Physicians' Perceptions and Experiences Regarding Leadership: A Link Between Beliefs and Identity Formation.

Introduction: Despite the development of national recommendations and training programs for effective leadership, junior and senior medical leaders often find themselves ill-prepared to take on these new responsibilities. This study aimed to explore physicians' perceptions, feelings, and beliefs regarding leadership and to provide recommendations regarding appropriate training and institutional post-training support. Methods: We conducted a qualitative study at the Geneva University Hospitals. A purposeful sample of residents (R), fellows (F), attending physicians (A), and chairpersons (CP) were invited to participate in focus groups (or semi-structured interviews) between April and June 2021. We investigated their understanding of leadership, self-perception as leaders, difficulties, and paths to improvement in their leadership skills. Focus groups were transcribed verbatim and analyzed both inductively and deductively using Fishbein's model of behavior prediction and Irby's professional identity formation framework. Results: We conducted ten focus groups (R=3; F=4, A=2, and CP=1) and one interview (CP). Physicians expressed poor self-efficacy at all hierarchical levels: feelings of insecurity and confusion (R and F), frustration (A), and feeling stuck between divisional and institutional governance (CP). Such negative feelings were nurtured by personal beliefs with an intuitive and idealized representation of leadership. Beliefs focused more on personal characteristics rather than on skills, processes, or perceived institutional norms. Unclear expectations regarding physicians' role as leaders, overemphasis on academic achievement, and silo professional organizations fueled their feelings. Participants reported developing their leadership through trial and error, observing role models, and turning to personal resources rather than formal training. Conclusion: Our results show that physicians' leadership skills are still mainly acquired intuitively and that institutional norms do not encourage clarification of leadership roles and processes. Physician training in leadership skills, together with more explicit and clear institutional processes, may help to improve physicians' self-efficacy and develop their identity as leaders.

Mental Health Consultations in Immigration Detention: What Can We Learn From Clinical Records?

Objectives: Knowledge on mental health consultations in immigration detention and characteristics of people receiving consultations is scarce. Based on a sample of 230 adult men in immigration detention in Switzerland, we aimed to: (1) Quantify the proportion of persons receiving mental health consultations during detention; and (2) Identify socio-demographic and clinical characteristics associated with mental health consultations. Methods: Retrospective observational study with a cross-sectional design. Prevalence estimates, logistic regressions, and contingency tables were used to analyse the data. Results: A total of 30% of the sample received mental health consultations during detention. Time spent in immigration detention, mental health problems during detention, use of psychotropic medication, and self-harm were associated with mental health consultations. Although mental health consultations are provided to people with more severe mental health problems, 41% of persons with assessed mental health needs during the initial screening and 26% of those who self-harmed during detention did not receive mental health consultations. Conclusion: Mental health resources and screening procedures could be improved to ensure that mental health consultations are matched to clinical need in immigration detention settings.

Non-invasive physical plasma for preventing radiation dermatitis in breast cancer: Results from an intrapatient-randomised double-blind placebo-controlled trial.

Background and Purpose: To investigate the effect of topical non-invasive physical plasma (NIPP), a volatile mix generated out of ambient air, on prevention of acute radiation dermatitis (RD) during and after whole-breast irradiation (WBI). Materials and Methods: Lateral and medial breast halves were randomised within each patient to receive either 120 s of NIPP or sham treatment daily during WBI. Standard skin care with urea lotion was applied to the whole breast. Blinded acute skin toxicity was assessed weekly for each breast half separately and included clinician- (CTCAE) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. As an additional external control, a comparable standard of care (SoC) patient collective from a previous prospective trial was used. Results: Sixty-four patients were included. There were no significant differences between breast halves. Post-hoc comparison with a similar SoC control collective revealed OR = 0.28 (95% CI 0.11-0.76; p = 0.014) for grade ≥ 2 RD upon WBI completion, along with less hyperpigmentation (p < 0.001), oedema (p = 0.020), dry (p < 0.001) and moist desquamation (p = 0.017), pain, itching, and burning (p < 0.001 for each). Tolerability of NIPP was excellent and side effects were not observed. Conclusion: Even though there were no differences between intrapatient-randomised breast halves, the overall incidence and severity of acute radiation-induced skin toxicity were considerably lower when compared to a prospectively collected SoC cohort. Our data suggest the potential benefit of NIPP in RD prevention. A randomised trial with a physical control group is warranted to confirm these promising results (DRKS00026225).

