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Cell therapy has significant therapeutic potential but is often limited by poor donor cell retention and viability at the host implantation site. Biomaterials can improve cell retention by providing cells with increased cell-cell and cell-matrix contacts and materials that allow three-dimensional cell culture to better recapitulate native cell morphology and function. In this study, we engineered a scaffold that allows for cell encapsulation and sustained three-dimensional cell culture. Since cell therapy is largely driven by paracrine secretions, the material was fabricated by electrospinning to have a large internal surface area, micrometer-thin walls, and nanoscale surface pores to allow for nutrient exchange without early cell permeation. The material is degradable, which allows for less invasive removal of the implant. Here, a biodegradable poly(lactic

Ischemic diseases including myocardial infarction (MI) and limb ischemia are some of the greatest causes of morbidity and mortality worldwide. Cell therapy is a potential treatment but is usually limited by poor survival and retention of donor cells injected at the target site. Since much of the therapeutic effects occur via cell-secreted paracrine factors, including extracellular vesicles (EVs), we developed a porous material for cell encapsulation which would improve donor cell retention and survival, while allowing EV secretion. Human donor cardiac mesenchymal cells were used as a model therapeutic cell and the encapsulation system could sustain three-dimensional cell growth and secretion of therapeutic factors. Secretion of EVs and protective growth factors were increased by encapsulation, and secreted EVs had hypoxia-protective, pro-angiogenic activities in in vitro assays. In a mouse model of limb ischemia the implant improved angiogenesis and blood flow, and in an MI model the system preserved ejection fraction %. In both instances, the encapsulation system greatly extended donor cell retention and survival compared to directly injected cells. This system represents a promising therapy for ischemic diseases and could be adapted for treatment of other diseases in the future.

Computer-aided detection systems for retinal fluid could be beneficial for disease monitoring and management by chronic age-related macular degeneration (AMD) and diabetic retinopathy (DR) patients, to assist in disease prevention via early detection before the disease progresses to a "wet AMD" pathology or diabetic macular edema (DME), requiring treatment. We propose a proof-of-concept AI-based app to help predict fluid via a "fluid score", prevent fluid progression, and provide personalized, serial monitoring, in the context of predictive, preventive, and personalized medicine (PPPM) for patients at risk of retinal fluid complications.The app comprises a convolutional neural network-Vision Transformer (CNN-ViT)-based segmentation deep learning (DL) network, trained on a small dataset of 100 training images (augmented to 992 images) from the Singapore Epidemiology of Eye Diseases (SEED) study, together with a CNN-based classification network trained on 8497 images, that can detect fluid vs. non-fluid optical coherence tomography (OCT) scans. Both networks are validated on external datasets.Internal testing for our segmentation network produced an IoU score of 83.0% (95% CI = 76.7-89.3%) and a DICE score of 90.4% (86.3-94.4%); for external testing, we obtained an IoU score of 66.7% (63.5-70.0%) and a DICE score of 78.7% (76.0-81.4%). Internal testing of our classification network produced an area under the receiver operating characteristics curve (AUC) of 99.18%, and a Youden index threshold of 0.3806; for external testing, we obtained an AUC of 94.55%, and an accuracy of 94.98% and an F1 score of 85.73% with Youden index.We have developed an AI-based app with an alternative transformer-based segmentation algorithm that could potentially be applied in the clinic with a PPPM approach for serial monitoring, and could allow for the generation of retrospective data to research into the varied use of treatments for AMD and DR. The modular system of our app can be scaled to add more iterative features based on user feedback for more efficient monitoring. Further study and scaling up of the algorithm dataset could potentially boost its usability in a real-world clinical setting.The online version contains supplementary material available at 10.1007/s13167-022-00301-5.

