Experts' decision-making processes in Swedish forensic psychiatric investigations: A case vignette study.

It has previously been demonstrated that decisions made by forensic experts can suffer from issues with both bias and poor reliability. The outcome of Swedish forensic psychiatric investigations can have a major impact on the courts' choice of sanction for a mentally disordered offender. These investigations are performed by multi-professional teams of experts, where each expert is obliged to state their opinion on whether the client has a severe mental disorder (SMD) or not. In the present study, a case vignette design was used to simulate the decision-making process of forensic psychiatric investigations. Of the 73 Swedish experts working with forensic psychiatric investigations, a total of 27 (37%) participated in the study. The results showed that the Swedish experts formulated multiple diagnostic hypotheses about cases throughout the process and revised these hypotheses when presented with new information. There was substantial variation between the experts in which hypotheses were seen as most relevant. While the experts grew more certain of their opinions on SMD during the simulated investigation, there was considerable variation in their opinions both throughout and at the end of the process. Although low statistical power and the sample not being randomized limit generalizations, the results indicate no idiosyncratic patterns in the decision-making processes of Swedish experts or signs of confirmation bias. If used properly, the variation in both process and outcome could be used to safeguard and possibly increase the reliability and validity of the final decision of Swedish forensic psychiatric investigations.

Selecting Counterions to Improve Ionized Hydrophilic Drug Encapsulation in Polymeric Nanoparticles.

Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid-state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion-drug-polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature (Tg; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and pKa with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π-π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811-free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation.

Terahertz frequency-domain sensing combined with quantitative multivariate analysis for pharmaceutical tablet inspection.

Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination (R2) for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6% for tablet density and API concentration models, respectively. In conclusion, terahertz spectroscopy demonstrated to be a complementary technique to Raman and NIR spectroscopy, which enables the characterization of physical properties of tablets like tablet density, and the characterization of API concentration with the advantage of low scattering effects.

ID23-2: an automated and high-performance microfocus beamline for macromolecular crystallography at the ESRF. Corrigendum.

A revised version of Table 2 of Nanao et al. [J. Synchrotron Rad. (2022). 29, 581-590] is provided.

Decision-Making Within Forensic Psychiatric Investigations: The Use of Various Information Sources by Different Expert Groups to Reach Conclusions on Legal Insanity.

Background: Which 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. Method: The 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. Results: The 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. Discussion: The 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.

ID23-2: an automated and high-performance microfocus beamline for macromolecular crystallography at the ESRF.

ID23-2 is a fixed-energy (14.2 keV) microfocus beamline at the European Synchrotron Radiation Facility (ESRF) dedicated to macromolecular crystallography. The optics and sample environment have recently been redesigned and rebuilt to take full advantage of the upgrade of the ESRF to the fourth generation Extremely Brilliant Source (ESRF-EBS). The upgraded beamline now makes use of two sets of compound refractive lenses and multilayer mirrors to obtain a highly intense (>1013 photons s-1) focused microbeam (minimum size 1.5 µm × 3 µm full width at half-maximum). The sample environment now includes a FLEX-HCD sample changer/storage system, as well as a state-of-the-art MD3Up high-precision multi-axis diffractometer. Automatic data reduction and analysis are also provided for more advanced protocols such as synchrotron serial crystallographic experiments.

The decision-making process in Swedish forensic psychiatric investigations.

Forensic psychiatric investigations in Sweden can have a major impact on the choice of sentence in criminal cases. Previous research shows that the decisions in several forensic fields, including forensic psychiatry, can be affected in a negative way by factors not relevant to the case. In the present study, the decision-making process of forensic psychiatric investigations was explored by using semi-structured interviews with experts (n = 38) and analyzing these interviews thematically. The results showed that the decision-making process is both complex and iterative, where the experts use and shape a substantial amount of information to reach their decisions. The experts work in teams, which add both benefits and risks to the process, and feel that particularly time constraints may reduce the quality of their decisions. In summary, the decision-making process of Swedish forensic psychiatric investigations creates a potential for high validity, but also contains risks for bias effects that could warrant further mitigation.

ID30A-3 (MASSIF-3) - a beamline for macromolecular crystallography at the ESRF with a small intense beam.

ID30A-3 (or MASSIF-3) is a mini-focus (beam size 18 µm × 14 µm) highly intense (2.0 × 1013 photons s-1), fixed-energy (12.81 keV) beamline for macromolecular crystallography (MX) experiments at the European Synchrotron Radiation Facility (ESRF). MASSIF-3 is one of two fixed-energy beamlines sited on the first branch of the canted undulator setup on the ESRF ID30 port and is equipped with a MD2 micro-diffractometer, a Flex HCD sample changer, and an Eiger X 4M fast hybrid photon-counting detector. MASSIF-3 is recommended for collecting diffraction data from single small crystals (≤15 µm in one dimension) or for experiments using serial methods. The end-station has been in full user operation since December 2014, and here its current characteristics and capabilities are described.