What Feedback Content Do Clinical Teachers Address During OSTEs?

Purpose: How to give feedback is widely taught and assessed during Faculty Development programs. As part of such programs, clinical teachers can attend objective structured teaching sessions (OSTEs), during which they are asked to give feedback to simulated residents on different tasks. Study aimed at: -analysing the feedback content provided during these OSTEs; -evaluating the impact of the training phase, medical discipline, or observed task; -assessing the alignment between feedback content addressed by clinical teachers and content identified as essential by experts. Methods: We conducted a multimethod study. Clinical teachers (N=89) from five departments were trained to give feedback to residents in a six-month training program. Before and after training, they completed three OSTE stations which focused on tasks involving communication, interprofessional, physical exam or procedural skills. We analysed feedback content descriptively. ANOVA test was applied to evaluate feedback contents' influencing factors (ie participants' training phase, medical discipline, type of task addressed). For each OSTE, we analysed the percentage of items identified as essential by 3 experts that were addressed by clinical teachers during the feedback. Results: We analysed 317 feedback sessions and coded 5388 occurrences. Feedback content distribution was: targeted content (73%), other clinical content (20%), learning strategies (4%), and self-management/other (3%). Feedback was often negative (73%). The training phase did not influence the content addressed while the topic of the observed task and clinical teachers' specialization slightly did. Alignment between content identified by experts and addressed by clinical teachers during OSTEs was low (3-38%). Conclusion: Clinical teachers give mostly negative and targeted feedback according to the task. The poor alignment in selecting key content to be addressed is striking and should be further explored since clinical teachers may address elements of competence more according to their personal preferences than to residents' needs and context priorities.

Do Barrier Films Impact Long-Term Skin Toxicity following Whole-Breast Irradiation? Objective Follow-Up of Two Randomised Trials.

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37-73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness (p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use.

Objective, Clinician- and Patient-Reported Evaluation of Late Toxicity Following Adjuvant Radiation for Early Breast Cancer: Long-Term Follow-Up Results of a Randomised Series.

Background and Purpose: This study aimed to differentially assess the frequency and severity of late radiation-induced toxicity following adjuvant whole-breast irradiation for early breast cancer with conventional fractionation (CF) and moderate hypofractionation (mHF). Materials and Methods: Patients recruited in a previous randomised controlled trial comparing acute toxicity between CF and mHF without disease recurrence were included in a post hoc analysis. Spectrophotometric and ultrasonographic examinations were performed for an objective evaluation and subsequent comparison of long-term skin toxicity. Furthermore, patient- and clinician-reported outcomes were recorded. Results: Sixty-four patients with a median age of 58 (37-81) years were included. The median follow-up was 57 (37-73) months. A total of 55% underwent CF and 45% mHF. A total of 52% received a sequential boost to the tumour bed. A significant decrease in mean L* (p = 0.011) and an increase in a* (p = 0.040) and b* values (p < 0.001) were observed, indicating hyperpigmentation. In comparison with the non-irradiated breast, there was a significant increase in both cutis (+14%; p < 0.001) and subcutis (+17%; p = 0.011) thickness, significantly more pronounced in CF patients (p = 0.049). In CF patients only, a sequential boost significantly increased the local cutis thickness and oedema compared to non-boost regions in the same breast (p = 0.001 and p < 0.001, respectively). Conclusions: mHF objectively resulted in reduced long-term skin toxicity compared to CF. A sequential boost increased the local fibrosis rate in CF, but not in mHF. This might explain the subjectively reported better cosmetic outcomes in patients receiving mHF and reinforces the rationale for favouring mHF as the standard of care.

