The backwoods of clinical and research assessment of psychosis

The aim of this thesis was to explore and improve methodology and utility of clinically applicable dimensional, staging and clinical profiling models for patients with psychotic and related disorders. This was approached at three levels: firstly, we evaluated the psychometric properties of the dimensional assessment of symptoms by the Clinician-Rated Dimensions of Psychosis Symptom Severity, and subsequently, determining the inter-rater reliability of the clinical staging model and profile characteristics. We evaluated inter-rater reliability with and without short training courses suitable for clinical practice (Part 1). Secondly, we evaluated the validity of the clinical staging model in schizophrenia spectrum disorders. We determined the construct and clinical validity of the staging model in ambulatory and clinically admitted patients. Furthermore, we assessed whether cognitive parameters are associated with higher clinical stages in a large sample of patients with psychotic disorders (Part 2). Thirdly, we evaluated the pre-training inter-rater reliability in clinical research. Moreover, we determined the proportion of reported inter-rater reliability coefficients and training procedures in double-blind randomized clinical trials with antipsychotic and antidepressant medication. Overall, we conclude that achieving sufficient inter-rater reliability of new diagnostic methods requires more attention, both in scientific research and in daily practice. This field of research can also be marked as the backwoods of clinical and research assessments — remote areas that could be neglected because of difficulties that may be encountered

Parallel computing and molecular dynamics of biological membranes

In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on the possible programming strategies. Liquids can be very satisfactorily simulated using the "systolic" method. For more complex systems, like the biological ones at which we are ultimately interested in, the "domain decomposition" approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of elementary components of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.Comment: 4 pages LaTeX, 2 figures included, espcrc2.sty require

Adaptive Resolution Simulation of Liquid Water

We present a multiscale simulation of liquid water where a spatially adaptive molecular resolution procedure allows for changing on-the-fly from a coarse-grained to an all-atom representation. We show that this approach leads to the correct description of all essential thermodynamic and structural properties of liquid water.Comment: 4 pages, 3 figures; changed figure

Polarization forces in water deduced from single molecule data

Intermolecular polarization interactions in water are determined using a minimal atomic multipole model constructed with distributed polarizabilities. Hydrogen bonding and other properties of water-water interactions are reproduced to fine detail by only three multipoles $\mu_H$, $\mu_O$, and $\theta_O$ and two polarizabilities $\alpha_O$ and $\alpha_H$, which characterize a single water molecule and are deduced from single molecule data.Comment: 4 revtex pages, 3 embedded color PS figure

Per la corretta attribuzione del "Romanzo delle donne contemporanee in Italia" (1863)

The use of free energy simulation techniques in the study of protein stability is critically evaluated. Results from two simulations of the thermostability mutation Asn218 to Ser218 in Subtilisin are presented. It is shown that components of the free energy change can be highly sensitive to the computational details of the simulation leading to the conclusion that free energy calculations cannot currently be used to reliably predict protein stability. The different factors that undermine the reliability are discussed

A Potential Energy Landscape Study of the Amorphous-Amorphous Transformation in H2_2O

We study the potential energy landscape explored during a compression-decompression cycle for the SPC/E (extended simple point charge) model of water. During the cycle, the system changes from low density amorphous ice (LDA) to high density amorphous ice (HDA). After the cycle, the system does not return to the same region of the landscape, supporting the interesting possibility that more than one significantly different configuration corresponds to LDA. We find that the regions of the landscape explored during this transition have properties remarkably different from those explored in thermal equilibrium in the liquid phase

Understanding the Scalability of Molecular Simulation Using Empirical Performance Modeling

The final authenticated publication is available online at https://doi.org/10.1007/978-3-030-17872-7_8.Molecular dynamics (MD) simulation allows for the study of static and dynamic properties of molecular ensembles at various molecular scales, from monatomics to macromolecules such as proteins and nucleic acids. It has applications in biology, materials science, biochemistry, and biophysics. Recent developments in simulation techniques spurred the emergence of the computational molecular engineering (CME) field, which focuses specifically on the needs of industrial users in engineering. Within CME, the simulation code ms2 allows users to calculate thermodynamic properties of bulk fluids. It is a parallel code that aims to scale the temporal range of the simulation while keeping the execution time minimal. In this paper, we use empirical performance modeling to study the impact of simulation parameters on the execution time. Our approach is a systematic workflow that can be used as a blue-print in other fields that aim to scale their simulation codes. We show that the generated models can help users better understand how to scale the simulation with minimal increase in execution time.BMBF, 01IH16008D, Verbundprojekt: TaLPas - Task-basierte Lastverteilung und Auto-Tuning in der PartikelsimulationDFG, 323299120, ExtraPeak - Automatische Leistungsmodellierung von HPC-Anwendungen mit multiplen Modellparameter

