Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

Rifaximin discontinuation during broad-spectrum antibiotic treatment in critically ill patients with hepatic encephalopathy

Hepatic encephalopathy(HE)is one of the main complications of cirrhosis,characterized by a wide spectrum of neuropsychiatric alterations that lead to an increase in mortality,morbidity and recurrent hospitalizations.Due to the central role in HE pathogenesis of ammonia and other neurotoxins primarily produced by the gut microbiota,the main therapeutic approaches for the treatment of HE are based on the modulation of the gut microbiota.Rifaximin is a non-absorbable broad-spectrum antibiotic,that is effective against ammonia-producing grampositive,gram-negative,and anaerobic species,approved for the treatment of HE in secondary prophylaxis.The chronic administration of rifaximin in this setting is associated with a lower risk of HE recurrence and mortality,while the role of rifaximin for the treatment of an overt-HE episode in inpatients is still unclear.Limited data exist about the coadministration of rifaximin and broad-spectrum antibiotics commonly used to treat concomitant infections,as patients receiving or recently treated with antibiotics were frequently excluded from clinical trials.In this editorial we comment on the article by Ward et al published in the recent issue of the World Journal of Hepatology.It is a single center,retrospective,quasiexperimental,pharmacist-driven protocol,with the aim to evaluate the feasibility and safety of rifaximin discontinuation in critically ill patients with HE and chronic liver disease receiving broad-spectrum antibiotic therapies in intensive care units.The study revealed no differences between the protocol and control group in terms of primary outcome(days alive and free of delirium and coma to day 14)and secondary outcomes which include:Intensive care mortality,intensive care length of stay,intravenous vasopressor requirement changes and adverse effects rate.Therefore,rifaximin discontinuation during broad-spectrum antibiotic therapy does not appear to negatively impact the clinical status of critically ill liver patients,with a similar safety profile and significant cost savings,as compared to the coadministration of rifaximin and broad-spectrum antibiotics.In agreement with Ward et al,a recently published double-blind,randomized controlled trial provided additional evidence to support the feasibility of withholding rifaximin during broad-spectrum antibiotic therapy in critically ill cirrhotic patients.However,given the limitations of these studies,further multicentric and prospective clinical trials,enrolling a larger sample of non-critically ill patients,are needed to better establish the role of rifaximin in this setting.

Timing, method and discontinuation of hydrocortisone administration for septic shock patients

AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone.It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31 st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic(ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h(range, 47.5-90.5) vs 108 h(range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute(range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute(range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus(83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock(r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81(P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75(P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse(RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio(OR), 5.3; P = 0.04] and hypokalemia(OR = 10.6; P = 0.01). CONCLUSION Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Reasons for discontinuation of sildenafil citrate after successful restoration of erectile function

Aim: To investigate the reasons for discontinuations of sildenafil after the successful restoration of erectile function. Methods: One hundred fifty six patients, whose scores of erectile function domain of the 15-item International Index of Erectile Function (IIEF) increased to 26 or more after sildenafil medication, were included in this study. Six-months after the first sildenafil prescription, compliance to medication and the reason for discontinuity were reviewed by chart or surveyed by telephone. Results: Fifty-four (34.6%) of the 156 successfully treated patients discontinued sildenafil medication. The r easons for discontinuance were shortcomings in the partners' or patients' emotional readiness for the restoration of sexual life after long-term abstinence (37.0%), fear of possible side effects (18.5 %), recovery of spontaneous erection (14.8 %), postponement of ED treatment because of co morbid disease treatment (11.1%), unwillingness to accept drug-dependent erection (7.4%), high drug cost (3.7%), unacceptability of planned sexual activity (3.7%) and lack of sexual interesi (3.7%). Conclusion: The reasons for discontinuing sildenafil medication were primarily emotional or relationship-oriented, which indicates that simple recovery of a rigid erection is insufficient to restore sexual activity. More education about the effects of drug and the counseling of both partners is recommended to promote the successful recovery of sexual activity.