As concerns over exposure to per- and polyfluoroalkyl substances (PFAS) are continually increasing, novel methods to monitor their presence and modifications are greatly needed, as some have known toxic and bioaccumulative characteristics while most have unknown effects. This task however is not simple, as the Environmental Protection Agency (EPA) CompTox PFAS list contains more than 9000 substances as of September 2020 with additional substances added continually. Nontargeted analyses are therefore crucial to investigating the presence of this immense list of possible PFAS. Here, we utilized archived and field-sampled pine needles as widely available passive samplers and a novel nontargeted, multidimensional analytical method coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) to evaluate the temporal and spatial presence of numerous PFAS. Over 70 PFAS were detected in the pine needles from this study, including both traditionally monitored legacy perfluoroalkyl acids (PFAAs) and their emerging replacements such as chlorinated derivatives, ultrashort chain PFAAs, perfluoroalkyl ether acids including hexafluoropropylene oxide dimer acid (HFPO-DA, "GenX") and Nafion byproduct 2, and a cyclic perfluorooctanesulfonic acid (PFOS) analog. Results from this study provide critical insight related to PFAS transport, contamination, and reduction efforts over the past six decades.

Acalabrutinib received approval for the treatment of adult patients with mantle cell lymphoma who received at least 1 prior therapy and adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study investigated the impact of hepatic impairment (HI) on acalabrutinib pharmacokinetics (PK) and safety at a single 50-mg dose in fasted subjects. This study was divided into 2 parts: study 1, an open-label, parallel-group study in Child-Pugh class A or B subjects and healthy subjects; and study 2, an open-label, parallel-group study in Child-Pugh class C subjects and healthy subjects. Baseline characteristics and safety profiles were similar across groups. Acalabrutinib exposure (area under the plasma concentration-time curve) increased slightly (1.90- and 1.48-fold) in subjects with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment compared with healthy subjects. In severe hepatic impairment (Child-Pugh class C), acalabrutinib exposure (area under the plasma concentration-time curve and maximum plasma concentration) increased ≈5.0- and 3.6-fold, respectively. Results were consistent across total and unbound exposures. Severe hepatic impairment did not impact total/unbound metabolite (ACP-5862) exposures; the metabolite-to-parent ratio decreased to 0.6 to 0.8 (vs 3.1-3.6 in healthy subjects). In summary, single oral dose of 50-mg acalabrutinib was safe and well tolerated in subjects with mild, moderate, and severe hepatic impairment and in healthy control subjects. In subjects with severe hepatic impairment, mean acalabrutinib exposure increased by up to 5-fold and should be avoided. Acalabrutinib does not require dose adjustment in patients with mild or moderate hepatic impairment.

In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide. Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI.In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model. Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values. Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnC) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivoderived senescence signature using a foreign body response (FBR) fibrosis model in a SnC reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell typespecific senescence associated secretory phenotypes (SASP). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single cell RNAseq (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34- CSF1R-TGFßR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify transcriptional profiles and SASP factors produced by SnCs that regulate tissue structure and pathology.

Background: The cardiovascular risk associated with different levels of hypertensive retinopathy, including mild, remains unclear. We performed an individual participant meta-analysis from 6 population-based cohort studies to determine the relationship of hypertensive retinopathy with incident cardiovascular outcomes. Methods: We identified cohort studies that objectively assessed hypertensive retinopathy from photographs, documented incident cardiovascular outcomes, and were population-based. Six studies contributed data from 11,013 individuals at baseline with 5–13 years follow-up. Participants were recruited if they had hypertension and did not have confounding conditions such as diabetic retinopathy. Main outcome measures were incident coronary heart disease (CHD), stroke and a composite endpoint of cardiovascular disease (CHD or stroke). Pooled estimates of incident risk ratios (IRR) were obtained after adjusting for age, gender, systolic blood pressure, serum total cholesterol, high density lipoprotein and smoking. Results: Among eligible participants with hypertension and without diabetes, there were 1018/9662 (10.5%) incident CHD events, 708/11,013 (6.4%) incident stroke events and 1317/9378 (14.0%) incident CVD events. Mild hypertensive retinopathy was associated with increased risk of CVD (IRR 1.13, 95% CI 1.00 to 1.27) and CHD (IRR 1.17, 95% CI 1.02 to 1.34) but not stroke; moderate hypertensive retinopathy was associated with increased risk of CVD (IRR 1.25 95% CI 1.02 to 1.53) but not stroke or CHD individually. Conclusions: In persons with hypertension, both mild and moderate hypertensive retinopathy were associated with higher CVD risk.

