Stability Of Patterns Research Articles

Comparing the Efficacy of Skills Training Based on Dialectical Behavior Therapy (DBT-ST) and Mindfulness-Based Cognitive Therapy (MBCT) on Distress Tolerance and Psychological Well-being in Individuals with Symptoms of Borderline Personality Disorder

Objective: Borderline Personality Disorder is a pervasive pattern of instability in interpersonal relationships, self-image, affect, and marked impulsivity beginning in early adulthood. The current study aimed to compare the efficacy of skills training based on Dialectical Behavior Therapy (DBT-ST) and Mindfulness-Based Cognitive Therapy (MBCT) on distress tolerance and psychological well-being in individuals with symptoms of Borderline Personality Disorder. Methods and Materials: This study was a quasi-experimental research with a pre-test-post-test design accompanied by a control group. The population consisted of all 18 to 45-year-old clients who visited counseling centers in Sari city in the first six months of the year 2022 and had a case file, among all individuals those who were willing to cooperate and had full consent for cooperation, 45 individuals were selected through purposive non-random sampling and then randomly assigned into three groups. To collect data, the Simons and Gaher (2005) Distress Tolerance Questionnaire and Ryff's (1980) Psychological Well-being Questionnaire were used. The first experimental group underwent skills training based on Dialectical Behavior Therapy by McKay, Wood, & Brantley (2007) in 12 weekly 90-minute group sessions, while the second experimental group underwent Mindfulness-Based Cognitive Therapy by Williams et al. (2002) in 8 weekly 90-minute group sessions. For data analysis, statistical tests with SPSS software, version 22, were used. Findings: The results indicated that skills training based on Dialectical Behavior Therapy and Mindfulness-Based Cognitive Therapy were effective on distress tolerance (p = 0.001) and psychological well-being (p = 0.001) in individuals with symptoms of Borderline Personality Disorder. Conclusion: There was a significant difference in the efficacy of skills training based on Dialectical Behavior Therapy and Mindfulness-Based Cognitive Therapy on distress tolerance and psychological well-being between the two experimental groups and the control group.

Generalized impedance model and interaction analysis for multiple grid-forming and grid-following converters

The growing use of power electronics converters in the power system leads to emerging stability issues. However, existing impedance models are insufficient for analysis of the converter-induced stability issues in the converter-congregated local area, especially faced with the hybrid integration of both grid-following (GFL) and grid-forming (GFM) converters. In this paper, a generalized impedance model in the d q frame is developed to facilitate the impedance-based analysis of any grid node with both GFL and GFM converters. With this model, closed-loop, internal and external stability performance can be accurately described and predicted. This paper shows that the internal stability of power converters has the feature of transferability. Therefore, to facilitate the internal stability analysis of multiple-input and multiple-output systems, this paper proposes a stability analysis method that utilizes the determinant of total admittance (matrices in high dimension) for direct stability demonstration, based on the recognition of instability pattern. Finally, the procedure for integrating power converters is considered to help with the stability-oriented design. The established impedance model, the proposed stability analysis method and the converter integration procedure are validated with control hardware-in-the-loop results in a study case of a multi-terminal network with current-controlled converters and virtual synchronous generators. • Impedance model describing any local area with GFL and GFM converters is proposed. • The determinant of total bus admittance is used for internal stability demonstration. • Impacts of critical system parameters on internal and external stability are studied. • A three-step procedure is adopted to facilitate the stability-oriented design.

Spectres of Caste/Contagion: Death Anxiety and Caste Anxiety in U.R. Ananthamurthy’s Samskara

The article critiques the traversal politics of caste and contagion through a critical dissection of what comes as a primarily biomedical excess of the outbreak—the dead body. It elucidates upon the becoming of the dead body into an untouchable where its “right to die with dignity” is deferred. The article reasons this stigmatisation of the deceased as a result of anxiety ensued in the living population facing the outbreak crisis. Through a close textual reading of U.R. Ananthamurthy’s novel Samskara (1965), the article elaborates on the othering discourse of outbreaks and discusses the type of socio-immune response exhibited by a casteist body politic. The novel centres its narrative around a plague-stricken Brahmin community where the contested dead body of pestilence triggers an endless debate of humanistic morals and ethics. By equipping the Derridean lens of hauntology, the article reads Samskara as an outbreak narrative which informs about the social unpreparedness and indecisiveness expressed by caste groups. The article discusses two types of anxieties expressed in such a caste-based society, namely death anxiety and caste anxiety. It mediates how these anxieties are produced in inversion, creating a unique pattern of social instability and inertia with relevance to the socio-political discourse of India. The epiphenomenon of inverted anxieties in India is presented as a subverted narrative from the global patterns of anxiety charged by microbial invasions. Finally, the article examines how the dead regains spectral agency in order to reveal the social pathology of a community doubly infected with caste and contagion.

