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The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)

We utilized the population-based New Hampshire Colonoscopy Registry to calculate false discovery rates (FDR) and positive predictive values (PPVs) using three ‘positive’ colonoscopy definitions. Understanding the frequency of meaningful ‘true positive’ mt-sDNA and Fecal Immunochemical Test (FIT) results can optimize the use of these colorectal cancer (CRC) screening tests. We calculated FDR (positive stool test followed by negative colonoscopy divided by all positive stool tests) and PPV for mt-sDNA and FIT cohorts using the following definitions:1) DeeP-C Study (CRC, adenomas/serrated polyps ≥ 1 cm, villous/High Grade Dysplasia);2) 1 cm, and 5–9 mm proximal HPs.The sample included 549 mt-sDNA + and 410 FIT + and patients (mean age 66.4, 43.0% male). Using the most limited definition of positive colonoscopy, DeeP-C, FDR was 71.9% for mt-sDNA + and 81.7% for FIT +. Using the USMSTF definition, FDR decreased substantially: mt-sDNA+:33.2% and FIT+:47.6%. Adding all CSSPs resulted in the lowest FDR: mt-sDNA+:32.2% and FIT+:47.1%. Decreasing FDRs corresponded to increasing PPVs: mt-sDNA+:28.1% and FIT+:18.3% (DeeP-C definition) and mt-sDNA+:67.8% and FIT+:52.9% (DeeP-C + USMSTF + CSSP) (Table 1).FDRs decreased substantially when the definition of positive exams included all significant precancerous findings. These data present a comprehensive understanding of false positive outcomes at colonoscopies following positive stool tests, which to our knowledge is the first such analysis.

Background Audience segmentation is an analysis technique that can identify meaningful subgroups within a population to inform the tailoring of dissemination strategies. We have conducted an empirical clustering audience segmentation study of licensed psychologists using survey data about the sources of knowledge they report most often consulting to guide their clinical decision-making. We identify meaningful subgroups within the population and inform the tailoring of dissemination strategies for evidence-based practice (EBP) materials. Method Data come from a 2018–2019 web-based survey of licensed psychologists who were members of the American Psychological Association (APA; N = 518, response rate = 29.8%). Ten dichotomous variables assessed sources that psychologists regularly consult to inform clinical decision-making (e.g., colleagues, academic literature, and practice guidelines). We used latent class analysis to identify segments of psychologists who turn to similar sources and named each segment based on the segment's most salient characteristics. Results Four audience segments were identified: the No-guidelines (45% of psychologists), Research-driven (16%), Thirsty-for-knowledge (9%), and No-reviews (30%). The four segments differed not only in their preferred sources of knowledge, but also in the types of evidence-based posttraumatic stress disorder (PTSD) treatments they provide, their awareness and usage intention of the APA PTSD clinical practice guideline, and attitudes toward clinical practice guidelines. Conclusion The results demonstrate that licensed psychologists are heterogeneous in terms of their knowledge-seeking behaviors and preferences for knowledge sources. The distinctive characteristics of these segments could guide the tailoring of dissemination materials and strategies to subsequently enhance the implementation of EBP among psychologists.

Antimicrobial resistance (AMR) is a global health crisis that threatens the health of humans and animals. The spread of resistance among species may occur through our shared environment. Prevention of AMR requires integrated monitoring systems, and these systems must account for the presence of AMR in the environment in order to be effective. The purpose of this study was to establish and pilot a set of procedures for utilizing freshwater mussels as a means of surveillance for microbes with AMR in Indiana waterways. One hundred and eighty freshwater mussels were sampled from three sites along the Wildcat Creek watershed in north-central Indiana. Specimens were evaluated for the presence of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), Escherichia coli, Campylobacter, and Salmonella species, and the isolates were tested for antimicrobial resistance. A total of 24 bacterial isolates were obtained from tissue homogenates of freshwater mussels collected at a site directly downstream from Kokomo, Indiana. Of these, 17 were Enterobacter spp., five were Escherichia coli, one was Pseudomonas aeruginosa, and one was Klebsiella pneumoniae. All isolates were resistant to three or more antimicrobial drug classes. Further work is necessary to determine the source of the bacterial species found in the mussels.