Fluorine (F)-free firefighting foams will be replacing per- and polyfluoroalkyl substances (PFAS)-containing aqueous film-forming foams (AFFFs) at U.S. military installations imminently, yet the environmental impacts of F-free foams are largely unknown. Ecotoxicity assessment of F-free foams is urgently needed to avoid replacement regret. In this study, we comparatively assessed phytotoxicity of six F-free formulations and one current short-chain fluorinated AFFF in terrestrial plant Brassica rapa. Five of six F-free formulations exerted higher toxicity than the short-chain AFFF to the growth and reproduction of B. rapa, with 8-51 times and10 times lower EC

Rates of development of the feeding larvae of marine invertebrates may often be limited by inadequate food, extending the length of the larval period and increasing overall larval mortality. A better understanding of the frequency and importance of this phenomenon requires knowledge of the food concentration below which larvae are limited, and above which they are not, as well as estimates of how strongly food supply affects length of the planktonic period. We addressed these issues using larvae of the sand dollarDendraster excentricusas a model and chlaconcentration as a metric of food abundance. We reared larvae in natural seawater collected from coastal southern California (USA), as well as in reduced and supplemented food treatments created from this natural seawater, 6 times from 2017 to 2019 to take advantage of temporal variation in chlaconcentration. Larvae showed morphological responses indicative of low food in nature in only 1 of 6 experiments and showed delayed time to 50% metamorphic competence in 2 of 6 experiments. Larvae appeared to be food limited below chlaconcentrations of ~2.4-3.0 µg l-1, but developed at maximal rates at higher food concentrations. Low natural food supplies delayed time to 50% competence by up to 1.25 d. An 11 yr record of chlaconcentration in waters of coastal southern California suggests that larvae ofD. excentricusare likely food limited in developmental rate throughout much of the year except for late winter to late spring.

BackgroundPain management is important for ensuring early mobilization after hip arthroplasty; however, the optimal components remain controversial. Recently, the quadratus lumborum block has been proposed as an analgesic option. The current study tested the hypothesis that the posterior quadratus lumborum block combined with multimodal analgesia decreases morphine consumption after hip arthroplasty.MethodsThis study was a prospective, randomized, double-blind, placebo-controlled trial. Before general anesthesia, 100 participating patients scheduled for elective total hip arthroplasty were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.33% ropivacaine (n = 50) or normal saline (n = 50). For all patients, multimodal analgesia included systematic administration of acetaminophen, ketoprofen, and a morphine intravenous patient-controlled analgesia. The primary outcome was total intravenous morphine consumption in the first 24 h. Secondary outcomes recorded intraoperative sufentanil consumption; morphine consumption in the postanesthesia care unit; pain scores at extubation and at 2, 6, 12, and 24 h; motor blockade; time to first standing and ambulation; hospital length of stay; and adverse events.ResultsThere was no significant difference in the 24-h total morphine consumption (ropivacaine group, median [interquartile range], 13 [7 to 21] versus saline group, 16 [9 to 21] mg; median difference, −1.5; 95% CI, −5 to 2; P = 0.337). Pain scores were not different between the groups (β = −0.4; 95% CI, −0.9 to 0.2; P = 0.199). There was no statistical difference between the two groups in intraoperative sufentanil consumption, morphine consumption in the postanesthesia care unit, motor blockade, times to first standing (median difference, 0.83 h; 95% CI, −1.7 to 3.4; P = 0.690) and ambulation (median difference, −1.85 h; 95% CI, −4.5 to 0.8; P = 0.173), hospital length of stay, and adverse events.ConclusionsAfter elective hip arthroplasty, neither morphine consumption nor pain scores were reduced by the addition of a posterior quadratus lumborum block to a multimodal analgesia regimen.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Applying dual, or mixed photon energies during radiation therapy is a common practice in 3-dimensional conformal radiation therapy (3D-CRT). Mixed photon energies are used to provide uniform dose coverage to a planning target volume (PTV) that ranges in depth from the skin surface. Though the application of mixed photon energies in 3D-CRT was once the convention for treating anal cancers with lymph node involvement (AC-LNI), the advantages offered by volumetric modulated arc therapy (VMAT) prove to be the optimal form of therapy for AC-LNI. Recently, multiple researchers have uncovered benefits in employing multiple photon energies in VMAT planning for prostate cancer. A retrospective study was completed to assess the impact of implementing mixed energy VMAT planning in comparison to conventional single energy VMAT planning for AC-LNI. Data from 20 patients with AC-LNI was collected to analyze the dosimetric effects of mixed energy VMAT treatments in terms of PTV conformity index, PTV homogeneity index, monitor unit usage, and organs at risk sparing. For each patient 3 treatment plans were created: a single energy 6 MV plan, a single energy 10 MV plan, and a mixed 6 MV and 10 MV energy plan. Analysis of the resulting dosimetric outcomes showed statistical significance. The current study concluded that mixed energy VMAT plans have some effect on treating AC-LNI when compared to single energy VMAT plans.

