Social Decision-Making Analysis: A General Approach to Inform Decisions on Resources in the Public Sector.

OBJECTIVES: Public expenditure aims to achieve social objectives by improving a range of socially valuable attributes of benefit (arguments in a social welfare function). Public expenditure is typically allocated to public sector budgets, where budget holders are tasked with meeting a subset of social objectives. METHODS: Decision makers require an evidence-based assessment of whether a proposed investment is likely to be worthwhile given existing levels of public expenditure. However, others also require some assessment of whether the overall level and allocation of public expenditure are appropriate. This article proposes a more general theoretical framework for economic evaluation that addresses both these questions. RESULTS: Using a stylized example of the economic evaluation of a new intervention in a simplified UK context, we show that this more general framework can support decisions beyond the approval or rejection of single projects. It shows that broader considerations about the level and allocation of public expenditure are possible and necessary when evaluating specific investments, which requires evidence of the range of benefits offered by marginal changes in different types of public expenditure and normative choices of how the attributes of benefit gained and forgone are valued. CONCLUSIONS: The proposed framework shows how to assess the value of a proposed investment and whether and how the overall level of public expenditure and its allocation across public sector budgets might be changed. It highlights that cost-benefit analysis and cost-effectiveness analysis can be viewed as special cases of this framework, identifying the weakness with each.

Unpacking the care-related quality of life effect of England's publicly funded adult social care. A panel data analysis.

Adult Social Care (ASC) is the publicly-funded long-term care program in England that provides support with activities of daily living to people experiencing mental and/or physical challenges. Existing evidence suggests that ASC expenditure improves service users' care-related quality of life (CRQoL). However, less is known about the channels through which this effect exists and the effect on outcomes other than CRQoL. We fill this gap by analyzing survey data on ASC service users who received long-term support from 2014/15 to 2019/20 using panel data instrumental variable methods. We find that the beneficial impact of ASC expenditure on the CRQoL of both new and existing users is mostly driven by users aged 18-64 without any learning disability and users with no learning disability aged 65 or older receiving community-based ASC. Moreover, control over daily life, occupation, and social participation are the CRQoL domains that are improved the most. We also find that ASC expenditure has a beneficial effect on several other outcomes beyond CRQoL for both new and existing users including user satisfaction and experience, the ability to carry out activities of daily living independently, whether their home is designed around needs, accessibility to local places, general health, and mental health through reduced anxiety and depression. Greater ASC expenditure, however, does not address the need for other forms of support such as unpaid informal and privately-funded care.

Genetic removal of p70 S6K1 corrects coding sequence length-dependent alterations in mRNA translation in fragile X syndrome mice.

Loss of the fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS). FMRP is widely thought to repress protein synthesis, but its translational targets and modes of control remain in dispute. We previously showed that genetic removal of p70 S6 kinase 1 (S6K1) corrects altered protein synthesis as well as synaptic and behavioral phenotypes in FXS mice. In this study, we examined the gene specificity of altered messenger RNA (mRNA) translation in FXS and the mechanism of rescue with genetic reduction of S6K1 by carrying out ribosome profiling and RNA sequencing on cortical lysates from wild-type, FXS, S6K1 knockout, and double knockout mice. We observed reduced ribosome footprint (RF) abundance in the majority of differentially translated genes in the cortices of FXS mice. We used molecular assays to discover evidence that the reduction in RF abundance reflects an increased rate of ribosome translocation, which is captured as a decrease in the number of translating ribosomes at steady state and is normalized by inhibition of S6K1. We also found that genetic removal of S6K1 prevented a positive-to-negative gradation of alterations in translation efficiencies (RF/mRNA) with coding sequence length across mRNAs in FXS mouse cortices. Our findings reveal the identities of dysregulated mRNAs and a molecular mechanism by which reduction of S6K1 prevents altered translation in FXS.

MocapMe: DeepLabCut-Enhanced Neural Network for Enhanced Markerless Stability in Sit-to-Stand Motion Capture.

