24 research outputs found
Synchrotron-generated microbeams induce hippocampal transections in rats
Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated gamma-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis
Nouvelle application de la radiothérapie par microfaisceaux (MRT) pour le traitement de l'épilepsie et des troubles cérébraux
Synchrotron-generated X-ray microplanar beams (microbeams, MBs) are characterized by the ability to avoid widespread tissue damage following delivery of doses ranging from hundreds to over a thousand of Grays. The resistance of normal tissues to high doses of MBs is likely related to the fast repair of the microvessels and to the wide interface between normal and irradiated tissue, allowing fast recolonization of the microbeam ablated columns of tissue. The preservation of the cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. In this Thesis microbeams transections were delivered to the rat cortex and hippocampus. MBs cortical transections were delivered to the sensory motor cortex (size 100 ”m/600 ”m, center-to-center distance of 400 ”m/1200 ”m, peak-valley doses of 360-240 Gy/150-100 Gy) of Wistar male healthy rats and rats developing seizures following cortical injections of Kainic Acid (KA)-. The motor performances following sensorimotor cortex transections was assessed by rotarod test. The effect of microbeam transections on cortical architecture was assessed by immunohistology with NeuN and GFAP, markers of mature neurons and astrocytes. No neurological deficit was observed in healthy animals undergoing sensorimotor cortex microbeam transections. Convulsive seizure duration was markedly reduced following transections in KA rats. MBs hippocampal transections (75 ”m thickness, 400 c-t-c distance and 600 Gy as peak entrance dose) were performed in adult healthy Wistar rats. MBs transections were compared with an uniformly delivered X-ray dose (broad beam, BB) at 10 Gy. Our aims were to quantify (i) the impact of microbeams versus conventional irradiation on neurogenesis (using proliferative cells markers such as BrdU and Ki-67), and (ii) to investigate on a long term (1 year) the correlation between neurogenesis and impairments in learning and memory. Preservation of proliferative cells in the microbeam treated group were observed. Microbeam transections delivered to the hippocampus did not induce significant behavioral impairment histological and immunohistochemical findings showed a preserved hippocampal structure with evidence of higly precise transections diving the hippocampus in columns. This work confirms the safe delivery of high doses of radiation to specific and radiosensitive parts of the brain, if performed using microbeams Additionally, the development of clinical devices delivering submillimetric beams able to generate cortical or hippocampal transections might become a new powerful new tool for the clinical treatment of epilepsy, pain and other functional brain disorders.Les microfaisceaux (MBs) de rayons X gĂ©nĂ©rĂ©s par un synchrotron permettent de dĂ©livrer des doses de radiation trĂšs Ă©levĂ©es, jusqu'Ă plusieurs centaines de gray (Gy), sans pour autant induire de dommages tissulaires irrĂ©versibles dans les zones avoisinant la lĂ©sion. La rĂ©activitĂ© du rĂ©seau vasculaire Ă se rĂ©gĂ©nĂ©rer grĂące aux cellules endothĂ©liales, est probablement un mĂ©canisme clef dans