Background The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). Objectives The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. Methods Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. Results For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. Conclusions Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term.

Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, and fire-fighting foams which have become environmental pollutants of concern due to their persistence, ubiquity, and associations with adverse human health outcomes, including in pregnant persons and their offspring. Multiple PFAS are associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver are not fully described. Here we performed transcriptomic analyses in the mouse to investigate the molecular mechanisms of hepatic toxicity in the dam and its fetus after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, known as GenX). Pregnant CD-1 mice were exposed via oral gavage from embryonic day (E) 1.5-17.5 to PFOA (0, 1, or 5 mg/kg-d) or GenX (0, 2, or 10 mg/kg-d). Maternal and fetal liver RNA was isolated (N = 5 per dose/group) and the transcriptome analyzed by Affymetrix Array. Differentially expressed genes (DEG) and differentially enriched pathways (DEP) were obtained. DEG patterns were similar in maternal liver for 5 mg/kg PFOA, 2 mg/kg GenX, and 10 mg/kg GenX (R

Background: To gain an understanding of the intersection of risk factors between the most prevalent eye health conditions that are associated with vision impairment and non-communicable diseases (NCDs). Methods: A series of rapid reviews of reviews reporting on non-modifiable risk factors, age and sex, and modifiable risk factors, including social determinants, were conducted for five common eye health conditions that are the leading causes of vision impairment globally (refractive error including uncorrected refractive error, cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy) and five prevalent NCDs (cancer, cardiovascular disease, chronic respiratory disease, dementia, and depressive disorders). Articles published within approximately 5 years to the end of 2019 were identified through expert recommendation, PubMED, Ovid Medline, the Lancet Global Burden of Disease series, the International Agency for Research on Cancer and World Cancer Research Fund. Results: Of 9,213 records identified, 320 records were eligible. Eye health conditions and NCDs share many risk factors. Increased age was found to be the most common shared risk factor, associated with increased risks of AMD, cataract, diabetic retinopathy, glaucoma, refractive error, cancer, cardiovascular disease, chronic obstructive pulmonary disease, and dementia. Other shared risk factors included smoking, obesity, alcohol consumption (mixed results), and physical activity was protective, though limited evidence was found for eye conditions. Social determinants are well documented as risk factors for NCDs. Conclusion: There is substantial overlap in common established risk factors for the most frequent vision impairing eye conditions and leading NCDs. Increasing efforts should be made to integrate preventative and risk reduction interventions to improve health, with greatest shared benefits for initiatives which aim to reduce smoking, improve diet, and promote physical activity.

As concerns continue to mount over exposure to per- and polyfluoroalkyl substances (PFAS), novel methods of profiling their presence and modifications are greatly needed as some have known toxic and bioaccumulative characteristics while others have unknown effects. This task however is not simple as over 5000 PFAS of interest have been named by the Environmental Protection Agency and this list continues to grow daily. In this work, we utilized widely available archived and field-sampled pine needles and a novel non-targeted analytical method to evaluate the temporal and spatial presence of numerous PFAS. Over 70 PFAS were detected in the pine needles from this study, providing information from the last six decades related to PFAS exposure, contamination, and reduction.