This study examined the efficacy of an optimized DeepLabCut (DLC) model in motion capture, with a particular focus on the sit-to-stand (STS) movement, which is crucial for assessing the functional capacity in elderly and postoperative patients. This research uniquely compared the performance of this optimized DLC model, which was trained using 'filtered' estimates from the widely used OpenPose (OP) model, thereby emphasizing computational effectiveness, motion-tracking precision, and enhanced stability in data capture. Utilizing a combination of smartphone-captured videos and specifically curated datasets, our methodological approach included data preparation, keypoint annotation, and extensive model training, with an emphasis on the flow of the optimized model. The findings demonstrate the superiority of the optimized DLC model in various aspects. It exhibited not only higher computational efficiency, with reduced processing times, but also greater precision and consistency in motion tracking thanks to the stability brought about by the meticulous selection of the OP data. This precision is vital for developing accurate biomechanical models for clinical interventions. Moreover, this study revealed that the optimized DLC maintained higher average confidence levels across datasets, indicating more reliable and accurate detection capabilities compared with standalone OP. The clinical relevance of these findings is profound. The optimized DLC model's efficiency and enhanced point estimation stability make it an invaluable tool in rehabilitation monitoring and patient assessments, potentially streamlining clinical workflows. This study suggests future research directions, including integrating the optimized DLC model with virtual reality environments for enhanced patient engagement and leveraging its improved data quality for predictive analytics in healthcare. Overall, the optimized DLC model emerged as a transformative tool for biomechanical analysis and physical rehabilitation, promising to enhance the quality of patient care and healthcare delivery efficiency.

Cost-effectiveness of 5 fraction and partial breast radiotherapy for early breast cancer in the UK: model-based multi-trial analysis.

PURPOSE: We estimated the cost-effectiveness of 4 radiotherapy modalities to treat early breast cancer in the UK. In a subgroup of patients eligible for all modalities, we compared whole-breast (WB) and partial breast (PB) radiotherapy delivered in either 15 (WB15F, PB15F) or 5 fractions (WB5F, PB5F). In a subgroup ineligible for PB radiotherapy, we compared WB15F to WB5F. METHODS: We developed a Markov cohort model to simulate lifetime healthcare costs and quality-adjusted life years (QALYs) for each modality. This was informed by the clinical analysis of two non-inferiority trials (FAST Forward and IMPORT LOW) and supplemented with external literature. The primary analysis assumed that radiotherapy modality influences health only through its impact on locoregional recurrence and radiotherapy-related adverse events. RESULTS: In the primary analysis, PB5F had the least cost and greatest expected QALYs. WB5F had the least cost and the greatest expected QALYs in those only eligible for WB radiotherapy. Applying a cost-effectiveness threshold of £15,000/QALY, there was a 62% chance that PB5F was the cost-effective alternative in the PB eligible group, and there was a 100% chance that WB5F was cost-effective in the subgroup ineligible for PB radiotherapy. CONCLUSIONS: Hypofractionation to 5 fractions and partial breast radiotherapy modalities offer potentially important benefits to the UK health system.

Astrocytes derived from ASD individuals alter behavior and destabilize neuronal activity through aberrant Ca2+ signaling.

The cellular mechanisms of autism spectrum disorder (ASD) are poorly understood. Cumulative evidence suggests that abnormal synapse function underlies many features of this disease. Astrocytes regulate several key neuronal processes, including the formation of synapses and the modulation of synaptic plasticity. Astrocyte abnormalities have also been identified in the postmortem brain tissue of ASD individuals. However, it remains unclear whether astrocyte pathology plays a mechanistic role in ASD, as opposed to a compensatory response. To address this, we combined stem cell culturing with transplantation techniques to determine disease-specific properties inherent to ASD astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. These in vivo phenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neurons in vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+ fluctuations in chimeric brains. Genetic modulation of evoked Ca2+ responses in ASD astrocytes modulates behavior and neuronal activity deficits. Thus, this study determines that astrocytes derived from ASD iPSCs are sufficient to induce repetitive behavior as well as cognitive deficit, suggesting a previously unrecognized primary role for astrocytes in ASD.

