The Importance of Digital Rectal Examination in Identifying Early-Onset Rectal Malignancies.

Colorectal cancer (CRC) is the second most diagnosed cancer and the second leading cause of cancer-related deaths in the United States. Rectal cancers, specifically, are the second most common cancer of the large intestine. Although once perceived as a disease of the elderly, the incidence of early-onset CRC (EO-CRC), classified as occurring in individuals less than 50 years old, has been paradoxically increasing. Although the incidence of rectal cancers has increased, the digital rectal exam (DRE) continues to be an underutilized physical exam maneuver when a patient presents with red-flag symptoms. Here, we present a case of a 38-year-old male from West Virginia who was referred to general surgery for complaints of rectal bleeding attributed to internal hemorrhoids. After undergoing a colonoscopy, the patient was found to have a rectal mass consistent with adenocarcinoma. We describe the importance of identifying red-flag signs to keep colorectal malignancy in the differential diagnosis in a young patient and highlight the importance of performing rectal exams to identify rectal cancers early to expedite treatment.

EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

Microbial competition for phosphorus limits the CO2 response of a mature forest.

The capacity for terrestrial ecosystems to sequester additional carbon (C) with rising CO2 concentrations depends on soil nutrient availability1,2. Previous evidence suggested that mature forests growing on phosphorus (P)-deprived soils had limited capacity to sequester extra biomass under elevated CO2 (refs. 3-6), but uncertainty about ecosystem P cycling and its CO2 response represents a crucial bottleneck for mechanistic prediction of the land C sink under climate change7. Here, by compiling the first comprehensive P budget for a P-limited mature forest exposed to elevated CO2, we show a high likelihood that P captured by soil microorganisms constrains ecosystem P recycling and availability for plant uptake. Trees used P efficiently, but microbial pre-emption of mineralized soil P seemed to limit the capacity of trees for increased P uptake and assimilation under elevated CO2 and, therefore, their capacity to sequester extra C. Plant strategies to stimulate microbial P cycling and plant P uptake, such as increasing rhizosphere C release to soil, will probably be necessary for P-limited forests to increase C capture into new biomass. Our results identify the key mechanisms by which P availability limits CO2 fertilization of tree growth and will guide the development of Earth system models to predict future long-term C storage.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation.

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

Implementing a shared decision-making intervention to support treatment decisions for patients following an anterior cruciate ligament rupture - a protocol for the POP-ACLR feasibility study.

BACKGROUND: Treatment for anterior cruciate ligament (ACL) rupture may follow a surgical or nonsurgical pathway. At present, there is uncertainty around treatment choice. Two shared decision-making tools have been codesigned to support patients to make a decision about treatment following an ACL rupture. The shared decision-making tools include a patient information leaflet and an option grid. We report the protocol for a mixed-methods feasibility study, with nested qualitative interviews, to understand feasibility, acceptability, indicators of effectiveness and implementation factors of these shared decision-making tools (combined to form one shared decision-making intervention). METHODS: A single-centre non-randomised feasibility study will be conducted with 20 patients. Patients diagnosed with an ACL rupture following magnetic resonance imaging will be identified from an orthopaedic clinic. The shared decision-making intervention will be delivered during a clinical consultation with a physiotherapist. The primary feasibility outcomes include the following: recruitment rate, fidelity, acceptability and follow-up questionnaire completion. The secondary outcome is the satisfaction with decision scale. The nested qualitative interview will explore experience of using the shared decision-making intervention to understand acceptability, implementation factors and areas for further refinement. DISCUSSION: This study will determine the feasibility of using a newly developed shared decision-making intervention designed to support patients to make a decision about treatment of their ACL rupture. The acceptability and indicators of effectiveness will also be explored. In the long term, the shared decision-making intervention may improve service and patient outcomes and ensure cost-effectiveness for the NHS; ensuring those most likely to benefit from surgical treatment proceed along this pathway. TRIAL REGISTRATION: Pending registration on ISRCTN.

Assessment of Embedded vs. Remote Pharmacist vs. Remote Student Pharmacist Outreach on Statin Prescribing.

