Making Landscapes Negotiable: Q-methodology as a Boundary-Spanning and Empowering Diagnostic.

Landscapes are conceptually fuzzy and rich, and subject to plural framings. They are places of inquiry and intervention for scientists and practitioners, but also concepts bound to peoples' dynamic identities, knowledge systems, inspiration, and well-being. These varying interpretations change the way landscapes function and evolve. Developed in the 1930s, Q-methodology is increasingly recognized for being useful in documenting and interrogating environmental discourses. Yet its application in the context of how integrated landscape approaches better navigate land-use dilemmas is still in its infancy. Based on our experience and emerging literature, such as the papers in this special collection, this article discusses the value of Q-methodology in addressing landscape sustainability issues. Q-methodology helps unravel and communicate common and contradicting landscape imaginaries and narratives in translational and boundary-spanning ways, thus bridging actors' different understandings of problems and solutions and revealing common or differentiated entry points for negotiating trade-offs between competing land uses. The methodology can be empowering for marginalized people by uncovering their views and aspirational values to decision-makers and policymakers. We argue that this potential can be further strengthened by using Q to identify counter-hegemonic discourses and alliances that combat injustices regarding whose knowledge and visions count. In this way, applying Q-methodology in integrated landscape approaches can become a key tool for transitioning toward just, inclusive, and sustainable landscapes.

Population pharmacokinetics and pharmacodynamics of nasal glucagon in patients with type 1 or 2 diabetes.

The objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of glucagon after injectable or nasal administration and confirm the appropriate therapeutic dose of nasal glucagon (NG) for adult patients. Six clinical studies with PK and five clinical studies with PD (glucose) data were included in the analysis. Doses ranging from 0.5 to 6 mg NG, and 0.5 to 1 mg injectable glucagon were studied. A total of 6284 glucagon and 7130 glucose concentrations from 265 individuals (patients and healthy participants) were available. Population PK/PD modeling was performed using NONMEM. Glucagon exposure and glucose response were simulated for patients administered various doses of NG to confirm the optimal dose. Glucagon PK was well-described with a single compartment disposition with first-order absorption and elimination processes. Bioavailability of NG relative to injectable glucagon was 16%. Exposure-response modeling revealed that lower baseline glucose was associated with higher maximum drug effect. The carry-over effect from prior insulin administration was incorporated into the model through a time-dependent increase in elimination rate of glucose. Simulations showed that more than 99% of hypoglycemic adult patients would experience treatment success, defined as an increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir within 30 min after administration of NG 3 mg. The population PK/PD model adequately described the PK and PD profiles of glucagon after nasal administration. Modeling and simulations confirmed that NG 3 mg is the most appropriate dose for rescue treatment during hypoglycemia emergencies.

Recognising the importance and impact of Imaging Scientists: Global guidelines for establishing career paths within core facilities.

In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.

The Affordable Care Act and income-based disparities in health care coverage and spending among nonelderly adults with cancer.

The Patient Protection and Affordable Care Act (ACA) significantly reduced uninsured individuals and improved financial protection; however, escalating costs of cancer treatment has led to substantial out-of-pocket expenses, causing severe financial and mental health distress for individuals with cancer. Mixed evidence on the ACA's ongoing impact highlights the necessity of assessing health-spending changes across income groups for informed policy interventions. In our nationally representative survey evaluating the early- and long-term effects of the ACA on nonelderly adult patients with cancer, we categorized individuals-based income subgroups defined by the ACA for eligibility. We found that ACA implementation increased insurance coverage, which was particularly evident after 2 years of implementation. Early post-ACA (within two years of implementation), there were declines in out-of-pocket spending for the lowest and low-income groups by 26.52% and 38.31%, respectively, persisting long-term only for the lowest-income group. High-income groups experienced continuously increased out-of-pocket and premium spending by 25.39% and 34.28%, respectively, with a notable 122% increase in the risk of high-burden spending. This study provides robust evidence of income-based disparities in financial burden for cancer care, emphasizing the need for health care policies promoting equitable care and addressing spending disparities across income brackets.

Characterising incident opioid use among incident users of prescription sedative hypnotics: A national cohort study.

