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Purpose Forensic psychiatric inpatient care in Sweden is characterized by strict regulations and adherence to court-mandated rules, with a median care time of 7 years. Comorbity has significant clinical implications, impacting health and well-being, violent behaviour and criminal recidivism, and prolonging inpatient stays. This study investigated the individual experiences and perspectives of Swedish patients in forensic psychiatric care with substance use (SU) disorders, focusing on past, present and future orientations. Methods Ten male forensic psychiatric inpatients were individually interviewed following a semi-structured interview guide. A qualitative content analysis was conducted to inductively analyse the participants’ experiences. The study adhered to the Standards for Reporting Qualitative Research. Results Under the main theme of “embracing harmony in opposition”, three categories emerged: (1) unveiling the beginning of SU and its impact on navigating challenges in care, (2) exploring current confined care and gratitude despite unease and (3) yearning for a somewhat normal life. Conclusions Participants’ subjective perspectives underscored the importance of factors such as forensic nurses/healthcare providers in forensic psychiatry considering the patients’ life narratives, their aspirations for the future, their need for a secure environment and patient—staff relationships. These findings highlight the need for structural interventions that emphasize the importance of tailored and comprehensive health plans within rehabilitation.

ABSTRACT Introduction There is a high prevalence of attention‐deficit/hyperactivity disorder (ADHD) in prison populations compared to the general population, and ADHD has also been shown to be associated with criminality and antisocial behavior. This systematic review examines the effect of pharmacological ADHD treatment on criminal recidivism, ADHD symptoms, and rehabilitation in inmates with ADHD. Methods Adhering to PRISMA 2020 and AMSTAR guidelines, we conducted a structured search on September 6, 2023 using PubMed. We focused on original research published in peer‐reviewed scientific journals, following the IMRaD format, written in English, containing the established search terms, based on participants who met the criteria for ADHD diagnosis (any edition of DSM), and who were incarcerated at the start of pharmacological treatment for ADHD. The primary outcome was criminal recidivism, the secondary outcomes were ADHD symptoms, and rehabilitation‐related factors such as global function, norm‐breaking/antisocial behavior, adaptation to society/institutional behavior, cognitive function, and well‐being. Results Five studies, based on three patient cohorts, were included in this systematic review. Surprisingly, only one study investigated criminal recidivism. That study indicated that self‐reported criminal recidivism was lower than expected among inmates who had received pharmacological ADHD treatment. The five studies showed varying results in the effectiveness of pharmacological ADHD treatment on ADHD symptoms and other rehabilitation‐related factors. The included studies also varied regarding participant characteristics, study design, dosage, adherence to treatment, treatment regimes, and measured outcomes. All studies reported using osmotic‐release oral system (OROS) methylphenidate as their drug of choice. Conclusion We conclude that there is limited empirical evidence to support the efficacy of pharmacological ADHD treatment on criminal recidivism in inmates diagnosed with ADHD. Still, evidence suggests that these treatments can reduce ADHD symptoms and enhance rehabilitation outcomes, which may, in turn, lower the rate of reoffending. We point to the need for more targeted research in this area.

[Background] In addition to theoretical education, clinical psychology programs should include practical skills training. This skill training may be tied to specific assessment and treatment methods; other skills, such as the ability to create a collaborative alliance with patients, are more generic. Previous research has shown that the ability to build a therapeutic alliance (TA) is often not systematically taught in clinical psychology programs and it is uncertain how this competence is examined. A lack of competence in establishing TA on the part of the psychologist might diminish the effects of psychotherapy. To meet the Bologna Declaration, European universities need to demonstrate constructive alignment, i.e. a relationship between elements of the course content and intended learning outcomes in course documents, and show how the acquired knowledge, abilities, and approaches are assessed. [Method] This conceptual paper reviewed the syllabuses for universities in Sweden offering the five-year clinical psychology program to illustrate how higher education in Sweden adheres to the Bologna recommendation on constructive alignment when teaching TA to future clinical psychologists. [Results] Only two universities out of all eleven universities in Sweden offering a psychology program described satisfactory constructive alignment concerning TA. [Conclusion] This conceptual paper raises awareness of the importance of pedagogic structure when teaching TA in higher education by pointing to the prevailing lack of constructive alignment in teaching TA. The increased awareness will hopefully lead to improved structuring in the teaching of TA.

