential CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts the viral burden in the lung. We find that SARS-CoV-2 triggers an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon-stimulated genes. Using RNA sequencing and flow cytometry approaches, we demonstrate that SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45
cells into the lung parenchyma that is dominated by monocyte-derived cells. Mechanistically, CCR2 signaling promoted the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified that the CCR2 pathway is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
Determining the cause for pulmonary hypertension is difficult in many patients. Pulmonary arterial hypertension (PAH) is differentiated from pulmonary venous hypertension (PVH) by a wedge pressure ...(PWP)>15 mm Hg in PVH. Patients undergoing right heart catheterization for evaluation of pulmonary hypertension may be dehydrated and have reduced intravascular volume, potentially leading to a falsely low measurement of PWP and an erroneous diagnosis of PAH. We hypothesized that a fluid challenge during right heart catheterization would identify occult pulmonary venous hypertension (OPVH).
We reviewed the results of patients undergoing fluid challenge in our pulmonary hypertension database from 2004 to 2011. Baseline hemodynamics were obtained and repeated after infusion of 0.5 L of normal saline for 5 to 10 minutes. Patients were categorized as OPVH if PWP increased to >15 mm Hg after fluid challenge. Baseline hemodynamics in 207 patients met criteria for PAH. After fluid challenge, 46 patients (22.2%) developed a PWP>15 mm Hg and were reclassified as OPVH. Patients with OPVH had a greater increase in PWP compared with patients with PAH, P<0.001, and their demographics and comorbid illnesses were similar to patients with PVH. There were no adverse events related to fluid challenge.
Fluid challenge at the time of right heart catheterization is easily performed, safe, and identifies a large group of patients diagnosed initially with PAH, but for whom OPVH contributes to pulmonary hypertension. These results have implications for therapeutic trials in PAH and support the routine use of fluid challenge during right heart catheterization in patients with risk factors for PVH.
In humans, the composition of microbial communities differs among body sites and between habitats within a single site. Patterns of variation in the distribution of organisms across time and space ...are referred to as “biogeography.” The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease. The biogeographic features of microbial communities residing in spatially distinct, but ecologically similar, environments on the human body, including the subgingival crevice, have not yet been adequately explored. The purpose of this paper is twofold. First, we seek to provide the dental community with a primer on biogeographic theory, highlighting its relevance to the study of the human oral cavity. We summarize what is known about the biogeographic variation of dental caries and periodontitis and postulate that disease occurrence reflects spatial patterning in the composition and structure of oral microbial communities. Second, we present a number of methods that investigators can use to test specific hypotheses using biogeographic theory. To anchor our discussion, we apply each method to a case study and examine the spatial variation of the human subgingival microbiota in 2 individuals. Our case study suggests that the composition of subgingival communities may conform to an anterior‐to‐posterior gradient within the oral cavity. The gradient appears to be structured by both deterministic and nondeterministic processes, although additional work is needed to confirm these findings. A better understanding of biogeographic patterns and processes will lead to improved efficacy of dental interventions targeting the oral microbiota.
The present research investigates the relationship between self-centeredness and social media use and suggests that fear of missing out (FOMO) is a key mechanism underlying this relationship. Three ...studies were conducted to test these relationships, including a survey (Study 1, n = 199 U.S. adults) and two experiments, including one where self-centeredness is manipulated (Study 2, n = 241 U.S. adults) and another where FOMO is primed (Study 3, n = 102 U.S. adults). It appears that self-centred individuals use social media more to assuage their FOMO than to bolster their self-centric worldview. The study results provide consistent evidence which could refute prior theory and explanatory processes. Contrary to self-construal theory, which would suggest that individuals with an independent self-construal (more self-centred) would be less likely to experience FOMO, present results suggest otherwise. Additional study contributions include the use of two experimental designs to assess the direction of causal flow between self-centeredness, FOMO, and social media use. (PsycInfo Database Record (c) 2023 APA, all rights reserved) (Source: journal abstract)
The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) ...for HIV preexposure prophylaxis (PrEP).
To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States.
Simulation, cost-effectiveness analysis.
Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed.
476 700 MSM/TGW at very high risk for HIV (VHR).
10 years.
Health care system.
CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP.
Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP.
Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year).
In a PrEP-eligible population at high risk for HIV, rather than at VHR (
= 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year).
Uncertain clinical and economic benefits of averting future transmissions.
Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA.
FHI 360;
National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.
The use of stereotactic body radiotherapy (SBRT) for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (BLINDED FOR REVIEW) ...aimed to determine the maximally tolerated dose (MTD) of SBRT for ultra-central (UC) non-small cell lung carcinoma (NSCLC), using a time-to-event continual reassessment methodology (TITE-CRM).
Patients with T1-3N0M0 (≤ 6 cm) NSCLC were eligible. The MTD was defined as the dose of radiotherapy associated with a ≤ 30% rate of grade (G) 3-5 pre-specified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume (PTV); tumors with endobronchial invasion were excluded. This primary analysis occurred two years after completion of accrual.
Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range: 65-87) and 17 (57%) were female. PTV was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%) and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range: 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia; the latter had CT findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% confidence interval CI: 52.3-85.3%), progression-free survival 66.1% (95% CI: 46.1-80.2%), local control 89.6% (95% CI: 71.2-96.5%), regional control 96.4% (95% CI: 77.2-99.5%) and distant control 85.9% (95% CI: 66.7-94.5%). Quality of life scores declined numerically over time, but the decreases were not clinically or statistically significant.
60 Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the pre-specified acceptability criteria, and results in excellent control for UC tumors.