OBJECTIVE: To evaluate co-prescribing of sedatives hypnotics and opioids. DESIGN: Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing. SETTING AND PARTICIPANTS: Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA. OUTCOME MEASURES: Coprescription of sedative-hypnotics and opioids. RESULTS: A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date. CONCLUSIONS: Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.

Opioid Overdose Hospitalizations During COVID-19: The Experience of Pennsylvania.

Objective: The COVID-19 pandemic placed extreme burden on hospitals, while opioid overdose is another challenging public health issue. This study aimed to examine the trends and outcomes of opioid overdose hospitalizations in Pennsylvania during 2018 to 2021. Design: We identified opioid overdose hospitalizations in the state of Pennsylvania using the state-wide hospital discharge database (PHC4) 2018 to 2021. We examined the number of opioid overdose hospitalizations, the corresponding mortality and discharges against medical advice comparing the pre-COVID period (2018-2019) and the COVID period (2020-2021). We also assessed what patient and hospital characteristics were associated with in-hospital death or leaving against medical advice. Results: A total of 13 446 opioid-related hospitalizations were identified in 2018 to 2021. Compared to pre-pandemic, a higher percentage of cases involving synthetics (17.0%vs 10.3%, P < .0001) were observed during COVID. After controlling for covariates, there was no significant difference in opioid overdose in-hospital deaths in the years 2020 to 2021 compared to 2018 to 2019 (OR = 0.846, 95% CI: 0.71-1.01, P = .065). The COVID period was significantly associated with more leaving against medical advice compared to years 2018 to 2019 (OR = 1.265, 95% CI: 1.11-1.44, P = .0003). Compared to commercial insurance, Medicaid insurance was associated with higher odds of both in-hospital death (OR = 1.383, 95% CI: 1.06-1.81, P = .0176) and leaving against medical advice (OR = 1.903, 95% CI: 1.56-2.33, P < .0001). Conclusion: There were no substantial changes in the number of overall opioid overdose cases and deaths at hospitals following the outbreak of COVID-19 in Pennsylvania. This observation suggests that an increased number of patients may have succumbed to overdoses outside of hospital settings, possibly due to a higher severity of overdoses. Further, we found that patients were more likely to leave against medical advice during the COVID-19 pandemic.

Pedicle screw pull-out testing in polyurethane foam blocks: Effect of block orientation and density.

Synthetic bone models such as polyurethane (PU) foam are a well-established substitute to cadaveric bone for screw pull-out testing; however, little attention has been given to the effect of PU foam anisotropy on orthopaedic implant testing. Compressive and screw pull-out performance in three PU foam densities; 0.16 g/cm3 (PCF 10), 0.32 g/cm3 (PCF 20) and 0.64 g/cm3 (PCF 40) were performed in each of the X, Y or Z orientations. The maximum compressive force, stiffness in the linear region, maximum stress and modulus were determined for all compression tests. Pedicle screws were inserted and pulled out axially to determine maximum pull-out force, energy to failure and stiffness. One-way ANOVA and post hoc tests were used to compare outcome variables between PU foam densities and orientations, respectively. Compression tests demonstrated the maximum force was significantly different between all orientations for PCF 20 (X, Y and Z) while stiffness and maximum stress were different between X versus Y and X versus Z. Maximum pull-out force was significantly different between all orientations for PCF 10 foam. No significant differences were noted for other foam densities. There is potential for screw pull-out testing results to be significantly affected by orientation in lower density PU foams. It is recommended that a single, known orientation of the PU foam block be used for experimental testing.

Strain-dependent modifiers exacerbate familial leukemia caused by GATA1-deficiency.

