Organic carbon accumulation in British saltmarshes.

Saltmarshes are a crucial component of the coastal carbon (C) system and provide a natural climate regulation service through the accumulation and long-term storage of organic carbon (OC) in their soils. These coastal ecosystems are under growing pressure from a changing climate and increasing anthropogenic disturbance. To manage and protect these ecosystems for C and to allow their inclusion in emissions and natural-capital accounting, as well as carbon markets, accurate and reliable estimates of OC accumulation are required. However, globally, such data are rare or of varying quality. Here, we quantify sedimentation rates and OC densities for 21 saltmarshes in Great Britain (GB). We estimate that, on average, saltmarshes accumulate OC at a rate of 110.88 ± 43.12 g C m-2 yr-1. This is considerably less than widely applied global saltmarsh averages. It is therefore highly likely that the contribution of northern European saltmarshes to global saltmarsh OC accumulation has been significantly overestimated. Taking account of the climatic, geomorphological, oceanographic, and ecological characteristics of all GB saltmarshes and the areal extent of different saltmarsh zones, we estimate that the 451.65 km2 of GB saltmarsh accumulates 46,563 ± 4353 t of OC annually. These low OC accumulation rates underline the importance of the 5.20 ± 0.65 million tonnes of OC already stored in these vulnerable coastal ecosystems. Going forward the protection and preservation of the existing stores of OC in GB saltmarshes must be a priority for the UK as this will provide climate benefits through avoided emissions several times more significant than the annual accumulation of OC in these ecosystems.

Effects of cyanoacrylate on leakage pressures of cooled canine cadaveric jejunal enterotomies.

OBJECTIVE: To compare the intraluminal initial and maximal pressures of enterotomies closed using three different techniques (single-layer appositional continuous closure; closure with cyanoacrylate; a single-layer appositional closure augmented with cyanoacrylate) in a cooled canine cadaveric jejunal model and to report the initial leak location in all samples. STUDY DESIGN: Experimental, ex-vivo study. SAMPLE POPULATION: Grossly normal chilled small intestine segments from three canine cadavers. METHODS: A total of 45 chilled jejunal segments (n = 15 segments/group) were assigned to a handsewn group (HSE), a cyanoacrylate only group (CE) and a handsewn and cyanoacrylate group (HS + CE). A 2 cm antimesenteric enterotomy was performed and closure with one of the above techniques. Initial leakage pressures (ILP), maximal intraluminal pressures (MIP) and initial leakage location were recorded by a single observer. RESULTS: Handsewn enterotomies leaked at higher ILP when augmented with cyanoacrylate (83.3 ± 4.6 mmHg, p < .001) compared to both the HSE group (43.8 ± 5.3 mmHg) and the CE group (18.6 ± 3.5 mmHg). Those sealed with cyanoacrylate only leaked at a lower MIP compared with the other groups (p < .001). Maximal intraluminal pressures did not differ between handsewn enterotomies, whether augmented or not (p = .19). CONCLUSION: Reinforcement of a sutured enterotomy closure with cyanoacrylate was easy to perform and resulted in significantly increased initial leak pressures in cadaveric jejunum. CLINICAL SIGNIFICANCE: The increased leakage pressures achieved by reinforcing enterotomies with cyanoacrylate could consequently reduce the incidence of postoperative intestinal leakage following an enterotomy and may result in reduced patient morbidity or mortality.

Why is safety in intrapartum electronic fetal monitoring so hard? A qualitative study combining human factors/ergonomics and social science analysis.

BACKGROUND: Problems in intrapartum electronic fetal monitoring with cardiotocography (CTG) remain a major area of preventable harm. Poor understanding of the range of influences on safety may have hindered improvement. Taking an interdisciplinary perspective, we sought to characterise the everyday practice of CTG monitoring and the work systems within which it takes place, with the goal of identifying potential sources of risk. METHODS: Human factors/ergonomics (HF/E) experts and social scientists conducted 325 hours of observations and 23 interviews in three maternity units in the UK, focusing on how CTG tasks were undertaken, the influences on this work and the cultural and organisational features of work settings. HF/E analysis was based on the Systems Engineering Initiative for Patient Safety 2.0 model. Social science analysis was based on the constant comparative method. RESULTS: CTG monitoring can be understood as a complex sociotechnical activity, with tasks, people, tools and technology, and organisational and external factors all combining to affect safety. Fetal heart rate patterns need to be recorded and interpreted correctly. Systems are also required for seeking the opinions of others, determining whether the situation warrants concern, escalating concerns and mobilising response. These processes may be inadequately designed or function suboptimally, and may be further complicated by staffing issues, equipment and ergonomics issues, and competing and frequently changing clinical guidelines. Practice may also be affected by variable standards and workflows, variations in clinical competence, teamwork and situation awareness, and the ability to communicate concerns freely. CONCLUSIONS: CTG monitoring is an inherently collective and sociotechnical practice. Improving it will require accounting for complex system interdependencies, rather than focusing solely on discrete factors such as individual technical proficiency in interpreting traces.