Reciprocal control of translation and transcription in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted patterns of interest and repetitive behaviors. ASD is genetically heterogeneous and is believed to be caused by both inheritable and de novo gene variations. Studies have revealed an extremely complex genetic landscape of ASD, favoring the idea that mutations in different clusters of genes interfere with interconnected downstream signaling pathways and circuitry, resulting in aberrant behavior. In this review, we describe a select group of candidate genes that represent both syndromic and non-syndromic forms of ASD and encode proteins that are important in transcriptional and translational regulation. We focus on the interplay between dysregulated translation and transcription in ASD with the hypothesis that dysregulation of each synthetic process triggers a feedback loop to act on the other, which ultimately exacerbates ASD pathophysiology. Finally, we summarize findings from interdisciplinary studies that pave the way for the investigation of the cooperative impact of different genes and pathways underlying the development of ASD.

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects.

OBJECTIVES: Oxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure. METHODS AND RESULTS: We first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IP-injected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B12 (fCy5-OT-B12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBB-impermeable OT (OT-B12 ), with equipotent binding at OT-R in vitro. In vivo, IP-injected OT and OT-B12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression. CONCLUSIONS: Together our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT-R may be a viable strategy to achieve appetite suppression with better patient outcomes.

Submandibular gland involvement in oral cavity squamous cell carcinoma: a retrospective multicenter study.

BACKGROUND: The submandibular gland (SMG) is routinely excised during neck dissection. Given the importance of the SMG in saliva production, it is important to understand its involvement rate by cancer tissue and the feasibility of its preservation. METHODS: Retrospective data were collected from five academic centers in Europe. The study involved adult patients affected by primary oral cavity carcinoma (OCC) undergoing tumor excision and neck dissection. The main outcome analyzed was the SMG involvement rate. A systematic review and a meta-analysis were also conducted to provide an updated synthesis of the topic. RESULTS: A total of 642 patients were enrolled. The SMG involvement rate was 12/642 (1.9%; 95% CI 1.0-3.2) when considered per patient, and 12/852 (1.4%; 95% CI 0.6-2.1) when considered per gland. All the glands involved were ipsilateral to the tumor. Statistical analysis showed that predictive factors for gland invasion were: advanced pT status, advanced nodal involvement, presence of extracapsular spread and perivascular invasion. The involvement of level I lymph nodes was associated with gland invasion in 9 out of 12 cases. pN0 cases were correlated with a reduced risk of SMG involvement. The review of the literature and the meta-analysis confirmed the rare involvement of the SMG: on the 4458 patients and 5037 glands analyzed, the involvement rate was 1.8% (99% CI 1.1-2.7) and 1.6% (99% CI 1.0-2.4), respectively. CONCLUSIONS: The incidence of SMG involvement in primary OCC is rare. Therefore, exploring gland preservation as an option in selected cases would be reasonable. Future prospective studies are needed to investigate the oncological safety and the real impact on quality of life of SMG preservation.

A Deep Learning-Driven Self-Conscious Distributed Cyber-Physical System for Renewable Energy Communities.

The Internet of Things (IoT) is transforming various domains, including smart energy management, by enabling the integration of complex digital and physical components in distributed cyber-physical systems (DCPSs). The design of DCPSs has so far been focused on performance-related, non-functional requirements. However, with the growing power consumption and computation expenses, sustainability is becoming an important aspect to consider. This has led to the concept of energy-aware DCPSs, which integrate conventional non-functional requirements with additional attributes for sustainability, such as energy consumption. This research activity aimed to investigate and develop energy-aware architectural models and edge/cloud computing technologies to design next-generation, AI-enabled (and, specifically, deep-learning-enhanced), self-conscious IoT-extended DCPSs. Our key contributions include energy-aware edge-to-cloud architectural models and technologies, the orchestration of a (possibly federated) edge-to-cloud infrastructure, abstractions and unified models for distributed heterogeneous virtualized resources, innovative machine learning algorithms for the dynamic reallocation and reconfiguration of energy resources, and the management of energy communities. The proposed solution was validated through case studies on optimizing renewable energy communities (RECs), or energy-aware DCPSs, which are particularly challenging due to their unique requirements and constraints; in more detail, in this work, we aim to define the optimal implementation of an energy-aware DCPS. Moreover, smart grids play a crucial role in developing energy-aware DCPSs, providing a flexible and efficient power system integrating renewable energy sources, microgrids, and other distributed energy resources. The proposed energy-aware DCPSs contribute to the development of smart grids by providing a sustainable, self-consistent, and efficient way to manage energy distribution and consumption. The performance demonstrates our approach's effectiveness for consumption and production (based on RMSE and MAE metrics). Our research supports the transition towards a more sustainable future, where communities adopting REC principles become key players in the energy landscape.