GATA1 plays a critical role in differentiation, proliferation, and apoptosis during erythropoiesis. We developed a Gata1 knock-down allele (Gata1.05) that results in GATA1 expression at 5% of endogenous level. In female mice heterozygous for both the Gata1.05 and wild-type alleles, we observed a predisposition to erythroblastic leukemia three to six months after birth. Since no male Gata1.05 progeny survive gestation, we originally maintained heterozygous females in a mixed genetic background of C57BL/6J and DBA/2 strains. Around 30% of these mice reproducibly develop leukemia, but the other subset did not develop leukemia, even though they harbor a high number of preleukemic erythroblasts. These observations prompted us to hypothesize that there may be potential influence of genetic determinants on the progression of Gata1.05-driven hematopoietic precursors to full-blown leukemia. In an initial examination of Gata1.05/X mice backcrossed into C3H/He, BALB/c, DBA/2, C57BL/6J and 129X1/SvJ strains, we discerned that the backgrounds of C57BL/6J and 129X1/SvJ significantly expedited leukemia onset in Gata1.05/X mice. Conversely, backgrounds of C3H/He, BALB/c and DBA/2 did not substantially modify the effect of the Gata1 mutation. This indicates the existence of genetic modifiers that accentuate Gata1.05 leukemogenesis. Subsequent cohort studies evaluated Gata1.05/X mice within mix backgrounds of BALB/c:129X1/SvJ and BALB/c:C57BL/6J. In these settings, Gata1.05-driven leukemia manifested in autosomal dominant patterns within the 129X1/SvJ background and in autosomal recessive patterns within C57BL/6J background. To the best of our knowledge, this study provides the inaugural evidence of genetic modifiers that can reshape the outcome based on leukemia-associated gene signatures.

The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice.

Transcription factor GATA1 controls the delicate balance between proliferation, differentiation and apoptosis in both the erythroid and megakaryocytic lineages. In addition to full-length GATA1, there is an GATA1 isoform, GATA1s, that lacks the amino-terminal transactivation domain. Somatic GATA1 mutations that lead to the exclusive production of GATA1s appear to be necessary and sufficient for the development of a preleukemic condition called transient myeloproliferative disorder (TMD) in Down syndrome newborns. Subsequent clonal evolution among latent TMD blasts leads to the development of acute megakaryoblastic leukemia (AMKL). We originally established transgenic mice that express only GATA1s, which exhibit hyperproliferation of immature megakaryocytes, thus mimicking human TMD; however, these mice never developed AMKL. Here, we report that transgenic mice expressing moderate levels of GATA1s, i.e., roughly comparable levels to endogenous GATA1, were prone to develop AMKL in young adults. However, when GATA1s is expressed at levels significantly exceeding that of endogenous GATA1, the development of leukemia was restrained in a dose dependent manner. If the transgenic increase of GATA1s in progenitors remains small, GATA1s supports the terminal maturation of megakaryocyte progenitors insufficiently, and consequently the progenitors persisted, leading to an increased probability for acquisition of additional genetic modifications. In contrast, more abundant GATA1s expression compensates for this maturation block, enabling megakaryocytic progenitors to fully differentiate. This study provides evidence for the clinical observation that the abundance of GATA1s correlates well with the progression to AMKL in Down syndrome.

Psychological Distress and the Risk of Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease.

BACKGROUND: Psychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear. OBJECTIVES: The purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction. METHODS: Pooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years. RESULTS: In both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved. CONCLUSIONS: Among patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

BioNAR: an integrated biological network analysis package in bioconductor.

Motivation: Biological function in protein complexes emerges from more than just the sum of their parts: molecules interact in a range of different sub-complexes and transfer signals/information around internal pathways. Modern proteomic techniques are excellent at producing a parts-list for such complexes, but more detailed analysis demands a network approach linking the molecules together and analysing the emergent architectural properties. Methods developed for the analysis of networks in social sciences have proven very useful for splitting biological networks into communities leading to the discovery of sub-complexes enriched with molecules associated with specific diseases or molecular functions that are not apparent from the constituent components alone. Results: Here, we present the Bioconductor package BioNAR, which supports step-by-step analysis of biological/biomedical networks with the aim of quantifying and ranking each of the network's vertices based on network topology and clustering. Examples demonstrate that while BioNAR is not restricted to proteomic networks, it can predict a protein's impact within multiple complexes, and enables estimation of the co-occurrence of metadata, i.e. diseases and functions across the network, identifying the clusters whose components are likely to share common function and mechanisms. Availability and implementation: The package is available from Bioconductor release 3.17: https://bioconductor.org/packages/release/bioc/html/BioNAR.html.