The voice characterisation checklist: psychometric properties of a brief clinical assessment of voices as social agents.

Aim: There is growing interest in tailoring psychological interventions for distressing voices and a need for reliable tools to assess phenomenological features which might influence treatment response. This study examines the reliability and internal consistency of the Voice Characterisation Checklist (VoCC), a novel 10-item tool which assesses degree of voice characterisation, identified as relevant to a new wave of relational approaches. Methods: The sample comprised participants experiencing distressing voices, recruited at baseline on the AVATAR2 trial between January 2021 and July 2022 (n = 170). Inter-rater reliability (IRR) and internal consistency analyses (Cronbach's alpha) were conducted. Results: The majority of participants reported some degree of voice personification (94%) with high endorsement of voices as distinct auditory experiences (87%) with basic attributes of gender and age (82%). While most identified a voice intention (75%) and personality (76%), attribution of mental states (35%) to the voice ('What are they thinking?') and a known historical relationship (36%) were less common. The internal consistency of the VoCC was acceptable (10 items, α = 0.71). IRR analysis indicated acceptable to excellent reliability at the item-level for 9/10 items and moderate agreement between raters' global (binary) classification of more vs. less highly characterised voices, κ = 0.549 (95% CI, 0.240-0.859), p < 0.05. Conclusion: The VoCC is a reliable and internally consistent tool for assessing voice characterisation and will be used to test whether voice characterisation moderates treatment outcome to AVATAR therapy. There is potential wider utility within clinical trials of other relational therapies as well as routine clinical practice.

Rapid Generation of P(V)-F Bonds Through the Use of Sulfone Iminium Fluoride Reagents.

Phosphorus-fluorine bonds have become increasingly relevant in the pharmaceutical industry. To continue their exploration, more efficient synthetic methods are needed. Here, we report the application of sulfone iminium fluoride (SIF) reagents to the synthesis of P(V)-F bonds. The SIF reagents promote the deoxyfluorination of phosphinic acids in just 60 s with excellent yields and scope. The same P(V)-F products can also be synthesized from secondary phosphine oxides using an SIF reagent.

Full-thickness endotracheal tube defect resulting in an anaesthetic circuit leak.

BACKGROUND: Loss of endotracheal tube (ETT) integrity secondary to dental damage is reported in the human literature. OBJECTIVE: To describe this problem in equine anaesthesia. STUDY DESIGN: Case report. CLINICAL SUMMARY: An 18-year-old Standardbred gelding presented out of hours with colic signs. Findings on clinical examination and pain refractory to analgesia meant that exploratory laparotomy was elected for. Prior to general anaesthesia (GA) leak testing of the anaesthetic machine was performed and the pilot balloon of the endotracheal tube (ETT) was inflated to confirm cuff integrity. Intermittent-positive pressure ventilation (IPPV) was initiated immediately following placement in dorsal recumbency and connection to the anaesthetic machine. During the inspiratory phase of IPPV, a loud gas leak was audible from the oropharynx and minimal thoracic excursion was observed, with repeated inflations of the ETT cuff unsuccessful at abolishing the leak. Due to suspicion of a defect within the silicone ETT itself, a support arm was used to abolish the curvature of the ETT, maintaining it in a straighter plane. This intervention abolished the leak allowing effective IPPV. After completion of GA, a close inspection of the ETT revealed a full-thickness laceration, thought to be a result of dental damage at an earlier date. MAIN LIMITATIONS: A single case is described. CONCLUSIONS: This report emphasises the importance of thorough inspection of the ETT prior to use to effectively secure the airway and enable IPPV provision in critical cases.

Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection.

