Hippocampal volumes in patients with bipolar-schizophrenic spectrum disorders and their unaffected first-degree relatives

BACKGROUND: schizophrenic and bipolar disorders are complex and disabling psychiatric diseases whose classical nosography and classification are still under challenging debate aiming to overcome the traditional “Kraepelinian Dichotomy”. For the past hundred years most clinical work and research in psychiatry has proceeded under the assumption that schizophrenia and bipolar disorderaredistinctentities with separate underlying disease processes and treatments. In more recent years there has been increasing evidence for phenomenological, biological and genetic overlap between the two disorders (Potash and Bienvenu 2009). Nowadays, the categorical approach to psychiatric nosography is in contrast with the recent neurobiological, neuropsychological and genetic findings in affective and schizophrenic disorders. Further, symptoms and signs constituting bipolar and schizophrenic disorders are continuously, not dichotomously, distributed; there may be no point of “real cleavage” (Phelps et al. 2008). This recognition has led some clinicians and researchers to call for a diagnostic model that, moving to a “dimensional perspective”, formally recognizes a continuous spectrum from schizophrenic to bipolar (and recurrent depressive) disorders. Kelsoe argued that the existing data coming from various fields of research in bipolar and schizophrenic disorders may best fit a model in which different set of genes predispose to overlapping phenotypes in a continuum. Given the apparent overlap of regions of the genome implicated in bipolar disorder with those for schizophrenia (Kelsoe 1999; Berrettini 2000), the data suggest the possibility that a common polygenic background predisposes to both bipolar disorder and schizophrenia, according to the so-called “multiple threshold model” (Kelsoe 2003). As highlighted by Craddock and Owen, the recent findings are compatible with a model of functional psychosis in which susceptibility to a spectrum of clinical phenotypes is under the influence of overlapping sets of genes, which, together with environmental and epigenetic factors, determine an individual’s expression of illness (Craddock and Owen 2005). A lot of interest is focusing on brain structural abnormalities in patients suffering from schizophrenia and bipolar disorder. A huge amount of neuroimaging studies has been published so far, however the literature is heterogeneous and there is still some degree of uncertainty concerning what key regions are involved in the pathogenesis of such disorders. Schizophrenia and Bipolar Disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. To date there is no consensus about whether, and to what extent, gray matter loss in Schizophrenia is mirrored in Bipolar Disorder and what is the effect of medication or other confounding factors. Studies in family members of patients, who share the risk of the disease but not the confounding factors, may help elucidate whether abnormalities in brain structures are shared by both illnesses. AIM OF THE STUDY: to investigate hippocampal gray matter volume differences in a group of patients with bipolar-schizophrenic spectrum disorders, a group of their unaffected first-degree relatives, and a group of healthy control subjects. METHODS: a total of 104 subjects - 36 schizophrenic or schizoaffective (SZ), 27 bipolar (BP), 2 major depression, 8 unaffected relatives (UR), and 31 healthy controls (HC) - underwent 1,5 T MRI scanning, with volumetric T1 3D acquisition protocol, at the Neuroradiology Unit of Conegliano Hospital. We calculate bilateral hippocampal gray matter volume (HV) and total cerebral volume (TCV) in a sample of 31 SZ, 27 BP, 8 UR and 26 HC, with a stereological method using ANALYZE 10.0 software. RESULTS: we found statistically significant reductions in bilateral HV in the BP-SZ patients compared to HC; the direct comparison between patient groups identified statistically significant reduction in the right HV of SZ, but no significant differences for left HV or TCV (however statistical significance was lost after normalization); statistically significant reduction in the left HV and a trend towards statistical significance for right HV in the UR compared to HC (a trend towards statistically significant reduction in bilateral HV persisted after normalization). CONCLUSION: it might be speculated that the alterations of the gray matter volume in the hippocampus highlighted in our study could be interpreted as a possible structural “biological marker” in the schizophrenic-bipolar spectrum

Multispecies structure-preserving particle discretization of the Landau collision operator

This paper proposes a novel numerical integrator for modeling multispecies Coulomb collisions in kinetic plasmas. The proposed scheme provides an energy-, momentum-, and positivity-preserving particle discretization of the nonlinear Landau collision operator, extending the works of J.A. Carrillo et al., Journal of Computational Physics, 7, 100066 (2020) and E. Hirvijoki, Plasma Physics and Controlled Fusion, 63, 044003 (2021). The discrete-time conservation properties are analyzed both algebraically and numerically, and an efficient, GPU-parallelized implementation is validated against inhomogeneous temperature relaxation, isotropization and thermalization examples. The results agree with analytical estimates, confirming the method capable of reproducing physics.Comment: 23 pages, 14 figure

