The multiverse of universes: A tutorial to plan, execute and interpret multiverses analyses using the R package multiverse.

Even when guided by strong theories and sound methods, researchers must often choose a singular course of action from multiple viable alternatives. Regardless of the choice, it, along with all other choices made during the research process, individually and collectively affects study results, often in unpredictable ways. The inability to disentangle how much of an observed effect is attributable to the phenomenon of interest, and how much is attributable to what have come to be known as researcher degrees of freedom (RDF), slows theoretical progress and stymies practical implementation. However, if one could examine the results from a particular set of RDF (known as a universe) against a systematically and comprehensively determined background of alternative viable universes (known as a multiverse), then the effects of RDF can be directly examined to provide greater context and clarity to future researchers, and greater confidence in the recommendations to practitioners. This tutorial demonstrates a means to map result variability directly and efficiently, and empirically investigate RDF impact on conclusions via multiverse analysis. Using the R package multiverse, we outline best practices in planning, executing and interpreting of multiverse analyses.

Cold Versus Hot Snare Endoscopic Resection of Large Nonpedunculated Colorectal Polyps: Randomized Controlled German CHRONICLE Trial.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing. METHODS: In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant. RESULTS: Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor both for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and high-grade dysplasia/cancer for residual adenoma (OR, 2.92). CONCLUSIONS: Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170.

Chromoendoscopy in Combination with Random Biopsies for Patients with Pathogenic CDH1 Mutations Undergoing Endoscopic Surveillance.

OBJECTIVES: Germline mutations in the CDH1-gene are identified as the cause of 30-40% of cases of hereditary diffuse gastric cancer, an autosomal-dominant inherited cancer predisposition syndrome. Given this high risk of developing diffuse gastric cancer, carriers of a pathogenic CDH1 germline mutation are advised to undergo prophylactic gastrectomy. For patients preferring conservative management, endoscopic surveillance is recommended. The detection of diffuse gastric cancer using white light endoscopy, however, remains challenging. METHODS: Patients with pathogenic CDH1 mutation underwent (chromo)endoscopic surveillance or endoscopy prior to surgery. Biopsies were taken at suspicious sites identified by chromoendoscopy. In addition, endoscopically normal areas were assessed with mapping biopsies. Detection rates from endoscopic biopsies (mapping vs. targeted) and gastrectomy specimen were then compared. RESULT: Between 11/2015 and 12/2020, ten patients from four families with a known CDH1 germline mutation had a total of n = 24 endoscopies with n = 518 total biopsies being examined. Three patients were diagnosed with GC during the study period. These patients all had suspicious chromoendoscopic lesions (= detection rate 100%). In two of three patients who had suspicious chromoendoscopic lesions, signet cell carcinoma was also detected in mapping biopsies and multiple additional cancer foci were identified in the gastrectomy specimen. CONCLUSION: Chromoendoscopy facilitated detection of gastric carcinoma foci in CDH1 mutation carriers. Chromoendoscopy identified all patients with gastric cancer, but not all cancer foci present in these patients. We conclude that for patients opting against prophylactic total gastrectomy, the addition of chromoendoscopy to white light could be used to enhance diagnostic reliability of endoscopic surveillance.

Constrained multiple instance learning for ulcerative colitis prediction using histological images.