Managing community engagement initiatives in health and social care: lessons learned from Italy and the United Kingdom.

BACKGROUND: Determining the different features and potential impacts of community initiatives aimed at health-related outcomes poses challenges for both researchers and policy makers. PURPOSE: This article explores the nature of heterogeneous "community engagement initiatives" (CEIs) considering both their social and organizational features in order to understand the managerial and policy implications to maximize their potential local health and social care-related impacts. METHODOLOGY: A threefold qualitative analysis was conducted: (a) Three frameworks were developed to classify and analyze different CEIs features, building upon the current literature debate; (b) primary data were collected from Italian CEIs; and (c) a comparative cross-case analysis of a total of 79 CEIs in Italy and the United Kingdom was implemented. FINDINGS: The results show two types of strategic policy and management implications: (a) CEI portfolios are very broad and differentiated; (b) different social networks have diversified social constructs, internal cultures, and organizational features; and (c) there is a consequent need to contextualize relational and steering approaches in order to maximize their potential community added value. CONCLUSION: CEIs are fundamental pillars of contemporary welfare systems because of both the changing demography and epidemiology and the disruptive impact of platform economy models. This challenging scenario and the related CEIs involve a complex social mechanism, which requires a new awareness and strengthened competences for public administrations' steering. PRACTICE IMPLICATIONS: It is crucial for policy makers and managers to become familiar with all the different CEIs available in order to choose which solution to implement, depending on their potential impacts related to local public health and social care priorities. They also need to select the related effective steering logic.

Cell-type-specific disruption of PERK-eIF2α signaling in dopaminergic neurons alters motor and cognitive function.

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) has been shown to activate the eIF2α kinase PERK to directly regulate translation initiation. Tight control of PERK-eIF2α signaling has been shown to be necessary for normal long-lasting synaptic plasticity and cognitive function, including memory. In contrast, chronic activation of PERK-eIF2α signaling has been shown to contribute to pathophysiology, including memory impairments, associated with multiple neurological diseases, making this pathway an attractive therapeutic target. Herein, using multiple genetic approaches we show that selective deletion of the PERK in mouse midbrain dopaminergic (DA) neurons results in multiple cognitive and motor phenotypes. Conditional expression of phospho-mutant eIF2α in DA neurons recapitulated the phenotypes caused by deletion of PERK, consistent with a causal role of decreased eIF2α phosphorylation for these phenotypes. In addition, deletion of PERK in DA neurons resulted in altered de novo translation, as well as changes in axonal DA release and uptake in the striatum that mirror the pattern of motor changes observed. Taken together, our findings show that proper regulation of PERK-eIF2α signaling in DA neurons is required for normal cognitive and motor function in a non-pathological state, and also provide new insight concerning the onset of neuropsychiatric disorders that accompany UPR failure.

Inositol polyphosphate multikinase mediates extinction of fear memory.

Inositol polyphosphate multikinase (IPMK), the key enzyme for the biosynthesis of higher inositol polyphosphates and phosphatidylinositol 3,4,5-trisphosphate, also acts as a versatile signaling player in regulating tissue growth and metabolism. To elucidate neurobehavioral functions of IPMK, we generated mice in which IPMK was deleted from the excitatory neurons of the postnatal forebrain. These mice showed no deficits in either novel object recognition or spatial memory. IPMK conditional knockout mice formed cued fear memory normally but displayed enhanced fear extinction. Signaling analyses revealed dysregulated expression of neural genes accompanied by selective activation of the mechanistic target of rapamycin (mTOR) regulatory enzyme p85 S6 kinase 1 (S6K1) in the amygdala following fear extinction. The IPMK mutants also manifested facilitated hippocampal long-term potentiation. These findings establish a signaling action of IPMK that mediates fear extinction.

UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.