Escherichia coli (E. coli) is the most common Gram-negative pathogen isolated in human infections. Antimicrobial resistant (AMR) E. coli originating from dogs may directly or indirectly cause disease in humans. The objective of this study was to calculate the proportion of antimicrobial susceptible E. coli isolated from canine specimens submitted to the Indiana Animal Disease Diagnostic Laboratory and to identify temporal patterns of susceptibility among these isolates. Susceptibility data of 2,738 E. coli isolates from dogs from 2010 through 2019 were used in this study. Proportions of isolates susceptible to the various antimicrobials were calculated using SAS statistical software and the Cochran-Armitage trend test was used to investigate the temporal trends in susceptibility. A multivariable binary logistic regression model was built to investigate the association between host factors and AMR. Overall, 553/2,738 (20.2%) of the isolates were susceptible to 17 of the 27 antimicrobials examined. Of the 2,638 isolates examined for amikacin susceptibility, 2,706 (97.5%) were susceptible, 2,657/2,673 (99.4%) isolates were susceptible to imipenem, and 2,099/2,670 (78.6%) were susceptible to marbofloxacin. A significant decreasing trend in susceptibility was observed for amoxicillin-clavulanic acid (P

Pythium insidiosum is an infectious oomycete affecting dogs that develop the cutaneous or gastrointestinal form of pythiosis with a poor prognosis. If left untreated, pythiosis may be fatal. This organism is not a true fungus because its cell wall and cell membrane lack chitin and ergosterol, respectively, requiring specific treatment. Identifying the organism is challenging, as a hematoxylin and eosin (H&E) stain poorly stain the P. insidiosum hyphae and cannot be differentiated conclusively from other fungal or fungal-like organisms (such as Lagenidium sp.) morphologically. Our study aimed to develop a nested PCR to detect P. insidiosum and compare it with the traditional histopathologic detection of hyphae. Formalin-fixed, paraffin-embedded (FFPE) tissue scrolls from 26 dogs with lesions suggesting the P. insidiosum infection were assessed histologically, and DNA was extracted from the FFPE tissue sections for nested PCR. Agreement between the histologic stains, (H&E), periodic acid–Schiff (PAS), and/or Grocott methenamine silver (GMS) and the nested PCR occurred in 18/26 cases. Hyphae consistent with Pythium sp. were identified via histopathology in 57.7% of the samples, whereas the nested PCR detected P. insidiosum in 76.9% of samples, aiding in the sensitivity of the diagnosis of pythiosis in dogs. Using this combination of techniques, we report 20 canine cases of pythiosis over 18 years in Indiana and Kentucky, an unexpectedly high incidence for temperate climatic regions. Using a combination of histopathology evaluation and nested PCR is recommended to aid in the accurate diagnosis of pythiosis.

Background Due in part to the heterogeneity of the pulmonary circulation in patients with tetralogy of Fallot and major aortopulmonary collateral arteries (MAPCAs), research on this condition has focused on relatively basic anatomic characteristics. We aimed to detail pulmonary artery (PA) and MAPCA anatomy in a large group of infants, assess relationships between anatomy and early surgical outcomes, and consider systems for classifying MAPCAs. Methods and Results All infants (

Background and study aims Adenoma detection rate (ADR), the proportion of an endoscopist’s screening colonoscopies in which at least one adenoma is found, is an established quality metric. Several publications have suggested that a technique referred to as “one and done,” where less attention is paid to additional polyp detection following discovery of one likely adenoma, may be occurring 1 2 3. To investigate whether this practice occurs and provide additional context to the significance of ADR, we examined ADR by single and multiple adenomas in the statewide New Hampshire Colonoscopy Registry (NHCR). Patients and methods A total of 25,324 NHCR patients receiving screening colonoscopies between 2009 and 2014 by 69 endoscopists were analyzed. ADR was dichotomized into high (≥ 20 %) and low ( 1 adenoma) was dichotomized at mean values into high (≥ 1.5) and low (

Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins. We have previously determined the X-ray structure of the A46 C-terminal domain; however, the structure and function of the A46 N-terminal domain and its relationship to the C-terminal domain have remained unclear. Here, we biophysically characterize residues 1-83 of the N-terminal domain of A46 and present the X-ray structure at 1.55 Å. Crystallographic phases were obtained by a recently developed ab initio method entitled ARCIMBOLDO_BORGES that employs tertiary structure libraries extracted from the Protein Data Bank; data analysis revealed an all β-sheet structure. This is the first such structure solved by this method which should be applicable to any protein composed entirely of β-sheets. The A46(1-83) structure itself is a β-sandwich containing a co-purified molecule of myristic acid inside a hydrophobic pocket and represents a previously unknown lipid-binding fold. Mass spectrometry analysis confirmed the presence of long-chain fatty acids in both N-terminal and full-length A46; mutation of the hydrophobic pocket reduced the lipid content. Using a combination of high resolution X-ray structures of the N- and C-terminal domains and SAXS analysis of full-length protein A46(1-240), we present here a structural model of A46 in a tetrameric assembly. Integrating affinity measurements and structural data, we propose how A46 simultaneously interferes with several TIR-domain containing proteins to inhibit NF-κB activation and postulate that A46 employs a bipartite binding arrangement to sequester the host immune adaptors TRAM and MyD88.