Brief education supported psychological treatment for adolescent borderline personality disorder: the BEST feasibility RCT

BackgroundBorderline personality disorder is a severe mental health condition characterised by a pattern of emotional instability, interpersonal dysfunction, disturbed self-image and impulsive behaviour, including self-harm. Symptoms of borderline personality disorder typically emerge during adolescence. Although there is compelling evidence in support of early intervention for borderline personality disorder, current evidence-based interventions are resource intensive, with the result that few young people access timely treatment. Therefore, there is an urgent need for accessible interventions to facilitate early intervention for adolescents with borderline personality disorder symptoms.ObjectivesThe first objective was to adapt a brief psychological treatment for adolescent borderline personality disorder that had previously been delivered within secondary mental health services for co-delivery within schools and colleges. The second objective was to assess the feasibility of evaluating the clinical effectiveness and cost-effectiveness of this intervention in a future randomised controlled trial.DesignWe first conducted a rapid evidence synthesis of barriers to and facilitators of the implementation of indicated mental health interventions for adolescents within educational settings and piloted the prototype intervention with three schools/colleges. Based on the findings of the evidence synthesis and pilot, we refined the intervention and study procedures in preparation for a feasibility randomised controlled trial. The feasibility randomised controlled trial involved 12 schools and colleges, whose pastoral staff members received training to deliver the intervention alongside a mental health practitioner. Participants were randomised in a 1 : 1 ratio to receive either the BEST (Brief Education Supported Treatment) intervention plus treatment as usual or treatment as usual alone. Participants were assessed pre randomisation (baseline) and at 12 and 24 weeks post randomisation. Mixed-methods process data were collected to understand how the intervention was implemented, to assess acceptability and to monitor contamination of the control arm.ParticipantsYoung people eligible to participate were aged 13–18 years, reported symptoms of borderline personality disorder above an established threshold and had a history of repeated self-harm.ResultsThe intervention was refined based on findings of the rapid evidence synthesis, which included 50 studies, feedback from staff participants in the pilot and analysis of session recordings. In the feasibility randomised controlled trial, we randomised 32 participants prior to the premature closure of recruitment. The rate of recruitment was slower than anticipated but would probably have narrowly surpassed our progression criterion over the full recruitment window. Participant retention was high (89.5% at 12 weeks and 73.7% at 24 weeks) and the performance of the proposed outcome measures was satisfactory. We did not find any evidence that participants allocated to the treatment-as-usual arm received the BEST intervention or its components. Fidelity of intervention delivery was high (93.5% of recordings rated as adherent) and the intervention was viewed as offering benefits for individual participants, practitioners involved in co-delivery and the wider school/college.LimitationsThe feasibility randomised controlled trial was disrupted by the closure of schools and colleges in response to the COVID-19 pandemic. This reduced the window for participant recruitment and limited the data that could be collected.ConclusionsThe refined BEST intervention was able to be delivered successfully within schools and colleges and was found to be acceptable to staff and young people. The findings provide support for continuing this programme of research and would inform the design of a future trial.Trial registrationThis trial is registered as ISRCTN16862589.FundingThis project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full inHealth and Social Care Delivery Research; Vol. 10, No. 37. See the NIHR Journals Library website for further project information.

Density correlations from analog Hawking radiation in the presence of atom losses

The sonic analog of Hawking radiation can now be experimentally recreated in Bose-Einstein condensates that contain an acoustic black hole. In these experiments the signal strength and approximate analog Hawking temperature increase for denser condensates, which however also suffer increased atom losses from inelastic collisions. To determine how these affect analog Hawking radiation, we numerically simulate creation of the latter in a Bose-Einstein condensate in the presence of atomic losses, including nonunitary quantum field dynamics using the truncated Wigner approximation. In particular we explore modifications of density-density correlations through which the radiation has been analyzed so far. We find no evidence that losses directly alter the basic picture of the analog Hawking effect; instead all consequences that we find are indirect: Losses increase the contrast of the correlation signal, which we attribute to condensate heating by the losses, in turn leading to a component of stimulated radiation in addition to the spontaneous one. Other indirect consequences are the modification of the white-hole instability pattern and a change of slope of the Hawking tongue.