Synaptic plasticity requires a tight control of mRNA levels in dendrites. RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. While the local translation of specific mRNAs has been implicated in synaptic plasticity, the tightly controlled mechanisms that regulate local quantity of specific mRNAs remain poorly understood. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the nonsense-mediated mRNA decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. Here, we show that neuron-specific disruption of UPF2, an NMD component, in adulthood attenuates learning, memory, spine density, synaptic plasticity (L-LTP), and potentiates perseverative/repetitive behavior in mice. We report that the NMD pathway operates within dendrites to regulate Glutamate Receptor 1 (GLUR1) surface levels. Specifically, UPF2 modulates the internalization of GLUR1 and promotes its local synthesis in dendrites. We identified neuronal Prkag3 mRNA as a mechanistic substrate for NMD that contributes to the UPF2-mediated regulation of GLUR1 by limiting total GLUR1 levels. These data establish that UPF2 regulates synaptic plasticity, cognition, and local protein synthesis in dendrites, providing fundamental insight into the neuron-specific function of NMD within the brain.

Does public long-term care expenditure improve care-related quality of life of service users in England?

Public long-term care (LTC) systems provide services to support people experiencing difficulties with their activities of daily living. This study investigates the marginal effect of changes in public LTC expenditure on care-related quality of life (CRQoL) of existing service users in England. The public LTC program for people aged 18 or older in England is called Adult Social Care (ASC) and it is provided and managed by local authorities. We collect data on the outcomes and characteristics of public ASC users, on public ASC expenditure, and on the characteristics of local authorities across England in 2017/18. We employ an instrumental variable approach using conditionally exogenous elements of the public funding system to estimate the effect of public ASC expenditure on user CRQoL. Our findings show that by increasing public ASC expenditure by £1000 per user, on average, local authorities increase user CRQoL by 0.0030. These results suggest that public ASC is effective in increasing users' quality of life but only to a relatively small extent. When combined with the other potential effects of LTC expenditure (e.g., on informal carers, mortality), this study can inform policy makers in the United Kingdom and internationally about whether social care provides good value for money.

Adequacy of the Italian National Tariff for Orthognathic Surgery: A Cost Analysis Using the Activity Based Costing (ABC) Method.

ABSTRACT: The reduced economic resources in health care and the consequent spending review have brought great interest in surgical costs. The aim of the study is to determine direct hospital costs for Orthognathic procedures using the Activity based costing method and evaluate the adequacy of the refund provided by the Italian National Health Service. From January 2017 to December 2017 9 consecutive patients underwent the following Orthognathic procedures at IRCCS Casa Sollievo della Sofferenza (San Giovanni Rotondo, Italy): bimaxillary osteotomy (n = 7), Le Fort I osteotomy (n = 1) and Bilateral Sagittal Split Osteotomy (BSSO) (n = 1). Activity based costing was used to obtain costs of each single hospitalization split into surgery, instay, and services. The mean total cost for a bimaxillary osteotomy was 7596.40€. We observed a total cost of 3925.00€ for Le Fort I osteotomy and of 4334.50€ for BSSO. The refund of 4378.00€ provided by the Italian National Health Service system for Orthognathic surgery seems insufficient to cover costs of bimaxillary osteotomy but consistent for single osteotomy (Le Fort I or BSSO).

Factors influencing adherence to adjuvant endocrine therapy in breast cancer-treated women: using real-world data to inform a switch from acute to chronic disease management.

PURPOSE: Adjuvant endocrine therapy (AET) for ≥ 5 years is generally recommended for women with hormone receptor-positive breast cancer to reduce cancer recurrence/mortality; however, adherence can be suboptimal. We tested determinants of AET adherence using patient characteristics, treatment pathways, AET initiation timing, and multiple healthcare facility use. An underlying objective was to explore how oncological pathways mirror chronic disease management to monitor adherence and target improvement interventions using administrative datasets. METHODS: Using patient-linked administrative health data from the Italian Lombardy Region, we identified 33.291 surviving patients starting AET in 2010-2016, with two (22.939 patients) or five years (8400 patients) follow-up, using a ≥ 80% prescription refill approach to measure adherence and logistic regression to test determinants of adherence. RESULTS: AET crude adherence falls significantly during follow-up, from 94% at 1 Year to 58% at 5 Years. At 5 Years, patients who were older (>70), prescribed tamoxifen-only (OR 0.69; 95% CI 0.57-0.83; p = 0.0001) vs. aromatase inhibitors-only or therapy switches, treated for depression (OR 0.68; 95% CI 0.60-0.78; p < 0.0001), with surgery performed in high-volume hospitals (OR 0.85; 95% CI 0.75-0.97; p = 0.0116) showed lower adherence. Loyalty, or continued care in the surgical hospital (OR 1.73; 95% CI 1.51-2.00; p < 0.0001), undergoing chemotherapy before AET (OR 2.65; 95% CI 2.02-3.48; p < 0.0001), and earlier AET initiation, positively influenced adherence. CONCLUSIONS: Chronic disease monitoring using administrative data can help oncologists focus efforts to ensure AET adherence. Results suggest addressing mental health, age, disease severity patient perceptions, timely AET initiation and therapy switches, and encouraging continued follow-up in the same hospital or better care coordination with outside follow-up specialists.