In semi-arid environmental settings with sparse canopy covers, obtaining remotely sensed information on soil and vegetative growth characteristics at finer spatial and temporal scales than most satellite platforms is crucial for validating and interpreting satellite data sets. In this study, we used a ground-based NDVI system to provide continuous time series analysis of individual shrub species and soil surface characteristics in two different semi-arid environmental settings located in the Great Basin (NV, USA). The NDVI system was a dual channel SKR-1800 radiometer that simultaneously measured incident solar radiation and upward reflectance in two broadband red and near-infrared channels comparable to Landsat-5 TM band 3 and band 4, respectively. The two study sites identified as Spring Valley 1 site (SV1) and Snake Valley 1 site (SNK1) were chosen for having different species composition, soil texture and percent canopy cover. NDVI time-series of greasewood (Sarcobatus vermiculatus) from the SV1 site allowed for clear distinction between the main phenological stages of the entire growing season during the period from January to November, 2007. NDVI time series values were significantly different between sagebrush (Artemisia tridentata) and rabbitbrush (Chrysothamnus viscidiflorus) at SV1 as well as between the two bare soil types at the two sites. Greasewood NDVI from the SNK1 site produced significant correlations with chlorophyll index (r = 0.97), leaf area index (r = 0.98) and leaf xylem water potential (r = 0.93). Whereas greasewood NDVI from the SV1 site produced lower correlations (r = 0.89, r = 0.73), or non significant correlations (r = 0.32) with the same parameters, respectively. Total percent cover was estimated at 17.5% for SV1 and at 63% for SNK1. Results from this study indicated the potential capabilities of using this ground-based NDVI system to extract spatial and temporal details of soil and vegetation optical properties not possible with satellite derived NDVI.

To establish the views of research volunteers on the consent process; to explore their views on the consent process in different research scenarios; to inform debate on emerging models of consent for participation in research.2,308 adult volunteers from the TwinsUK Registry (www.twinsuk.ac.uk) completed an online survey about their views on the consent process for use of their DNA and medical information in research. Their views on the re-consenting process in different scenarios were assessed.The majority of volunteers preferred to be informed of the identity of the main researcher of a study in which they are participating, which is contrary to current practice. Over 80% were willing to complete the consent process online instead of face to face. On the whole, respondents did not view their DNA differently from their medical information with regard to the consent process. Research participants were more willing to give broad consent to cover future research if their DNA was to be used by the original researcher than by another researcher, even if the disease under investigation varied, in contrast to the traditional 'gold standard' whereby specific consent is required for all new research projects.In some scenarios, research participants reported that they would be comfortable with not signing a new consent form for future research uses of their data and DNA, and are comfortable with secure, online consent processes rather than traditional face-to-face consent processes. Our findings indicate that the perceived relationship between research participants and researchers plays an important role in shaping preferences regarding the consent process and suggest that this relationship is not captured by traditional consent processes. We argue that the development of new formats of consent should be informed by empirical research on volunteers' perceptions and preferences regarding the consent process.

Qualitative researchers must be aware of and explicit about their social background as well as political and ideological assumptions. To facilitate this awareness, we believe that researchers need to begin with their own story as they seek to understand the stories of others. Taking into account the vulnerable act of storytelling, it is salient to consider how to share personal narratives in an authentic way within academic settings. In this article, we share our process and reflections of engaging in reflexive and dialogical storytelling. The focus of the article is the re-storying of one researcher's experience as she and her research team explore her emotions and positionality prior to conducting research on First Nations men's narratives of identity. We integrate a series of methodological lessons concerning reflexivity throughout the re-storying.