la radio-tolĂ©rance des tissus sains, puisqu'il permet une recolonisation rapide des zones tissulaires lĂ©sĂ©es. Cette mĂ©thode permet ainsi de reproduire de façon non invasive une incision chirurgicale prĂ©cise du cortex tout en prĂ©servant son architecture. Cette caractĂ©ristique prĂ©sente un intĂ©rĂȘt certain et permet d'envisager le dĂ©veloppement de nouveaux modĂšles neurobiologiques expĂ©rimentaux ouvrant la voie Ă des traitements innovants pour de nombreux troubles cĂ©rĂ©braux. Durant cette thĂšse, les microfaisceaux ont Ă©tĂ© utilisĂ©s sur la structure corticale et l'hippocampe de rats. Concernant le cortex, les MBs ont Ă©tĂ© appliquĂ©s au niveau du cortex sensori-moteur (taille 100 ”m/600 ”m, of 400 ”m/1200 ”m crĂȘte Ă crĂȘte, dose pics - vallĂše de 360-240 Gy/150-100 Gy) chez des rats males Wistar sains ainsi que chez des rats dĂ©veloppant des attaques cĂ©rĂ©brales consĂ©cutivement Ă l'injection corticale d'Acide KaĂŻnique (KA). Suite aux traitements par MBs, les performances motrices Ă©taient Ă©valuĂ©es par le test du Rotarod et les structures corticales Ă©tudiĂ©es par immunohistochimie grĂące au marquage par NeuN et GFAP des neurones et astrocytes matures. Aucun dĂ©ficit neurologique n'a Ă©tĂ© observĂ© chez les rats sains soumis au protocole de traitement par MBs et une diminution significative (normalement lĂ il faut mettre des statistiques ou au moins les avoir sinon tu peux dire diminution importante) de la durĂ©e des crises de convulsions a pu ĂȘtre observĂ©e chez les rats KA. L'incidence des MBs (9 microfaisceaux de 75 ÎŒm de largeur sĂ©parĂ©s de 400 ÎŒm crĂȘte Ă crĂȘte, dose d'entrĂ©e: 1000 Gy) dĂ©livrĂ©s au niveau de l'hippocampe de rats Wistar sains a Ă©tĂ© comparĂ©e avec un traitement par rayons X de 10 Gy dĂ©livrĂ© uniformĂ©ment. Le but de cette expĂ©rience Ă©tait d'Ă©valuer l'impact d'un traitement par microfaisceaux par rapport aux techniques d'irradiation conventionnelles. Pour cela, une Ă©valuation quantitative (i) comparative a Ă©tĂ© faite sur la neurogĂ©nĂšse grĂące Ă l'utilisation de marqueurs cellulaires (BrdU et Ki-67). Une Ă©tude (ii) a aussi Ă©tĂ© menĂ©e sur le long terme (1 an) pour mettre en Ă©vidence la corrĂ©lation entre la neurogĂ©nĂšse, les troubles de l'apprentissage et de la mĂ©moire. Une prĂ©servation des cellules prolifĂ©ratives a Ă©tĂ© observĂ©e au sein du groupe traitĂ© par MBs. Les transsections de l'hippocampe de rats par MBs n'induisent pas de troubles significatifs (lĂ aussi, il faut avoir des stat ou alors utiliser troubles marquants) du comportement de plus, l'observation histologique et immunohistochimique des tissus a permis de mettre en Ă©vidence la conservation de sa structure.Le travail effectuĂ© au cours de cette thĂšse confirme que le traitement spĂ©cifique de zones radiosensibles du cerveau par les microfaisceaux est sĂ»r et permet d'amĂ©liorer le pronostique des animaux traitĂ©s par rapport aux techniques conventionnelles. Ainsi, le dĂ©veloppement d'appareils permettant de dĂ©livrer des faisceaux de rayons submillimĂ©triques capables de gĂ©nĂ©rer une destruction prĂ©cise et limitĂ©e au niveau du cortex ou de l'hippocampe pourra permettre une prise en charge innovante plus sĂ»re de nombreuses pathologies fonctionnelles cĂ©rĂ©brales comme l'Ă©pilepsie ou certaines douleurs
A new application of microbeam radiation therapy (MRT) on the treatment of epilepsy and brain disorders.
