Unveiling the Ir single atoms as selective active species for the partial hydrogenation of butadiene by operando XAS.

Single-atom catalysts represent an intense topic of research due to their interesting catalytic properties for a wide range of reactions. Clarifying the nature of the active sites of single-atom catalysts under realistic working conditions is of paramount importance for the design of performant materials. We have prepared an Ir single-atom catalyst supported on a nitrogen-rich carbon substrate that has proven to exhibit substantial activity toward the hydrogenation of butadiene with nearly 100% selectivity to butenes even at full conversion. We evidence here, by quantitative operando X-ray absorption spectroscopy, that the initial Ir single atoms are coordinated with four light atoms i.e., Ir-X4 (X = C/N/O) with an oxidation state of +3.2. During pre-treatment under hydrogen flow at 250 °C, the Ir atom loses one neighbour (possibly oxygen) and partially reduces to an oxidation state of around +2.0. We clearly demonstrate that Ir-X3 (X = C/N/O) is an active species with very good stability under reactive conditions. Moreover, Ir single atoms remain isolated under a reducing atmosphere at a temperature as high as 400 °C.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

Emotional, cognitive and social factors of antimicrobial prescribing: can antimicrobial stewardship intervention be effective without addressing psycho-social factors?

There is increasing evidence that psycho-social factors can influence antimicrobial prescribing practice in hospitals and the community, and represent potential barriers to antimicrobial stewardship interventions. Clinicians are conditioned both by emotional and cognitive factors based on fear, uncertainty, a set of beliefs, risk perception and cognitive bias, and by interpersonal factors established through social norms and peer and doctor-patient communication. However, a gap is emerging between research and practice, and no stewardship recommendation addresses the most appropriate human resource allocation or modalities to account for psycho-social determinants of prescribing. There is a need for translation of the evidence available from human behaviour studies to the design and implementation of stewardship interventions and policies at hospital and community levels. The integration of behaviour experts into multidisciplinary stewardship teams seems essential to positively impact on prescribers' communication and decision-making competencies, and reduce inappropriate antibiotic prescribing.

Verbal Fluency Development Across Childhood: Normative Data from Brazilian-Portuguese Speakers and Underlying Cognitive Processes.

OBJECTIVE: Verbal fluency (VF) tasks are widely used to investigate children's lexical knowledge and executive functions skills. Consistency of measurement of the strategic retrieval components is still an issue and performance of Brazilian-Portuguese speaking children are currently not available. A cross-sectional study investigated the effects of age, school type (public × private) and the influence of language, memory and inhibitory control on VF. METHOD: We assessed 414 Brazilian children, aged 6-12, in the number of words produced and both clustering and switching components, with two measures of VF: letter (LVF) and semantic (SVF). RESULTS: Analysis of the number of words produced showed a significant increase between 6-8-year-olds, 9-10-year-olds and 11-12-year-olds in SVF, while in LVF, the differences were significant only in the later age group. In SVF, the numbers of clusters and switches increased with age, whereas in LVF, the number of switches increased in all age groups, but clusters increased only in the older group. Structural equation model analyses showed that oral and written language, verbal memory and inhibitory control are associated with VF performance and IQ, while age mediated VF performance. CONCLUSIONS: The results indicate a different development pattern between LVF and SVF in the number of words produced and in clustering and switching, with the latter predicting VF performance in words produced. VF development is shown to depend on language, memory and inhibitory control. Our results have important implications to clinical neuropsychology.

Cardiovascular assessment of supportive doctor-patient communication using multi-scale and multi-lag analysis of heartbeat dynamics.

Emphatic doctor-patient communication has been associated with improved psycho-physiological well-being involving cardiovascular and neuroendocrine responses. Nevertheless, a comprehensive assessment of heartbeat linear and nonlinear dynamics throughout the communication of a life-threatening disease has not been performed yet. To this extent, we studied linear heartbeat dynamics through the extraction of time-frequency domain measurements, as well as heartbeat nonlinear and complex dynamics through novel approaches to compute multi-scale and multi-lag series analyses: namely, the multi-scale distribution entropy and lagged Poincaré plot symbolic analysis. Heart rate variability series were recorded from 54 healthy female subjects who were blind to the aim of the experiment. Participants were randomly assigned into two groups: 27 subjects watched a video where an oncologist discloses the diagnosis of a cancer metastasis to a patient, whereas the remaining 27 watched the same video including four additional supportive comments by the clinician. Considering differences between the beginning and the end of each communication video, results from non-parametric Wilcoxon tests demonstrated that, at a group level, significant differences occurred in heartbeat linear and nonlinear dynamics, with lower complexity during nonsupportive communication. Furthermore, a support vector machine algorithm, validated using a leave-one-subject-out procedure, was able to discern the supportive experience at a single-subject level with an accuracy of 83.33% when nonlinear features were considered, dropping to 51.85% when using standard HRV features only. In conclusion, heartbeat nonlinear and complex dynamics can be a viable tool for the psycho-physiological evaluation of supportive doctor-patient communication. Graphical Abstract Scheme of the three main stages of the study: signal acquisition during doctor-patient communication, ECG signal processing and pattern recognition results.

An overview of the possible therapeutic role of SUMOylation in the treatment of Alzheimer's disease.

Nowadays, Alzheimer's disease (AD) is recognized as a multifactorial neurological pathology whose complexity is the cause of our still low achievements in the understanding of the associated mechanisms as well the discovery of a possible definitive cure. Clinicians are aware of the few possibilities offered by medicine to cure Alzheimer's patients, restore their memory and take them back to normal life. Unfortunately, the therapeutic tools available today are not able to contrast the pathology. In the last years the tendency of the research is to formulate new hypotheses that can help to develop future effective drugs. Here we propose an overview about an interesting intracellular mechanism called SUMOylation which belongs to the post-translational modification family. SUMOylation is currently studied from few decades and it has been observed to be implicated in the molecular mechanisms of several neurological disorders including AD. Interestingly, the unbalance between SUMOylation/deSUMOylation seems to be involved in the switch from physiological to pathological behaviours of several proteins implied into AD etiology. Nevertheless, there are no pharmacological treatments known to modulate SUMOylation/deSUMOylation equilibrium. We hereby listed some natural compounds that, due to their effects on this molecular mechanism, they deserve attention for inspire the development of future convincing therapies.

Characterization of doctor-patient communication using heartbeat nonlinear dynamics: A preliminary study using Lagged Poincaré Plots.

Emphatic doctor-patient communication has been associated with an improved psycho-physiological well-being involving cardiovascular and neuroendocrine responses. Nevertheless, a comprehensive assessment of heartbeat linear and nonlinear/complex dynamics throughout the communication of a life-threatening disease has not been performed yet. To this extent, we here study heart rate variability (HRV) series gathered from 17 subjects while watching a video where an oncologist discloses the diagnosis of a cancer metastasis to a patient. Further 17 subjects watched the same video including additional affective emphatic contents. For the assessment of the two groups, linear heartbeat dynamics was quantified through measures defined in the time and frequency domains, whereas nonlinear/complex dynamics referred to measures of entropy, and combined Lagged Poincare Plots (LPP) and symbolic analyses. Considering differences between the beginning and the end of the video, results from non-parametric statistical tests demonstrated that the group watching emphatic contents showed HRV changes in the LF/HF ratio exclusively. Conversely, the group watching the purely informative video showed changes in vagal activity (i.e., HF power), LF/HF ratio, as well as LPP measures. Additionally, a Support Vector Machine algorithm including HRV nonlinear/complex information was able to automatically discern between groups with an accuracy of 76.47%. We therefore propose the use of heartbeat nonlinear/complex dynamics to objectively assess the empathy level of healthy women.

Isolated new onset 'atypical' optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up.

Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab(neg) patients. 37 AQP4-Ab positive (AQP4-Ab(pos)) and 32 AQP4-Ab negative (AQP4-Ab(neg)) patients (8 with MOG-Ab) were identified. The AQP4-Ab(neg) group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab(neg) patients, AQP4-Ab(pos) patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Ab(neg) patients with RION also had poor visual outcome. Up to 35% of AQP4-Ab(neg) patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab(neg) patients (25%) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0-6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab(neg) RION also had a poor visual outcome. Of those without AQP4-Ab, 25% had MOG-Ab and another 25% developed MS; thus, MOG-Ab is associated with AQP4-Ab(neg) non-MS ON.

Multiple sclerosis in Japan appears to be a milder disease compared to the UK.

Multiple sclerosis (MS) is relatively common in the West, but rare in Japan. In the literature, there are few comparative data regarding disease severity throughout the world. The objective of this study was to compare disability in patients from a UK and a Japanese MS cohort. We retrospectively analysed the clinical features of patients with MS from a UK and Japanese MS centre. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Expanded Disability Status Scale score according to disease duration, was used as a marker of disease severity. One thousand one hundred forty-eight UK patients and 104 Japanese patient were identified representing the relative national prevalence. Demographics and disease duration did not differ between the groups. Median MSSS was significantly different between the two groups (Japan 3.34 vs. UK 5.87, p < 0.001). Primary progressive MS was more common in the UK (12.9%) than in the Japanese cohort (3%, p = 0.044). The majority of Japanese patients (83.7% vs. UK 17%) had been exposed to disease modifying treatments (DMTs). Exposure to DMTs did not show a significant effect on disability. In conclusion, this study suggests that MS in Japan may be associated with less disability than in UK. More Japanese patients were treated with DMTs. Differences in treatments do not seem to explain the disparity in disability severity. This suggests either genetic or environmental influences on disease severity.

Nanoalloying bulk-immiscible iridium and palladium inhibits hydride formation and promotes catalytic performances.

The hydrogen sorption properties of oxide-supported Ir-Pd nanoalloys have been determined for the first time, and correlated with their catalytic behavior. The addition of Ir to Pd suppresses hydride formation and leads to improved catalytic performances with respect to pure metals in the preferential oxidation of CO in H2 excess (PROX).

Asking questions during breast cancer consultations: does being alone or being accompanied make a difference?

PURPOSE: Companions often accompany patients to cancer consultations. The number of questions asked by patients and companions is an indicator of their active participation. The present study aims to provide first descriptive evidence on the characteristics of unaccompanied and accompanied Italian breast cancer patients that attend the first consultation after surgery and to analyse companions contribution to the type and quantity of questions asked during the consultation. METHOD: Seventy consultations of female patients with breast cancer were audio taped. Questions were transcribed and coded by content. Companion's questions were also classified in terms of function. Socio-demographic and clinical data, patients' role preference and confidence in decision making measures were gathered for each patient. Post consultation satisfaction with decision and the perceived level of shared decision making were collected either for the patient and the companion. RESULTS: 69% of patients were accompanied, usually by one close family member, either husband or adult child. Non employed or retired patients and those with a preference for passive role in decision making were more likely to be accompanied. Unaccompanied patients and accompanied patients had comparable levels of anxiety, emotional distress and depression and were equally active in asking questions. These levels were far greater than those reported for other cancer patients in the literature. Companions did not increase significantly the number of questions per consultation. CONCLUSION: Accompanied and non accompanied patients differed more in socio-demographic than clinical characteristics. Companions sustained the patient and shared information without reducing the level of patient involvement.

People-centred care: new research needs and methods in doctor-patient communication. Challenges in mental health.

Communication in psychiatry is nowadays called to create bridges between different levels of observation (biological, functional and relational levels) and therapeutic intervention (social and educational) with important implications for therapeutic practice and communication research in the mental health context. New research challenges and windows of opportunity for therapeutic practice will be addressed in this contribution, as they relate to the three main tasks that psychiatrists have to meet when talking with their patients: understanding patient's problems and concerns; establishing the therapeutic alliance by acknowledging and responding to patient's emotion; informing and involving patients and their families, when appropriate. Therapeutic decisions need the elaboration of valid strategies of shared decision-making, which still have to be implemented and adapted to psychiatric context. Moreover, in the research field, emerging biomarker research may contribute to better explain what makes the difference in an empathic relationship either in terms of psycho-physiological reactions and in brain changes. Finally, the influence of new technologies and of Internet has to be more and more considered during clinical consultations.

Advanced magnetic resonance imaging of neuromyelitis optica: a multiparametric approach.

BACKGROUND: Several authors have used advanced magnetic resonance imaging (MRI) techniques to investigate whether patients with neuromyelitis optica (NMO) have occult damage in normal-appearing brain tissue, similarly to multiple sclerosis (MS). To date, the literature contains no data derived from the combined use of several advanced MRI techniques in the same NMO subjects. OBJECTIVE: We set out to determine whether occult damage could be detected in the normal-appearing brain tissue of a small group of patients with NMO using a multiparametric MRI approach. METHODS: Eight female patients affected by NMO (age range 44-58 years) and seven sex- and age-matched healthy controls were included. The techniques used on a 1.5 T MRI imaging scanner were magnetization transfer imaging, diffusion tensor imaging, tract-based spatial statistics, spectroscopy and voxel-based morphometry in order to analyse normal-appearing white matter and normal-appearing grey matter. RESULTS: Structural and metabolic parameters showed no abnormalities in normal-appearing white matter of patients with NMO. Conversely, tract-based spatial statistics demonstrated a selective alteration of the optic pathways and the lateral geniculate nuclei. Diffusion tensor imaging values in the normal-appearing grey matter were found to be significantly different in the patients with NMO versus the healthy controls. Moreover, voxel-based morphometry analysis demonstrated a significant density and volume reduction of the sensorimotor cortex and the visual cortex. CONCLUSIONS: Our data disclosed occult structural damage in the brain of patients with NMO, predominantly involving regions connected with motor and visual systems. This damage seems to be the direct consequence of transsynaptic degeneration triggered by lesions of the optic nerve and spine.