Predictors of Discontinuation of Antipsychotic Therapy in Patients with Acute Schizophrenia: A 1-Year Observational Study with More Than 1000 Patients

Discontinuation of antipsychotic therapy has been a significant clinical issue among patients with schizophrenia, since the patients who discontinued antipsychotic treatment showed worse clinical and functional outcomes, and higher risks of relapse of schizophrenia symptoms and hospitalization. We conducted a post-hoc analysis of a post-marketing research with a 12-month follow-up period to identify the predictors for discontinuation of antipsychotic monotherapy in Japan. This is a prospective, naturalistic multicenter observational study, designed to evaluate the discontinuation rates of olanzapine monotherapy and non-olanzapine antipsychotic monotherapy in Japanese adult patients with acute schizophrenia. Patients were treatment-naive, or had switched from other antipsychotics or from poly-pharmacotherapy to oral antipsychotic monotherapy. We analyzed the correlation of discontinuation of antipsychotic monotherapy with baseline characteristics of patients. A total of 1089 patients (578 patients treated with olanzapine and 511 with non-olanzapine antipsychotics) were eligible for analysis. By the end of the 12-month study period, 614 patients (56.4%) discontinued antipsychotic therapy. Multivariate logistic regression analyses indicated significantly lower discontinuation rates in all patients treated with antipsychotics: older age (Odds ratio [OR], 0.871;95% confidence interval [CI], 0.797 to 0.953;p = 0.003), outpatient status (OR, 0.508;95% CI, 0.383 to 0.675;p < 0.001), prior use of antipsychotics (OR, 0.693;95% CI, 0.516 to 0.930;p = 0.015), and olanzapine group showed lower discontinuation rate than that of non-olanzapine group (OR, 1.416;95% CI, 1.086 to 1.846;p = 0.010). The present study indicated that the outpatient status, older age, and prior use of antipsychotics have better adherence to antipsychotic treatment. In addition to these factors, use of anti-parkinson agents showed lower discontinuation rates in the olanzapine monotherapy group.

Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia

Clinical trials have demonstrated that some patients with chronic myeloid leukemia(CML)treated for several years with tyrosine kinase inhibitors(TKIs)who have maintained a molecular response can successfully discontinue treatment without relapsing.Treatment free remission(TFR)can be reached by approximately 50%of patients who discontinue.Despite having similar levels of deep molecular response and an identical duration of treatment,the factors that influence the successful discontinuation of CML patients remain to be determined.In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR.We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.

Discontinuation of AEDs: When and how?

Once a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the decision to discontinue AED should be balanced against continuation of AED therapy indefinitely. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs. However, there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period. There are several factors that would increase risk of recurrences which will be reviewed and discussed. As a consequence, the decision to withdraw or withhold treatment must be still individualized. In any patient, the decision to discontinue treatment should also take into effect the social aspects like driving license, job and leisure activities as well as emotional and personal factors and patients with adverse effects or drug interactions. Patients will ultimately have to decide themselves whether they wish to discontinue drug treatment.

Discontinuation of Statin Treatment in Relation to Chronic Diseases and Laboratory Findings

Purpose: The aim was to study discontinuation of statin treatment, especially with respect to clinical characteristics and adverse effect measured by clinical laboratory tests indicating muscle damage (plasma creatine kinase, CK) and liver AEs (plasma alanine aminotransferase, ALAT). Methods: The initial study population included 60,488 individuals who had purchased first time statin prescription in Helsinki-Uusimaa region between 01-01-2007 and 31-12-2009. The follow-up started when first statin prescription was purchased and ended 31-12-2009 or death, which ever occurred first. From this population 54,172 individuals were defined to eligible to study population of this study. Clinical laboratory measurements were obtained from Helsinki-Uusimaa University Hospital (HUSLAB) that which provides the laboratory tests for the Helsinki-Uusimaa region serving about a population of 1.5 million. Results: In this fairly large real-life study the occurrence of ALAT-AE and mild CK-elevations after initiation of first statin treatments were relatively low. Increasing age and the presence of co-morbidities increased the risk of these AEs. Further, the ALAT-AEs implied increased risk of discontinuation of treatment. Diabetic patients discontinued treatment more often than non-diabetics, whereas the presence of other chronic conditions implied higher persistence of statin treatment. Conclusions: It is essential that those who would benefit from statin therapy actually are treated and by far in most patients treatment seems to be safe and well tolerated. For those who cannot tolerate statins new therapeutic options are needed.

Asian Case of Metastatic Melanoma in Which a Complete Response Was Maintained after Discontinuation of Dabrafenib and Trametinib

A 54-year-old man diagnosed with metastatic melanoma of the right inguinal node with occult primary developed liver and bone metastases. The combination of dabrafenib plus trametinib was initiated, and a complete response (CR) was achieved 24 months after starting treatment. One month later, the target therapy was discontinued at the patient’s decision, and he has remained free from progression for 21 months since discontinuation. To the extent of our knowledge, real-world data in Asian melanoma concerning the discontinuation of dabrafenib plus trametinib after achieving CR have not been published;therefore, our case is a meaningful one for considering to cease target drugs and to rescue their financial toxicity.