Growth-Induced Wrinkles and Dotlike Patterns of a Swollen Fluoroalkylated Thin Film by the Reaction of Surface-Attached Polymethylhydrosiloxane.

The design of hydrophobic surfaces requires a material which has a low solid surface tension and a simple fabrication process for anchoring and controlling the surface morphology. A generic method for the spontaneous formation of robust instability patterns is proposed through the hydrosilylation of a fluoroalkene bearing dangling chains, Rf = C6F13(CH2)3-, with a soft polymethylhydrosiloxane (PMHS) spin-coated gel polymer (0.8 μm thick) using Karstedt catalyst. These patterns were easily formed by an irreversible swelling reaction due to the attachment of a layer to various substrates. The buckling instability was created by two different approaches for a gel layer bound to a rigid silicon wafer substrate (A) and to a soft nonswelling silicone elastomer foundation (B). The observations of grafted Rf-PMHS films in the swollen state by microscopy revealed two distinct permanent patterns on various substrates: dotlike of wavelength λ = 0.4-0.7 μm (A) or wrinkle of wavelength λ = 4-7 μm (B). The elastic moduli ratios of film/substrate were determined using PeakForce quantitative nanomechanical mapping. The characteristic wavelengths (λ) of the patterns for systems A and B were quantitatively estimated in relation to the thickness of the top layer. A diversity of wrinkle morphologies can be achieved by grafting different side chains on pristine PMHS films. The water contact angle (WCA) hysteresis of fluorinated chain (Rf) was enhanced upon roughening the surfaces, giving highly hydrophobic surface properties for water with static/hysteresis WCAs of 136°/74° in the resulting wrinkle (B) and 119°/41° in the dotlike of lower roughness (A). The hydrophobic properties of grafted films on A with various mixtures of hexyl/fluoroalkyl chains were characterized by static CA: WCA 104-119°, ethylene glycol CA 80-96°, and n-hexadecane CA 17-61°. A very low surface energy of 15 mN/m for Rf-PMHS was found on the smoother dotlike pattern.

Rare case of intra-articular biceps incarceration following traumatic massive rotator cuff tear

Rare case of intra-articular biceps incarceration following traumatic massive rotator cuff tear

Posterolateral rotatory instability of the elbow

Posterolateral rotatory instability (PLRI) of the elbow is the most common chronic instability pattern identified. It is the resultant ulno-humeral instability secondary to compromised lateral ligament complex. The characteristic injury is the avulsion of the lateral ulnar collateral ligament (LUCL) from its humeral attachment. Acute PLRI can present following simple or complex elbow dislocations. Chronic PLRI mostly follows trauma but also can be the result of iatrogenic injury.

Chromosome instability in neuroblastoma: A pathway to aggressive disease.

For over 100-years, genomic instability has been investigated as a central player in the pathogenesis of human cancer. Conceptually, genomic instability includes an array of alterations from small deletions/insertions to whole chromosome alterations, referred to as chromosome instability. Chromosome instability has a paradoxical impact in cancer. In most instances, the introduction of chromosome instability has a negative impact on cellular fitness whereas in cancer it is usually associated with a worse prognosis. One exception is the case of neuroblastoma, the most common solid tumor outside of the brain in children. Neuroblastoma tumors have two distinct patterns of genome instability: whole-chromosome aneuploidy, which is associated with a better prognosis, or segmental chromosomal alterations, which is a potent negative prognostic factor. Through a computational screen, we found that low levels of the de- ubiquitinating enzyme USP24 have a highly significant negative impact on survival in neuroblastoma. At the molecular level, USP24 loss leads to destabilization of the microtubule assembly factor CRMP2 - producing mitotic errors and leading to chromosome missegregation and whole-chromosome aneuploidy. This apparent paradox may be reconciled through a model in which whole chromosome aneuploidy leads to the subsequent development of segmental chromosome alterations. Here we review the mechanisms behind chromosome instability and the evidence for the progressive development of segmental alterations from existing numerical aneuploidy in support of a multi-step model of neuroblastoma progression.

Right-left digit ratios, a novel form of asymmetry: Patterns of instability in children and relationships to platelet counts and hospitalization in adults with COVID-19.