Barrier films for the prevention of acute radiation dermatitis in breast cancer: A systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Radiation dermatitis (RD) is the most common side effect of adjuvant whole-breast or chest wall irradiation, majorly impacting quality of life in numerous patients. The use of barrier films (polyurethane dressings such as Hydrofilm® and Mepitel® film remaining on the skin for the duration of the radiation treatment) has been investigated as a prophylactic measure in several prospective trials. Here, we critically appraise the available evidence behind preventive barrier film application in the context of breast cancer treatment. METHODS: International literature was reviewed and high-quality randomised controlled trials (RCTs) were included in this meta-analysis. RESULTS: The results of 5 RCTs (663 patients; >90% Caucasian) were analysed. Overall, barrier films lead to improved clinician- and patient-reported outcomes: fewer grade ≥2 RD (11% vs. 42%; OR = 0.16; p < 0.001) and moist desquamation (2% vs. 16%; OR = 0.12; p = 0.006), as well as less patient-reported pain (standardised mean difference [SMD] -0.51; p < 0.001), itching (SMD -0.52; p = 0.001), burning (SMD -0.41; p = 0.011), and limitations in daily activities (SMD -0.20; p = 0.007). Furthermore, barrier films have a high acceptance rate among patients, as well as a favourable cost-benefit ratio. Possible side effects due to its application are mild and mostly self-limiting. Overall, there was a lack of information on the radiation treatment techniques used. CONCLUSION: The evidence presented in this meta-analysis suggests that barrier films are an excellent tool in the prevention of RD among Caucasian patients receiving whole-breast or chest wall irradiation. Its use should therefore be considered routinely in these patients.

[Migration and administrative detention: the challenges for medical practice]. / Migration et détention administrative : les défis pour la pratique médicale.

Administrative detention or deprivation of liberty of migrants is a response to a decision by the authorities to remove those who have refused to leave voluntarily. These people are incarcerated not for having committed a crime, but for staying illegally in Switzerland. They often find themselves in a precarious situation, suffering from psychological or somatic illnesses that may be linked to their migration path. In most cases, they do not wish to return to their country and have many psychological or physical defences to oppose the decision of the authorities organising the removal. The health care provider is therefore faced with many challenges in order to carry out the many tasks of prison medicine while respecting fundamental ethical principles.

La détention administrative, ou privation de liberté des personnes migrantes, répond à une décision de renvoi de la part des autorités des personnes ayant refusé de partir volontairement. Elles sont incarcérées pour seul motif : leur séjour illégal en Suisse. Elles sont souvent précarisées et souffrent de maladies psychiques ou somatiques. Dans la majorité des cas, ces personnes ne souhaitent pas repartir dans leur pays et présentent de nombreuses défenses psychologiques ou physiques pour s'opposer à la décision des autorités. Les récents changements légaux visant à faciliter le renvoi sont problématiques du point de vue de la déontologie médicale. Le soignant se trouve donc face à de ­nombreux défis pour accomplir les multiples missions de la ­médecine en milieu pénitentiaire en respectant les principes éthiques fondamentaux.

Effects of high-frequency speech therapy on speech-related quality of life and objective speech intelligibility of oral cancer patients.

To analyze objective and subjective progression of speech intelligibility in oral cancer patients undergoing high-frequency speech therapy during early rehabilitation. Oral cancer patients in the Department of Maxillofacial Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany, participated in the study from March 2016 to November 2017. Speech intelligibility was analyzed preoperatively (t1), post radiation (t2), and post speech therapy (t3). Objective measures were the Munich Intelligibility Profile (Online) and the Frenchay Dysarthria Assessment-2 (FDA-2). Subjective measures were the Speech Handicap Index (SHI), the speech subscale of the EORTC QLQ-C30&HN35, and the WHO-5 Index II. For nine patients with complete data, progression analyses showed a non-existent-to-low intelligibility impairment at t1 (means/SDs: e.g. FDA-2: 8.96/0.11, SHI: 17.5/15.15), increasing towards t2 (means/SDs/p-values for difference from t1: e.g. FDA-2: 7.40/0.80/0.000, SHI: 21.7/14.24/0.213), and then decreasing towards t3, without ever reaching the initial level (means/SDs/p-values for difference from t1: e.g. FDA-2: 8.22/0.60/0.005, SHI: 23.5/15.85/0.481). The objective changes in intelligibility were significant; the subjective changes were not. Overall, the ability to speak intelligibly after oral cancer treatment follows a typical pattern. Therefore, high-frequency speech therapy in the early rehabilitation phase might be recommendable. It might help patients to adapt to their situation after surgery, and facilitates compensating for possible functional deficits.