Direct simulation of ion beam induced stressing and amorphization of silicon

Using molecular dynamics (MD) simulation, we investigate the mechanical response of silicon to high dose ion-irradiation. We employ a realistic and efficient model to directly simulate ion beam induced amorphization. Structural properties of the amorphized sample are compared with experimental data and results of other simulation studies. We find the behavior of the irradiated material is related to the rate at which it can relax. Depending upon the ability to deform, we observe either the generation of a high compressive stress and subsequent expansion of the material, or generation of tensile stress and densification. We note that statistical material properties, such as radial distribution functions are not sufficient to differentiate between different densities of amorphous samples. For any reasonable deformation rate, we observe an expansion of the target upon amorphization in agreement with experimental observations. This is in contrast to simulations of quenching which usually result in denser structures relative to crystalline Si. We conclude that although there is substantial agreement between experimental measurements and most simulation results, the amorphous structures being investigated may have fundamental differences; the difference in density can be attributed to local defects within the amorphous network. Finally we show that annealing simulations of our amorphized samples can lead to a reduction of high energy local defects without a large scale rearrangement of the amorphous network. This supports the proposal that defects in amorphous silicon are analogous to those in crystalline silicon.Comment: 13 pages, 12 figure

Association of cognitive performance with clinical staging in schizophrenia spectrum disorders:a prospective 6-year follow-up study

BACKGROUND: Clinical staging has been developed to capture the large heterogeneity in schizophrenia spectrum disorders. Including cognitive performance in the staging model may improve its clinical validity. Moreover, cognitive functioning could predict transition across stages. However, current evidence of the association between cognition and clinical staging is inconsistent. Therefore, we aim to assess whether cognitive parameters are associated with clinical stages in a large sample of patients with schizophrenia spectrum disorders and to identify cognitive markers at baseline that are associated with stage-transition at three and six-year follow-up. METHODS: We applied the staging model of Fusar-Poli et al. (2017) in 927 patients with non-affective psychotic disorders, assessed at baseline, and after three and six-year follow-up. Cognitive performance was assessed with a standard test battery. Generalized linear mixed models were used to analyze associations of cognitive performance with staging and stage-transition at follow-up. RESULTS: Findings showed that higher stages of illness were significantly associated with lower processing speed (F = 3.688, p = 0.025) and deficits in working memory (F = 6.365, p = 0.002) across assessments. No associations between cognitive parameters at baseline and stage-transition at three- and six-year follow-up were found. CONCLUSION: We conclude that processing speed and working memory were modestly associated with higher stages of illness in schizophrenia spectrum disorders, thereby slightly improving its clinical validity. However, associations were small and we found no evidence for predictive validity

Effect of New Zealand Blackcurrant Extract on Substrate Oxidation and Cycling Performance in Normobaric Hypoxia

Blackcurrant is high in anthocyanin content. We have shown enhanced whole-body fat oxidation and increased time trial performance during cycling, in addition to increased femoral artery diameter during a sustained submaximal isometric contraction of the m.quadriceps with intake of New Zealand blackcurrant (NZBC) extract in normobaric normoxia (Cook et al., 2015, 2017). The effect of blackcurrant on metabolic and physiological responses and performance during cycling in normobaric hypoxia are not known. PURPOSE: To examine the effect of NZBC extract on intensity-dependent physiological and metabolic responses and 16.1-km cycling time trial in trained cyclists in normobaric hypoxia. METHODS: The study used a double-blind randomized cross-over design. Eleven healthy men from cycling and triathlon clubs with at least 3 yrs experience and cycling 8-10 hr·wk−1 (age: 38±11 yrs, height: 179±4 cm, body mass: 76±8 kg, V̇O2max: 47±5 mL·kg−1·min−1, maximum power: 398±38 W, mean±SD) ingested NZBC extract (600 mg·day−1 containing 220 mg anthocyanins) or placebo (PL) for 7 days (washout 14 days). Participants performed bouts of 10 min at 45, 55 and 65% V̇O2max, using indirect calorimetry and blood sampling, followed by a 16.1 km timetrial on a SRM ergometer (SRM International, Germany). Participants were familiarized for the time-trial. All testing took place in a temperature controlled (15°C) normobaric hypoxic chamber set at an altitude of ~2500 m (15% FiO2) (TIS Services, Medstead, UK) in morning sessions. Data was analysed using paired t-tests. RESULTS: At each intensity, NZBC extract had no effect on metabolic and physiological responses (e.g. at 65% V̇O2max, heart rate - PL: 133±12, NZBC; 132±12 beats·min-1); fat oxidation - PL: 0.24±0.12, NZBC: 0.20±0.16 g·min-1; carbohydrate oxidation - PL: 2.34±0.42, NZBC: 2.48±0.35 g·min-1; lactate - PL: 1.37±0.45, NZBC: 1.56±0.57 mmol·L-1). No improvements in 16.1 km time-trial performance were observed (PL: 1685±92, NZBC: 1685±99 sec). CONCLUSION: Seven day intake of New Zealand blackcurrant extract does not change whole-body fat oxidation and 16.1 km time-trial performance during cycling in normobaric hypoxia