High right minus left (R-L) asymmetry of digit ratios has been reported to be linked to hospitalization for COVID-19. Here we examined the developmental patterns of this novel form of asymmetry in children and further explored their relationships to platelet counts and hospitalization for COVID-19 in adult patients. We considered ratios calculated from four digits (2D, 3D, 4D, 5D) in: (i) a sample of healthy participants aged 2 years to 18 years (n = 680, 340 males) and (ii) 96 adult patients (42 males) hospitalized for COVID-19 and 100 controls (53 males). The protocol for (ii) included a questionnaire and laboratory test results. In sample (i) of the six unsigned digit ratio asymmetries, those which included 5D had the highest mean asymmetry with the greatest between-individual variation and they were unstable over the age range of 2 years to 18 years. In sample (ii) patients showed higher asymmetries than controls in four ratios (2D:4D, 2D:5D, 3D:5D, 4D:5D) and a sum of asymmetries of the two independent ratios (2D:4D+3D:5D) correlated positively with platelet counts and hospitalization. Conclusion: Means and SDs of digit ratio asymmetry that include the 5th digit are high and age-unstable. Digit ratio asymmetry, particularly 5th digit ratio asymmetry and a composite measure of 2D:4D + 3D:5D asymmetry, may be positively linked to high platelet counts in COVID-19 patients and to an elevated risk of hospitalization.

Evolution of Thin-Film Wrinkle Patterns on a Soft Substrate: Direct Simulations and the Effects of the Deformation History.

Surface wrinkling instability in thin films attached to a compliant substrate is a well-recognized form of deformation under mechanical loading. The influence of the loading history on the formation of instability patterns has not been studied. In this work, the effects of the deformation history involving different loading sequences were investigated via comprehensive large-scale finite element simulations. We employed a recently developed embedded imperfection technique which is capable of direct numerical predictions of the surface instability patterns and eliminates the need for re-defining the imperfection after each analysis step. Attention was devoted to both uniaxial compression and biaxial compression. We show that, after the formation of wrinkles, the surface patterns could still be eliminated upon complete unloading of the elastic film–substrate structure. The loading path, however, played an important role in the temporal development of wrinkle configurations. With the same final biaxial state, different deformation histories could lead to different surface patterns. The finding brings about possibilities for creating variants of wrinkle morphologies controlled by the actual deformation path. This study also offers a mechanistic rationale for prior experimental observations.

Modeling interfacial instability patterns during debonding a rigid spherical indenter from thin elastic films

Adhesive contact of soft materials has many significant applications, including the fabrication of microelectronic systems, transfer of flexible electronic devices, and antifouling coatings. Many experiments found that cavitation and fingering instabilities will appear at the adhesive interface between rigid indenters and soft films. However, most of these studies focus on flat indenters. Thus, for the adhesive of spherical indenters and soft films, how to modulate the instability patterns and how interfacial instabilities impact the mechanical responses of the film are still poorly understood. Here, we study the detachment of a spherical indenter from a thin elastic film by using 2D and 3D finite-element simulations. Consistently with previous experimental observations of flat indenters, we find that the critical pull-off force increases exponentially with the confinement ratio when the interface separation is stable. But the interface separation becomes unstable when the confinement ratio is bigger than a certain critical value, causing a reduction in the pull-off force. Moreover, we can also study the effects of parameters difficult to handle experimentally and show that the initial instability pattern can be either cavitation or fingerings depending on the indentation depth, indenter radius, and adhesion energy density between the indenter and the film. Finally, we find that allowing the film to slip freely in the lateral direction can significantly suppress the fingering instabilities. Together, our work identifies the key factors that control interfacial instability patterns and the methods that impede interfacial instabilities, which will provide meaningful guidance for regulating the interfacial adhesion of soft materials.

Patellar Instability in Young Athletes.

This article summarizes the latest research related to pediatric patellar instability. The epidemiology, patterns of patellar instability, and underlying pathoanatomy are unique in children and adolescents. Information related to the natural history and predictive factors of patellar instability in young patients would allow for better patient counseling and management decisions. The components of nonoperative treatment for first patellar dislocation are outlined. Physeal-respecting surgical techniques, including medial patellofemoral ligament reconstruction in skeletally immature patients, are discussed. The indications and outcomes for quadricepsplasty to address more complex instability patterns are presented. Evaluation and management strategies for specific anatomic risk factors is provided.

