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BACKGROUND The development and characteristics of inflammatory bowel disease (IBD) in Ethiopian Jewish immigrants to Israel were investigated. METHODS A case-control study was conducted in 7 tertiary care hospitals in Israel. Patients of Ethiopian origin with IBD >6 months were included. Time of disease onset after immigration and age at diagnosis were recorded. Randomly chosen patients with IBD of Ashkenazi Jewish origin served as controls. Demographics and clinical parameters were compared between the 2 cohorts. RESULTS Thirty-two Ethiopian patients with IBD were compared with 33 Ashkenazi Jewish patients with IBD. Crohn's disease (CD) was more prevalent than ulcerative colitis (UC) in the Ethiopian group compared with the Ashkenazi group (94% versus 73%, P = 0.02). No Ethiopian-origin patient had a positive family history of IBD compared with 42% of Ashkenazi-origin patients (P < 0.001). Arthritis was more common in Ashkenazi than in Ethiopian patients (27% versus 3%, P < 0.01). One Ashkenazi patient with CD had upper gastrointestinal involvement compared with 7 (23%) in the Ethiopian group (P < 0.02). All other clinical measures were similar between the 2 cohorts. The Ethiopian group lived in Israel with a mean of 13 ± 5 years, and 75% were born in Ethiopia. The shortest time between immigration and developing IBD was 8 years (range, 8-26; median 16 yrs). No Ethiopian patient was diagnosed before immigration. CONCLUSIONS Ethiopian Jews migrating to Israel are at risk of developing IBD. Larger cohorts are needed to determine the relative importance of environmental and genetic factors that cause IBD in these patients.

BACKGROUND AND THE STUDY AIM Crohn's disease (CD) is a chronic inflammatory disorder defined as a transmural inflammation of the bowel wall, affecting the small and large intestine. The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity. We extended the Niv score to the colon and have a comprehensive view of the whole intestine. METHODS We evaluated 3 parameters of intestinal pathology: A, Inflammation; B, Extent of disease; C, Presence of strictures. The scoring formula is as follows: CEDCAIic=(A1×B1+C1)+(A2×B2+C2)+(A3×B3+C3)+(A4×B4+C4) (1=proximal small bowel, 2=distal small bowel, 3=right colon, 4=left colon). RESULTS The median CECDAIic score was 15.5 (range, 0 to 42), and the mean±SD score was 17.2±11.5. The CECDAIic scores per patient were similar among the 5 observers. Kendall's coefficient of concordance was high and significant for almost all the parameters examined except for strictures in the proximal small bowel and distal colon. Nevertheless, the coefficients for the small bowel and for the whole intestine were high, 0.85 and 0.77, P

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice.This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation.The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components.A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

Background and study aims A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. Patients and methods In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. Results 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). Conclusions The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Background Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. Aim To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. Materials and methods Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. Results Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. Conclusions In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.

Background Capsule endoscopy is a relatively new imaging tool for the detection of small bowel pathology. The assessment of the severity of Crohn’s disease by capsule endoscopy is not standardized and is limited by interobserver variations in interpreting the findings. Aim To develop, assess and validate a new, simple capsule endoscopy Crohn’s disease activity index (CECDAI) in order to grade the severity of small bowel capsule endoscopy findings. Methods The system involves dividing the small bowel into proximal and distal segments according to transit time and then rating each segment on the basis of three parameters: inflammation (A), extent of disease (B) and presence of strictures (C). The segmental score is calculated by multiplying the inflammation subscore by the disease-subextent score and adding the stricture subscore (A × B + C); the final score is calculated by adding the two segmental scores: CECDAI = (A1 × B1 + C1) + (A2 × B2 + C2). In the present study, four senior endoscopists (two with experience in capsule endoscopy interpretation) independently reviewed coded capsule endoscopy videos of 20 patients with Crohn’s disease and rated them according to the CECDAI. Interobserver variability was analyzed by Spearman’s correlation test. Results The CECDAI total scores for the 20 patients ranged from 0 to 26. The correlation for the total score assigned between every two observers was 0.867 (0.700−1.000 = strong degree association; WHO classification; P < 0.0001). The Kappa statistics for agreement among all observers for the subscores and total scores were as follows: A1, 0.31 ± 0.05; B1, 0.25 ± 0.05; C1 (no cases); A2, 0.51 ± 0.05; B2, 0.57 ± 0.05; C2, 0.27 ± 0.07. All examiners reported that the system was simple to learn and apply. Conclusions The CECDAI score may serve as a convenient, reliable and reproducible diagnostic and follow-up tool for use by experienced endoscopists in the evaluation of patients with Crohn’s disease of the small bowel.