En 2017 con la adopción del Tratado sobre la prohibición de las armas nucleares (TPAN) se abrió una etapa superior en las negociaciones relativas a los temas nucleares, que sitúa al hombre en el centro de las preocupaciones de la agenda internacional para las cuestiones de paz y seguridad. Desde fines del siglo XX, a partir de la incorporación de disposiciones humanitarias al texto de la nueva norma y tras un revolucionario proceso de gestación, se ha revelado la existencia de un desarme de nuevo tipo al que algunos estudiosos han denominado humanitario. En virtud de lo anterior, el presente artículo examina los rasgos principales del proceso de negociación que condujo a la aprobación del TPAN. Para ello, se emplearon los métodos analítico-sintético e histórico-lógico en la realización de la investigación, acompañados del uso de la revisión bibliográfica y el análisis de contenido como principales técnicas, desde un enfoque cualitativo.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

El régimen mundial de no proliferación y desarme nuclear está atravesando por una de las etapas más complejas del Sistema Internacional; debido, esencialmente, a la ocurrencia de serios conflictos que involucran a potencias nucleares, y otras bajo su sombrilla, y comprometen la paz y la seguridad internacionales ante la posibilidad de uso de este tipo de armamento. En consecuencia, desde Naciones Unidas se ha exhortado a impulsar la causa del desarme y promover un mundo libre de armas nucleares, con el propósito de preservar a las generaciones actuales y venideras del flagelo de una guerra nuclear; lo cual justifica, en gran medida, el creciente interés en tópicos vinculados a los esfuerzos de Estados no nucleares como México, tendientes al desarme y la no proliferación. Ciertamente, México ha sido un actor histórico incuestionable en esa labor: lideró la adopción del Tratado de Tlatelolco, mediante el cual se estableció la primera Zona Libre de Armas Nucleares en el mundo; y contribuyó, de forma significativa, a la aprobación del Tratado para la Prohibición de las Armas Nucleares (TPAN), texto que ha hecho la más clara contribución a codificar en el Derecho Internacional la ilegitimidad e ilegalidad de estas armas. En virtud de lo anterior, el presente artículo pretende evaluar los aportes de México a la construcción y fortalecimiento del régimen internacional del desarme nuclear, con énfasis en el Tratado de Tlatelolco y el TPAN.

Background: Patients in the forensic mental health services (FMHS) with a mental disorder, a co-occurring substance use disorder (SUD), and high risk of aggressive antisocial behavior (AAB) are sometimes referred to as the ‘triply troubled’. They suffer poor treatment outcomes, high rates of criminal recidivism, and increased risk of drug related mortality. To improve treatment for this heterogeneous patient group, more insight is needed concerning their co-occurring mental disorders, types of substances used, and the consequent risk of AAB. Methods: A three-step latent class analysis (LCA) was used to identify clinically relevant subgroups in a sample of patients (n = 98) from a high-security FMHS clinic in Sweden based on patterns in their history of mental disorders, SUD, types of substances used, and AAB. Results: A four-class model best fit our data: class 1 (42%) had a high probability of SUD, psychosis, and having used all substances; class 2 (26%) had a high probability of psychosis and cannabis use; class 3 (22%) had a high probability of autism and no substance use; and class 4 (10%) had a high probability of personality disorders and having used all substances. Both polysubstance classes (1 and 4) had a significantly more extensive history of AAB compared to classes 2 and 3. Class 3 and class 4 had extensive histories of self-directed aggression. Conclusions: The present study helps disentangle the heterogeneity of the ‘triply troubled’ patient group in FMHS. The results provide an illustration of a more person-oriented perspective on patient comorbidity and types of substances used which could benefit clinical assessment, treatment planning, and risk-management among patients in forensic psychiatric care.

El Estado cubano defiende la eliminación de las armas nucleares de forma total, transparente, irreversible, verificable y dentro de plazos multilateralmente acordados, como una contribución efectiva para el logro y mantenimiento de la paz y la seguridad internacionales. En tal sentido, reconoce los principales tratados del actual régimen internacional sobre desarme y no proliferación nuclear. Sin embargo, la tardía ratificación por Cuba del Tratado sobre la No Proliferación de las Armas Nucleares (TNP) ha sido cuestionada; lo cual no tiene en cuenta que la implementación del acuerdo ha estado plagada de serias deficiencias, como la permanente tendencia al privilegio de la no proliferación horizontal, la continuidad de la política de disuasión nuclear, el sostenido desarrollo de nuevos tipos de armas nucleares y el repetido fracaso de las Conferencias de Examen del Tratado. En virtud de lo anterior, el presente artículo se propone evaluar la posición de Cuba frente al TNP; y, posteriormente, examinar los principales elementos que han sustentado la posición de Cuba en relación con el Tratado sobre la Prohibición de las Armas Nucleares, como instrumento necesario para avanzar, efectivamente, en la disposición del desarme nuclear contenida en el Artículo VI del TNP, ante la renuencia de los Estados poseedores de estas armas a dar pasos concretos con tal propósito.