Marangoni convection instabilities in an evaporating droplet on a non-isothermal substrate

• The maximum number of LRs is smaller than that on the isothermal substrate • The instability patterns preferentially occur at the lower temperature side • LRs continuously propagate along azimuthal direction towards cold side • Propagation speed increases with increase of the temperature gradient • Critical contact angles for the onset of LRs decrease with increasing Ma The Marangoni convection instabilities are investigated in a sessile ethanol droplet as it evaporates on a non-isothermal substrate. The instability structures consistently, preferentially occur at the lower temperature side of substrate. Drifted by the azimuthal thermocapillary flow under externally imposed temperature gradient, the longitudinal rolls are found to propagate from the hot side to the cold side for the droplet, while a radial propagation of the BM cells directly from the cold side to the hot side along the droplet diameter occurs at the last period of evaporation process. The azimuthal propagation speed of longitudinal rolls increases with the increase of temperature gradient, but is independent of the mean temperature of the substrate. Effects of the mean temperature of substrate and the temperature gradient on the Marangoni instabilities are investigated, and the critical conditions for the onset of longitudinal rolls are determined.

Geometrical incompatibility guides pattern selection in growing bilayer tubes

Pattern selection and subsequent morphological evolution are of remarkable significance, since they are critical for living creatures to fulfill certain biological functions and also have widespread potential applications from disease diagnosis to advanced manufacturing. Geometrical incompatibility is omnipresent in biological systems and plays a critical role in pattern selection of the growing soft biological tissues. However, how geometrical incompatibility guides pattern selection in growing soft matter remains poorly understood. Here, we present a theoretical model to investigate the influence of geometrical incompatibility on pattern selection of growing bilayer tubes. Our linear stability analysis illustrates that an increase of the geometrical incompatibility parameter provokes the instability pattern transition from a longitudinal pattern to a two-dimensional (2D) pattern and then to a circumferential pattern. Based on the theoretical model, a series of quantificational experiments and finite element simulations are implemented to study how geometrical incompatibility guides pattern selection of growing bilayer tubes and explore the post-buckling evolution of the emerging patterns. Both the numerical simulations and experimental observations agree well with our theoretical predictions. In particular, with further growth far beyond the threshold, a secondary bifurcation is observed in the post-buckling evolution of the 2D pattern. This study suggests that geometrical incompatibility can serve as an implementable experimental tool to quantificationally guide pattern selection and subsequent morphological evolution of growing soft matter, which can be used for growth self-assembly and multifunctional surface manufacturing.

Energy-based analysis of 3D wind-induced-flutter mechanism of a three-tower suspension structure

Three-tower suspension bridges have broad application prospects in water-crossing and island-linking projects. The large span, flexibility, and slight rigidity of the central tower of three-tower suspension bridges make them extremely sensitive to wind action and wind-induced flutter, which mechanisms have not been clarified yet. In this paper, the Ma’anshan Yangtze River Bridge in China was taken as an example, and the mechanism of its flutter instability was analyzed from the flutter energy standpoint. Upon formulating the main principles of the three-dimensional (3D) flutter analysis of bridges, the respective method was proposed and applied to the bridge under study, yielding the main vibration modes and the movement decoupling in the time domain analysis. The relevant energy calculation was programmed for the 3D flutter energy analysis of the bridge under study. At the flutter onset, the energies of the torsional and heaving movement systems slightly increased and decreased, respectively, the latter being converted into the former and resulting in its divergence. Aerodynamic damping was the main factor in the system stability, while aerodynamic stiffness slightly influenced its flutter instability pattern.

Individual-specific levels of CTG•CAG somatic instability are shared across multiple tissues in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age) also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle have an earlier age at onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA nor levels of DMPK sense and anti-sense transcripts could obviously explain individual- or tissue-specific patterns of somatic instability.

Non-Linear Instability of Pin-Ended Functionally Graded Material Arches Under Locally Distributed Radial Loads

The arch is a common structural form in bridge engineering; its collapse is often caused by instability. In this article, in-plane nonlinear instability of pin-ended functionally graded material (FGM) arches with two cross-sectional types under local radial loads is studied. New analytical solutions to nonlinear equilibrium paths, limit point instability, bifurcation instability, and multiple limit point instability of pin-ended FGM arches under local radial load are obtained. Modified slenderness corresponding to different instability patterns of FGM arches is also derived. Comparison with the numerical results of ANSYS demonstrates that the analytical solution is accurate. The results show that cross-sectional types of FGM arches have a great influence on limit-point instability and bifurcation instability. Localized parameters increase lead-to-limit point instability load and bifurcation instability load increases, while increasing the modified slenderness ratio results in decreased limit point instability load and bifurcation instability load. In addition, a material proportion coefficient and power law index increase can also lead to limit point instability load and bifurcation instability load decrease.