BACKGROUND: The Statin Use in Persons with Diabetes (SUPD) measure is a Star measure by the Center for Medicare & Medicaid Services. The Duke Population Health Management Office (PHMO) has a team of pharmacists and pharmacy students who conduct targeted outreach to patients at risk of failing statin quality measures. Pharmacy services are embedded in select primary care clinics and other clinics are supported remotely. OBJECTIVE: The primary objective of this review is to compare the initiation rates of recommended statin prescriptions between embedded pharmacist vs remote pharmacist vs remote student pharmacist outreach groups, all of which have different levels of autonomy within pharmacy practice. The secondary objectives are to identify the barriers to the implementation of statin therapy and to assess the statin drugs and intensity of the statins prescribed. METHODS: A single-center, retrospective chart review was performed for SUPD patients with Medicare insurance. SUPD patients included patients 40-75 years of age, diagnosed with type 2 diabetes, and were not dispensed at least one statin medication of any intensity during the 6-month measurement period. The primary outcome was the initiation of recommended statin medications prescribed, or pended for the PCP to prescribe, for qualifying patients by embedded, remote, and remote student pharmacists. Secondary outcomes included the reasons for the non-implementation of statin recommendations, reasons statin therapy was not prescribed to patients contributing to the SUPD measure gap, and statin drug and dose prescribed for appropriateness. RESULTS: A total of 189 patients were included in the evaluation. In this study, 34.9% of the patients filled the prescribed or pended statin prescription and 83.3% of patients filled the prescribed or pended statin prescription at the recommended intensity according to the ACC/AHA guidelines, effectively closing the SUPD measure gap. The initiation rates of recommended statin prescriptions between the embedded pharmacist, remote pharmacist, and remote student pharmacist outreach were numerically different at 36.7%, 28.2%, and 36.7%, respectively, even though not statistically different (p=0.61). CONCLUSION: Remote student pharmacists' performance was equal to that of the embedded pharmacists when comparing the initiation rates of statin medications prescribed or pending the PCP's approval. The most common reason for non-implementation of statin therapy is that the statin was refused by the patient. Atorvastatin and rosuvastatin were the two most commonly prescribed statins.

Mindfulness in the Clinic Waiting Room May Decrease Pain: Results from Three Pilot Randomized Controlled Trials.

Introduction: Mindfulness interventions can improve a broad range of patient outcomes, but traditional mindfulness-based interventions are time and resource intensive. Emerging evidence indicates brief, single-session mindfulness interventions can also improve patient outcomes, and brief mindfulness interventions can be embedded into medical care pathways with minimal disruption. However, the direct impact of a brief mindfulness intervention on patients' pain while waiting in the clinic waiting room remains unexamined. Objective: A series of three, pilot, randomized controlled trials (RCTs) were conducted to examine the impact of a brief, audio-recorded, mindfulness intervention on patients' pain in the clinic waiting room. Method: Study 1 examined an 8-min mindfulness recording delivered before a provider visit; Study 2 examined a 5-min mindfulness recording after a provider visit; and Study 3 examined a 4-min mindfulness recording before a provider visit. Time- and attention-matched control conditions were used in each study. Studies 1 and 2 were conducted in an academic cancer hospital. Study 3 was conducted at a walk-in orthopedic clinic. Pain intensity was measured in each of the three studies. Anxiety and depression symptoms were measured in Studies 2 and 3. Pain unpleasantness was measured in Study 3. Results: A brief (i.e., 4- to 8-min), audio-recorded mindfulness intervention decreased patients' pain intensity in the clinic waiting room, whether delivered before (Study 1 Cohen's d=1.01, Study 3 Cohen's d=0.39) or after (Study 2 Cohen's d=0.89) a provider visit. Mindfulness had a significant effect on anxiety symptoms in both studies in which it was measured. No effect on depression symptoms was observed. Conclusions: Results from these three pilot RCTs indicate brief, audio-recorded, mindfulness interventions may be capable of quickly decreasing clinical symptoms. As such, embedding brief, audio-recorded, mindfulness interventions in clinic waiting rooms may have the potential to improve patient outcomes. The continued investigation of this intervention approach is needed. Clinical Trial Registrations: NCT04477278 and NCT06099964.

A review on the safety of growth factors commonly used in cultivated meat production.