Development of the German Speech Intelligibility Index for the treatment of oral cancer patients.

OBJECTIVES: This study aimed at 1) adapting the well-established Speech Handicap Index (SHI) to German, 2) testing the suitability of the instrument for assessing speech-related quality of life, 3) comparing it to the German Voice-Handicap-Index (VHI), in order to support treatment of oral cancer patients who experience posttreatment speech difficulties that affect their quality of life. MATERIAL AND METHODS: Participants completed a web-based survey that employed a 2 (experienced problem: speech/articulation-related vs. voice-related) x 2 (SHI vs. VHI) between-subject experimental design, enabling it to distinguish between the experiences of voice and intelligibility impairments, and to determine the discriminatory ability of the two instruments. RESULTS: The German SHI reliably assessed speech intelligibility and articulation-related Quality of life. While voice impairments were equally well assessed by both, VHI: M 2.48, SD 0.65; SHI: M 2.52, SD 0.63; only the latter appropriately registered intelligibility handicap in speech impairments (VHI: M 2.05, SD 0.70; SHI: 2.68, SD 0.73). The responsivity of the SHI in capturing the experienced handicap was significantly greater in the speech/articulation-impairment condition (p = .001). CONCLUSION: The German SHI is a reliable and responsive measure for speech intelligibility and articulation-related quality of life that should be chosen in preference to the VHI.

Access to treatment in prison: an inventory of medication preparation and distribution approaches.

The preparation and distribution of medication in prisons or jails are critical for individuals to access their treatment. This process is resource-intensive for healthcare professionals and may violate principles of confidentiality, autonomy, respect, and dignity if non-qualified staff are involved. However, there are no published best practices on the topic. This report aims to bridge this gap by presenting the results of a mapping exercise on different models of medication preparation and delivery. Authors call upon healthcare professionals to enrich this live document to inform health services research further and improve access to prescribed medications for people experiencing incarceration.

Well-being and quality of life among oral cancer patients - Psychological vulnerability and coping responses upon entering initial treatment.

BACKGROUND: Little is known about the psychological constitution and potential coping mechanisms of oral cancer patients when they enter initial treatment. This study aimed at 1) establishing a feasible study protocol and 2) implementing it to examine patients' coping and psychological responses during the initial treatment phase in the hospital. METHODS: In three consecutive feasibility phases a study procedure including measurement time points and instrumentation as well as a patient recruitment strategy was developed. To assess patients' responses, the following qualitative (interviews) and quantitative (questionnaires) measures were applied: WOC-CA, briefCOPE, HADS, EORTCQlQC30- H&N35 and SAM/POMS. RESULTS: Results revealed a highly burdened and distressed patient group that had not yet developed clear coping strategies. Further, one third of examined patients showed severe levels of anxiety and depression, indicating a high vulnerability to develop psychological disorders. CONCLUSION: At this early stage of oral cancer treatment, potential psychosocial interventions should prioritize addressing anxiety and depression to enable patients to develop functional coping strategies later on.

N-terminal chemical protein labeling using the naturally split GOS-TerL intein.