There are conflicting data about level and duration of Abs to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children after symptomatic or asymptomatic infection. In this human population, we enrolled adults and children in a prospective 6-mo study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n = 8; adults, n = 16), 2) symptomatic, PCR-, or untested (children, n = 27), 3) asymptomatic exposed (children, n = 13), and 4) asymptomatic, no known exposure (children, n = 19). Neutralizing Abs (nAbs) and IgG Abs to SARS-CoV-2 Ags and spike protein variants were measured by multiplex serological assay. All SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 mo was not significant in symptomatic children (100 to 87.5%; p = 0.32) in contrast to adults (81.3 to 50.0%; p = 0.03). Among children with nAb (n = 22), nAb titers and change in titers over 6 mo were similar in symptomatic and asymptomatic children. In children and adults, nAb levels postinfection were 10-fold lower than those reported after SARS-CoV-2 mRNA vaccination. Levels of IgG Abs in children to SARS-CoV-2 Ags and spike protein variants were similar to those in adults. IgG levels to primary Ags decreased over time in children and adults, but levels to three spike variants decreased only in children. Children with asymptomatic or symptomatic SARS-CoV-2 infection develop nAbs that remain present longer than in adults but wane in titer over time and broad IgG Abs that also wane in level over time. However, nAb levels were lower postinfection than those reported after immunization.

Crowdsourcing citation-screening in a mixed-studies systematic review: a feasibility study.

BACKGROUND: Crowdsourcing engages the help of large numbers of people in tasks, activities or projects, usually via the internet. One application of crowdsourcing is the screening of citations for inclusion in a systematic review. There is evidence that a 'Crowd' of non-specialists can reliably identify quantitative studies, such as randomized controlled trials, through the assessment of study titles and abstracts. In this feasibility study, we investigated crowd performance of an online, topic-based citation-screening task, assessing titles and abstracts for inclusion in a single mixed-studies systematic review. METHODS: This study was embedded within a mixed studies systematic review of maternity care, exploring the effects of training healthcare professionals in intrapartum cardiotocography. Citation-screening was undertaken via Cochrane Crowd, an online citizen science platform enabling volunteers to contribute to a range of tasks identifying evidence in health and healthcare. Contributors were recruited from users registered with Cochrane Crowd. Following completion of task-specific online training, the crowd and the review team independently screened 9546 titles and abstracts. The screening task was subsequently repeated with a new crowd following minor changes to the crowd agreement algorithm based on findings from the first screening task. We assessed the crowd decisions against the review team categorizations (the 'gold standard'), measuring sensitivity, specificity, time and task engagement. RESULTS: Seventy-eight crowd contributors completed the first screening task. Sensitivity (the crowd's ability to correctly identify studies included within the review) was 84% (N = 42/50), and specificity (the crowd's ability to correctly identify excluded studies) was 99% (N = 9373/9493). Task completion was 33 h for the crowd and 410 h for the review team; mean time to classify each record was 6.06 s for each crowd participant and 3.96 s for review team members. Replicating this task with 85 new contributors and an altered agreement algorithm found 94% sensitivity (N = 48/50) and 98% specificity (N = 9348/9493). Contributors reported positive experiences of the task. CONCLUSION: It might be feasible to recruit and train a crowd to accurately perform topic-based citation-screening for mixed studies systematic reviews, though resource expended on the necessary customised training required should be factored in. In the face of long review production times, crowd screening may enable a more time-efficient conduct of reviews, with minimal reduction of citation-screening accuracy, but further research is needed.

Validity of the Occupational Performance Scale of the Sensory Processing Three Dimensions Measure.

IMPORTANCE: The Sensory Processing Three Dimensions (SP3D) Occupational Performance Scale (OPS) is a new parent-report measure developed for use as part of a comprehensive occupational therapy evaluation for children with sensory processing and integration challenges. OBJECTIVE: To examine the internal consistency and discriminant validity of the SP3D OPS, examine relations between sensory processing subtypes and areas of occupational performance (OP), and determine the extent to which specific sensory processing challenges predict problems with OP. DESIGN: Nonexperimental, descriptive design using correlations, group comparisons, and stepwise regression. SETTING: Three outpatient clinic sites in the United States. PARTICIPANTS: Parents of 66 children (33 typically developing and 33 with clinical problems) ranging in age from 4 to 12 yr. OUTCOMES AND MEASURES: The SP3D OPS and SP3D Inventory were completed by parents to address psychometrics of the SP3D OPS and determine the association between sensory processing and integration challenges with OP. RESULTS: Internal consistency reliability and discriminant validity of the SP3D OPS were supported. Scores on the Dyspraxia and Sensory Overresponsivity subscales best predicted deficits in OP. Significant relations were found between sensory processing and integration and competency in multiple OP areas. CONCLUSIONS AND RELEVANCE: The SP3D OPS shows promise as a measure of OP. The OP deficits among children with sensory processing and integration challenges are in part due to subtype presentation. Further studies of the SP3D OPS's reliability and validity are needed. WHAT THIS ARTICLE ADDS: This new occupational performance measure shows associations between sensory processing and OP areas. It can provide information to support therapists in identifying family concerns relevant to goal setting and intervention.