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Background & Aims Capsule colonoscopy is a minimally invasive imaging method. We measured the accuracy of this technology in detecting polyps 6 mm or larger in an average-risk screening population. Methods In a prospective study, asymptomatic subjects (n = 884) underwent capsule colonoscopy followed by conventional colonoscopy (the reference) several weeks later, with an endoscopist blinded to capsule results, at 10 centers in the United States and 6 centers in Israel from June 2011 through April 2012. An unblinded colonoscopy was performed on subjects found to have lesions 6 mm or larger by capsule but not conventional colonoscopy. Results Among the 884 subjects enrolled, 695 (79%) were included in the analysis of capsule performance for all polyps. There were 77 exclusions (9%) for inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes, 45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%−84%) and 93% specificity (95% CI, 91%–95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%−86%) and 97% specificity (95% CI, 96%–98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%−93) and 82% specificity (95% CI, 80%–83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%–97%) and 95% specificity (95% CI, 94%–95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively, of false-negative findings from capsule analyses. Conclusions In an average-risk screening population, technically adequate capsule colonoscopy identified individuals with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity and 82% specificity. Capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional studies are needed to improve capsule detection of serrated lesions. Clinicaltrials.gov number: NCT01372878.

The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure.

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 +/- 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 +/- 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.

The present case study is of an 8-year old male who was found to have refractive instability due to corneal distortions that were associated with chronic habit of abnormal eye rubbing (CHAR). Psychiatric evaluation and treatment alleviated the CHAR and at the same time refraction stabilized and the cornea resumed a regular shape. Treatment of this case was made possible by close collaboration between the health care professionals caring for this child.

Introduction Colonoscopy of asymptomatic, healthy individuals for colorectal cancer screening rarely causes complications and adverse events. Thus, quality of life (QOL) of the participants should not be affected by the procedure. Aim The aim of the study was to isolate the influence of colonoscopy, by investigation QOL before and after the procedure in a cohort of consecutive patients with different indications. Methods This study is a prospective, longitudinal study, designed to compare the potential influence of colonoscopy on QOL. For a cohort of consecutive patients undergoing colonoscopy for various reasons and indications, we filled a QOL short form-36 and a short feedback questionnaire before, immediately after, and a month after the procedure. We also measured the quality of the endoscopy, the outcome in patients, and acceptability among patients. Results There was no significant change before and immediately after colonoscopy in any of the short form-36 parameters. Physical functioning, role limitation physical, pain, general health, vitality, social functioning, role limitation mental, and mental health had very similar scores before and 2-3 h after the procedure. There was a decrease in the physical functioning a month after the procedure (P=0.01). The same was found for non-inflammatory bowel disease patients, but not for inflammatory bowel disease patients. Conclusion Colonoscopy did not affect QOL in the short or the long duration after the procedure. As such, colonoscopy may be suitable as a part of screening programs. We believe that QOL estimation should be an integral part of assessment of a screening program.