The Landau Collision Integral in the Particle Basis in the PETSc Library

The Landau collision integral is often considered the gold standard in the context of kinetic plasma simulation due to its conservative properties, despite challenges involved in its discretization. The primary challenge when implementing an efficient computation of this operator is conserving physical properties of the continuum equation when the system is discretized. Recent work has achieved continuum discretizations using the method of Finite Elements which maintain conservation of mass, momentum, and energy, but which lacks monotonic entropy production. More recently, a particle discretization has been introduced which conserves mass, momentum, and energy, but maintains the benefit of monotonic entropy production necessary for the metriplecticity of the system. We present here an implementation of the particle basis Landau collision integral in the Portable Extensible Toolkit for Scientific Computing in 2 and 3V for the construction of a full geometry solver with a novel approach to computation of the entropy functional gradients. Verification of the operator is achieved with thermal equilibration and isotropization tests. All examples are available, open source, in the PETSc repository for reproduction

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Hippocampal volumes in patients with bipolar-schizophrenic spectrum disorders and their unaffected first-degree relatives

BACKGROUND: schizophrenic and bipolar disorders are complex and disabling psychiatric diseases whose classical nosography and classification are still under challenging debate aiming to overcome the traditional “Kraepelinian Dichotomy”. For the past hundred years most clinical work and research in psychiatry has proceeded under the assumption that schizophrenia and bipolar disorderaredistinctentities with separate underlying disease processes and treatments. In more recent years there has been increasing evidence for phenomenological, biological and genetic overlap between the two disorders (Potash and Bienvenu 2009). Nowadays, the categorical approach to psychiatric nosography is in contrast with the recent neurobiological, neuropsychological and genetic findings in affective and schizophrenic disorders. Further, symptoms and signs constituting bipolar and schizophrenic disorders are continuously, not dichotomously, distributed; there may be no point of “real cleavage” (Phelps et al. 2008). This recognition has led some clinicians and researchers to call for a diagnostic model that, moving to a “dimensional perspective”, formally recognizes a continuous spectrum from schizophrenic to bipolar (and recurrent depressive) disorders. Kelsoe argued that the existing data coming from various fields of research in bipolar and schizophrenic disorders may best fit a model in which different set of genes predispose to overlapping phenotypes in a continuum. Given the apparent overlap of regions of the genome implicated in bipolar disorder with those for schizophrenia (Kelsoe 1999; Berrettini 2000), the data suggest the possibility that a common polygenic background predisposes to both bipolar disorder and schizophrenia, according to the so-called “multiple threshold model” (Kelsoe 2003). As highlighted by Craddock and Owen, the recent findings are compatible with a model of functional psychosis in which susceptibility to a spectrum of clinical phenotypes is under the influence of overlapping sets of genes, which, together with environmental and epigenetic factors, determine an individual’s expression of illness (Craddock and Owen 2005). A lot of interest is focusing on brain structural abnormalities in patients suffering from schizophrenia and bipolar disorder. A huge amount of neuroimaging studies has been published so far, however the literature is heterogeneous and there is still some degree of uncertainty concerning what key regions are involved in the pathogenesis of such disorders. Schizophrenia and Bipolar Disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. To date there is no consensus about whether, and to what extent, gray matter loss in Schizophrenia is mirrored in Bipolar Disorder and what is the effect of medication or other confounding factors. Studies in family members of patients, who share the risk of the disease but not the confounding factors, may help elucidate whether abnormalities in brain structures are shared by both illnesses. AIM OF THE STUDY: to investigate hippocampal gray matter volume differences in a group of patients with bipolar-schizophrenic spectrum disorders, a group of their unaffected first-degree relatives, and a group of healthy control subjects. METHODS: a total of 104 subjects - 36 schizophrenic or schizoaffective (SZ), 27 bipolar (BP), 2 major depression, 8 unaffected relatives (UR), and 31 healthy controls (HC) - underwent 1,5 T MRI scanning, with volumetric T1 3D acquisition protocol, at the Neuroradiology Unit of Conegliano Hospital. We calculate bilateral hippocampal gray matter volume (HV) and total cerebral volume (TCV) in a sample of 31 SZ, 27 BP, 8 UR and 26 HC, with a stereological method using ANALYZE 10.0 software. RESULTS: we found statistically significant reductions in bilateral HV in the BP-SZ patients compared to HC; the direct comparison between patient groups identified statistically significant reduction in the right HV of SZ, but no significant differences for left HV or TCV (however statistical significance was lost after normalization); statistically significant reduction in the left HV and a trend towards statistical significance for right HV in the UR compared to HC (a trend towards statistically significant reduction in bilateral HV persisted after normalization). CONCLUSION: it might be speculated that the alterations of the gray matter volume in the hippocampus highlighted in our study could be interpreted as a possible