Antiretroviral Therapy Discontinuation among Adults Receiving HIV Care in Kadoma City in 2015-2019

Background: Discontinuation remains a legitimate threat to the long-term success of antiretroviral therapy (ART) scale-up in Zimbabwe. Furthermore, the characteristics associated with ART discontinuation and trends are poorly understood in developing countries like Zimbabwe. We analysed the HIV/AIDS data to describe the characteristics associated with ART discontinuation and the trends from 2015 to 2019. Methods: We conducted an analytical cross- sectional study using secondary data from Electronic Patient Management System (ePMS) in Kadoma City. We interviewed eighteen health care workers to find the reasons for ART discontinuation. Data were analysed using Microsoft Office Excel 2016 and Epi info 7 version 7.2.2.6. Microsoft office excel was used to generate linear graphs to demonstrate the trends in ART discontinuation in Kadoma City in 2015-2019. Epi info 7 was used to generate frequencies, means, prevalence odds ratios p-values, and 95% confidence intervals (CI) and significance testing. Backward stepwise logistic regression analysis was done to determine the independent factors associated with discontinuation. Results: A total number of 2833 patients were enrolled on ART from 2015 to 2019. One hundred and seventy-three 173/2833 (6.1%) discontinued ART, 415/2833 (14.7%) transferred out, 69/2833 (2.4%) died and 2176/2833 (76.8%) were retained on ART. Out of those who discontinued ART, sixty-five percent (112/173) were females. Approximately two-thirds had immunological failure 110/173 (64%). The trend in ART discontinuation decreased over the years but was not statistically significant (R2 = 0.57, p > 0.05). ART discontinuation was independently associated with being Conclusion: We concluded that the characteristics associated with ART discontinuation were having never attended school, being less than forty years of age and having immunological failure. The reasons why patients discontinue ART were health state not improving, participating in artisanal mining activities, change in marital status, medical side effects of ART, living far from health facilities, and relocating to neighbouring countries. We recommended continuous provision of health education, enhanced adherence counselling sessions to those with unsuppressed viral loads and investigating the cause of virologic failure.

How to reduce bacillus Calmette-Guerin discontinuation in patients with severe functional impairment

Background:Severe functional impairment is often considered a contraindication to intravesical therapy for nonmuscle-invasive bladder cancer(NMIBC).A tailored intravesical bacillus Calmette-Guérin(BCG)procedure was evaluated in high-risk(HR)-NMIBC patients with severe functional impairment.Materials and methods:Patients with a Katz Index score of 2 or less and an initial diagnosis of HR-NMIBC with atraumatic insertion of a Foley-type indwelling catheter,bladder emptying,and BCG instillation were prospectively treated;after 2 hours,the bladder was emptied and the catheter was removed(group A).After propensity score matching,52 patients in group A were compared with that of 52 consecutive patients in group B using a retrospective database,with similar baseline/oncological characteristics and treated with standard intermittent catheterization.Moreover,groups A and B were compared with that of 130 consecutive patients(group C)retrospectively evaluated,with similar oncological characteristics but with a Katz Index score of 3 or greater and treated with standard intermittent catheterization.Results:The discontinuation rates were 11.5%,35%,and 9%in groups A,B,and C,respectively(A vs.B,log-rank score 42.52[po<0.05];B vs.C,107.6[p<0.05];A vs.C,3.45[p>0.05]).The overall adverse event rates were 38.5%,57.7%,and 39.2%,respectively(A vs.B,p=0.04;B vs.C,0.03;A vs.C,0.92).The rates of severe adverse events were 1.9%,1.9%,and 1.5%,respectively,without statistically significant differences.The cumulative HR disease-free survival rates were 63.4%,48%,and 69.2%,respectively(A vs.B,log-rank score 154.9[p<0.05];B vs.C,415[p<0.05];A vs.C,244[p<0.05]).Conclusions:A tailored intravesical instillation procedure may reduce BCG discontinuation and adverse effects.