Les microfaisceaux (MBs) de rayons X gĂ©nĂ©rĂ©s par un synchrotron permettent de dĂ©livrer des doses de radiation trĂšs Ă©levĂ©es, jusqu'Ă plusieurs centaines de gray (Gy), sans pour autant induire de dommages tissulaires irrĂ©versibles dans les zones avoisinant la lĂ©sion. La rĂ©activitĂ© du rĂ©seau vasculaire Ă se rĂ©gĂ©nĂ©rer grĂące aux cellules endothĂ©liales, est probablement un mĂ©canisme clef dans la radio-tolĂ©rance des tissus sains, puisqu'il permet une recolonisation rapide des zones tissulaires lĂ©sĂ©es. Cette mĂ©thode permet ainsi de reproduire de façon non invasive une incision chirurgicale prĂ©cise du cortex tout en prĂ©servant son architecture. Cette caractĂ©ristique prĂ©sente un intĂ©rĂȘt certain et permet d'envisager le dĂ©veloppement de nouveaux modĂšles neurobiologiques expĂ©rimentaux ouvrant la voie Ă des traitements innovants pour de nombreux troubles cĂ©rĂ©braux. Durant cette thĂšse, les microfaisceaux ont Ă©tĂ© utilisĂ©s sur la structure corticale et l'hippocampe de rats. Concernant le cortex, les MBs ont Ă©tĂ© appliquĂ©s au niveau du cortex sensori-moteur (taille 100 ”m/600 ”m, of 400 ”m/1200 ”m crĂȘte Ă crĂȘte, dose pics - vallĂše de 360-240 Gy/150-100 Gy) chez des rats males Wistar sains ainsi que chez des rats dĂ©veloppant des attaques cĂ©rĂ©brales consĂ©cutivement Ă l'injection corticale d'Acide KaĂŻnique (KA). Suite aux traitements par MBs, les performances motrices Ă©taient Ă©valuĂ©es par le test du Rotarod et les structures corticales Ă©tudiĂ©es par immunohistochimie grĂące au marquage par NeuN et GFAP des neurones et astrocytes matures. Aucun dĂ©ficit neurologique n'a Ă©tĂ© observĂ© chez les rats sains soumis au protocole de traitement par MBs et une diminution significative (normalement lĂ il faut mettre des statistiques ou au moins les avoir sinon tu peux dire diminution importante) de la durĂ©e des crises de convulsions a pu ĂȘtre observĂ©e chez les rats KA. L'incidence des MBs (9 microfaisceaux de 75 ÎŒm de largeur sĂ©parĂ©s de 400 ÎŒm crĂȘte Ă crĂȘte, dose d'entrĂ©e: 1000 Gy) dĂ©livrĂ©s au niveau de l'hippocampe de rats Wistar sains a Ă©tĂ© comparĂ©e avec un traitement par rayons X de 10 Gy dĂ©livrĂ© uniformĂ©ment. Le but de cette expĂ©rience Ă©tait d'Ă©valuer l'impact d'un traitement par microfaisceaux par rapport aux techniques d'irradiation conventionnelles. Pour cela, une Ă©valuation quantitative (i) comparative a Ă©tĂ© faite sur la neurogĂ©nĂšse grĂące Ă l'utilisation de marqueurs cellulaires (BrdU et Ki-67). Une Ă©tude (ii) a aussi Ă©tĂ© menĂ©e sur le long terme (1 an) pour mettre en Ă©vidence la corrĂ©lation entre la neurogĂ©nĂšse, les troubles de l'apprentissage et de la mĂ©moire. Une prĂ©servation des cellules prolifĂ©ratives a Ă©tĂ© observĂ©e au sein du groupe traitĂ© par MBs. Les transsections de l'hippocampe de rats par MBs n'induisent pas de troubles significatifs (lĂ aussi, il faut avoir des stat ou alors utiliser troubles marquants) du comportement de plus, l'observation histologique et immunohistochimique des tissus a permis de mettre en Ă©vidence la conservation de sa structure.Le travail effectuĂ© au cours de cette thĂšse confirme que le traitement spĂ©cifique de zones radiosensibles du cerveau par les microfaisceaux est sĂ»r et permet d'amĂ©liorer le pronostique des animaux traitĂ©s par rapport aux techniques conventionnelles. Ainsi, le dĂ©veloppement d'appareils permettant de dĂ©livrer des faisceaux de rayons submillimĂ©triques capables de gĂ©nĂ©rer une destruction prĂ©cise et limitĂ©e au niveau du cortex ou de l'hippocampe pourra permettre une prise en charge innovante plus sĂ»re de nombreuses pathologies fonctionnelles cĂ©rĂ©brales comme l'Ă©pilepsie ou certaines douleurs.Synchrotron-generated X-ray microplanar beams (microbeams, MBs) are characterized by the ability to avoid widespread tissue damage following delivery of doses ranging from hundreds to over a thousand of Grays. The resistance of normal tissues to high doses of MBs is likely related to the fast repair of the microvessels and to the wide interface between normal and irradiated tissue, allowing fast recolonization of the microbeam ablated columns of tissue. The preservation of the cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. In this Thesis microbeams transections were delivered to the rat cortex and hippocampus. MBs cortical transections were delivered to the sensory motor cortex (size 100 ”m/600 ”m, center-to-center