To describe the prevalence, risk factors, and associations of vitreoretinal interface (VRI) abnormalities in a population-based study of older adults.Cross-sectional analysis of cohort study participants.Of the 1149 participants (mean age, 76.1 ± 6.9 years) in the 15-year Blue Mountains Eye Study follow-up examination from 2007 through 2009, 905 (1791 eyes) had gradable time-domain or spectral-domain OCT scans of the macula from at least 1 eye.OCT scans were graded according to the International Vitreomacular Traction Study Group classification system of VRI abnormalities. Best-corrected visual acuity (BCVA) was recorded.Prevalence of VRIs.Overall, 451 participants showed any VRI abnormality (49.8%). Prevalence of VRI abnormality by person was: vitreomacular adhesion (VMA), 33.6%; vitreomacular traction (VMT), 1.6%; epiretinal membrane (ERM), 21.4%; full-thickness macular hole (FTMH), 0.7%; and lamellar macular hole (LMH), 0.7%. Twenty-two percent of VMAs were focal, and 78% were broad based; 76% of VMTs were focal, and 24% were broad based. All FTMHs observed were large (400 μm), with mean aperture size of 573 μm (range, 459-771 μm). Increased age was associated with higher ERM and lower VMA prevalence (The prevalence of VRI abnormalities is high in older individuals. Epiretinal membrane was associated with increasing age, pseudophakia, and myopia. Epiretinal membrane and FTMH may account for significant visual loss in the affected eye. This study provided useful population-based data on the prevalence of VRI abnormalities in older individuals.

BACKGROUND In this paper, we describe the design, program details, and baseline demographics and oral health of participants in ForsythKids, a regional, comprehensive, school-based mobile caries prevention program. METHODS We solicited all Massachusetts elementary schools with greater than 50% of students receiving free or reduced-price meals. Six schools initially elected to participate, ultimately followed by over 50 schools. Interventions were based on systematic reviews and randomized controlled caries prevention trials. Participating students received semiannual dental examinations, followed by comprehensive preventive care. Summary statistics regarding oral health indicators were derived from individual tooth- and surface-level data. RESULTS Over a 6-year period, data were collected on 6927 children. The number of students per school ranged from 58 to 681. The overall participation rate was 15%, ranging from 10% to 29%. Overall, 57% of the children were younger than 8 years at baseline. Approximately, 54% of children experienced dental decay on any tooth at baseline; 32% had untreated decay on any tooth, 29% had untreated decay on primary teeth, and 10% untreated decay on permanent teeth. CONCLUSIONS Untreated dental decay was double the national average, even in schools within several blocks of community dental clinics. These data demonstrate the need for caries prevention beyond the traditional dental practice.

Background: Complete revascularization with routine percutaneous coronary intervention of nonculprit lesions after primary percutaneous coronary intervention improves outcomes in ST-segment–elevation myocardial infarction. Whether this benefit is associated with nonculprit lesion vulnerability is unknown. Methods: In a prospective substudy of the COMPLETEs trial (Complete vs Culprit-Only Revascularization to Treat Multi-Vessel Disease After Early PCI for STEMI), we performed optical coherence tomography of at least 2 coronary arteries before nonculprit lesion percutaneous coronary intervention in 93 patients with ST-segment–elevation myocardial infarction and multivessel disease; and the ST-segment–elevation myocardial infarction culprit vessel if there was unstented segment amenable to imaging. Nonculprit lesions were categorized as obstructive (≥70% stenosis by visual angiographic assessment) or nonobstructive, and as thin-cap fibroatheroma (TCFA) or non-TCFA by optical coherence tomography criteria. TCFA was defined as a lesion with mean fibrous cap thickness 90°. Results: On a patient level, at least one obstructive TCFA was observed in 44/93 (47%) of patients. On a lesion level, there were 58 TCFAs among 150 obstructive nonculprit lesions compared with 74 TCFAs among 275 nonculprit lesions (adjusted TCFA prevalence: 35.4% versus 23.2%, P =0.022). Compared with obstructive non-TCFAs, obstructive TCFAs had similar lesion length (23.1 versus 20.8 mm, P =0.16) but higher lipid quadrants (55.2 versus 19.2, P P P P P =0.11), but more lipid quadrants (36.4 versus 13.5, P P Conclusions: Among patients who underwent optical coherence tomography imaging in the COMPLETE trial, nearly 50% had at least one obstructive nonculprit lesion containing complex vulnerable plaque. Obstructive lesions more commonly harbored vulnerable plaque morphology than nonobstructive lesions. This may help explain the benefit of routine percutaneous coronary intervention of obstructive nonculprit lesions in patients with ST-segment–elevation myocardial infarction and multivessel disease. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01740479s.