Murine erythroid differentiation kinetics in vivo under normal and anemic stress conditions.

Our current understanding of the kinetics and dynamics of erythroid differentiation is based almost entirely on the ex vivo expansion of cultured hematopoietic progenitor cells. In this study, we used an erythroid-specific, inducible transgenic mouse line to investigate for the first time, the in vivo erythroid differentiation kinetics under steady-state conditions. We demonstrated that bipotent premegakaroycyte/erythroid (PreMegE) progenitor cells differentiate into erythroid-committed proerythroblast/basophilic erythroblasts (ProBasoE) after 6.6 days under steady-state conditions. During this process, each differentiation phase (from PreMegE to precolony forming unit-erythroid [PreCFU-E], PreCFU-E to CFU-E, and CFU-E to ProBasoE) took ∼2 days in vivo. Upon challenge with 5-flurouracil (5-FU), which leads to the induction of stress erythropoiesis, erythroid maturation time was reduced from 6.6 to 4.7 days. Furthermore, anemia induced in 5-FU-treated mice was shown to be due not only to depleted bone marrow erythroid progenitor stores but also to a block in reticulocyte exit from the bone marrow into the circulation, which differed from the mechanism induced by acute blood loss.

Dose Rationale of Nasal Glucagon in Japanese Pediatric Patients with Diabetes Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation.

BACKGROUND: Nasal glucagon (NG) 3 mg is approved in Japan to treat hypoglycemia in pediatric patients with diabetes, but an NG clinical study has not been performed in Japanese children because of practical and ethical concerns. OBJECTIVE: The aim of this study is to support the dose rationale for NG 3 mg in Japanese pediatric patients with diabetes using modeling and simulation. METHODS: We used a pharmacokinetic/pharmacodynamic bridging approach to extrapolate the available clinical data to Japanese pediatric patients. Population pharmacokinetic/pharmacodynamic modeling was performed using data from seven clinical studies, including five studies in non-Japanese adults, one study in Japanese adults, and one study in non-Japanese pediatric patients. Simulation was then used to estimate glucagon exposure and glucose response after NG 3-mg administration for three age categories of Japanese pediatric patients: 4 to < 8, 8 to < 12, and 12 to < 18 years. Treatment success was defined as an increase in blood glucose to ≥ 70 or ≥ 20 mg/dL from nadir within 30 min after administration of NG 3 mg. Safety was assessed in relation to the predicted maximum glucagon concentration of NG 3 mg using NG clinical trial data and published data on intravenous and intramuscular glucagon. RESULTS: The data showed a rapid and robust glucose response following NG 3 mg in Japanese and non-Japanese adults and non-Japanese pediatric patients, with some differences in glucagon exposure observed across studies. The pharmacokinetic/pharmacodynamic model described the observed clinical data well, and simulations indicated that > 99% of hypoglycemic Japanese pediatric patients in all three age groups would achieve treatment success. Predicted glucose responses to NG 3 mg in Japanese pediatric patients were comparable to those of intramuscular glucagon. Maximum concentration was not associated with the occurrence and severity of common adverse events (nausea, vomiting, and headache) in NG clinical studies. Furthermore, the predicted maximum concentration in Japanese pediatric patients, despite being higher than the observed maximum concentration in NG clinical studies, was substantially lower than the observed maximum concentration of 1 mg of intravenous glucagon, without serious safety issues. CONCLUSIONS: This analysis suggests NG 3 mg has robust efficacy without serious safety concerns in Japanese pediatric patients with diabetes.

Preoperative Pain Catastrophizing and Neuropathic Pain Do Not Predict Length of Stay and Early Post-Operative Complications following Total Joint Arthroplasty.