Growth factors are commonly added to cell culture media in cellular agriculture to mimic the endogenous process of proliferation and differentiation of cells. Many of these growth factors are endogenous to humans and known to be present in the edible tissues and milk of food animals. However, there is little or no information on the use of growth factors intentionally added in food production before the advent of cultivated meat. Ten commonly used growth factors have been reviewed to include information on their mode of action, bioavailability, occurrence in food and food animals, endogenous levels in humans, as well as exposure and toxicological information drawn from relevant animal studies and human clinical trials with a focus on oral exposure. In addition, a comparison of homology of growth factors was done to compare the sequence homology of growth factors from humans and domestic animal species commonly consumed as food, such as bovine, porcine, and poultry. This information has been gathered as the starting point to determine the safety of use of growth factors in cultivated meat meant for human consumption. The change in levels of growth factors measured in human milk and bovine milk after pasteurization and high-temperature treatment is discussed to give an indication of how commercial food processing can affect the levels of growth factors in food. The concept of substantial equivalence is also discussed together with a conservative exposure estimation. More work on how to integrate in silico assessments into the routine safety assessment of growth factors is needed.

1H, 13C, and 15N resonance assignments of the La Motif of the human La-related protein 1.

Human La-related protein 1 (HsLARP1) is involved in post-transcriptional regulation of certain 5' terminal oligopyrimidine (5'TOP) mRNAs as well as other mRNAs and binds to both the 5'TOP motif and the 3'-poly(A) tail of certain mRNAs. HsLARP1 is heavily involved in cell proliferation, cell cycle defects, and cancer, where HsLARP1 is significantly upregulated in malignant cells and tissues. Like all LARPs, HsLARP1 contains a folded RNA binding domain, the La motif (LaM). Our current understanding of post-transcriptional regulation that emanates from the intricate molecular framework of HsLARP1 is currently limited to small snapshots, obfuscating our understanding of the full picture on HsLARP1 functionality in post-transcriptional events. Here, we present the nearly complete resonance assignment of the LaM of HsLARP1, providing a significant platform for future NMR spectroscopic studies.

Social preferences and psychopathy in a sample of male prisoners-a pilot study.

Social decisions are influenced by a person's social preferences. High psychopathy is defined by antisocial behaviour, but the relationship between psychopathy and social preferences remains unclear. In this study, we used a battery of economic games to study social decision-making and social preferences in relation to psychopathy in a sample of 35 male prison inmates, who were arrested for sexual and severe violent offenses (mean age = 39 years). We found no evidence for a relationship between social preferences (measured with the Dictator and Ultimatum Games, Social Value Orientation, and one-shot 2 × 2 games) and psychopathy (measured by the overall Hare Psychopathy Checklist-Revised score and both factors). These results are surprising but also difficult to interpret due to the small sample size. Our results contribute to the ongoing debate about psychopathy and social decision-making by providing crucial data that can be combined with future datasets to reach large sample sizes that can provide a more nuanced understanding about the relationship between psychopathy and social preferences.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

AOP report: Development of an adverse outcome pathway for deposition of energy leading to cataracts.

Cataracts are one of the leading causes of blindness, with an estimated 95 million people affected worldwide. A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose-, time-, incidence-concordance) across the adjacent (directly linked) relationships using well-established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.

Modelling changes in vegetation productivity and carbon balance under future climate scenarios in southeastern Australia.

Australia, characterized by extensive and heterogeneous terrestrial ecosystems, plays a critical role in the global carbon cycle and in efforts to mitigate climate change. Prior research has quantified vegetation productivity and carbon balance within the Australian context over preceding decades. Nonetheless, the responses of vegetation and carbon dynamics to the evolving phenomena of climate change and escalating concentrations of atmospheric carbon dioxide remain ambiguous within the Australian landscape. Here, we used LPJ-GUESS model to assess the impacts of climate change on Gross Primary Productivity (GPP) and Net Biome Productivity (NBP) of carbon for the state of New South Wales (NSW) in southeastern Australia. LPJ-GUESS simulations were driven by an ensemble of 27 global climate models under different emission scenarios. We investigated the change of GPP for different vegetation types and whether NSW ecosystems will be a net sink or source of carbon under climate change. We found that LPJ-GUESS successfully simulated GPP for the period 2003-2021, demonstrating a comparative performance with GPP derived from upscaled eddy covariance fluxes (R2 = 0.58, nRMSE = 14.2 %). The simulated NBP showed a larger interannual variation compared with flux data and other inversion products but could capture the timing of rainfall-driven carbon sink and source variations in 2015-2020. GPP would increase by 10.3-19.5 % under a medium emission scenario and 19.7-46.8 % under a high emission scenario. The mean probability of NSW acting as a carbon sink in the future showed a small decrease with a large uncertainty with >8 of the 27 climate models indicating an increased potential for carbon sink. These findings emphasize the significance of emission scenarios in shaping future carbon dynamics but also highlight considerable uncertainties stemming from different climate projections. Our study represents a baseline for understanding natural ecosystem dynamics and their key role in governing land carbon uptake and storage in Australia.