Fecal immunochemical test (FIT) is gaining popularity as a screening tool for colorectal cancer. The introduction of capsule endoscopy (CE) enables an assessment of the relationship between small bowel (SB) lesions and FIT results.To determine whether SB lesions found by CE are associated with an increased rate of positive FIT.Consecutive patients undergoing CE for obscure occult gastrointestinal bleeding also underwent FIT. CE was performed using the PillCam SB and FIT was performed with OC-Micro (three samples, threshold 75 and 100 ng/ml).Fifty-one patients were included; the mean lowest hemoglobin was 9.1 ± 2.1 g/dl. Twenty-six patients (51.0%) had SB lesions identified by CE and were classified as the probable or suspected source of bleeding. At the threshold of 75 and 100 ng/ml, 12 of 26 (46.1%) and 10 of 26 (38.4%), respectively had a positive FIT. In contrast, only two of 25 (8.0%) patients without SB lesions had a positive FIT at both thresholds (P=0.002 and 0.010 respectively). The mean fecal hemoglobin in patients with SB lesions classified as probable or suspected source of bleeding versus patients with normal SB was 345.6 ± 773 and 25.0 ± 37.7 ng/ml, respectively (P=0.025).A positive FIT can be explained by significant SB lesions detected by CE. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and nonexplanatory colonoscopy should undergo further study of the SB.

BackgroundGastric carcinoid tumours type 1 (GCA1) originate from hyperplastic enterochromaffin-like (ECL) cells secondary to hypergastrinaemia. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. We conducted a multicentre prospective study to assess the effects of long-acting SSA on hypergastrinaemia and ECL-cell proliferation in patients with GCA1.MethodsWe studied 15 patients with GCA1 treated with monthly long-acting release octreotide (LAR) (20–30 mg; n=14) or Lanreotide 90 mg (n=1) for at least 6 months. Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from both tumours and surrounding mucosa before, and every 6–12 months following treatment. Sections were immunostained for neuroendocrine markers. The cell proliferation index Ki-67, intensity of staining before and after treatment and the degree of gastric wall invasion were also assessed.ResultsAll patients tolerated treatment well (mean follow-up of 18 months). In 11 patients (73%), a complete disappearance of the tumours at 1 year of treatment was observed on endoscopy, while in three patients (20%), the tumours decreased significantly in number and size. Gastrin levels normalized in 25% of patients, and were reduced by more than 80% in the remaining 75%.ConclusionsTreatment with SSAs in GCA1 leads to a substantial tumour load reduction, with a concomitant decrease of serum gastrin levels. Our data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1.

Successful colonoscopy depends on good preparation of the colon before the procedure. Inadequate preparation may lead to cancelled or repeat procedures and compromise patient safety, quality of care, and cost effectiveness. The primary aim of this study was to isolate factors that affect preparation success, especially in older, more severely ill, bedridden patients. The secondary aim was to examine the possible differences in preparation quality between ambulatory and hospitalized patients and the impact of a staff educational program on the preparation of hospitalized patients for colonoscopy. The study group included 303 consecutive ambulatory patients and 104 hospitalized patients referred for colonoscopy between January and March 2002, before the department introduced an educational program on colonoscopy preparation, and 310 ambulatory patients and 105 hospitalized patients referred for colonoscopy between January and March 2003. All patients completed an ad hoc questionnaire, and the findings were compared between ambulatory and hospitalized patients and between patients treated before and after the educational program. Polyethylene glycol was used significantly more often for colonoscopy preparation in hospitalized patients than in ambulatory patients (53.1% versus 8.8%; P=.0001). The hospitalized group was characterized by more incomplete or repeated colonoscopies and poorer preparation quality. On multivariate analysis, the variables found to be independent predictors of good preparation were successful patient completion of the preparatory procedure according to instructions, colonoscopy performed for follow-up after polypectomy, and preparation with sodium phosphate. The educational intervention had no impact on the quality of preparation. In conclusion, sodium phosphate preparation and complete adherence to preparation instructions are the most important factors for successful colonoscopy preparation. Current preparatory methods for hospitalized and severely ill patients need to be revised.

The wide use of surgical clips in laparoscopic surgery has led to a variety of complications. We describe two cases in which a surgical clip was incorporated into a duodenal ulcer after laparoscopic cholecystectomy. The presenting symptom was acute gastrointestinal bleeding. Both patients were treated endoscopically, and the bleeding stopped after the clip was removed from the ulcer base. Although the mechanism by which a surgical clip migrates into the duodenum is unclear, we recommend meticulous Calot's triangle dissection and removal of any wandering or misplaced clips. Endoscopic removal is recommended when a surgical clip is discovered in a bleeding ulcer.