A comparative anatomy of protein crystals: lessons from the automatic processing of 56†000 samples.

The fully automatic processing of crystals of macromolecules has presented a unique opportunity to gather information on the samples that is not usually recorded. This has proved invaluable in improving sample-location, characterization and data-collection algorithms. After operating for four years, MASSIF-1 has now processed over 56 000 samples, gathering information at each stage, from the volume of the crystal to the unit-cell dimensions, the space group, the quality of the data collected and the reasoning behind the decisions made in data collection. This provides an unprecedented opportunity to analyse these data together, providing a detailed landscape of macromolecular crystals, intimate details of their contents and, importantly, how the two are related. The data show that mosaic spread is unrelated to the size or shape of crystals and demonstrate experimentally that diffraction intensities scale in proportion to crystal volume and molecular weight. It is also shown that crystal volume scales inversely with molecular weight. The results set the scene for the development of X-ray crystallography in a changing environment for structural biology.

CM01: a facility for cryo-electron microscopy at the European Synchrotron.

Recent improvements in direct electron detectors, microscope technology and software provided the stimulus for a `quantum leap' in the application of cryo-electron microscopy in structural biology, and many national and international centres have since been created in order to exploit this. Here, a new facility for cryo-electron microscopy focused on single-particle reconstruction of biological macromolecules that has been commissioned at the European Synchrotron Radiation Facility (ESRF) is presented. The facility is operated by a consortium of institutes co-located on the European Photon and Neutron Campus and is managed in a similar fashion to a synchrotron X-ray beamline. It has been open to the ESRF structural biology user community since November 2017 and will remain open during the 2019 ESRF-EBS shutdown.

MXCuBE2: the dawn of MXCuBE Collaboration.

MXCuBE2 is the second-generation evolution of the MXCuBE beamline control software, initially developed and used at ESRF - the European Synchrotron. MXCuBE2 extends, in an intuitive graphical user interface (GUI), the functionalities and data collection methods available to users while keeping all previously available features and allowing for the straightforward incorporation of ongoing and future developments. MXCuBE2 introduces an extended abstraction layer that allows easy interfacing of any kind of macromolecular crystallography (MX) hardware component, whether this is a diffractometer, sample changer, detector or optical element. MXCuBE2 also works in strong synergy with the ISPyB Laboratory Information Management System, accessing the list of samples available for a particular experimental session and associating, either from instructions contained in ISPyB or from user input via the MXCuBE2 GUI, different data collection types to them. The development of MXCuBE2 forms the core of a fruitful collaboration which brings together several European synchrotrons and a software development factory and, as such, defines a new paradigm for the development of beamline control platforms for the European MX user community.

New features of arabinoxylan ethers revealed by using multivariate analysis.

Hemicelluloses are a relatively unused renewable resource. One reason is their broad structure variety that makes it hard to understand structure-property relations. In this study arbinoxylan, extracted from barley husk, was chemically modified into hydroxypropyl methyl-, hydroxypropyl- and methyl arabinoxylan. The relationship between structure and phase behavior was investigated by using multivariate analysis. The arabinoxylan ethers were characterized using mid-infrared FTIR spectroscopy and from principal components analysis, PCA, structural or physical variations between samples were visualized. With orthogonal projections to latent structures, OPLS, vibrations specific for arabinoxylan hydroxypropyl and methyl substitutions was assigned. Among the observed differences between chemical derivatives was an intensity change in the water vibration. The differences in hydration were related to clouding phase behavior of the arabinoxylan ethers. This study shows that multivariate analysis methods are useful for finding unexpected and/or hidden features in the polysaccharide structure.

Associations Between Conduct Disorder, Neurodevelopmental Problems and Psychopathic Personality Traits in a Swedish Twin Youth Population.

Previous research has found a complex relationship between psychopathic traits, neurodevelopmental problems (NDPs), and conduct disorder (CD) in children. This study explores associations between psychopathic traits, assessed with the Child Problematic Traits Inventory-Short Version (CPTI-SV), and CD in children with and without coexisting NDPs (i.e., attention deficit/hyperactivity disorder [ADHD] and autism spectrum disorder [ASD]) in a community-based sample of Swedish twins (n = 8762). Findings indicate weak to moderately strong correlations between psychopathic traits and CD, ADHD, and ASD, respectively. Furthermore, in univariable analyses, both psychopathic traits and NDPs displayed significant positive associations with being screened positive for CD, though only the grandiose-deceitful dimension of CPTI-SV and the ADHD domain concentration and attention deficits remained significantly associated with CD in a multivariable regression model. The results are relevant to screening and assessment in child and youth psychiatry, as a grandiose and deceitful interpersonal style may also be a valid sign of children at risk of developing CD.

ID30B - a versatile beamline for macromolecular crystallography experiments at the ESRF.