Enhancing Congenital Cardiac Postprocedural Care: A QR Code-Enabled Medical Bracelet Pilot Study.

The study aimed to evaluate the feasibility of using QR code-enabled medical bracelets for congenital heart disease (CHD) patients after hospital discharge to ensure quick communication of vital information to other medical personnel in emergency situations. A prospective study was conducted where QR code-enabled medical bracelets were given to families of postoperative pediatric cardiac patients. The QR code linked to a secure medical information sheet detailing the patient's cardiac history. Post-study surveys were completed by providers and families to assess their experiences with the bracelet. Of the 20 participants enrolled, 65% used the QR bracelet when seeking medical care. 55% found the bracelet useful, and 70% rated their experience as either "positive" or "very positive". Additionally, 80% recommended the bracelet for other patients undergoing cardiac procedures. The use of QR code bracelets for postoperative CHD patients has shown high levels of satisfaction from families and providers, potentially reducing medical errors and treatment delays.

Vessel and Airway Characteristics in One-Year CT-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationship with vascular and airway pathophysiology remain unclear. Objective: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial (PA) dilation measured via computed tomography (CT) are associated with a 1-year index of emphysema (EI: %voxels<-950HU) progression. Methods: 599 GOLD 0-3 former and never-smokers were evaluated from the SubPopulations and InterMediate Outcome Measures in COPD Study (SPIROMICS) cohort: rapid-emphysema-progressors (RP, n=188; 1-year ΔEI>1%), non-progressors (NP, n=301; 1-year ΔEI±0.5%) and never-smokers (NS: N=110). Segmental PA cross-sectional areas were standardized to associated airway luminal areas (Segmental : Pulmonary Artery-to-Airway Ratio: PAARseg). Full inspiratory CT scan-derived total (arteries + veins) pulmonary vascular volume (TPVV) was compared to vessel volume with radius smaller than 0.75mm (SVV.75/TPVV). Airway-to-lung ratios (an index of dysanapsis and COPD risk) were compared to TPVV-lung-volume-ratios. Results: Compared with NP, RP exhibited significantly larger PAARseg (0.73±0.29 vs. 0.67±0.23; p=0.001), lower TPVV-to-lung-volume ratio (3.21%±0.42% vs. 3.48%±0.38%; p=5.0 x 10-12), lower airway-to-lung-volume ratio (0.031±0.003 vs. 0.034±0.004; p=6.1 x 10-13) and larger SVV.75/TPVV (37.91%±4.26% vs. 35.53±4.89; p=1.9 x 10-7). In adjusted analyses, a 1-SD increment in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95%CI: 29 to 206%; p = 0.002) and 79.3% higher in odds of being in the rapid emphysema progression group (95%CI: 24% to 157%; p = 0.001). At year-2 followup, the CT-defined RP group demonstrated a significant decline in post-bronchodilator-FEV1% predicted. Conclusion: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Pathways from research to sustainable development: Insights from ten research projects in sustainability and resilience.

Drawing on collective experience from ten collaborative research projects focused on the Global South, we identify three major challenges that impede the translation of research on sustainability and resilience into better-informed choices by individuals and policy-makers that in turn can support transformation to a sustainable future. The three challenges comprise: (i) converting knowledge produced during research projects into successful knowledge application; (ii) scaling up knowledge in time when research projects are short-term and potential impacts are long-term; and (iii) scaling up knowledge across space, from local research sites to larger-scale or even global impact. Some potential pathways for funding agencies to overcome these challenges include providing targeted prolonged funding for dissemination and outreach, and facilitating collaboration and coordination across different sites, research teams, and partner organizations. By systematically documenting these challenges, we hope to pave the way for further innovations in the research cycle.

Airway tree caliber heterogeneity and airflow obstruction among older adults.

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV1), FEV1/forced vital capacity (FEV1/FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV1 (adjusted mean difference: -125 mL, 95%CI: -171,-79), lower FEV1/FVC (adjusted mean difference: -0.01, 95%CI: -0.02,-0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01-2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV1 and FEV1/FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry.NEW & NOTEWORTHY In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD.