Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum.

BACKGROUND: In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). METHODS: A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. RESULTS: A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper-hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. CONCLUSIONS: Our study reports a strong correlation between autism spectrum and CS.

Incremental design of water symbiosis networks with prior knowledge: The case of an industrial park in Kenya.

Industrial parks have a high potential for recycling and reusing resources such as water across companies by creating symbiosis networks. In this study, we introduce a mathematical optimization framework for the design of water network integration in industrial parks formulated as a large-scale standard mixed-integer non-linear programming (MINLP) problem. The novelty of our approach relies on i) developing a multi-level incremental optimization framework for water network synthesis, ii) including prior knowledge of water demand growth and projected water scarcity to evaluate the significance of water-saving solutions, iii) incorporating a comprehensive formulation of the water network synthesis problem including multiple pollutants and different treatment units and iv) performing a multi-objective optimization of the network including freshwater savings and relative cost of the network. The significance of the proposed optimization framework is illustrated by applying it to an existing industrial park in a water-scarce region in Kenya. Firstly, we illustrated the benefits of including prior knowledge to prevent an over-design of the network at the early stages. In the case study, we achieved a more flexible and expandable water network with 36% lower unit cost at the early stage and 15% lower unit cost at later stages for overall maximum freshwater savings of 25%. Secondly, multi-objective analysis suggests an optimum freshwater savings of 14% to reduce the unit cost of the network by half. Moreover, the significance of symbiosis networks is highlighted by showing that intra-company connections can only achieve a maximum freshwater savings of 17% with significantly higher unit cost (+45%). Finally, we showed that the values of symbiosis connectivity index in the Pareto front correspond to higher freshwater savings, indicating the significant role of the symbiosis network in the industrial park under study. This is the first study, where all the above elements have been taken into account simultaneously for the design of a water reuse network.

Mood symptoms and suicidality across the autism spectrum.

BACKGROUND: Autism spectrum is a psychopathological dimension which encompasses a wide range of clinical presentations: from subthreshold forms and autistic traits (AT), that can be found in the general population, to full-blown autism spectrum disorder (ASD). Many studies reported high rates of comorbidity between both ASD and AT and mood disorders, as well as a high prevalence of suicidal ideation among patients with ASD/AT. The aim of this study was to investigate the presence of mood symptoms and suicidal ideation and behaviors in patients with full-blown ASD and in subjects with AT, as well in a healthy control (HC) group, with a specific focus on which of the autistic features may be predictive of suicidal ideation and behaviors. METHODS: We recruited 262 adult subjects: 34 with ASD without intellectual impairment or language disability (ASD group), 68 fulfilling only one symptom criterion for ASD according to DSM-5 but who do not meet criteria for a full-blown diagnosis of ASD (AT group), and 160 HC. All subjects were assessed with the Structured Clinical Interview for DSM-5 (SCID-5); in addition, they were asked to fill two questionnaires: The Mood Spectrum, Self-report (MOODS-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). RESULTS: ASD subjects reported significantly higher AdAS Spectrum and MOODS-SR total scores, as well as higher MOODS-SR depressive component total scores, when compared with AT and HC subjects. AT subjects scored significantly higher than the HC group. No significant differences were reported between ASD and AT subjects for the suicidality score according to MOODS-SR, despite both groups scored significantly higher than the HC group. The strongest predictor of suicidality score were MOODS-SR depressive component score and AdAS Spectrum Restricted interests and rumination domain score. CONCLUSIONS: Our results highlight a correlation between autism and mood spectrum, as well as between suicidality and both ASD and AT. Subthreshold forms of ASD should be accurately investigated due to their relationship with suicidal thoughts and behaviors.

Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition.

OBJECTIVE: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. METHOD: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. RESULTS: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). CONCLUSION: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Frequency of use of the International Classification of Diseases ICD-10 diagnostic categories for mental and behavioural disorders across world regions.

AIMS: The study aimed to examine variations in the use of International Classification of Diseases, Tenth Edition (ICD-10) diagnostic categories for mental and behavioural disorders across countries, regions and income levels using data from the online World Psychiatric Association (WPA)-World Health Organization (WHO) Global Survey that examined the attitudes of psychiatrists towards the classification of mental disorders. METHODS: A survey was sent to 46 psychiatric societies which are members of WPA. A total of 4887 psychiatrists participated in the survey, which asked about their use of classification, their preferred system and the categories that were used most frequently. RESULTS: The majority (70.1%) of participating psychiatrists (out of 4887 psychiatrists) reported using the ICD-10 the most and using at least one diagnostic category once a week. Nine out of 44 diagnostic categories were considerably variable in terms of frequency of use across countries. These were: emotionally unstable personality disorder, borderline type; dissociative (conversion) disorder; somatoform disorders; obsessive-compulsive disorder (OCD); mental and behavioural disorders due to the use of alcohol; adjustment disorder; mental and behavioural disorders due to the use of cannabinoids; dementia in Alzheimer's disease; and acute and transient psychotic disorder. The frequency of use for these nine categories was examined across WHO regions and income levels. The most striking differences across WHO regions were found for five out of these nine categories. For dissociative (conversion) disorder, use was highest for the WHO Eastern Mediterranean Region (EMRO) and non-existent for the WHO African Region. For mental and behavioural disorders due to the use of alcohol, use was lowest for EMRO. For mental and behavioural disorders due to the use of cannabinoids, use was lowest for the WHO European Region and the WHO Western Pacific Region. For OCD and somatoform disorders, use was lowest for EMRO and the WHO Southeast Asian Region. Differences in the frequency of use across income levels were statistically significant for all categories except for mental and behavioural disorders due to the use of alcohol. The most striking variations were found for acute and transient psychotic disorder, which was reported to be more commonly used among psychiatrists from countries with lower income levels. CONCLUSIONS: The differences in frequency of use reported in the current study show that cross-cultural variations in psychiatric practice exist. However, whether these differences are due to the variations in prevalence, treatment-seeking behaviour and other factors, such as psychiatrist and patient characteristics as a result of culture, cannot be determined based on the findings of the study. Further research is needed to examine whether these variations are culturally determined and how that would affect the cross-cultural applicability of ICD-10 diagnostic categories.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Subthreshold autism spectrum disorder in patients with eating disorders.

AIM: Increasingly data suggest a possible overlap between psychopathological manifestations of eating disorders (EDs) and autism spectrum disorders (ASD). The aim of the present study was to assess the presence of subthreshold autism spectrum symptoms, by means of a recently validated instrument, in a sample of participants with EDs, particularly comparing participants with or without binge eating behaviours. METHODS: 138 participants meeting DSM-5 criteria for EDs and 160 healthy control participants (HCs), were recruited at 3 Italian University Departments of Psychiatry and assessed by the SCID-5, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Eating Disorders Inventory, version 2 (EDI-2). ED participants included: 46 with restrictive anorexia (AN-R); 24 with binge-purging type of Anorexia Nervosa (AN-BP); 34 with Bulimia Nervosa (BN) and 34 with Binge Eating Disorder (BED). The sample was split in two groups: participants with binge eating behaviours (BEB), in which were included participants with AN-BP, BN and BED, and participants with restrictive behaviours (AN-R). RESULTS: participants with EDs showed significantly higher AdAS Spectrum total scores than HCs. Moreover, EDs participants showed significantly higher scores on all AdAS Spectrum domains with the exception of Non verbal communication and Hyper-Hypo reactivity to sensory input for AN-BP participants, and Childhood/Adolescence domain for AN-BP and BED participants. Participants with AN-R scored significantly higher than participants with BEB on the AdAS Spectrum total score, and on the Inflexibility and adherence to routine and Restricted interest/rumination AdAS Spectrum domain scores. Significant correlations emerged between the Interpersonal distrust EDI-2 sub-scale and the Non verbal communication and the Restricted interest and rumination AdAS Spectrum domains; as well as between the Social insecurity EDI-2 sub-scale and the Inflexibility and adherence to routine and Restricted interest and rumination domains in participants with EDs. CONCLUSIONS: Our data corroborate the presence of higher subthreshold autism spectrum symptoms among ED participants with respect to HCs, with particularly higher levels among restrictive participants. Relevant correlations between subthreshold autism spectrum symptoms and EDI-2 Subscale also emerged.

Impaired cortisol awakening response in eating disorder women with childhood trauma exposure: evidence for a dose-dependent effect of the traumatic load.

BACKGROUND: Childhood trauma is a non specific risk factor for adult eating disorders (ED), and the hypothalamic-pituitary-adrenal (HPA) axis seems to mediate such a risk. Here we explored the impact of different types of childhood trauma and of traumatic load on the cortisol awakening response (CAR) of women with anorexia nervosa (AN) or bulimia nervosa (BN). METHODS: Saliva samples were collected at awakening and after 15, 30, 60 min to measure cortisol levels by 121 women (44 AN patients, 36 BN patients and 41 healthy women). Participants filled in the Childhood Trauma Questionnaire. RESULTS: AN and BN patients with childhood maltreatment exhibited an attenuated CAR compared with non-maltreated ones. In the whole ED patient group, the CAR showed a progressive impairment with the increasing number of reported trauma types. Although significant negative correlations emerged between the type or the number of traumas and the CAR, only the number of traumas remained significantly associated with the CAR in a stepwise multiple regression analysis. CONCLUSIONS: Present findings confirm that childhood trauma is associated with an impaired CAR in adult AN and BN patients and demonstrate for the first time a negative dose-dependent effect of the traumatic load on HPA axis activity.

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

AIM: Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. METHODS: 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. RESULTS: The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper- and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis* Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD1) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED0) and those with one ASD symptom criterion (FED1), a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED0, ASD1, FED1 was shown. CONCLUSIONS: The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits.

Social cognition in people with schizophrenia: a cluster-analytic approach.

BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. CONCLUSIONS: If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

Is dialdehyde starch a valuable cross-linking agent for collagen/elastin based materials?

Collagen and elastin are the main structural proteins in mammal bodies. They provide mechanical support, strength, and elasticity to various organs and tissues, e.g. skin, tendons, arteries, and bones. They are readily available, biodegradable, biocompatible and they stimulate cell growth. The physicochemical properties of collagen and elastin-based materials can be modified by cross-linking. Glutaraldehyde is one of the most efficient cross-linking agents. However, the unreacted molecules can be released from the material and cause cytotoxic reactions. Thus, the aim of our work was to investigate the influence of a safer, macromolecular cross-linking agent--dialdehyde starch (DAS). The properties of hydrogels based on collagen/elastin mixtures (95/5, 90/10) containing 5 and 10% of DAS and neutralized via dialysis against deionized water were tested. The homogenous, transparent, stiff hydrogels were obtained. The DAS addition causes the formation of intermolecular cross-linking bonds but does not affect the secondary structure of the proteins. As a result, the thermal stability, mechanical strength, and, surprisingly, swelling ability increased. At the same time, the surface properties test and in vitro study show that the materials are attractive for 3T3 cells. Moreover, the materials containing 10% of DAS are more resistant to enzymatic degradation.

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity.

PURPOSE: Hedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. In this study, we investigated the responses of AEA, 2-AG, OEA and PEA to hedonic eating in obese individuals. METHODS: Peripheral levels of AEA, 2-AG, OEA and PEA were measured in 14 obese patients after eating favourite (hedonic eating) and non-favourite (nonhedonic eating) foods in conditions of no homeostatic needs. RESULTS: Plasma levels of 2-AG increased after eating the favourite food, whereas they decreased after eating the non-favourite food, with the production of the endocannabinoid being significantly enhanced in hedonic eating. Plasma levels of AEA decreased progressively in nonhedonic eating, whereas they showed a decrease after the exposure to the favourite food followed by a return to baseline values after eating it. No significant differences emerged in plasma OEA and PEA responses to favourite and non-favourite food. CONCLUSION: Present findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity.

Feasibility of a psychoeducational family intervention for people with bipolar I disorder and their relatives: Results from an Italian real-world multicentre study.

BACKGROUND: Despite several guidelines recommend the use of psychoeducational family interventions (PFIs) as add-on in the treatment of patients with bipolar I disorder, their implementation on a large scale remains limited. The aim of the present study is to identify obstacles for the feasibility of PFIs in routine care. METHODS: This was a multicentre, real-world, controlled, outpatient trial, carried out in 11 randomly recruited Italian mental health centres. Two mental health professionals from each center attended a modular training course on PFI and provided the intervention. Difficulties and benefits experienced by mental health professionals in implementing the intervention were assessed through the Family Intervention Schedule (FIS-R), which was administered six times. RESULTS: Sixteen out of the 22 recruited professionals completed the training and administered the PFI to 70 patients with bipolar I disorder and their relatives. The retention rate of families receiving the intervention was 93%. Mental health professionals reported high levels of organizational difficulties, several benefits in their daily clinical work and low levels of intervention-related difficulties. The most important organizational obstacles were related to the need to integrate the intervention with other work responsibilities and to the lack of time to carry out the intervention. These difficulties did not decrease over time. Intervention-related difficulties were rated as less problematic since the first time assessment and tended to improve over time. LIMITATIONS: Low number of recruited professionals; use of a not previously validated assessment instrument. CONCLUSIONS: PFIs are feasible in routine care for the treatment of patients with bipolar I disorder and their relatives, and main obstacles are related to the organization/structure of mental health centres, and not to the characteristics of the intervention itself.

Collagen/elastin hydrogels cross-linked by squaric acid.

Hydrogels based on collagen and elastin are very valuable materials for medicine and tissue engineering. They are biocompatible; however their mechanical properties and resistance for enzymatic degradation need to be improved by cross-linking. Up to this point many reagents have been tested but more secure reactants are still sought. Squaric acid (SqAc), 3,4-dihydroxy 3-cyclobutene 1,2-dione, is a strong, cyclic acid, which reacts easily with amine groups. The properties of hydrogels based on collagen/elastin mixtures (95/5, 90/10) containing 5%, 10% and 20% of SqAc and neutralized via dialysis against deionized water were tested. Cross-linked, 3-D, transparent hydrogels were created. The cross-linked materials are stiffer and more resistant to enzymatic degradation than those that are unmodified. The pore size, swelling ability and surface polarity are reduced due to 5% and 10% of SqAc addition. At the same time, the cellular response is not significantly affected by the cross-linking. Therefore, squaric acid would be regarded as a safe, effective cross-linking agent.

Clinical decision making and outcome in the routine care of people with severe mental illness across Europe (CEDAR).

AIMS: Shared decision making has been advocated as a means to improve patient-orientation and quality of health care. There is a lack of knowledge on clinical decision making and its relation to outcome in the routine treatment of people with severe mental illness. This study examined preferred and experienced clinical decision making from the perspectives of patients and staff, and how these affect treatment outcome. METHODS: "Clinical Decision Making and Outcome in Routine Care for People with Severe Mental Illness" (CEDAR; ISRCTN75841675) is a naturalistic prospective observational study with bimonthly assessments during a 12-month observation period. Between November 2009 and December 2010, adults with severe mental illness were consecutively recruited from caseloads of community mental health services at the six study sites (Ulm, Germany; London, UK; Naples, Italy; Debrecen, Hungary; Aalborg, Denmark; and Zurich, Switzerland). Clinical decision making was assessed using two instruments which both have parallel patient and staff versions: (a) The Clinical Decision Making Style Scale (CDMS) measured preferences for decision making at baseline; and (b) the Clinical Decision Making Involvement and Satisfaction Scale (CDIS) measured involvement and satisfaction with a specific decision at all time points. Primary outcome was patient-rated unmet needs measured with the Camberwell Assessment of Need Short Appraisal Schedule (CANSAS). Mixed-effects multinomial regression was used to examine differences and course over time in involvement in and satisfaction with actual decision making. The effect of clinical decision making on the primary outcome was examined using hierarchical linear modelling controlling for covariates (study centre, patient age, duration of illness, and diagnosis). Analysis were also controlled for nesting of patients within staff. RESULTS: Of 708 individuals approached, 588 adults with severe mental illness (52% female, mean age = 41.7) gave informed consent. Paired staff participants (N = 213) were 61.8% female and 46.0 years old on average. Shared decision making was preferred by patients (χ 2 = 135.08; p < 0.001) and staff (χ 2 = 368.17; p < 0.001). Decision making style of staff significantly affected unmet needs over time, with unmet needs decreasing more in patients whose clinicians preferred active to passive (-0.406 unmet needs per two months, p = 0.007) or shared (-0.303 unmet needs per two months, p = 0.015) decision making. CONCLUSIONS: Decision making style of staff is a prime candidate for the development of targeted intervention. If proven effective in future trials, this would pave the ground for a shift from shared to active involvement of patients including changes to professional socialization through training in principles of active decision making.

High frequency ultrasonography: a complementary diagnostic method in evaluation of primary cutaneous melanoma.

AIM: The aim of our study was to assess the usefulness of high frequency ultrasonography in the diagnosis of melanoma. METHODS: We examined 84 patients with suspicious melanocytic skin lesions, including 19 cases of melanoma. In vivo high-resolution ultrasonography (30 MHz) was performed prior to excision. RESULTS: In ultrasound scans early melanomas presented as flat oval or fusiform shaped structures and were clearly demarcated, while advanced melanomas were characterized by a roundish shape with less distinct borders. The ultrasonographic thickness of in situ melanomas ranged from 0.02 to 0.85 mm. In the case of invasive tumors, the mean thickness evaluated by high frequency ultrasonography was 10.7% higher compared to the Breslow Score (1.44±0.8 mm and 1.3±0.88 mm, respectively). In all melanomas of Breslow Score of 1 mm or more ultrasound also indicated a Breslow Score of 1 mm or more. CONCLUSION: High frequency ultrasound examination has limited value in differential diagnosis of melanoma, but it gives a clear picture of the size and depth of the tumor. The method should be used as a complementary method (after dermoscopy and, where applicable, reflectance confocal microscopy) in preoperative evaluation of the tumor. In some cases of locally advanced melanoma, ultrasound examination may allow to reduce the number of surgical procedures and favor the decision of a one-time surgical treatment (removal of primary tumor and sentinel lymph node biopsy at the same time).