Myasthenia gravis: a changing pattern of incidence.

The annual incidence of myasthenia gravis (MG) ranges from 3 to 30 per 1,000,000 people. Since the mid-1980s, an increasing incidence has been reported, mainly due to late-onset MG. Whether the increase was due to population aging, improved diagnosis and case collection, or a true excess of incidence cases is still under debate. We used a complete enumeration approach by reviewing all possible sources of case collection in the province of Ferrara, Italy, to estimate the MG incidence and its temporal trend over the study period (1985-2007). The mean annual age-adjusted incidence of MG was 18 per 1,000,000, without any significant temporal trend. The incidence rates in the period 1985-1990 were 14 both for early and late-onset MG. Thereafter, a significant increase in incidence of late-onset MG (p < 0.05), and a decrease in early onset MG were detected (p < 0.01). These findings were related to nonthymoma MG. The median age at onset of the disease steadily increased over time. A changing pattern of MG incidence with an increase in frequency of late-onset and a decrease of early onset MG was found in the last years, giving a significant shift to older age at onset of the disease. Unknown environmental factors may have driven this change in MG epidemiology.

The evaluation of training in patient-centred interviewing skills for psychiatric residents.

BACKGROUND: Communication skills are considered 'core skills' in the curriculum of psychiatry but studies evaluating the effectiveness of a time-limited training course in interviewing skills in psychiatry have remained rare. The aim was to assess the effectiveness of training in patient-centred interviewing on the interview performance of psychiatric residents. METHOD: Psychiatric residents (n=10) each interviewed 12 different anonymized standardized patients (SPs), eight before and another four after training. SPs simulated psychiatric out-patients who attended for a first visit to the psychiatric out-patient clinic. The consultations were videotaped, transcribed and coded with a classification scheme developed for psychiatric consultations from which an interview performance index was derived. An interrupted time-series design and a segmented regression analysis with multilevel analysis explored the performance trend within the series of consultations. RESULTS: The regression model evidenced a horizontal slope at pre- and post-training, with a significant level change. These findings excluded the presence of a practice effect and indicated a significant effect of training. Performance variability between and within residents over the series of consultations increased at post-training. CONCLUSIONS: The training improved patient-centred interviewing performance. More post-training exercise time and supervised practice are necessary to establish consistent performance patterns at a higher skill level.

Decisional strategies for the attribution of emotional distress in primary care.

BACKGROUND: In primary care the General Health Questionnaire (GHQ) is used to provide an independent assessment of probable caseness of psychological disorder against which to test the ability of the general practitioner (GP) to recognize patients with current emotional problems. METHOD: The aim of the present study was to identify those clinical and psychosocial data on patients that increase the likelihood of GPs' attribution of emotional distress (GP model) and those that predict patients' emotional distress as defined by the GHQ-12 (GHQ model). The associations were explored using a classification tree technique (CHAID) and compared using bivariate logistic regression. Six GPs and 444 primary care patients took part. RESULTS: The accuracy indices of the hierarchical GP and GHQ models were 72% and 69% respectively. The availability of information on patients' psychopharmacological and psychiatric/psychological treatment in the last year was the most important predictor of attribution. Occupational, financial and housing problems and life events of loss were the most important predictors of the GHQ-12 case definition. The overall accuracy of the bivariate model was 73%. Compared with the GHQ-12, GPs gave significantly more importance to psychiatric treatment, psychopharmacological drug use and chronic illness. CONCLUSIONS: The findings suggest that to improve the detection of current emotional distress in primary care patients GPs should pay foremost and systematic attention to social problems and recent life events of loss. These problems are important clues for the possible presence of emotional distress, whereas critical patient data, in particular psychiatric history and psychopharmacological treatment, increase the probability of attribution errors.

Differences in verbal behaviours of patients with and without emotional distress during primary care consultations.