Patterns of homelessness and housing instability and the relationship with mental health disorders among young people transitioning from out-of-home care: Retrospective cohort study using linked administrative data.

ObjectivesThe study examined the relationship between mental health, homelessness and housing instability among young people aged 15–18 years old who transitioned from out-of-home in 2013 to 2014 in the state of Victoria, Australia with follow-up to 2018. We determined the various mental health disorders and other predictors that were associated with different levels of homelessness risk, including identifying the impact of dual diagnosis of mental health and substance use disorder on homelessness.MethodologyUsing retrospective de-identified linked administrative data from various government departments we identified various dimensions of homelessness which were mapped from the European Topology of Homelessness (ETHOS) framework and associated mental health variables which were determined from the WHO ICD-10 codes. We used ordered logistic regression and Poisson regression analysis to estimate the impact of homelessness and housing instability respectively.ResultsA total homelessness prevalence of 60% was determined in the care-leaving population. After adjustment, high risk of homelessness was associated with dual diagnosis of mental health and substance use disorder, intentional self-harm, anxiety, psychotic disorders, assault and maltreatment, history of involvement with the justice system, substance use prior to leaving care, residential and home-based OHC placement and a history of staying in public housing.ConclusionsThere is clearly a need for policy makers and service providers to work together to find effective housing pathways and integrated health services for this heterogeneous group of vulnerable young people with complex health and social needs. Future research should determine longitudinally the bidirectional relationship between mental health disorders and homelessness.

210O Mutational signature analysis reveals patterns of genomic instability linked to resistance to endocrine therapy (ET) +/- CDK 4/6 inhibition (CDK4/6i) in estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC)

APOBEC mutagenesis is enriched in MBCs. The predictive role of APOBEC and other mutational processes on standard regimens in the MBC setting is largely unknown. We retrieved clinical and genomic data of 4,595 BCs that underwent targeted sequencing by an FDA-cleared panel comprising >400 genes. Mutational signatures were computed by the SigMA algorithm for samples with at least 5 single nucleotide variants and manually reviewed. BCs were classified as APOBEC+, HRD+ or APOBEC-/HRD- based on the dominant mutational process as defined by SigMA. Progression-free survival (PFS) to any line (L) of therapy was assessed using univariate and multivariate Cox models. APOBEC+ and HRD+ were found at higher proportion in MBCs than in primary tumors (24% and 24% vs 15% and 13%; p<0.001). APOBEC+ were highly represented in ER+/HER2- (19%) and HER2+ (47%) subtypes, while HRD+ in triple-negative (36%). Lobular BCs had a higher proportion of APOBEC+ than HRD+ and APOBEC-/HRD- (34% vs 10% vs 21%, p<0.001). ER+/HER2- MBCs with APOBEC displayed lower ESR1 hotspot mutations (p<0.001). Survival analyses were restricted to patients with available pre-treatment samples. In ER+/HER2- MBCs treated with 1L or 2L ET monotherapy (n=395), APOBEC+ tumors were independently associated to shorter mPFS (HR 1.6, 95%CI 1.2-2.2, p=0.001), regardless of the ET agent. APOBEC+ and HRD+ MBCs were associated with lower mPFS on 1L CDK4/6i+ET (n=419) than APOBEC-/HRD- (HR 1.5, 95%CI 1.1-2, p=0.01 and HR 1.7, 95%CI 1.2-2.5, p=0.006, respectively), regardless of ET partner. HRD+ BCs had a reduced mPFS on 2L (n=207) and 3L (n=372) of CDK4/6i+ET (HR 2.1, 95%CI 1-4.1, p=0.03 and HR 1.8, 95%CI 1.3-2.5, p=0.001, respectively). Patients with APOBEC+ and HRD+ ER+/HER2- MBCs experience shorter survival on ET +/- CDK4/6i, suggesting that the genomic instability conferred by APOBEC and HRD results in early resistance. Novel treatments tailored on these BC subgroups are needed. Additional genomic analyses to unravel mutational patterns related to APOBEC and HRD in this setting are underway.