Members of lesbian, gay, bisexual and transsexual (LGBT) populations are sexual and gender minorities and are at risk for significant health disparities compared to heterosexual populations. This study examined occupational therapy students’ and recent graduates’ (n=435) basic knowledge, clinical preparedness and attitudinal awareness for working with LGBT clients using the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS; Bidell, 2017). Students in the study generally rated themselves low (between three and four on a seven-point scale) on questions related to clinical preparedness, indicating they felt they did not have adequate training relative to working with LGBT clients. Both basic knowledge and clinical preparedness for working with LGBT populations was positively influenced by hours of curriculum content related to sexual minority populations. However, 21% (n=91) of participants reported the topic was not covered in the curriculum, while an additional 68% (n=295) reported less than two hours of time developed to LGBT topics. It is suggested that education focus on terminology, health disparities, an examination of personal and societal attitudes that affect outcomes, important health and psychosocial needs, culturally sensitive communication, creating inclusive practice setting and clinical practice and communication unique to this population.

Many areas of social psychological research investigate how social information may bias judgment. However, most measures of social judgment biases are (1) low in reliability because they use a single response, (2) not indicative of individual differences in bias because they use between-subjects designs, (3) inflexible because they are designed for a particular domain, and (4) ambiguous about magnitude of bias because there is no objectively correct answer. We developed a measure of social judgment bias, the Judgment Bias Task, in which participants judge profiles varying in quality for a certain outcome based on objective criteria. The presence of ostensibly irrelevant social information provides opportunity to assess the extent to which social biases undermine the use of objective criteria in judgment. The JBT facilitates measurement of social judgment biases by (1) using multiple responses, (2) indicating individual differences by using within-subject designs, (3) being adaptable for assessing a variety of judgments, (4) identifying an objective magnitude of bias, and (5) taking 6 min to complete on average. In nine pre-registered studies (N > 9000) we use the JBT to reveal two prominent social judgment biases: favoritism towards more physically attractive people and towards members of one's ingroup. We observe that the JBT can reveal social biases, and that these sometimes occur even when the participant did not intend or believe they showed biased judgment. A flexible, objective, efficient assessment of social judgment biases will accelerate theoretical and empirical progress.

Purpose: To describe the prevalence, risk factors, and associations of vitreoretinal interface (VRI) abnormalities in a population-based study of older adults. Design: Cross-sectional analysis of cohort study participants. Participants: Of the 1149 participants (mean age, 76.1 ± 6.9 years) in the 15-year Blue Mountains Eye Study follow-up examination from 2007 through 2009, 905 (1791 eyes) had gradable time-domain or spectral-domain OCT scans of the macula from at least 1 eye. Methods: OCT scans were graded according to the International Vitreomacular Traction Study Group classification system of VRI abnormalities. Best-corrected visual acuity (BCVA) was recorded. Main Outcome Measures: Prevalence of VRIs. Results: Overall, 451 participants showed any VRI abnormality (49.8%). Prevalence of VRI abnormality by person was: vitreomacular adhesion (VMA), 33.6%; vitreomacular traction (VMT), 1.6%; epiretinal membrane (ERM), 21.4%; full-thickness macular hole (FTMH), 0.7%; and lamellar macular hole (LMH), 0.7%. Twenty-two percent of VMAs were focal, and 78% were broad based; 76% of VMTs were focal, and 24% were broad based. All FTMHs observed were large (>400 μm), with mean aperture size of 573 μm (range, 459–771 μm). Increased age was associated with higher ERM and lower VMA prevalence (P < 0.001 for both). Pseudophakia and myopia were associated with ERM (age- and sex-adjusted odds ratios [ORs], 1.48 [95% confidence interval (CI), 1.01–2.17] and 1.72 [95% CI, 1.05–2.81], respectively). Moderate or severe ERM and FTMH were associated with worse BCVA of 9.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI, 3.4–15.0 ETDRS letters; P = 0.008) and 26.0 ETDRS letters (95% CI, 10.9–41.1 ETDRS letters; P = 0.001), respectively. Conclusions: The prevalence of VRI abnormalities is high in older individuals. Epiretinal membrane was associated with increasing age, pseudophakia, and myopia. Epiretinal membrane and FTMH may account for significant visual loss in the affected eye. This study provided useful population-based data on the prevalence of VRI abnormalities in older individuals.