El Estado cubano defiende la eliminación de las armas nucleares de forma total, transparente, irreversible, verificable y dentro de plazos multilateralmente acordados, como una contribución efectiva para el logro y mantenimiento de la paz y la seguridad internacionales. En tal sentido, reconoce los principales tratados del actual régimen internacional sobre desarme y no proliferación nuclear. Sin embargo, la tardía ratificación por Cuba del Tratado sobre la No Proliferación de las Armas Nucleares (TNP) ha sido cuestionada; lo cual no tiene en cuenta que la implementación del acuerdo ha estado plagada de serias deficiencias, como la permanente tendencia al privilegio de la no proliferación horizontal, la continuidad de la política de disuasión nuclear, el sostenido desarrollo de nuevos tipos de armas nucleares y el repetido fracaso de las Conferencias de Examen del Tratado. En virtud de lo anterior, el presente artículo se propone evaluar la posición de Cuba frente al TNP; y, posteriormente, examinar los principales elementos que han sustentado la posición de Cuba en relación con el Tratado sobre la Prohibición de las Armas Nucleares, como instrumento necesario para avanzar, efectivamente, en la disposición del desarme nuclear contenida en el Artículo VI del TNP, ante la renuencia de los Estados poseedores de estas armas a dar pasos concretos con tal propósito.

El Estado cubano defiende la eliminación de las armas nucleares de forma total, transparente, irreversible, verificable y dentro de plazos multilateralmente acordados, como una contribución efectiva para el logro y mantenimiento de la paz y la seguridad internacionales. En tal sentido, reconoce los principales tratados del actual régimen internacional sobre desarme y no proliferación nuclear. Sin embargo, la tardía ratificación por Cuba del Tratado sobre la No Proliferación de las Armas Nucleares (TNP) ha sido cuestionada; lo cual no tiene en cuenta que la implementación del acuerdo ha estado plagada de serias deficiencias, como la permanente tendencia al privilegio de la no proliferación horizontal, la continuidad de la política de disuasión nuclear, el sostenido desarrollo de nuevos tipos de armas nucleares y el repetido fracaso de las Conferencias de Examen del Tratado. En virtud de lo anterior, el presente artículo se propone evaluar la posición de Cuba frente al TNP; y, posteriormente, examinar los principales elementos que han sustentado la posición de Cuba en relación con el Tratado sobre la Prohibición de las Armas Nucleares, como instrumento necesario para avanzar, efectivamente, en la disposición del desarme nuclear contenida en el Artículo VI del TNP, ante la renuencia de los Estados poseedores de estas armas a dar pasos concretos con tal propósito.

Abstract Background The Externalizing Spectrum Inventory-Brief Form (ESI-BF) [1] is a 160-item self-report instrument designed for the assessment of externalizing psychopathology, yet few studies to date have evaluated its psychometric properties, structural fit, and criterion validity in forensic psychiatric settings. Methods Here, we investigated these aspects in a sample of forensic psychiatric inpatients (n = 77) from a maximum-security forensic psychiatric hospital in Sweden. We firstly investigated the reliability. Secondly, using confirmatory factor analysis, the structure of the ESI-BF. And thirdly, using a Bayesian approach, assessed how the three ESI-BF subfactors relate to criterion measures of antisocial behaviors, substance use, and lifetime externalizing spectrum diagnoses. Results The ESI-BF demonstrated good to adequate reliability and internal consistency, with all but four facet scales exhibiting α and ω values ≥ 0.80. Average inter-item correlations for the facet scales ranged from 0.31 to 0.74. However, all structural models exhibited poor to mediocre fit, with model fit values for the CFI being 0.66, 0.79 and 0.87 and RMSEA values of 0.14, 0.12 and 0.09. for the unidimensional correlated factors and bifactor model, respectively. Regarding criterion validity, all subscales of the item-based ESI-BF three-factor model exhibited robust correlations with the Life History of Aggression total, aggression and antisocial/consequences subscales, with correlations ranging from 0.29 to 0.55. All ESI-BF subfactors demonstrated robust associations, yet with different externalizing outcomes, lending tentative support to its criterion validity. Conclusion Despite remaining ambiguities regarding its structural fit, the ESI-BF may be promising for assessing externalizing psychopathology in forensic psychiatric populations. However, further investigation of the ESI-BF is needed before any firm conclusions can be drawn about its appropriateness in forensic psychiatric settings.