Predictor of discontinuation with paliperidone palmitate in patients with schizophrenia

Objective To explore the influence of demographic characteristics,psychiatric symptoms and medication on the adherence of long-acting injectable paliperidone palmitate(PP)treatment in schizophrenia patients.Methods In this one year,naturalistic longitudinal study,156 consecutive patients with schizophrenia were initi-

Discontinuation of Recycled Lead Refineries Planned in Jiangxi Province

The first round of rectification action of the Central Environmental Inspection Group will be fully implemented in the near future.Six Central Environmental Inspection Groups will successively station in 10 provinces,including Henan,Hebei,Inner Mongolia,Heilongjiang,Jiangsu,Jiangxi,Guangdong,Guangxi。

Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Review on the plastic instability of medium -Mn steels for identifying the formation mechanisms of Lüders and Portevin -Le Chatelier bands

Plastic instability,including both the discontinuous yielding and stress serrations,has been frequently observed during the tensile deformation of medium-Mn steels(MMnS)and has been intensively studied in recent years.Unfortunately,research results are controversial,and no consensus has been achieved regarding the topic.Here,we first summarize all the possible factors that affect the yielding and flow stress serrations in MMnS,including the morphology and stability of austenite,the feature of the phase interface,and the deformation parameters.Then,we propose a universal mechanism to explain the conflicting experimental results.We conclude that the discontinuous yielding can be attributed to the lack of mobile dislocation before deformation and the rapid dislocation multiplication at the beginning of plastic deformation.Meanwhile,the results show that the stress serrations are formed due to the pinning and depinning between dislocations and interstitial atoms in austenite.Strain-induced martensitic transformation,influenced by the mechanical stability of austenite grain and deformation parameters,should not be the intrinsic cause of plastic instability.However,it can intensify or weaken the discontinuous yielding and the stress serrations by affecting the mobility and density of dislocations,as well as the interaction between the interstitial atoms and dislocations in austenite grains.

Production induced fracture closure of deep shale gas well under thermo-hydro-mechanical conditions

Deep shale gas reservoirs have geological characteristics of high temperature,high pressure,high stress,and inferior ability to pass through fluids.The multi-stage fractured horizontal well is the key to exploiting the deep shale gas reservoir.However,during the production process,the effectiveness of the hydraulic fracture network decreases with the closure of fractures,which accelerates the decline of shale gas production.In this paper,we addressed the problems of unclear fracture closure mechanisms and low accuracy of shale gas production prediction during deep shale gas production.Then we established the fluid—solid—heat coupled model coupling the deformation and fluid flow among the fracture surface,proppant and the shale matrix.When the fluid—solid—heat coupled model was applied to the fracture network,it was well solved by our numerical method named discontinuous discrete fracture method.Compared with the conventional discrete fracture method,the discontinuous discrete fracture method can describe the three-dimensional morphology of the fracture while considering the effect of the change of fracture surface permeation coefficient on the coupled fracture—matrix flow and describing the displacement discontinuity across the fracture.Numerical simulations revealed that the degree of fracture closure increases as the production time proceeds,and the degree of closure of the secondary fractures is higher than that of the primary fractures.Shale creep and proppant embedment both increase the degree of fracture closure.The reduction in fracture surface permeability due to proppant embedment reduces the rate of fluid transfer between matrix and fracture,which has often been overlooked in the past.However,it significantly impacts shale gas production,with calculations showing a 24.7%cumulative three-year yield reduction.This study is helpful to understand the mechanism of hydraulic fracture closure.Therefore,it provides the theoretical guidance for maintaining the long-term effectiveness of hydraulic fractures.

Discontinuity development patterns and the challenges for 3D discrete fracture network modeling on complicated exposed rock surfaces

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls.This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope,and the qualitative and quantitative study of the complex phenomena impact on threedimensional(3D)discrete fracture network(DFN)modeling.As the studies of the outcrop fracture pattern have been so far focused on local variations,thus,we put forward a statistical analysis of global variations.The entire outcrop is partitioned into several subzones,and the subzone-scale variability of fracture geometric properties is analyzed(including the orientation,the density,and the trace length).The results reveal significant variations in fracture characteristics(such as the concentrative degree,the average orientation,the density,and the trace length)among different subzones.Moreover,the density of fracture sets,which is approximately parallel to the slope surface,exhibits a notably higher value compared to other fracture sets across all subzones.To improve the accuracy of the DFN modeling,the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed.Subsequently,the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions.The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3e4 times.The study results present precise geological structural information,improve modeling accuracy,and provide practical solutions for addressing complex outcrop issues.