Background People with vision impairment are at an increased risk of falls compared with their sighted peers, but have very little access to existing community fall prevention programs. The Lifestyle-integrated Functional Exercise (LiFE) program can prevent falls in older people and may be suitable for adults aged ≥50 with vision impairment. Methods The LiFE program was adapted for older adults with vision impairment (v-LiFE) and delivered by Orientation and Mobility Specialists (Instructors), who are experienced with individualised programs for people with vision impairment. Perspectives of older adults with vision impairment (recipients) receiving the v-LiFE program and their Instructors were explored through semi-structured interviews. Results Of 73 trained Instructors, 51(70%) delivered at least one session to a total of 240 older adults with vision impairment between March 2017 and May 2019. Of these, 11/51(22%) Instructors and 154/172(90%) of invited recipients (until thematic saturation was reached) were interviewed. Six key themes were identified relating to recipient (delivery aptitude; social norms; habit formation) and Instructor (individualised adaptation; complimentary to scope of practice; challenges to delivery) perspectives. Instructors considered delivering v-LiFE as an extension of their scope of work. Conclusions Older adults with vision impairment demonstrated positive attitudes towards the program, but younger or more physically fit recipients considered the program too easy for them. The perspectives of recipients and instructors indicate that the v-LiFE program delivered within existing services may fill the gap for a fall prevention program for people with vision impairment.

A significant proportion of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). Following successful culprit lesion percutaneous coronary intervention (PCI) for STEMI, the question of whether to routinely revascularize non-culprit lesions or manage them conservatively with optimal medical therapy (OMT) alone is a common dilemma facing clinicians. METHODS: COMPLETE is a prospective, randomized, international, multicenter, parallel group, open-label trial with blinded evaluation of outcomes. Following successful PCI (contemporary drug eluting stents recommended) of the culprit lesion for STEMI, a total of 4041 patients from 140 centers in 31 countries were randomized to receive either complete revascularization, consisting of staged PCI of all suitable non-culprit lesions plus optimal medical therapy (OMT), or to culprit lesion-only PCI, consisting of OMT alone. OMT comprises evidence-based therapy for STEMI, including and dual antiplatelet therapy with ticagrelor, HTN and lipid management. All coronary angiograms in the trial are being evaluated in a central angiographic core lab to assess quality and completeness of revascularization. The co-primary outcomes are (1): the composite of CV death or new non-fatal MI and (2 the composite of CV death, new non-fatal MI or ischemia-driven revascularization at a median follow-up of 3 years. CONCLUSIONS: The COMPLETE trial is an international multicenter randomized trial that will help determine whether complete revascularization involving staged PCI of non-culprit lesions improves outcomes in patients with STEMI and multivessel CAD. (clinicaltrials.govNCT01740479).

IntroductionDriving is one of the main modes of transport with safe driving requiring a combination of visual, cognitive and physical skills. With population ageing, the number of people living with vision impairment is set to increase in the decades ahead. Vision impairment may negatively impact an individual’s ability to safely drive. The association between vision impairment and motor vehicle crash involvement or driving participation has yet to be systematically investigated. Further, the evidence for the effectiveness of vision-related interventions aimed at decreasing crashes and driving errors has not been synthesised.Methods and analysisA search will be conducted for relevant studies on Medline (Ovid), EMBASE and Global Health from their inception to March 2020 without date or geographical restrictions. Two investigators will independently screen abstracts and full texts using Covidence software with conflicts resolved by a third investigator. Data extraction will be conducted on all included studies, and their quality assessed to determine the risk of bias using the Joanna Briggs Institute Critical Appraisal Tools. Outcome measures include crash risk, driving cessation and surrogate measures of driving safety (eg, driving errors and performance). The results of this review will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. Meta-analysis will be undertaken for outcomes with sufficient data and reported following the Meta-analyses of Observational Studies in Epidemiology guideline. Where statistical pooling is not feasible or appropriate, narrative summaries will be presented following the Synthesis Without Meta-analysis in systematic reviews guideline.Ethics and disseminationThis review will only report on published data thus no ethics approval is required. Results will be included in the Lancet Global Health Commission on Global Eye Health, published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration numberCRD42020172153.