BACKGROUND: Both pain catastrophizing and neuropathic pain have been suggested as prospective risk factors for poor postoperative pain outcomes in total joint arthroplasty (TJA). OBJECTIVE: We hypothesized that pain catastrophizers, as well as patients with pain characterized as neuropathic, would exhibit higher pain scores, higher early complication rates and longer lengths of stay following primary TJA. METHODS: A prospective, observational study in a single academic institution included 100 patients with end-stage hip or knee osteoarthritis scheduled for TJA. In pre-surgery, measures of health status, socio-demographics, opioid use, neuropathic pain (PainDETECT), pain catastrophizing (PCS), pain at rest and pain during activity (WOMAC pain items) were collected. The primary outcome measure was the length of stay (LOS) and secondary measures were the discharge destinations, early postoperative complications, readmissions, visual analog scale (VAS) levels and distances walked during the hospital stay. RESULTS: The prevalence of pain catastrophizing (PCS ≥ 30) and neuropathic pain (PainDETECT ≥ 19) was 45% and 20.4%, respectively. Preoperative PCS correlated positively with PainDETECT (rs = 0.501, p = 0.001). The WOMAC positively correlated more strongly with PCS (rs = 0.512 p = 0.01) than with PainDETECT (rs = 0.329 p = 0.038). Neither PCS nor PainDETECT correlated with the LOS. Using multivariate regression analysis, a history of chronic pain medication use was found to predict early postoperative complications (OR 38.1, p = 0.47, CI 1.047-1386.1). There were no differences in the remaining secondary outcomes. CONCLUSIONS: Both PCS and PainDETECT were found to be poor predictors of postoperative pain, LOS and other immediate postoperative outcomes following TJA.

Evaluation of Discharge Opioid Prescribing in Coronary Artery Bypass Patients Following an Opioid Stewardship Intervention for Providers.

Introduction: Opioid stewardship efforts can promote safe and effective use of opioids to optimize pain control and minimize unintended consequences. The purpose of this study is to assess the difference in post-operative opioid discharge prescribing in patients undergoing coronary artery bypass graft (CABG) surgery following implementation of a tripartite opioid stewardship intervention. Methods: This was a single-center, quality improvement study at a large, quaternary academic medical center. Adult patients undergoing CABG from July 2019 to June 2020 (pre-intervention) and November 2020 to February 2021 (post-intervention) were included. The intervention included adopting hospital-wide post-surgical opioid discharge prescribing guidelines, discharge prescriber education, and electronic medical record changes. The primary outcome was the proportion of patients receiving an opioid prescription at discharge. Secondary outcomes included total morphine milligram equivalents (MME) prescribed and non-opioid analgesics prescribed at discharge. Results: A total of 200 patients were included in the study; 100 pre- and 100 post-intervention. There was no difference in opioid discharge prescribing at discharge (74% pre-intervention vs. 72% post-intervention; P = .87). There was no difference in MMEs prescribed at discharge (145.6 ± 57 pre- vs. 162.2 ± 95 post-; P = .202). No difference was seen in non-opioid analgesic prescriptions prescribed at discharge (35% pre- vs. 40% post-; P = .56). Conclusion: A multipronged opioid stewardship intervention did not lead to a reduction in opioid prescribing at discharge. Post-intervention, there was a non-statistically significant increase in the proportion of patients who received non-opioid analgesics discharge. Future studies should assess the effect of different stewardship interventions on prescribing and patient outcomes.

Wounding patterns in pediatric firearm fatalities.

INTRODUCTION: Pediatric firearm injury became the leading cause of death among U.S. children in 2020. Studies evaluating wounding patterns in military and mass casualty shootings have provided insights into treatment and potential salvageability in adults, however, similar studies in the pediatric population do not exist. Hence, our study aimed to analyze wounding patterns of pediatric firearm fatalities and associated demographics and characteristics, such as place of death, to better understand pediatric firearm injuries, potential salvageability, and opportunities to reduce firearm deaths among vulnerable pediatric populations. METHODS: A retrospective review of the National Violent Death Reporting System from 2005-2017 was performed on patients 18 and younger. Mortalities were stratified by patient age: <12 years and 13-18 years and by intent- homicide, suicide, and unintentional. Comparative and exploratory analyses of demographics, location of death and anatomic location of wounds were performed. RESULTS: Of 8,527 pediatric firearm mortalities identified, 4,728 were homicides, 3,180 were suicides and 619 were unintentional injuries. Suicide victims were most likely to be dead on scene and >90% of suicide victims suffered head/neck injuries. For victims of homicide, younger children were more likely to die on scene (61% vs 44% p < 0.001). The pattern of injury in homicides differed for younger children compared to adolescents, with younger children with more head/neck injuries and older children more thoracic, thoracoabdominal, abdominal, and junctional injuries. In both age groups, children with extremity, abdominal and thoracoabdominal injuries were more likely to die later in the emergency department or inpatient setting. CONCLUSIONS: Wounding patterns across pediatric firearm mortalities in the U.S. vary by age and intent. The majority of pediatric firearm deaths were due to head/neck injuries. Children with homicide and unintentional deaths had more wounding pattern variation, including more injuries to the thorax and abdomen, and a much lower rate of dead-on scene than suicide victims. Our study of wounding patterns among U.S. children killed by firearms highlights the complexity of these injuries and offers opportunities for tailored public health strategies across varying vulnerable pediatric populations.