Objectives: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. Methods: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction—based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. Results: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. Conclusions: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism. Semin Arthritis Rheum 30:132-137. Copyright © 2000 by W.B. Saunders Company

OBJECTIVES: Cowden syndrome (CS), associated with germline PTEN mutations, is an autosomal-dominant disorder with increased frequencies of thyroid and breast cancers. Recent reports document the occurrence of gastrointestinal (GI) polyps and increased risk of colon cancer in PTEN mutation carriers. Studies to date, however, have not been based on mutation carriers undergoing active, systematic, routine-interval GI surveillance. Our objective is to document the upper and lower GI findings in CS patients undergoing such an active GI surveillance program. METHODS: In a 5-year period, 3,000 consecutive patients were referred to our high-risk GI cancer clinic for various reasons. Of these 3,000, 10 met full-blown clinical criteria for the diagnosis of CS. Individuals with identified PTEN mutations underwent annual upper and lower endoscopy surveillance programs using dual white light and narrow-band imaging. All biopsies including archived materials were reviewed by a single dedicated GI pathologist. RESULTS: Ten PTEN mutation carriers from different ethnic backgrounds were invited and all participated in the active GI surveillance program. Eight patients had colonic polyps, mostly hyperplastic (eight patients) and hamartomatous (five patients), but also adenomatous (three patients), ganglioneuromatous (three patients), and juvenile polyps (two patients). One patient (10%) had an early-onset rectal cancer (aged 44 years), which was null for PTEN expression on immunohistochemistry. All patients had gastric polyps and nine (90%) had duodenal polyps, mostly hyperplastic and hamartomatous. Additional three patients (30%) had adenomatous duodenal polyps. CONCLUSIONS: PTEN mutation–positive CS patients have a higher frequency of upper GI polyps than previously believed. They appear prone to develop adenomatous upper and lower tract dysplastic polyps and cancer. Thus, the polyps encountered during upper or lower endoscopy in these patients should not be automatically considered innocent hamartomas without malignant potential. Active surveillance programs in specialized centers should be considered in these patients.

Institutions Institutions are listed at the end of article.submitted 10. March 2011accepted after revision:27. July 2011BibliographyDOI http://dx.doi.org/10.1055/s-0031-1291385Endoscopy 2011; 43: 1–6© Georg Thieme Verlag KGStuttgart · New YorkISSN 0013-726XCorresponding authorY. Niv, MDDepartment ofGastroenterologyRabin Medical CenterBeilinson Hospital35 Jabotinski StreetPetach Tikva 49100IsraelFax: +972-3-9210313yniv@clalit.org.il

15 pages, Mesophotic coral ecosystems (MCEs) and temperate mesophotic ecosystems (TMEs) have received increasing research attention during the last decade as many new and improved methods and technologies have become more accessible to explore deeper parts of the ocean. However, large voids in knowledge remain in our scientific understanding, limiting our ability to make scientifically based decisions for conservation and management of these ecosystems. Here, we present a list of key research and conservation questions to enhance progress in the field. Questions were generated following an initial open call to MCE and TME experts, representing a range of career levels, interests, organizations (including academia, governmental, and nongovernmental), and geographic locations. Questions were refined and grouped into eight broad themes: (1) Distribution, (2) Environmental and Physical Processes, (3) Biodiversity and Community Structure, (4) Ecological Processes, (5) Connectivity, (6) Physiology, (7) Threats, and (8) Management and Policy. Questions were ranked within themes, and a workshop was used to discuss, refine, and finalize a list of 25 key questions. The 25 questions are presented as a guide for MCE and TME researchers, managers, and funders for future work and collaborations, JT, EG, and GE would like to thank ICRS for their student travel grants to attend the ECRS conference. JT would also like to acknowledge funding from BHP and the Ningaloo Outlook Program for their support. Lastly, we are grateful for thoughtful comments on this manuscript from nine reviewers (Sam Kahng, Yehuda Benayahu, Richard Appeldoorn, Heather Spalding, Anthony Montgomery, Shirley A. Pomponi, and three anonymous reviewers) and the editor Kimberly Puglise. GE has received funding for this project from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 796025