Nurse educators are challenged with providing meaningful clinical experiences for students. However, patient safety regulations constrain what nursing students are able to accomplish in the pediatric setting. So, what are students actually doing in their clinical rotation? This pilot observational study was undertaken to provide a snapshot of the experiences available to nursing students that develop the six Quality and Safety Education for Nurses (QSEN) competencies. Students were directly observed during pediatric clinical and pediatric simulation rotations, and their time-on-task was calculated and categorized. Three of the six QSEN competencies were observed more often than the others during both the simulation and clinical experiences. Much work needs to be done to include all QSEN-related knowledge and skills into prelicensure clinical rotations. [ J Nurs Educ. 2013;52(9):534–538.]

An organization’s preparedness agenda bears a direct relationship to its crisis response capabilities and its capacity to respond to and manage a crisis. To clarify the current level of crisis capabilities, this study investigates the level of capacity that exists in health and allied health organizations by assessing the level of planning in existence for eleven different types of crises. This evidence-based study draws on responses provided by executive decision-makers from chiropractic, physiotherapy and podiatry practices, dental and medical clinics, pharmacies, aged care facilities, and hospitals. Results show that physiotherapy, podiatry and chiropractic practices possess little crisis capacity, pharmacies are somewhat capable and medical clinics, hospitals and aged care organizations are somewhat to reasonably capable. Dental clinics are an anomaly since their performance is similar to allied health organizations rather than to health organizations. The data suggest that the organizations surveyed have fallen into the pattern of developing capabilities for certain common, expected threats rather than for what they consider unlikely or what they have not experienced. The presence of a disconnect between what is planned for and what is actually experienced is of considerable concern because it suggests that planners lack sufficient awareness of threats that their organizations encounter.

Premature infants in the neonatal intensive care unit are at risk for necrotizing enterocolitis (NEC) and bowel perforation. Unfortunately the mortality and morbidity for intestinal perforation in neonates, especially extremely low-birth-weight infants (VLBW), is high. The criterion standard traditional management for bowel perforation has been exploratory laparotomy (LAP). Another less invasive alternative treatment modality for selected intestinal perforation is primary peritoneal drainage (PPD). The role and efficacy of PPD as a definitive treatment instead of laparotomy remains to be determined. To better appreciate the emergence and evolving role of PPD in the management of intestinal perforation in NEC or isolated intestinal perforation, 8 selected research articles will be reviewed. Findings from these studies will be summarized to address the original purpose of PPD as a rescue and stabilizing measure for VLBW infants with complicated NEC, the expanded and superior role of PPD when it is used for VLBW infants with isolated ileal perforation, and PPD not as a sole surgical management but as an adjunct therapy to LAP in perforated NEC for the VLBW infants.

The purpose of this study was to evaluate the importance of nitric oxide (NO) upon outcome following hemorrhagic shock. l -Arginine, an NO precursor, and l -NMMA, an inhibitor of NO synthesis, were added to resuscitation in a prospective, randomized, and double-blinded experimental model, and the effects upon blood pressure and survival were measured. Methods: 60 Sprague-Dawley rats were anesthetized and subjected to phlebotomy to induce hemorrhagic shock. After a 45 min shock period, animals were resuscitated with either lactated Ringer's alone (control), l -NMMA in lactated Ringer's, or l -arginine in lactated Ringer's. Blood pressure was monitored, and animals were observed for survival. As an additional control experiment, 15 additional animals underwent the same protocol, but underwent sham shock, i.e. were not haemorrhaged. Results: l -NMMA increased blood pressure transiently following sham shock, but increased blood pressure to a greater extent and for a longer duration following hemorrhage. However, l -NMMA had no effect upon survival. l -Arginine had no measurable effect upon blood pressure, but significantly increased survival. Conclusion: NO may play an important role following hemorrhage. The effectiveness of l -NMMA as a pressor suggests that NO contributes to hypotension following hemorrhage. However, reversing hypotension with l -NMMA did not improve survival in this model. In contrast, l -arginine did not further lower blood pressure, but had significant survival benefit. This suggests a possible protective effect of NO after hemorrhage, perhaps by improving the distribution of capillary blood flow and/or by decreasing platelet aggregation and leukocyte adhesion within the microcirculation.