structural “biological marker” in the schizophrenic-bipolar spectrum.INTRODUZIONE: schizofrenia e disturbo bipolare sono malattie psichiatriche complesse e invalidanti, il cui inquadramento nosografico è oggetto di continuo dibattito nel superamento della classica “dicotomia Kraepeliniana” tra Dementia Praecox e Malattia Maniaco-Depressiva. Negli ultimi cento anni, buona parte della pratica clinica e della ricerca in psichiatria sono state basate sull’assunto che schizofrenia e disturbo bipolare fossero entità categorialmente distinte, separate da distinti meccanismi patologici e trattamenti. In anni più recenti invece, si sono accumulate numerose evidenze a supporto di una parziale sovrapposizione fenomenologica, biologica e genetica tra questi disturbi (Potash e Bienvenu 2009). Attualmente, l’approccio nosografico “categoriale” nei disturbi affettivi e schizofrenici è in contrasto con le più recenti scoperte in ambito neurobiologico, neuropsicologico e genetico. Inoltre è stato evidenziato come, nemmeno dal punto di vista clinico vi sia un reale punto di “separazione” tra i due disturbi, che presentano segni e sintomi comuni e sovrapponibili (Phelps et al. 2008). Tale consapevolezza ha portato clinici e ricercatori a orientarsi verso un modello diagnostico che, spostandosi in una prospettiva “dimensionale”, formalmente riconosce l’esistenza di uno spettro tra disturbi schizofrenici e bipolari. Kelsoe afferma che i dati provenienti dai vari filoni di ricerca nei disturbi bipolari e schizofrenici potrebbero essere meglio spiegati da un modello in cui differenti set di geni predispongono a fenotipi clinici che si sovrappongono in un continuum. Data la documentata sovrapposizione fra regioni genomiche implicate nel disturbo bipolare con quelle della schizofrenia (Kelsoe 1999; Berrettini 2000), le evidenze suggeriscono la possibilità che un substrato poligenico comune possa conferire una predisposizione a entrambi i disturbi, secondo il cosiddetto modello delle “soglie multiple” (Kelsoe 2003). Come sottolineato da Craddock e Owen, le più recenti scoperte in tale ambito sono compatibili con un modello di psicosi funzionale, nel quale la suscettibilità ad uno spettro di fenotipi clinici è sotto l’influenza di un set di geni condivisi, che, insieme a fattori ambientali ed epigenetici, determina l’espressione di malattia in ciascun individuo (Craddock e Owen 2005). Notevole interesse si sta inoltre focalizzando sulle alterazioni strutturali cerebrali in pazienti affetti da schizofrenia e disturbo bipolare. Nonostante l’ingente mole di studi di neuroimaging finora pubblicati, la letteratura sull’argomento è molto eterogenea ed esiste ancora notevole incertezza su quali siano le specifiche regioni cerebrali coinvolte nella patogenesi di tali disturbi. Schizofrenia e Disturbo Bipolare condividono una serie di sintomi e fattori di rischio, ma non è ancora stato chiarito se questi disturbi siano caratterizzati da comuni modificazioni morfometriche cerebrali e se tali alterazioni riflettano l’impatto di geni comuni di suscettibilità sulla morfologia del cervello. Ad oggi, non è stato definitivamente chiarito se, e fino a che punto, la documentata perdita di sostanza grigia nella Schizofrenia si rifletta anche nel Disturbo Bipolare e su quali siano gli effetti della farmacoterapia o di altri fattori di confondimento. Gli studi sui membri non affetti di pazienti schizofrenici e bipolari, che condividono la predisposizione genetica ai disturbi, ma non i fattori di confondimento, posso rivelarsi utili nel verificare se le varie anomalie cerebrali siano condivise nelle due patologie. SCOPO DELLO STUDIO: analizzare eventuali differenze volumetriche nella sostanza grigia ippocampale in un gruppo di pazienti dello spettro bipolare-schizofrenico, un gruppo di familiari di primo grado non affetti e un gruppo di soggetti sani di controllo. MATERIALI E METODI: un totale di 104 sogetti - 36 pazienti con disturbo schizofrenico o schizoaffettivo (SZ), 27 pazienti con disturbo bipolare (BP), 2 pazienti affetti da depressione maggiore ricorrente, 8 familiari di primo grado non affetti (UR) e 31 controlli sani (HC) sono stati sottoposti ad una procedura di Risonanza Magnetica cerebrale ad 1,5 Tesla, secondo un protocollo di acquisizione di sequenze T1 3D volumetriche, presso l’Unità Operativa di Neuroradiologia del Presidio Ospedaliero di Conegliano. Mediante l’utilizzo del Software ANALYZE 10.0, sono stati calcolati, con un metodo stereologico, i volumi bilaterali della sostanza grigia ippocampale (HV) ed il volume cerebrale totale (TCV) in un campione di 31 SZ, 27 BP, 8 UR e 26 HC. RISULTATI: sono state riscontrate riduzioni volumetriche statisticamente significative della sostanza grigia di ippocampo destro e sinistro tra i gruppi di pazienti dello spettro bipolare-schizofrenico rispetto ai controlli; nel confronto diretto tra il gruppo di pazienti schizofrenici e quello dei bipolari è stata identificata una riduzione statisticamente significativa del volume della sostanza grigia dell’ippocampo destro (tale significatività non persiste in seguito a normalizzazione) e nessuna significativa differenza nei volumi della sostanza grigia dell’ippocampo sinistro o nel volume cerebrale totale; nel confronto tra il gruppo di familiari di primo grado non affetti rispetto al gruppo di soggetti sani di controllo è stata evidenziata una significativa riduzione volumetrica della sostanza grigia dell’ippocampo sinistro e un trend verso la significatività statistica per l’ippocampo destro (tali riduzioni volumetriche della grigia ippocampale mantenevano bilateralmente tale trend verso la significatività statistica anche dopo la normalizzazione). CONCLUSIONE: la alterazione volumetrica della sostanza grigia ippocampale evidenziata nel nostro studio potrebbe essere interpretata come un possibile “marker biologico” strutturale nei disturbi dello spettro schizofrenico-bipolare