The proportion of positive Leptospira microscopic agglutination tests for 23,005 dogs significantly increased from 2002 to 2004 (p

ABSTRACT The Pseudomonas aeruginosa extracytoplasmic functioning (ECF) sigma factor σ22 is encoded by algT/algU and is inhibited by anti-sigma factor MucA. σ22 was originally discovered for its essential role in the expression of the exopolysaccharide alginate by mucoid strains associated with chronic pulmonary infection. However, σ22 is now known to also have a large regulon associated with the response to cell wall stress. Our recent transcriptome analysis identified 293 open reading frames (ORFs) in the σ22 stress stimulon that include genes for outer envelope biogenesis and remodeling, although most of the genes have undefined functions. To better understand the σ22-dependent stress response, mutants affected in 27 genes of the σ22 stimulon were examined and expression was studied with lacZ fusions. Mutants constructed in the 27 genes showed no major change in response to cell wall-acting antibiotics or growth at elevated temperatures nor in alginate production. The mutants were examined for their effects on the expression of the σ22-dependent promoter of the alginate biosynthetic operon (PalgD) as a measure of σ22 derepression from MucA. By testing PalgD expression under both planktonic and sessile growth conditions, 11 genes were found to play a role in the stress response that activates σ22. Some mutations caused an increase or a decrease in the response to cell wall stress. Interestingly, mutations in 7 of the 11 genes caused constitutive PalgD expression under nonstressed conditions and thus showed that these genes are involved in maintaining envelope homeostasis. Mutations in PA0062 and PA1324 showed constitutive PalgD expression during both the planktonic and the sessile modes of growth. However, the PA5178 mutation caused constitutive PalgD expression only during planktonic growth. In contrast, mutations in PA2717, PA0567, PA3040, and PA0920 caused constitutive PalgD expression only in the sessile/biofilm mode of growth. This provides evidence that the σ22 stimulon for cell envelope homeostasis overlaps with biofilm control mechanisms. IMPORTANCE During chronic lung infections, such as in cystic fibrosis patients, Pseudomonas aeruginosa produces the exopolysaccharide alginate and forms biofilms that shield the organisms from the immune response and increase resistance to antibiotics. Activation of alginate genes is under the control of an extracytoplasmic stress response system that releases an alternative sigma factor (σ22) in response to cell wall stress and then activates expression of a large regulon. In this study, a mutant analysis of 27 members of the regulon showed that 11 play a role in envelope homeostasis and affect the stress response system itself. Interestingly, some genes demonstrate effects only in either the planktonic (free-swimming) or the sessile (biofilm) mode of growth, which leads to persistence and antibiotic tolerance. The studies presented here provide an important initial step in dissecting the mechanisms that regulate a critical signal transduction pathway that impacts P. aeruginosa pathogenesis.

Giant cell tumor of soft tissue originally described in 1972 in two different series by Salm and Sissons is a rare entity, which is clinically and histopathologically indistinguishable from giant cell tumor of bone. Usually involve thigh, trunk, and lower extremities but rarely involve the hands. GCT-ST is a benign tumor, which can transform into malignant form and also has potential for recurrence and metastasis. We present an otherwise healthy, middle age female who originally presented with swellings on her left finger was diagnosed with giant cell tumor of soft tissue hand.

In view of the increasing availability of commercial internet-based Personal Genome Testing (PGT), this study aimed to explore the reasons why people would consider taking such a test and how they would use the genetic risk information provided.A self-completion questionnaire assessing public awareness and interest in PGT and motivational reasons for undergoing PGT was completed by 4,050 unselected adult volunteers from the UK-based TwinsUK register, aged 17 to 91 (response rate 62%). Only 13% of respondents were aware of the existence of PGT. After reading a brief summary about PGT, one in twenty participants (5%) were potentially interested at current prices (£250), however this proportion rose to half (50%) if the test was free of charge. Nearly all respondents who were interested in free PGT reported they would take the test to encourage them to adopt a healthier lifestyle if found to be at high genetic risk of a disease (93%). Around 4 in 5 respondents would have the test to convey genetic risk information to their children and a similar proportion felt that having a PGT would enable their doctor to monitor their health more closely. A TwinsUK research focus group also indicated that consumers would consult their GP to help interpret results of PGT.This hypothetical study suggests that increasing publicity and decreasing costs of PGT may lead to increased uptake, driven in part by the general public's desire to monitor and improve their health. Although the future extent of the clinical utility of PGT is currently unknown, it is crucial that consumers are well informed about the current limitations of PGT. Our results suggest that health professionals will inevitably be required to respond to individuals who have undergone PGT. This has implications for health service providers regarding both cost and time.

Increasingly research involving Indigenous people is being undertaken by Indigenous researchers, who bring forward worldviews that shape the approach of the research, the theoretical and conceptual frameworks, and the epistemology, methodology, and ethics. Many times such research bridges Western practices and Indigenous knowledges; however, bringing together these two worldviews can also present challenges. In this paper the author explores the challenges and lessons learned in the practical application of an Indigenous research framework and qualitative inquiry. Two qualitative Indigenous research methods, sharing circles and Anishnaabe symbol-based reflection, will be discussed.