Microstructural evolution and dynamic recrystallization mechanisms of additively manufactured TiAl alloy with heterogeneous microstructure during hot compression

Microstructural evolution and dynamic recrystallization(DRX)mechanisms of a Ti-48Al-2Cr-2Nb(at.%)alloy prepared by selective electron beam melting(SEBM)during hot deformation at 1150℃and 0.1 s^(-1)were investigated by hot compression tests,optical microscope(OM),scanning electron microscope(SEM),electron back-scattered diffraction(EBSD)and transmission electron microscope(TEM).The results show that the initial microstructure of the as-SEBMed alloy exhibits layers of coarseγgrains and fineγ+α_(2)+(α_(2)/γ)lamellar mixture grains alternately along the building direction.During the early stage of hot deformation,deformation twins tend to form within the coarse grains,facilitating subsequent deformation,and a small number of DRX grains appear in the fine-grained regions.With the increase of strain,extensive DRX grains are formed through different DRX mechanisms in both coarse and fine-grained regions,involving discontinuous dynamic recrystallization mechanism(DDRX)in the fine-grained regions and a coexistence of DDRX and continuous dynamic recrystallization(CDRX)in the coarsegrained regions.

Fracture network characterisation of the Balmuccia peridotite using drone-based photogrammetry,implications for active-seismic site survey for scientific drilling

The presence of discontinuities(e.g.faults,fractures,veins,layering)in crystalline rocks can be challenging for seismic interpretations because the wide range of their size,orientation,and intensity,which controls the mechanical properties of the rock and elastic wave propagation,resulting in equally varying seismic responses at different scales.The geometrical characterisation of adjacent outcrop discontinuity networks allows a better understanding of the nature of the subsurface rocks and aids seismic interpretation.In this study,we characterise the discontinuity network of the Balmuccia peridotite(BP)in the IvreaeVerbano Zone(IVZ),northwestern Italy.This geological body is the focus of the Drilling the Ivrea eVerbano zonE(DIVE),an international continental scientific drilling project,and two active seismic surveys,SEismic imaging of the Ivrea ZonE(SEIZE)and high-resolution SEIZE(Hi-SEIZE),which aim to resolve the subsurface structure of the DIVE drilling target through high-resolution seismic imaging.For fracture characterisation,we developed two drone-based digital outcrop models(DOMs)at two different resolutions(10^(-3)-10 m and 10^(-1)-10^(3)m),which allowed us to quantitatively characterise the orientation,size,and intensity of the main rock discontinuities.These properties affect the seismic velocity and consequently the interpretation of the seismic data.We found that(i)the outcropping BP discontinuity network is represented by three more sets of fractures with respect to those reported in the literature;(ii)the discontinuity sizes follow a power-law distribution,indicating similarity across scales,and(iii)discontinuity intensity is not uniformly distributed along the outcrop.Our results help to explain the seismic behaviour of the BP detected by the SEIZE survey,suggesting that the low P-wave velocities observed can be related to the discontinuity network,and provide the basic topological parameters(orientation,density,distribution,and aperture)of the fracture network unique to the BP.These,in turn,can be used for interpretation of the Hi-SEIZE seismic survey and forward modelling of the seismic response.

Experimental investigation on shear strength deterioration at the interface between different rock types under cyclic loading

The shear strength deterioration of bedding planes between different rock types induced by cyclic loading is vital to reasonably evaluate the stability of soft and hard interbedded bedding rock slopes under earthquake;however,rare work has been devoted to this subject due to lack of attention.In this study,experimental investigations on shear strength weakening of discontinuities with different joint wall material(DDJM)under cyclic loading were conducted by taking the interface between siltstone and mudstone in the Shaba slope of Yunnan Province,China as research objects.A total of 99 pairs of similar material samples of DDJM(81 pairs)and discontinuities with identical joint wall material(DIJM)(18 pairs)were fabricated by inserting plates,engraved with typical surface morphology obtained by performing three-dimensional laser scanning on natural DDJMs sampled from field,into mold boxes.Cyclic shear tests were conducted on these samples to study their shear strength changes with the cyclic number considering the effects of normal stress,joint surface morphology,shear displacement amplitude and shear rate.The results indicate that the shear stress vs.shear displacement curves under each shear cycle and the peak shear strength vs.cyclic number curves of the studied DDJMs are between those of DIJMs with siltstone and mudstone,while closer to those of DIJMs with mudstone.The peak shear strengths of DDJMs exhibit an initial rapid decline followed by a gradual decrease with the cyclic number and the decrease rate varies from 6%to 55.9%for samples with varied surface morphology under different testing conditions.The normal stress,joint surface morphology,shear displacement amplitude and shear rate collectively influence the shear strength deterioration of DDJM under cyclic shear loading,with the degree of influence being greater for larger normal stress,rougher surface morphology,larger shear displacement amplitude and faster shear rate.