Study of variational symplectic algorithms for the numerical integration of guiding center equations of motion

Questa tesi presenta una discussione dei più moderni algoritmi simplettici variazionali per l'integrazione delle equazioni del moto del centro di guida in particelle cariche in campi magnetici arbitrari statici, utili nello studio di plasmi debolmente collisionali. Differenti varianti degli algoritmi sono presentate, insieme a studi numerici ed analitici che ne evidenziano la stabilità numerica, o la relativa mancanza di essa

Theoretical and numerical methods for kinetic simulation of plasmas

Understanding and simulating the dynamics of plasmas in Tokamak devices is a crucial aspect of the plasma physics research, especially with the upcoming ITER device. The development of numerical schemes that possess conservation laws over the vast time scale that covers the dynamics of charged particles in fusion plasmas is an intimidating yet a very important task. This thesis presents novel numerical and theoretical techniques to tackle this problem. First, an overview of the kinetic theory, in particular the derivations of the Vlasov equation, the Fokker-Planck equation and the Vlasov-Maxwell equation in a variational setting, is given. The Euler-Poincar\'{e} reduction, which is a powerful mathematical tool that allows to derive the the Vlasov-Maxwell equations in a straightforward way, is presented as well. A multi-species, marker based, structure-preserving numerical code for the Landau equation is presented. The code is able to preserve energy and momentum to machine precision and leverages GPU-computing to efficiently scale with the dimension of the system. The scheme was validated against relaxation, isotropization and thermalization theoretical estimates for different mass-ratio of the species, including a real electron-deuteron case, showing good agreement in all performed tests. Finally, the problem of fast ions is tackled by introducing the Backward Monte Carlo (BMC) scheme. The approach aims at increasing the poor statistics of current Forward Monte Carlo simulations by integrating the probability of fast ions backward in time and taking into account deterministically the spread of the Monte Carlo collision operator. The scheme was implemented as a module of the orbit following code ASCOT5, enabling high performance simulations especially with modern supercomputers, and test cases with realistic plasma profiles, magnetic fields and wall geometries. The BMC scheme was applied to a realistic ASDEX Upgrade configuration of beam-ion distributions, with a Fast-Ion Loss Detector (FILD) placed near the divertor. The results shows a substantial increase of wall hits compared to a standard Forward Monte Carlo simulation