BACKGROUND AND OBJECTIVE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) affecting the colon and the rectum characterized by a remitting-relapsing course. To detect mucosal inflammation associated with UC, histology is considered the most stringent criteria. In turn, histologic remission (HR) correlates with improved clinical outcomes and has been recently recognized as a desirable treatment target. The leading biomarker for assessing histologic remission is the presence or absence of neutrophils. Therefore, the finding of this cell in specific colon structures indicates that the patient has UC activity. However, no previous studies based on deep learning have been developed to identify UC based on neutrophils detection using whole-slide images (WSI). METHODS: The methodological core of this work is a novel multiple instance learning (MIL) framework with location constraints able to determine the presence of UC activity using WSI. In particular, we put forward an effective way to introduce constraints about positive instances to effectively explore additional weakly supervised information that is easy to obtain and enjoy a significant boost to the learning process. In addition, we propose a new weighted embedding to enlarge the relevance of the positive instances. RESULTS: Extensive experiments on a multi-center dataset of colon and rectum WSIs, PICASSO-MIL, demonstrate that using the location information we can improve considerably the results at WSI-level. In comparison with prior MIL settings, our method allows for 10% improvements in bag-level accuracy. CONCLUSION: Our model, which introduces a new form of constraints, surpass the results achieved from current state-of-the-art methods that focus on the MIL paradigm. Our method can be applied to other histological concerns where the morphological features determining a positive WSI are tiny and similar to others in the image.

Analysis on the healing of gastrointestinal ulceration by using Hemospray.

Healing of gastrointestinal ulcers after Hemospray application was reported in literature. The pathophysiological mechanism of action of hemostatic powders is not elucidated so far. A prospective animal model was performed to evaluate the effect of Hemospray application on the healing process of artificially induced ulcers of the upper and lower gastrointestinal tract. In 10 pigs, 20 ulcers were created in each the upper and the lower gastrointestinal tract by endoscopic mucosal resection. 50% of the pigs were immediately treated with Hemospray application, the others were not treated. Ulcer size was measured endoscopically on day 0, 2, and 7. On day 7 the ulcers were histopathological evaluated for capillary ingrowth and the thickness of the collagen layer. After 7 days the sizes of the ulcers decreased significantly (stomach: - 22.8% with Hemospray application, - 19% without Hemospray application; rectum: - 50.8% with Hemospray application, - 49.5% without Hemospray application; p = 0.005-0.037), but without significant difference between both groups. This study shows no significant effect of the hemostatic powder Hemospray on ulcer healing in the upper and lower gastrointestinal tract compared with untreated controls, neither harmful nor beneficial. However, some trends merit further trials in patients and may indicate a possible mechanism of accelerated mucosal healing.

The "Goldilocks Zone": (Too) many confidence intervals in tests of mediation just exclude zero.

Questionable research practices (QRPs) can occur whenever one result is favored over another, and tests of mediation are no exception. Given mediation's ubiquity and importance to both theory and practice, QRPs in tests of mediation pose a serious threat to the advancement of psychology. We investigate this issue through the introduction of a straightforward means of detecting the presence and magnitude of QRPs in tests of mediation and validate this methodology with a series of sensitivity tests and simulations. We then apply this method to 2,569 tests of mediation published in five leading psychology journals in 2018 and 2019. We find that despite most hypothesized tests of mediation being likely underpowered, most (76%) were nevertheless supported. Furthermore, confidence intervals (CIs) that just barely exclude zero are 3.6 to 4.4 times as prevalent as those CIs that just barely include zero. We also find a number of study- and test-level factors, such as whether the test of mediation was hypothesized, explain both whether the CI excluded zero (odds ratio [OR] = 17.87, p < .001) as well as the CI's proximity to zero (b = .27, p < .001). In addition, other factors, most notably sample size, do predict the CI's proximity to zero (γ = .00, p < .001), but surprisingly do not predict the CI's exclusion of zero (OR = .99, p = .803). We conclude with actionable QRP curtailment strategies so that both, academics and practitioners, can have greater and well-founded confidence in tests of mediation in psychological research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Graphene Quantum Hall Effect Devices for AC and DC Electrical Metrology.

A new type of graphene-based quantum Hall standards is tested for electrical quantum metrology applications at alternating current (ac) and direct current (dc). The devices are functionalized with Cr(CO)3 to control the charge carrier density and have branched Hall contacts based on NbTiN superconducting material. The work is an in-depth study about the characteristic capacitances and related losses in the ac regime of the devices and about their performance during precision resistance measurements at dc and ac.