distance of 400 ”m/1200 ”m, peak-valley doses of 360-240 Gy/150-100 Gy) of Wistar male healthy rats and rats developing seizures following cortical injections of Kainic Acid (KA)-. The motor performances following sensorimotor cortex transections was assessed by rotarod test. The effect of microbeam transections on cortical architecture was assessed by immunohistology with NeuN and GFAP, markers of mature neurons and astrocytes. No neurological deficit was observed in healthy animals undergoing sensorimotor cortex microbeam transections. Convulsive seizure duration was markedly reduced following transections in KA rats. MBs hippocampal transections (75 ”m thickness, 400 c-t-c distance and 600 Gy as peak entrance dose) were performed in adult healthy Wistar rats. MBs transections were compared with an uniformly delivered X-ray dose (broad beam, BB) at 10 Gy. Our aims were to quantify (i) the impact of microbeams versus conventional irradiation on neurogenesis (using proliferative cells markers such as BrdU and Ki-67), and (ii) to investigate on a long term (1 year) the correlation between neurogenesis and impairments in learning and memory. Preservation of proliferative cells in the microbeam treated group were observed. Microbeam transections delivered to the hippocampus did not induce significant behavioral impairment histological and immunohistochemical findings showed a preserved hippocampal structure with evidence of higly precise transections diving the hippocampus in columns. This work confirms the safe delivery of high doses of radiation to specific and radiosensitive parts of the brain, if performed using microbeams Additionally, the development of clinical devices delivering submillimetric beams able to generate cortical or hippocampal transections might become a new powerful new tool for the clinical treatment of epilepsy, pain and other functional brain disorders
Nouvelle application de la radiothérapie par microfaisceaux (MRT) pour le traitement de l'épilepsie et des troubles cérébraux
Synchrotron-generated X-ray microplanar beams (microbeams, MBs) are characterized by the ability to avoid widespread tissue damage following delivery of doses ranging from hundreds to over a thousand of Grays. The resistance of normal tissues to high doses of MBs is likely related to the fast repair of the microvessels and to the wide interface between normal and irradiated tissue, allowing fast recolonization of the microbeam ablated columns of tissue. The preservation of the cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. In this Thesis microbeams transections were delivered to the rat cortex and hippocampus. MBs cortical transections were delivered to the sensory motor cortex (size 100 ”m/600 ”m, center-to-center distance of 400 ”m/1200 ”m, peak-valley doses of 360-240 Gy/150-100 Gy) of Wistar male healthy rats and rats developing seizures following cortical injections of Kainic Acid (KA)-. The motor performances following sensorimotor cortex transections was assessed by rotarod test. The effect of microbeam transections on cortical architecture was assessed by immunohistology with NeuN and GFAP, markers of mature neurons and astrocytes. No neurological deficit was observed in healthy animals undergoing sensorimotor cortex microbeam transections. Convulsive seizure duration was markedly reduced following transections in KA rats. MBs hippocampal transections (75 ”m thickness, 400 c-t-c distance and 600 Gy as peak entrance dose) were performed in adult healthy Wistar rats. MBs transections were compared with an uniformly delivered X-ray dose (broad beam, BB) at 10 Gy. Our aims were to quantify (i) the impact of microbeams versus conventional irradiation on neurogenesis (using proliferative cells markers such as BrdU and Ki-67), and (ii) to investigate on a long term (1 year) the correlation between neurogenesis and impairments in learning and memory. Preservation of proliferative cells in the microbeam treated group were observed. Microbeam transections delivered to the hippocampus did not induce significant behavioral impairment histological and immunohistochemical findings showed a preserved hippocampal structure with evidence of higly precise transections diving the hippocampus in columns. This work confirms the safe delivery of high doses of radiation to specific and radiosensitive parts of the brain, if performed using microbeams