Evaluating Sensory Integration/Sensory Processing Treatment: Issues and Analysis.

For more than 50 years, "Sensory Integration" has been a theoretical framework for diagnosing and treating disabilities in children under the umbrella of "sensory integration dysfunction" (SID). More recently, the approach has been reframed as "the dimensions of sensory processing" or SPD in place of SID, so the review herein describes this collective framework as sensory integration/sensory processing treatment (SI/SP-T) for ASD. This review is not focused on diagnosis of SI/SPD. Broadly, the SI/SPD intervention approach views a plethora of disabilities such as ADHD, ASD, and disruptive behavior as being exacerbated by difficulties in modulating and integrating sensory input with a primary focus on contributions from tactile, proprioceptive, and vestibular systems which are hypothesized to contribute to core symptoms of the conditions (e.g., ASD). SI/SP intervention procedures include sensory protocols designed to enhance tactile, proprioceptive, and vestibular experiences. SI/SP-T procedures utilize equipment (e.g., lycra swings, balance beams, climbing walls, and trampolines), specific devices (e.g., weighted vests, sensory brushes) and activities (e.g., placing hands in messy substances such as shaving cream, sequenced movements) hypothesized to enhance sensory integration and sensory processing. The approach is reviewed herein to provide a framework for testing SI/SP-T using widely accepted clinical trials and event coding methods used in applied behavior analysis (ABA) and other behavioral interventions. Also, a related but distinct neuroscientific paradigm, multisensory integration, is presented as an independent test of whether SI/SP-T differentially impacts sensory integration and/or multisensory integration. Finally, because SI/SP-T activities include many incidental behavioral events that are known as developmental facilitators (e.g., contingent verbal models/recasts during verbal interactions), there is a compelling need to control for confounds to study the unique impact of sensory-based interventions. Note that SI/SP-T includes very specific and identifiable procedures and materials, so it is reasonable to expect high treatment fidelity when testing the approach. A patient case is presented that illustrates this confound with a known facilitator (recast intervention) and a method for controlling potential confounds in order to conduct unbiased studies of the effects of SI/SP-T approaches that accurately represent SI/SP-T theories of change.

Wireless Measurement of Sympathetic Arousal During in vivo Occupational Therapy Sessions.

PURPOSE: One goal of occupational therapists working with children who have sensory processing challenges is the regulation of arousal. Regulation strategies have not been evaluated using an empirical measure of physiological arousal. OBJECTIVE: To establish the feasibility of using an objective physiologic measure of sympathetic arousal in therapeutic settings and explore the relation between therapeutic activities and sympathetic arousal. To evaluate changes in electrodermal activity (EDA) during occupational therapy sessions. METHODS: Twenty-two children identified with sensory modulation dysfunction (SMD) wore a wireless EDA sensor during 50 min occupational therapy sessions (n = 77 sessions). RESULTS: All children were able to wear the sensor on the lower calf without being distracted by the device. The five insights below are based on a comparison of EDA recordings in relation to therapists' reflections describing how sympathetic arousal might correspond to therapeutic activities. CONCLUSION: Objective physiological assessment of a child's sympathetic arousal during therapy is possible using a wireless EDA measurement system. Changes in EDA may correspond directly with therapeutic activities. The article provides a foundation for designing future therapeutic studies that include continuous measures of EDA.

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes.

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)-containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA-GLUT4-GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA-GLUT4-GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells.

Early Identification of Sensory Processing Difficulties in High-Risk Infants.

OBJECTIVE: Our objective was to determine the extent to which young children at high risk for sensory processing difficulties differed from those who were at low risk. METHOD: We compared high- versus low-risk young children using standardized measures. High-risk participants had older siblings identified as having sensory processing difficulties after a comprehensive occupational therapy evaluation (n = 13); low-risk participants (n = 16) had typically developing siblings and no family history of sensory or other neurological disorders. RESULTS: High-risk infants scored significantly lower on the Language and Cognitive scales of the Bayley Scales of Infant and Toddler Development-Third Edition. The high-risk group presented with more atypical positions on the Toddler and Infant Motor Evaluation and fewer sensation-seeking behaviors on the Toddler Sensory Profile-2. CONCLUSION: Results suggest that sensory, motor, cognitive, and language dimensions may be associated with sensory processing difficulties. Implications exist for the design of future studies and for early intervention.