Abstract The formins constitute a large class of multi-domain polymerases that catalyze the localization and growth of unbranched actin filaments in cells from yeast to mammals. The conserved FH2 domains form dimers that bind actin at the barbed end of growing filaments and remain attached as new subunits are added. Profilin–actin is recruited and delivered to the barbed end by formin FH1 domains via the binding of profilin to interspersed tracts of poly-l-proline. We present a structural model showing that profilin–actin can bind the FH2 dimer at the barbed end stabilizing a state where profilin prevents its associated actin subunit from directly joining the barbed end. It is only with the dissociation of profilin from the polymerase that an actin subunit rotates and docks into its helical position, consistent with observations that under physiological conditions optimal elongation rates depend on the dissociation rate of profilin, independently of cellular concentrations of actin subunits.

BackgroundThere are contradictory research findings regarding whether individuals with Autism Spectrum Disorders (ASDs) are more or less likely to commit crimes. The aims of the current study were to: (1) Describe psychiatric and crime-related characteristics of a large group of offenders with ASD who had undergone a Forensic Psychiatric Investigation (FPI). (2) Identify clinical subgroups among this group of offenders. (3) Investigate associations between the identified clinical subgroups and (a) psychiatric comorbidity (b) types of crimes and (c) criminal responsibility.MethodsThe study cohort consists of all subjects (n = 831) who received an ASD-diagnosis at an FPI between 2002 and 2018 in Sweden. Descriptive and clinical, as well as crime related variables were obtained from the FPIs. Non-parametric (Pearson χ2, Fisher's exact and Mann-Whitney U-test) inferential statistics were used for analyses of between-group differences and effect sizes were reported. A Latent Class Analysis was used to identify homogeneous subgroups (or classes) from categorical characteristics.ResultsThe cohort consisted of 708 men and 123 women, aged 18 to 74 yrs. Two-thirds (66.7%) of the cohort had at least one other psychiatric diagnosis, the most prevalent was substance use disorder (SUD). A severe mental disorder, equivalent to lack of criminal responsibility, was most often reported among offenders with a comorbid diagnosis of schizophrenia spectrum disorder. The most common type of crime was violent crime. Three person-oriented clinical subgroups were identified; (1) ASD with few other diagnoses; (2) ASD and very high levels of SUDs, plus moderate levels of other externalizing disorders and psychotic psychopathology and (3) ASD and moderate to high levels of personality disorders (other than ASPD) and SUDs.ConclusionOur results highlight the importance of all parts of the CJS to be prepared to handle offenders with ASD, often with high levels of additional psychiatric problems. Traditional approaches in treatment or other psychosocial interventions for ASD may need to be adapted to at least three general clinical profiles– one with mainly neurodevelopmental problems, one with a spectrum of externalizing problems and one with complex personality related difficulties.

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn’s disease (CD) ( n = 68) and ulcerative colitis (UC) ( n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey–Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale ( p

AimIn studies on lethal and severe violence, male offenders have historically been in focus while female offenders, in comparison, have often been excluded. In this study, we aimed to characterize female violent offenders and compared those with and without a severe mental disorder (SMD).MethodAll females charged with lethal or attempted lethal violence, who had undergone forensic psychiatric investigations (FPI) in Sweden between 2000 and 2014, constituting the two groups SMD (n = 84) and no SMD (n = 91), were included. Information from their FPI reports and court verdicts was collected regarding background and demographics, mental health, substance use, and crime characteristics.ResultsOverall, both groups were often unemployed, previously victimized within close relations, had psychiatric health issues, and more than half of them had previously attempted suicide. Specifically, the SMD group more often had psychotic disorders, had attempted homicide-suicide (at the time of the crime), and had children or friends/acquaintances as victims. The no-SMD group more often manifested patterns of anxiety, personality disorders, and substance use disorders compared to the SMD group. The no-SMD group also differed from the SMD group by more often having a previous criminal record, being charged with lethal index violence, having male adult intimate partners/ex-intimate partners as victims who had abused the offender, and both offender and victim had more often been under the influence of a substance. ConclusionFemale offenders of lethal and severe violence had a high prevalence of previous violent victimization which should be considered in forensic assessment and treatment regardless of the offender’s SMD status. However, more focus on substance use disorders and intimate partner relations appears relevant for females without an SMD. Contrary to that, early interventions regarding psychotic processes are probably a helpful preventive measure for females with an SMD. In sum, the heterogeneity of female offenders of lethal and severe violence emphasizes the necessity of developing nuanced interventions to meet their rehabilitative needs as well as the requirements of community protection.

Generally, the testimony of intoxicated witnesses has been considered relatively unreliable, but recent research has nuanced the knowledge base regarding these vulnerable witnesses.PurposeTo demonstrate the application of recent research findings regarding intoxicated witnesses to the statements made by a key witness to the murder of Olof Palme, Sweden's prime minister, in 1986. An additional purpose was to illustrate the use of a nuanced calculation of blood alcohol concentration (BAC) for researchers.MethodsThe Palme murder has been debated since the crime was committed and no one has yet been sentenced. One of the witnesses was intoxicated and to estimate a range for his BAC at the time, a comprehensive BAC calculation was conducted in this study to illustrate important factors to consider in these types of cases.ResultsThrough the demonstration of the use of a nuanced BAC formula and by applying recent research results from studies on intoxicated witnesses, it was estimated that the possible BAC of the witness in the Palme-case at the time of the witnessed crime ranged between BAC = 0 to BAC = 0.13, depending on the type of alcoholic beverage consumed and whether the witness was a social or heavy drinker. This puts the witness either well within the span of maintained completeness as well as maintained accuracy rate (if considering: lowest dose and heavy drinker), or slightly exceeding this span into the BAC-range of reduced completeness but maintained accuracy rate (if considering: highest dose and social drinker). He was questioned immediately, and thereafter repeatedly, and he reported similar information throughout the interviews, which is in line with previous results on information maintenance over repeated interviews among intoxicated witnesses.ConclusionThe current case example shows how recent research on intoxicated witnesses can be applied in praxis, illustrating important factors for legal practitioners to consider when interpreting information from intoxicated witnesses. It also provides legal practitioners and researchers with an example of a structured approach to more nuanced BAC-calculations.

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.

BackgroundWhich type of information experts use to make decisions regarding legal insanity within forensic psychiatric investigations (FPI) is relatively unknown, both in general and when considering variations due to case context. It is important to explore this area to be able to counteract the effects of various kinds of cognitive bias.MethodThe aim was to explore whether FPI expert groups differed regarding case-specific as well as general use of information types required to make decisions on severe mental disorder (SMD). Three FPI case vignettes were presented to three professional groups involved in FPIs in Sweden (n = 41): forensic psychiatrists (n = 15), psychologists (n = 15), and social workers (n = 11). The participants reported which types of information they required to reach conclusions regarding SMD in each case. They also reported which types of information they had used within general FPI praxis during the previous year and the information types’ perceived usefulness.ResultsThe expert groups differed somewhat regarding what type of information they required for the cases (e.g., results from cognitive testing), but some information was required in all cases (e.g., client’s self-report). Regarding the preliminary assessment of SMD in the three cases, minor differences were found. Within the general FPI praxis, experts reported using several information types, while the general perceived usefulness of these sources varied.DiscussionThe professional groups relied partly on a “core” of information sources, but some case-specific adaptations were found. The professional groups’ inclination to suspect SMD also varied somewhat. This indicates a need to explore the potential consequences of these similarities and differences.

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients ( p

Substance abuse, conduct disorder (CD) and attention deficit/hyperactivity disorder (ADHD) are all known risk factors for developing aggressive behaviors, criminality, other psychiatric comorbidity and substance use disorders (SUD). Since early age of onset is important for aggravating the impact of several of these risk factors, the aim of the present study was to investigate whether young adult violent offenders with different patterns of early onset externalizing problems (here: substance use < age 15, ADHD, CD) had resulted in different criminality profiles, substance use problem profiles and psychiatric comorbidity in young adult age. A mixed-method approach was used, combining a variable-oriented approach (with Kruskal Wallis tests) and a person-oriented approach (with Configural frequency analysis). Overall, this combined approach indicated that persons with combined ADHD+CD and persons with CD + early onset of substance use had a more varied history of violent crimes, a more comprehensive history of aggressive behaviors in general, and more psychiatric comorbidity, as well as more varied SUD and destructive substance abuse in adult age, than persons without ADHD, CD or early SU. Results are in line with previous variable-oriented research, but also indicate that individuals in this group with heavy problem aggregation early in life have a wider spectrum of problems in young adult age. Importantly, among these young violent offenders, problem aggregation was the overwhelming norm, and not the exception, as in studies of the general population. This emphasizes the need for early coordinated interventions, but also that treatment within correctional facilities in adult age needs to be comprehensive and take individual patterns of comorbidity into account.

CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥ 70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease.ClinicalTrials.gov NCT00306215.

Abstract Background Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity. Methods Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months. Results Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time. Conclusions IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.