Chemoselective and regioselective chemical protein labeling is of great importance, yet no current technique is sufficiently general and simple to perform. Protein trans-splicing by split inteins can be used to ligate short tags with chemical labels to either the N or the C terminus of a protein. The CysTag approach exploits split intein fragments without a cysteine fused with such a short tag containing a single cysteine that is easily amenable to selective modification using classical cysteine bioconjugation. Labeling of the protein of interest is achieved through transfer of the pre-labeled tag by protein trans-splicing. This protocol keeps other cysteines unmodified. While split inteins for C-terminal CysTag labeling were previously reported, no high-yielding and naturally split intein for N-terminal labeling has been available. In this work, the recently discovered GOS-TerL intein was explored as the only known naturally split intein that both lacks a cysteine in its N-terminal fragment and is active under ambient conditions. Thioredoxin as a model protein and a camelid nanobody were labeled with a synthetic fluorophore by transferring the pre-labeling CysTag in the protein trans-splicing reaction with yields of about 50 to 90%. The short N-terminal intein fragment was also chemically synthesized with a tag to enable protein labeling by semi-synthetic protein trans-splicing. Our results expand the scope of the CysTag labeling strategy, which achieves selective chemical modification without the requirement for sophisticated biorthogonal functional groups and rather builds on the plethora of commercially available reagents directed at the thiol side chain of cysteine. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Evaluation of Global Histone Acetylation Levels in Bladder Cancer Patients.

BACKGROUND/AIM: Alterations of global histone modification levels have been identified in various tumor entities, including bladder cancer (BCA). Our study was designed to investigate the value of global histone acetylation levels as diagnostic and prognostic biomarker for BCA patients. MATERIALS AND METHODS: A tissue microarray with formalin-fixed paraffin-embedded tissues (271 BCA and 29 normal urothelial samples) was used to determine global histone acetylation levels (histone H3 acetylation (H3Ac); histone H3 lysine 18 acetylation (H3K18Ac); histone H4 acetylation (H4Ac)). RESULTS: Global H3Ac levels were decreased in BCA patients, whereas H3K18Ac and H4Ac levels were similar in both groups. All studied histone acetylation markers were lower in muscle-invasive BCA compared to non-muscle invasive BCA and normal urothelial tissue, thereby indicating a possible prognostic relevance. CONCLUSION: Global histone acetylation levels undergo quantitative alterations during bladder cancer progression and could be helpful to identify patients at risk for early cancer recurrence.

An Unprecedented Combination of Serine and Cysteine Nucleophiles in a Split Intein with an Atypical Split Site.

Protein splicing mediated by inteins is a self-processive reaction leading to the excision of the internal intein domain from a precursor protein and the concomitant ligation of the flanking sequences, the extein-N and extein-C parts, thereby reconstituting the host protein. Most inteins employ a splicing pathway in which the upstream scissile peptide bond is consecutively rearranged into two thioester or oxoester intermediates before intein excision and rearrangement into the new peptide bond occurs. The catalytically critical amino acids involved at the two splice junctions are cysteine, serine, or threonine. Notably, the only potential combination not observed so far in any of the known or engineered inteins corresponds to the transesterification from an oxoester to a thioester, which suggested that this formal uphill reaction with regard to the thermodynamic stability might be incompatible with intein-mediated catalysis. We show that corresponding mutations also led to inactive gp41-1 and AceL-TerL inteins. We report the novel GOS-TerL split intein identified from metagenomic databases as the first intein harboring the combination of Ser1 and Cys+1 residues. Mutational analysis showed that its efficient splicing reaction indeed follows the shift from oxoester to thioester and thus represents a rare diversion from the canonical pathway. Furthermore, the GOS-TerL intein has an atypical split site close to the N terminus. The Int(N) fragment could be shortened from 37 to 28 amino acids and exchanged with the 25-amino acid Int(N) fragment from the AceL-TerL intein, indicating a high degree of promiscuity of the Int(C) fragment of the GOS-TerL intein.

Microbial respiration and natural attenuation of benzene contaminated soils investigated by cavity enhanced Raman multi-gas spectroscopy.