Sensory over-responsivity: parent report, direct assessment measures, and neural architecture.

Background: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. Methods: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. Results: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. Conclusions: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR.

Initial Studies of Validity of the Sensory Processing 3-Dimensions Scale.

AIMS: This study examined the validity of a new measure of sensory processing for children, the Sensory Processing 3-Dimensions Scale (SP-3D). The SP-3D is a performance-based measure for children ages three to thirteen years, designed to assess sensory processing abilities, and identify the three patterns of sensory processing disorder (SPD) and related subtypes, including sensory modulation, sensory discrimination, and sensory-based motor disorders. METHODS: Age trends were explored using descriptive statistics and graphing techniques with a sample of children with and without SPD. SP-3D scores were correlated with scores from the Sensory Processing Measure (SPM) to examine criterion-related validity. Discriminant validity was assessed by comparing SP-3D scores from children with and without SPD. RESULTS: Age trends of SP-3D scores supported sensory discrimination, praxis and postural functions as developmental constructs. Several mild to moderate correlations were found between the scores of the SP-3D and the SPM, indicating that the tools are measuring similar constructs, and supporting the SP-3D as a measure of sensory processing. Modulation and Motor Behavior Scores from the SP-3D discriminated typically developing children from those with SPD, while results from subtests measuring sensory discrimination, postural and praxis were mixed regarding capacity for discrimination suggesting revision to several items. CONCLUSION: The study provides preliminary evidence of the SP-3D as a valid measure of sensory processing abilities and dysfunction. Further research regarding the reliability and validity of the SP-3D are needed.

Endovascular Repair of Superior Mesenteric Arteriovenous Fistula Causing Early Mesenteric Steal Syndrome Following Abdominal Gunshot Injury.

INTRODUCTION: Superior mesenteric arteriovenous fistulae (SMAVF) are rare, usually secondary to trauma or iatrogenic injury and typically present sometime after the initial insult. REPORT: A 30 year old male underwent immediate laparotomy for abdominal gunshot injury. The small bowel mesentery contained a large haematoma and a palpable thrill. CT demonstrated a large SMAVF. At re-look laparotomy, small bowel ischaemia was noted and following this endovascular SMA stent graft insertion was performed, with excellent angiographic and clinical results. CONCLUSION: The first report of immediate traumatic SMAVF leading to acute mesenteric steal syndrome and successful management with endovascular stent insertion is presented.

Investigating Misophonia: A Review of the Empirical Literature, Clinical Implications, and a Research Agenda.

Misophonia is a neurobehavioral syndrome phenotypically characterized by heightened autonomic nervous system arousal and negative emotional reactivity (e. g., irritation, anger, anxiety) in response to a decreased tolerance for specific sounds. The aims of this review are to (a) characterize the current state of the field of research on misophonia, (b) highlight what can be inferred from the small research literature to inform treatment of individuals with misophonia, and (c) outline an agenda for research on this topic. We extend previous reviews on this topic by critically reviewing the research investigating mechanisms of misophonia and differences between misophonia and other conditions. In addition, we integrate this small but growing literature with basic and applied research from other literatures in a cross-disciplinary manner.

Complete Remission Following Pembrolizumab in a Woman with Mismatch Repair-Deficient Endometrial Cancer and a Germline BRCA1 Mutation.

Endometrial cancer is the most common gynecologic malignancy in the U.S. and, although the majority of cases present at an early stage and can be treated with curative intent, those who present with advanced disease, or develop metastatic or recurrent disease, have a poorer prognosis. A subset of endometrial cancers exhibit mismatch repair (MMR) deficiency. It is now recognized that MMR-deficient cancers are particularly susceptible to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, and in a landmark judgement in 2017, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab for these tumors, the first tumor-agnostic approval of a drug. However, less is known about the sensitivity to PD-1 blockade among patients with known mutations in double-strand break DNA repair pathways involving homologous recombination, such as those in BRCA1 or BRCA2. Here we report a case of a patient with an aggressive somatic MMR-deficient endometrial cancer and a germline BRCA1 who experienced a rapid complete remission to pembrolizumab. KEY POINTS: Endometrial cancers, and in particular endometrioid carcinomas, should undergo immunohistochemical testing for mismatch repair proteins.Uterine cancers with documented mismatch repair deficiency are candidates for treatment with programmed cell death protein 1 inhibition.Genomic testing of recurrent, advanced, or metastatic tumors may be useful to determine whether patients are candidates for precision therapies.