Monte Carlo simulation and analytical calculation methods to investigate the potential of nanoparticles for INTRABEAM® IORT machine.

In the present study, Monte Carlo (MC) simulation and analytical calculation methods were used to investigate the potential of cancer treatment for the combination of IORT with nanoparticles (NPs). The Geant4 MC toolkit was used to simulate ZEISS INTRABEAM® IORT machine and its smallest applicator with 1.5 cm diameter. The dose enhancement effects (DEFs) were obtained for silver (Ag), gold (Au), bismuth (Bi), copper (Cu) and iron (Fe) spherical NPs considering different concentrations. In addition, analytical calculations were performed based on attenuation coefficient formula for sample NPs. Our MC results showed that the use of different NPs led to an increase in DEF up to 40%. Among different NPs, Au had the maximum DEF. In addition, analytical calculations revealed a significant increase, using NPs as well. Our study has suggested that the use of NPs in combination with IORT has the potential to enhance treatment outcomes.

The effect of stereotactic body radiotherapy (SBRT) using flattening filter-free beams on cardiac implantable electronic devices (CIEDs) in clinical situations.

PURPOSE: This study focused on determining risks from stereotactic radiotherapy using flattening filter-free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs. METHODS: A retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6-MV and 10-MV FFF beams. First, a repetition-rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single-fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom. RESULTS: Between 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep-rate tests, inappropriate sensing occurred, starting at a rep-rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT-SBRT with a 10-MV FFF beam were observed. CONCLUSIONS: The study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG-203. Correspondingly, it was found that for FFF beams although there is small risk from dose-rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high-dose rate to CIEDs positioned in close vicinity of the PTV may present issues.

P4UIoT: Pay-Per-Piece Patch Update Delivery for IoT Using Gradual Release.

P 4 UIoT-pay-per-piece patch update delivery for IoT using gradual release-introduces a distributed framework for delivering patch updates to IoT devices. The framework facilitates distribution via peer-to-peer delivery networks and incentivizes the distribution operation. The peer-to-peer delivery network reduces load by delegating the patch distribution to the nodes of the network, thereby protecting against a single point of failure and reducing costs. Distributed file-sharing solutions currently available in the literature are limited to sharing popular files among peers. In contrast, the proposed protocol incentivizes peers to distribute patch updates, which might be relevant only to IoT devices, using a blockchain-based lightning network. A manufacturer/owner named vendor of the IoT device commits a bid on the blockchain, which can be publicly verified by the members of the network. The nodes, called distributors, interested in delivering the patch update, compete among each other to exchange a piece of patch update with cryptocurrency payment. The pay-per-piece payments protocol addresses the problem of misbehavior between IoT devices and distributors as either of them may try to take advantage of the other. The pay-per-piece protocol is a form of a gradual release of a commodity like a patch update, where the commodity can be divided into small pieces and exchanged between the sender and the receiver building trust at each step as the transactions progress into rounds. The permissionless nature of the framework enables the proposal to scale as it incentivizes the participation of individual distributors. Thus, compared to the previous solutions, the proposed framework can scale better without any overhead and with reduced costs. A combination of the Bitcoin lightning network for cryptocurrency incentives with the BitTorrent delivery network is used to present a prototype of the proposed framework. Finally, a financial and scalability evaluation of the proposed framework is presented.