Soil and groundwater contamination with benzene can cause serious environmental damage. However, many soil microorganisms are capable to adapt and are known to strongly control the fate of organic contamination. Innovative cavity enhanced Raman multi-gas spectroscopy (CERS) was applied to investigate the short-term response of the soil micro-flora to sudden surface contamination with benzene regarding the temporal variations of gas products and their exchange rates with the adjacent atmosphere. (13)C-labeled benzene was spiked on a silty-loamy soil column in order to track and separate the changes in heterotrophic soil respiration - involving (12)CO2 and O2- from the natural attenuation process of benzene degradation to ultimately form (13)CO2. The respiratory quotient (RQ) decreased from a value 0.98 to 0.46 directly after the spiking and increased again within 33 hours to a value of 0.72. This coincided with the maximum (13)CO2 concentration rate (0.63 µmol m(-2) s(-1)), indicating the highest benzene degradation at 33 hours after the spiking event. The diffusion of benzene in the headspace and the biodegradation into (13)CO2 were simultaneously monitored and 12 days after the benzene spiking no measurable degradation was detected anymore. The RQ finally returned to a value of 0.96 demonstrating the reestablished aerobic respiration.

Generation of a genetically encoded, photoactivatable intein for the controlled production of cyclic peptides.

Cyclic peptides are important natural products and hold great promise for the identification of new bioactive molecules. The split-intein-mediated SICLOPPS technology provides a generic access to fully genetically encoded head-to-tail cyclized peptides and large libraries thereof (SICLOPPS=split-intein circular ligation of peptides and proteins). However, owing to the spontaneous protein splicing reaction, product formation occurs inside cells, making peptide isolation inconvenient and precluding traditional in vitro assays for inhibitor discovery. The design of a genetically encoded, light-dependent intein using the photocaged tyrosine derivative ortho-nitrobenzyltyrosine incorporated at an internal, non-catalytic position is now reported. Stable intein precursors were purified from the E.coli expression host and subsequently subjected to light activation in vitro for both the regular protein splicing format and cyclic peptide production, including the natural product segetalin H as an example. The activity of the intein could also be triggered in living cells.

Ligation of synthetic peptides to proteins using semisynthetic protein trans-splicing.

Protein trans-splicing using split inteins is a powerful and convenient reaction to chemically modify recombinantly expressed proteins under mild conditions. In particular, semisynthetic protein trans-splicing with one intein fragment short enough to be accessible by solid-phase peptide synthesis can be used to transfer a short peptide segment with the desired synthetic moiety to the protein of interest. In this chapter, we provide detailed protocols for two such split intein systems. The M86 mutant of the Ssp DnaB intein and the MX1 mutant of the AceL-TerL intein are two highly engineered split inteins with very short N-terminal intein fragments of only 11 and 25 amino acids, respectively, and allow the efficient N-terminal labeling of proteins.

Chemical-tag labeling of proteins using fully recombinant split inteins.

Chemical-tag labeling of proteins involving split inteins is an approach for the selective chemical modification of proteins without the requirement of any chemical synthesis to be performed. In a two-step protocol, a very short tag fused to a split intein auxiliary protein is first labeled in a bioconjugation reaction with a synthetic moiety either at its N-terminus (amine-tag) or at the side chain of an unnatural amino acid (click-tag). The labeled protein is then mixed with the protein of interest fused to the complementary intein fragment. In the resulting spontaneous protein trans-splicing reaction the split intein fragments remove themselves and ligate the tag to the protein of interest in a virtually traceless fashion. The reaction can be performed either using a purified protein of interest or to label a protein in the context of a living cell. All protein components are recombinantly expressed and all chemical reagents are commercially available.

[What is new in ambulatory general internal medicine in 2013?]. / Médecine interne générale ambulatoire.

This article provides an overview of 10 important articles published in year 2013 in the field of ambulatory general internal medicine. The newest guidelines about glaucoma screening are detailed. In the midst of the lung cancer screening controversy, an article summarizes new guidelines for the management of solitary pulmonary nodules. Cohort studies are detailed, which have shown association between high calcium intake and cardiovascular mortality, grade 2 or 3 obesity and mortality, aspirin use and lower melanoma incidence, and a reduction of the prevalence of dementia in last 20 years. Finally, 2 publications clarify the optimal length of corticoid treatment for COPD exacerbations and the most appropriate treatment regimen for Helicobacter Pylori eradication.