Additionally, the development of clinical devices delivering submillimetric beams able to generate cortical or hippocampal transections might become a new powerful new tool for the clinical treatment of epilepsy, pain and other functional brain disorders.Les microfaisceaux (MBs) de rayons X gĂ©nĂ©rĂ©s par un synchrotron permettent de dĂ©livrer des doses de radiation trĂšs Ă©levĂ©es, jusqu'Ă plusieurs centaines de gray (Gy), sans pour autant induire de dommages tissulaires irrĂ©versibles dans les zones avoisinant la lĂ©sion. La rĂ©activitĂ© du rĂ©seau vasculaire Ă se rĂ©gĂ©nĂ©rer grĂące aux cellules endothĂ©liales, est probablement un mĂ©canisme clef dans la radio-tolĂ©rance des tissus sains, puisqu'il permet une recolonisation rapide des zones tissulaires lĂ©sĂ©es. Cette mĂ©thode permet ainsi de reproduire de façon non invasive une incision chirurgicale prĂ©cise du cortex tout en prĂ©servant son architecture. Cette caractĂ©ristique prĂ©sente un intĂ©rĂȘt certain et permet d'envisager le dĂ©veloppement de nouveaux modĂšles neurobiologiques expĂ©rimentaux ouvrant la voie Ă des traitements innovants pour de nombreux troubles cĂ©rĂ©braux. Durant cette thĂšse, les microfaisceaux ont Ă©tĂ© utilisĂ©s sur la structure corticale et l'hippocampe de rats. Concernant le cortex, les MBs ont Ă©tĂ© appliquĂ©s au niveau du cortex sensori-moteur (taille 100 ”m/600 ”m, of 400 ”m/1200 ”m crĂȘte Ă crĂȘte, dose pics - vallĂše de 360-240 Gy/150-100 Gy) chez des rats males Wistar sains ainsi que chez des rats dĂ©veloppant des attaques cĂ©rĂ©brales consĂ©cutivement Ă l'injection corticale d'Acide KaĂŻnique (KA). Suite aux traitements par MBs, les performances motrices Ă©taient Ă©valuĂ©es par le test du Rotarod et les structures corticales Ă©tudiĂ©es par immunohistochimie grĂące au marquage par NeuN et GFAP des neurones et astrocytes matures. Aucun dĂ©ficit neurologique n'a Ă©tĂ© observĂ© chez les rats sains soumis au protocole de traitement par MBs et une diminution significative (normalement lĂ il faut mettre des statistiques ou au moins les avoir sinon tu peux dire diminution importante) de la durĂ©e des crises de convulsions a pu ĂȘtre observĂ©e chez les rats KA. L'incidence des MBs (9 microfaisceaux de 75 ÎŒm de largeur sĂ©parĂ©s de 400 ÎŒm crĂȘte Ă crĂȘte, dose d'entrĂ©e: 1000 Gy) dĂ©livrĂ©s au niveau de l'hippocampe de rats Wistar sains a Ă©tĂ© comparĂ©e avec un traitement par rayons X de 10 Gy dĂ©livrĂ© uniformĂ©ment. Le but de cette expĂ©rience Ă©tait d'Ă©valuer l'impact d'un traitement par microfaisceaux par rapport aux techniques d'irradiation conventionnelles. Pour cela, une Ă©valuation quantitative (i) comparative a Ă©tĂ© faite sur la neurogĂ©nĂšse grĂące Ă l'utilisation de marqueurs cellulaires (BrdU et Ki-67). Une Ă©tude (ii) a aussi Ă©tĂ© menĂ©e sur le long terme (1 an) pour mettre en Ă©vidence la corrĂ©lation entre la neurogĂ©nĂšse, les troubles de l'apprentissage et de la mĂ©moire. Une prĂ©servation des cellules prolifĂ©ratives a Ă©tĂ© observĂ©e au sein du groupe traitĂ© par MBs. Les transsections de l'hippocampe de rats par MBs n'induisent pas de troubles significatifs (lĂ aussi, il faut avoir des stat ou alors utiliser troubles marquants) du comportement de plus, l'observation histologique et immunohistochimique des tissus a permis de mettre en Ă©vidence la conservation de sa structure.Le travail effectuĂ© au cours de cette thĂšse confirme que le traitement spĂ©cifique de zones radiosensibles du cerveau par les microfaisceaux est sĂ»r et permet d'amĂ©liorer le pronostique des animaux traitĂ©s par rapport aux techniques conventionnelles. Ainsi, le dĂ©veloppement d'appareils permettant de dĂ©livrer des faisceaux de rayons submillimĂ©triques capables de gĂ©nĂ©rer une destruction prĂ©cise et limitĂ©e au niveau du cortex ou de l'hippocampe pourra permettre une prise en charge innovante plus sĂ»re de nombreuses pathologies fonctionnelles cĂ©rĂ©brales comme l'Ă©pilepsie ou certaines douleurs
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Economic benefits of substance use disorder treatment: A systematic literature review of economic evaluation studies from 2003 to 2021