ID30B is an undulator-based high-intensity, energy-tuneable (6.0-20 keV) and variable-focus (20-200 µm in diameter) macromolecular crystallography (MX) beamline at the ESRF. It was the last of the ESRF Structural Biology Group's beamlines to be constructed and commissioned as part of the ESRF's Phase I Upgrade Program and has been in user operation since June 2015. Both a modified microdiffractometer (MD2S) incorporating an in situ plate screening capability and a new flexible sample changer (the FlexHCD) were specifically developed for ID30B. Here, the authors provide the current beamline characteristics and detail how different types of MX experiments can be performed on ID30B (http://www.esrf.eu/id30b).

Multi-position data collection and dynamic beam sizing: recent improvements to the automatic data-collection algorithms on MASSIF-1.

Macromolecular crystallography is now a mature and widely used technique that is essential in the understanding of biology and medicine. Increases in computing power combined with robotics have not only enabled large numbers of samples to be screened and characterized but have also enabled better decisions to be taken on data collection itself. This led to the development of MASSIF-1 at the ESRF, the first beamline in the world to run fully automatically while making intelligent decisions taking user requirements into account. Since opening in late 2014, the beamline has processed over 42 000 samples. Improvements have been made to the speed of the sample-handling robotics and error management within the software routines. The workflows initially put into place, while highly innovative at the time, have been expanded to include increased complexity and additional intelligence using the information gathered during characterization; this includes adapting the beam diameter dynamically to match the diffraction volume within the crystal. Complex multi-position and multi-crystal data collections have now also been integrated into the selection of experiments available. This has led to increased data quality and throughput, allowing even the most challenging samples to be treated automatically.

The complex analysis of X-ray mesh scans for macromolecular crystallography.

In macromolecular crystallography, mesh (raster) scans are carried out either as part of X-ray-based crystal-centring routines or to identify positions on the sample holder from which diffraction images can be collected. Here, the methods used in MeshBest, software which automatically analyses diffraction images collected during a mesh scan and produces a two-dimensional crystal map showing estimates of the dimensions, centre positions and diffraction qualities of each crystal contained in the mesh area, are presented. Sample regions producing diffraction images resulting from the superposition of more than one crystal are also distinguished from regions with single-crystal diffraction. The applicability of the method is demonstrated using several cases.

X-ray and UV radiation-damage-induced phasing using synchrotron serial crystallography.

Specific radiation damage can be used to determine phases de novo from macromolecular crystals. This method is known as radiation-damage-induced phasing (RIP). One limitation of the method is that the dose of individual data sets must be minimized, which in turn leads to data sets with low multiplicity. A solution to this problem is to use data from multiple crystals. However, the resulting signal can be degraded by a lack of isomorphism between crystals. Here, it is shown that serial synchrotron crystallography in combination with selective merging of data sets can be used to determine high-quality phases for insulin and thaumatin, and that the increased multiplicity can greatly enhance the success rate of the experiment.

A quality control method enhancement concept-Continual improvement of regulatory approved QC methods.

Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.

Facilitating best practices in collecting anomalous scattering data for de novo structure solution at the ESRF Structural Biology Beamlines.

The constant evolution of synchrotron structural biology beamlines, the viability of screening protein crystals for a wide range of heavy-atom derivatives, the advent of efficient protein labelling and the availability of automatic data-processing and structure-solution pipelines have combined to make de novo structure solution in macromolecular crystallography a less arduous task. Nevertheless, the collection of diffraction data of sufficient quality for experimental phasing is still a difficult and crucial step. Here, some examples of good data-collection practice for projects requiring experimental phasing are presented and recent developments at the ESRF Structural Biology beamlines that have facilitated these are illustrated.

Boldness and its relation to psychopathic personality: Prototypicality analyses among forensic mental health, criminal justice, and layperson raters.

Research on psychopathic personality has been dominated by a focus on criminality and social deviance, but some theoretical models argue that certain putatively adaptive features are important components of this construct. In 3 samples (forensic mental health practitioners, probation officers and a layperson community sample), we investigated adaptive traits as conceptualized in the Triarchic model of psychopathy (Patrick et al., 2009), specifically the relevance of boldness to construals of psychopathic personality. Participants completed prototypicality ratings of psychopathic traits, including 3 items created to tap components of boldness (Socially bold, Adventurous, Emotionally stable), and they also rated a series of attitudinal statements (e.g., perceived correlates of being psychopathic, moral judgments about psychopaths). The composite Boldness scale was rated as moderately to highly prototypical among forensic mental health practitioners and probation officers and positively associated with other theoretically relevant domains of psychopathy. Across samples, higher composite Boldness ratings predicted greater endorsement of adaptive traits (e.g., social skills) as characteristic of psychopathy. For the individual items, Socially bold was rated as highly prototypical and was associated with theoretically relevant correlates. Adventurous also was seen as prototypical, though to a lesser degree. Only forensic mental health practitioners endorsed Emotionally stable as characteristic of psychopathy. Our results provide partial support for the contention that the boldness concept is viewed as an important component of psychopathy, particularly among professionals who work directly with offender populations. (PsycINFO Database Record