Leader-Member Exchange Fosters Beneficial and Prevents Detrimental Workplace Behavior: Organizational Identification as the Linking Pin.

Discretionary behaviors, such as counterproductive work behavior (CWB) and organizational citizenship behavior (OCB), directly refer to an organization's normative expectations. As such, employees engaging in these behaviors violate or exceed organizational norms, respectively. An employee's relationship quality with his or her supervisor [i.e., leader-member exchange (LMX)] has been found to be a prominent antecedent of employees' workplace behavior. However, the actual mechanisms that link LMX and discretionary behaviors (i.e., CWB and OCB) are not yet well understood. Integrating social exchange as well as the social identity theory, we present an employee's organizational identification (OI) as a mechanism that sheds light on why LMX leads to employees' subsequent discretionary behavior. Across four empirical studies employing complementary study designs, we demonstrate that LMX is positively associated with OI, which, in turn, curbs CWB and fosters OCB. Specifically, this pattern of findings is consistent across (1) a cross-sectional study with 188 Swiss employees, (2) a time-lagged study with 502 Swiss employees, (3) an online recall experiment with 131 US participants, and (4) an online vignette experiment with 139 US participants. In sum, we present an integrative theoretical model and respective empirical support to shed light on OI as a pivotal mechanism that can explain why the relationship quality with one's supervisor can simultaneously serve as a deterrent for CWB and foster OCB.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2020.

The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 : ESGE recommends colonic stenting to be reserved for patients with clinical symptoms and radiological signs of malignant large-bowel obstruction, without signs of perforation. ESGE does not recommend prophylactic stent placement.Strong recommendation, low quality evidence. 2 : ESGE recommends stenting as a bridge to surgery to be discussed, within a shared decision-making process, as a treatment option in patients with potentially curable left-sided obstructing colon cancer as an alternative to emergency resection.Strong recommendation, high quality evidence. 3 : ESGE recommends colonic stenting as the preferred treatment for palliation of malignant colonic obstruction.Strong recommendation, high quality evidence. 4 : ESGE suggests consideration of colonic stenting for malignant obstruction of the proximal colon either as a bridge to surgery or in a palliative setting.Weak recommendation, low quality evidence. 5 : ESGE suggests a time interval of approximately 2 weeks until resection when colonic stenting is performed as a bridge to elective surgery in patients with curable left-sided colon cancer.Weak recommendation, low quality evidence. 6 : ESGE recommends that colonic stenting should be performed or directly supervised by an operator who can demonstrate competence in both colonoscopy and fluoroscopic techniques and who performs colonic stenting on a regular basis.Strong recommendation, low quality evidence. 7 : ESGE suggests that a decompressing stoma as a bridge to elective surgery is a valid option if the patient is not a candidate for colonic stenting or when stenting expertise is not available.Weak recommendation, low quality evidence.

Multimodal Treatment Strategies for Esophageal Perforation.

PURPOSE: Esophageal perforation constitutes a potentially life-threatening condition, and this study aimed to evaluate the indications and outcome for the different treatment modalities. PATIENTS AND METHODS: In total, 43 patients with esophageal perforation were considered for this retrospective analysis. Age, sex, length of hospital stay and intensive care treatment, in-hospital mortality, localization of perforation and etiology, treatment modality, and 90-day morbidity were analyzed. RESULTS: Most patients suffered from Boerhaave syndrome and from iatrogenic esophageal perforation. In total, 63% of patients (26/41) received successful nonoperative treatment, whereas 36% required additional surgery. Two patients (5%) underwent primary surgery. In all cases no esophagectomy was necessary. In-hospital mortality was 7%. During the 90-day follow-up 1 patient with stenosis required repetitive dilatations. CONCLUSIONS: Initial endoscopic treatment, either by stent or by endosponge, alone or combined with an additional operative treatment, seems feasible in patients suffering from esophageal perforation. In all patients, there was no need for esophagectomy.