The economic burden of substance use disorder (SUD) is significant, comprising costs of health care and social services, criminal justice resources, loss of productivity, and premature mortality. This study assembles and synthesizes two decades of evidence describing the benefits of SUD treatment across five main outcome domains; 1) health care utilization; 2) self-reported criminal activity by offense type; 3) criminal justice involvement collected from administrative records or self-reported; 4) productivity assessed through working hours or wages earned; and 5) social services (e.g., a day spent in transitional housing).
This review included studies if they reported the monetary value of the intervention outcomes, most commonly through a cost-benefit or cost-effectiveness framework. The search included studies from 2003 to the present day as of this writing (up to October 15, 2021). Summary cost estimates were adjusted using the US Consumer Price Index (CPI) to reflect the 12-month benefits per client in USD 2021. We followed the PRISMA methodology for study selection and assessed quality using the Checklist for Health Economic Evaluation Reporting Standards (CHEERS).
The databases yielded 729 studies after removing duplicates, and we ultimately selected 12 for review. Studies varied widely regarding analytical approaches, time horizons, outcome domains, and other methodological factors. Among the ten studies that found positive economic benefits, reductions in criminal activity or criminal justice costs represented the largest or second largest component of these benefits (range 193,440 per client).
Consistent with previous findings, a reduction in criminal activity costs is driven by the relatively high societal cost per criminal offense, notably for violent crimes, such as aggravated assault and rape/sexual assault. Accepting the economic rationale for increased investment in SUD interventions will require recognizing that more benefits accrue to individuals by avoiding being victims of a crime than to governments through budget offsets resulting from savings in non-SUD program expenses. Future studies should explore individually tailored interventions to optimize care management, which may yield unexpected economic benefits to services utilization, and criminal activity data to estimate economic benefits across a broad range of interventions.
âąThe greatest economic benefits over one year resulted from a reduction in criminal activity.âąAlcohol use disorder interventions were associated with a decrease in healthcare utilization costs.âąReduced productivity following intervention was generally due to reduced labor force participation and lost earnings
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Start-Up and Implementation Costs for the Trust Based Relational Intervention
Capturing costs associated with prevention activities related to substance use disorders (SUD) and mental health (MH) is critical. In this study, Trust Based Relational Intervention (TBRIÂź), an attachment-based, trauma-informed intervention, is conceptualized as a preventive intervention to reduce substance and opioid use among youth involved with the legal system. When implemented alongside community reentry, TBRI leverages family systems as youth transition from secure residential care into communities through emotional guidance and role modeling. Activity-based cost (ABC) analysis was used to guide cost data collection and analysis for both start-up and implementation of the TBRI intervention. Start-up costs were estimated using data across eight sites during their start-up phase. All components, activities, personnel involved, and time associated with implementation of TBRI sessions according to protocol were defined. National wages were extracted from O*NET and utilized to calculate total costs for each TBRI component. Total and average TBRI intervention costs were calculated with a breakdown by TBRI sessions and number of staff and participants. A sensitivity analysis was conducted to estimate TBRI implementation costs with travel. The total cost for the TBRI intervention, representing 42 sessions, ranges from 12,298, with travel expenses. The average per family cost ranges from 2,460 (with travel). Costs are primarily generated by time investments from primary interventionists. The sensitivity analysis shows costs for responsive coaching would double with travel costs included. Results aim to show that using ABC for prevention activities, like TBRI, to understand cost drivers can facilitate future intervention sustainability.Clinical Trail.gov ID: NCT04678960.Capturing costs associated with prevention activities related to substance use disorders (SUD) and mental health (MH) is critical. In this study, Trust Based Relational Intervention (TBRIÂź), an attachment-based, trauma-informed intervention, is conceptualized as a preventive intervention to reduce substance and opioid use among youth involved with the legal system. When implemented alongside community reentry, TBRI leverages family systems as youth transition from secure residential care into communities through emotional guidance and role modeling. Activity-based cost (ABC) analysis was used to guide cost data collection and analysis for both start-up and implementation of the TBRI intervention. Start-up costs were estimated using data across eight sites during their start-up phase. All components, activities, personnel involved, and time associated with implementation of TBRI sessions according to protocol were defined. National wages were extracted from O*NET and utilized to calculate total costs for each TBRI component. Total and average TBRI intervention costs were calculated with a breakdown by TBRI sessions and number of staff and participants. A sensitivity analysis was conducted to estimate TBRI implementation costs with travel. The total cost for the TBRI intervention, representing 42 sessions, ranges from 12,298, with travel expenses. The average per family cost ranges from 2,460 (with travel). Costs are primarily generated by time investments from primary interventionists. The sensitivity analysis shows costs for responsive coaching would double with travel costs included. Results aim to show that using ABC for prevention activities, like TBRI, to understand cost drivers can facilitate future intervention sustainability.Clinical Trail.gov ID: NCT04678960
Microradiosurgical cortical transections generated by synchrotron radiation
Purpose: Microplanar X-ray beams (microbeams) originated by synchrotron sources have been delivered to the visual brain cortex regions in rodents to create microscopically narrow lesions. The effects of microbeams mimic those generated by microsurgical subpial transections (also known as multiple subpial transections) but are obtained in a low-invasive way.Methods: Image-guided atlas-based microbeam cortical transections have been generated on seven 1 month-old Wistar rats. An array of 10 parallel beams of 25 microns in thickness and spaced of 200 micron center-to-center was centered on the visual cortex and deposited an incident dose of 600 Gy.Results: The procedure was well tolerated by rats. After recovery, rats showed regular behavior, no sign of gross visual impairment and regular weight gain. After 3 months, rats were sacrificed and brains histologically examined. Cortical transections resembling those obtained through a surgical incision were found over the irradiated region. Remarkable sparing of the cortical columns adjacent to the transections was observed. No sign of radionecrosis was evident at least at this time point.Conclusions: The visual brain cortex transected by synchrotron-generated microbeams showed an incision-like path of neuronal loss while adjacent non irradiated columns remained intact. These preliminary findings, to be further investigated also using other techniques, suggest that microbeam radiosurgery can affect the cortex at a cellular level providing a potential novel and attractive tool to study cortical function. (C) 2015 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica. This is an open access article under the CC BY-NC-ND license
Rat sensorimotor cortex tolerance to parallel transections induced by synchrotron-generated X-ray microbeams
Microbeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats underwent irradiation with arrays of parallel microbeams. Beam thickness, spacing and incident dose were 100 or 600â”m, 400 or 1200â”m and 360 or 150âGy, respectively. Motor performance was carried over a 3-month period. Three months after irradiation rats were sacrificed to evaluate the effects of irradiation on brain tissues by histology and immunohistochemistry. Microbeam irradiation of sensorimotor cortex did not affect weight gain and motor performance. No gross signs of paralysis or paresis were also observed. The cortical architecture was not altered, despite the presence of cell death along the irradiation path. Reactive gliosis was evident in the microbeam path of rats irradiated with 150âGy, whereas no increase was observed in rats irradiated with 360âGy