Infection control behaviours, intra-household transmission and quarantine duration: a retrospective cohort analysis of COVID-19 cases.

OBJECTIVES: To study COVID-19 (Delta Variant) cases and close contacts co-located within households. Focusing on epidemiology of transmission of COVID-19, quarantine duration and utilisation of infection control behaviours under a telehealth model of care in an elimination setting. METHODS: A retrospective cohort analysis examined household spread of infection, duration of quarantine and change in PCR CT value during illness. A survey explored infection control behaviours used by household members during isolation and quarantine. RESULTS: The cohort was 141 individuals in 35 households. Thirty-seven were index cases, and 48 became positive during quarantine, most within 10 days. Whole-household infection occurred in 12 households with multiple members. Behaviours focused on fomite transmission reduction rather than preventing aerosol transmission. The median duration of close contact household quarantine was 25 days. The majority of COVID-19 cases were de-isolated after 14 days with no evidence of further community transmission. CONCLUSION: Intrahousehold transmission was not universal and, if it occurred, usually occurred quickly. Behaviours utilised focused on fomites, suggesting a need for improved education regarding the potential utilisation of strategies to prevention the transmission of aerosols. Households experienced long durations of home-based quarantine. IMPLICATIONS FOR PUBLIC HEALTH: The impact of long quarantine durations must be considered, particularly where most community benefit from quarantine is achieved within 10 days from exposure in the setting of the Delta Variant. Education of households regarding aerosol risk reduction is a potential strategy in the household setting of individuals at risk of disease progression.

Association between depression and epigenetic age acceleration: A co-twin control study.

INTRODUCTION: Prior studies have shown inconsistent findings of an association between depression and epigenetic aging. DNA methylation (DNAm) age acceleration can measure biological aging. We adopted a robust co-twin control study design to examine whether depression is associated with DNAm age acceleration after accounting for the potential confounding influences of genetics and family environment. METHODS: We analyzed data on a sub-cohort of the Vietnam Era Twin Registry. A total of 291 twins participated at baseline and 177 at follow-up visit after a mean of 11.7 years, with 111 participants having DNA samples for both time points. Depression was measured using the Beck Depression Inventory II (BDI-II). Six measures of DNAm age acceleration were computed at each time point, including Horvath's DNAm age acceleration (HorvathAA), intrinsic epigenetic age acceleration (IEAA), Hannum's DNAm age acceleration (HannumAA), extrinsic epigenetic age acceleration (EEAA), GrimAge acceleration (GrimAA), and PhenoAge acceleration (PhenoAA). Mixed-effects modeling was used to assess the within-pair association between depression and DNAm age acceleration. RESULTS: At baseline, a 10-unit higher BDI-II total score was associated with HannumAA (0.73 years, 95% confidence interval [CI] 0.13-1.33, p = .019) and EEAA (0.94 years, 95% CI 0.22-1.66, p = .012). At follow-up, 10-unit higher BDI-II score was associated with PhenoAA (1.32 years, 95% CI 0.18-2.47, p = .027). CONCLUSION: We identified that depression is associated with higher levels of DNAm age acceleration. Further investigation is warranted to better understand the underlying mechanisms for the potential causal relationship between depression and accelerated aging.