BACKGROUND: In primary care consultations patients with emotional distress tend to give verbal cues or symptom reports with psychological or psychiatric contents. This study examined the cue behaviour defined not only by psychological, but also by medical, social and life episodes related contents in patients with and without emotional distress, recognized and not by their GP. The GP's verbal behaviour in relation to patients' cue emission was also investigated. METHOD: For the six participating GPs two groups of matched pairs of patients (N = 238) were created. The two groups comprised either patients considered by GPs as being without emotional distress or patients considered as emotionally distressed. Within each pair, one patient was a case (GHQ-12 score > 2) and the other was the matched control (GHQ-12 score < 3). The medical interviews with these patients were transcribed and classified according to the Verona Medical Interview Classification System (VR-MICS). RESULTS: GHQ positive patients of both groups gave more cues in terms of total proportion than their matched controls (GHQ negative patients). The proportion of cues given by patients was related also to GP's verbal behaviour, increasing with closed psychosocial questions and decreasing with the use of active interview techniques. Attribution of emotional distress was more frequent when patients were high attenders and had a past psychiatric history. The content of cues changed in relation to GP's attribution: recognized patients gave more cues and more often with psychological content, patients not recognized as distressed gave mainly cues related to their lifestyle and life episodes. CONCLUSIONS: To improve the recognition of those emotionally distressed patients most likely to be missed GPs should increase their attention to cues related to life style and life episodes.

[Patient-centered interviews in general practice]. / Il colloquio con il paziente in medicina generale.

Many studies have confirmed that the interview approach adopted by the physician influences the quality of the doctor-patient relationship as well as the accuracy and validity of information which is elicited during the medical interview. A correct interview approach is also the basis for diagnosis and treatment. This paper summarizes the main characteristics of the patient-centred interview approach which has to integrate the doctor centred approach in order to render the medical interview efficient in terms of data collection, doctor-patient relationship and time. The first part of the interview with the patient has always to be patient-centred. The patient is facilitated to report all the information regarding his symptoms and their psychosocial context and to express his ideas and expectations, after which the interview style becomes more directive and doctor-led. In this phase the doctor remaining however attentive to patient's cues. Some data are presented which describe the prevailing interview approach of general practitioners without any formal training in patient-centred interview techniques. The analysis of doctors' verbal behaviour during the consultation confirmed the necessity of educational interventions focalized on the improvement of doctors' interview skills.

[Psychosocial problem disclosure during primary care consultations]. / La presentazione di problemi psicosociali durante la consultazione in medicina generale.

OBJECTIVE: To examine how primary care patients with psychosocial problems actually introduce and present these topics. To examine the influence of some personality traits (emotional dependency and health locus of control) on psychosocial problem disclosure. DESIGN: "Case control". Cases had a GHQ-12 score equal or higher than three. Controls were matched with cases according to GP, GPs' attribution of absence or presence of emotional distress sex, age and presence of chronic illness. SETTING: Six single handed primary care practices. MEASURES: Clinical and Socio-demographic data, Social Problems List, List of 12 Threatening Life Events, GHQ-12, Multidimensional Health Locus of Control, Interpersonal Dependency Inventory and a Social Support Index. RESULTS: The introduction of psychosocial topics by patients is related to the attribution of emotional distress by GP. Patients identified correctly as not distressed present less often psychosocial topics compared to patients recognised as distressed. Distressed patients not recognised as such more often than the others did not offer any psychosocial cue. The personality measures did not influence the presentation of psychosocial problems. CONCLUSIONS: The lack of psycho-social cues from patients and of patient-centred skills contributed to the non recognition of emotional distressed patients. GPs' active facilitation of the presentation of psychosocial topics in such patients would improve the recognition of emotional distress.

Focal cognitive impairment in mitochondrial encephalomyopathies: a neuropsychological and neuroimaging study.

Mitochondrial encephalomyopathies (ME) are a multisystemic group of diseases characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance. We studied the neuropsychological profile, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) data in a group of ME patients in order to look for common or specific cognitive defects and a possible correlation with related brain areas. Three main cognitive areas were assessed: general intelligence, memory functions and visuo-perceptual skills. Our sample included 16 ME patients (nine males, seven females) aged 25-68 years (mean age 45.2, SD 13.0). No sign of mental deterioration was found in the group of elderly subjects. Despite subjects showing no global cognitive impairment they scored lower in nonverbal versus verbal tasks. Visuo-spatial skills and short-term memory were selectively impaired. There was no correlation between neuropsychological results and age, illness duration, age of onset, clinical phenotypes, genetic mitochondrial alterations and pharmacological therapy. The most frequent SPECT pattern observed was the hypoperfusion of temporal lobes, with a direct localization in the temporal cortex and with prevalent mesial involvement. The neuropsychological profile and SPECT imaging revealed similarities with focal defects.