Cyclic nucleotides (cAMP and cGMP) regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB) domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels) using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1) the phosphate binding cassette (PBC), which binds the cAMP ribose-phosphate, 2) the "hinge," a flexible helix, which contacts the PBC, 3) the beta(2,3) loop, which provides precise positioning of an invariant arginine from the PBC, and 4) a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif). The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the beta(2,3) loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP) represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.

Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

The role of transposable elements in sculpting the genome is well appreciated but remains poorly understood. Some organisms, such as humans, do not have active transposons; however, transposable elements were presumably active in their ancestral genomes. Of specific interest is whether the DNA surrounding the sites of transposon excision become recombinogenic, thus bringing about homologous recombination. Previous studies in maize and Drosophila have provided conflicting evidence on whether transposon excision is correlated with homologous recombination. Here we take advantage of an atypical Dissociation (Ds) element, a maize transposon that can be mobilized by the Ac transposase gene in Arabidopsis thaliana, to address questions on the mechanism of Ds excision. This atypical Ds element contains an adjacent 598 base pairs (bp) inverted repeat; the element was allowed to excise by the introduction of an unlinked Ac transposase source through mating. Footprints at the excision site suggest a micro-homology mediated non-homologous end joining reminiscent of V(D)J recombination involving the formation of intra-helix 3' to 5' trans-esterification as an intermediate, a mechanism consistent with previous observations in maize, Antirrhinum and in certain insects. The proposed mechanism suggests that the broken chromosome at the excision site should not allow recombinational interaction with the homologous chromosome, and that the linked inverted repeat should also be mobilizable. To test the first prediction, we measured recombination of flanking chromosomal arms selected for the excision of Ds. In congruence with the model, Ds excision did not influence crossover recombination. Furthermore, evidence for correlated movement of the adjacent inverted repeat sequence is presented; its origin and movement suggest a novel mechanism for the evolution of repeated elements. Taken together these results suggest that the movement of transposable elements themselves may not directly influence linkage. Possibility remains, however, for novel repeated DNA sequences produced as a consequence of transposon movement to influence crossover in subsequent generations.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P

It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype. We summarize what we have learned since the first structure, published in 1991, why our journey is still ongoing, and why it has been essential to share our structural information. For regulation of kinase activity, we focus on the cAMP-binding protein kinase regulatory subunits. By exploring full-length macromolecular complexes, we discovered not only allostery but also an essential motif originally attributed to crystal packing. Massive genomic data on disease mutations allows us to now revisit crystal packing as a treasure chest of possible protein:protein interfaces where the biological significance and disease relevance can be validated. It provides a new window into exploring dynamic intrinsically disordered regions that previously were deleted, ignored, or attributed to crystal packing. Merging of crystallography with cryo-electron microscopy, cryo-electron tomography, NMR, and millisecond molecular dynamics simulations is opening a new world for the signaling community where those structure coordinates, deposited in the Protein Data Bank, are just a starting point!

The public health impact of psychological science is maximized when it is disseminated clearly and compellingly to audiences who can act on it. Dissemination research can generate knowledge to help achieve this, but dissemination is understudied in the field of implementation science. As a consequence, the designs of dissemination strategies are typically driven by anecdote, not evidence, and are often ineffective. We address this issue by synthesizing key theory and findings from consumer psychology and detailing a novel research approach for "data-driven dissemination." The approach has 3 parts: (a) formative audience research, which characterizes an audience's awareness about, adoption of, and attitudes toward an intervention, as well as preferences for receiving information about it; (b) audience segmentation research, which identifies meaningful subgroups within an audience to inform the tailoring of dissemination strategies; and (c) dissemination effectiveness research, which determines the strategies that are most effective. This approach is then illustrated using the dissemination of the American Psychological Association's (APA, 2017) Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder (PTSD) in Adults as a case study. Data are presented from a 2018-2019 survey of licensed APA-member psychologists who treat adults with PTSD (n = 407, response rate = 29.8%). We present survey findings on awareness about, attitudes toward, and adoption of the guideline and find significant differences across these domains between psychologists who do and do not regularly use clinical practice guidelines. We conclude by discussing future directions to advance dissemination research and practice. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background and Rationale: ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice.Purpose and Objectives: This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting.Methods: An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law.Main Results: The committee designed its policy recommendations to promote five ethical goals: 1) to protect highly vulnerable patients, 2) to demonstrate respect for persons, 3) to provide appropriate medical care, 4) to safeguard against unacceptable discrimination, and 5) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6) institutions should employ this fair process even when state law authorizes procedures with less oversight.Conclusions: This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting.