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- Dalmo, Johanna, et al.
(författare)
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Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
- 2017
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase 177Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177Lu-octreotate priming dose followed 24 h later by a second injection of 177Lu-octreotate compared to a single administration of 177Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. RESULTS: Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE, BAX, CDKN1A, and GADD45A. CONCLUSIONS: Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects.
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- Forssell, Henrik, et al.
(författare)
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A proposed model for prediction of survival based on a follow-up study in unresectable pancreatic cancer
- 2013
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 3:12, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To define an easy-to-use model for prediction of survival time in patients with unresectable pancreatic cancer in order to optimise patient' care. DESIGN: An observational retrospective study on patients with unresectable pancreatic cancer. The initial radiographs at presentation of symptoms were reviewed and the maximum diameter of the primary tumour was determined. The occurrence of liver metastases and performance status that determines initiation of chemotherapy was also used in the regression analysis to identify prognostic subgroups. SETTING: County hospital in south-east of Sweden. POPULATION: Consecutive patients with unresectable pancreatic cancer who were diagnosed between January 2003 and May 2010 (n=132). MAIN OUTCOME MEASURES: Statistical analyses were performed using Stata V.13. Survival time was assessed with Kaplan-Meier analysis, log-rank test for equality of survivor functions and Cox regression for calculation of individual hazard based on tumour diameter, presence of liver metastases and initiation of chemotherapy treatment according to patient performance status. RESULTS: The individual hazard was log h=0.357 tumour size+1.181 liver metastases-0.989 performance status/chemotherapy. Three prognostic groups could be defined: a low-risk group with a median survival time of 6.7 (IQR 9.7) months, a medium-risk group with a median survival time of 4.5 (IQR 4.5) months and a high-risk group with a median survival time of 1.2 (IQR 1.7) months. CONCLUSIONS: The maximum diameter of the primary tumour and the presence of liver metastases found at the X-ray examination of patients with pancreatic cancer, in conjunction with whether or not chemotherapy is initiated according to performance status, predict the survival time for patients who do not undergo surgical resection. The findings result in an easy-to-use model for predicting the survival time.
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- Forssell, Henrik, et al.
(författare)
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An update on pathophysiological mechanisms related to idiopathic oro-facial pain conditions with implications for management
- 2015
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Ingår i: Journal of Oral Rehabilitation. - : Wiley. - 0305-182X .- 1365-2842. ; 42:4, s. 300-322
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Forskningsöversikt (refereegranskat)abstract
- Chronic oro-facial pain conditions such as persistent idiopathic facial pain (PIFP), atypical odontalgia (AO) and burning mouth syndrome (BMS), usually grouped together under the concept of idiopathic oro-facial pain, remain a diagnostic and therapeutic challenge. Lack of understanding of the underlying pathophysiological mechanisms of these pain conditions is one of the important reasons behind the problems in diagnostic and management. During the last two decades, neurophysiological, psychophysical, brain imaging and neuropathological methods have been systematically applied to study the trigeminal system in idiopathic oro-facial pain. The findings in these studies have provided evidence for neuropathic involvement in the pathophysiology of PIFP, AO and BMS. The present qualitative review is a joint effort of a group of oro-facial pain specialists and researchers to appraise the literature on idiopathic oro-facial pain with special focus on the currently available studies on their pathophysiological mechanisms. The implications of the findings of these studies for the clinical diagnosis and treatment of idiopathic oro-facial pain conditions are discussed.
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- Forssell, Henrik, et al.
(författare)
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Constructive reflection principles for regular theories
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Classically, any structure for a signature Σ may be completed to a model of a desired regular theory T by means of the chase construction or small object argument. Moreover, this exhibits Mod(T) as weakly reflective in Str(Σ).We investigate this in the constructive setting. The basic construction is unproblematic, however, it is no longer a weak reflection. Indeed, we show that various reflection principles for models of regular theories are equivalent to choice principles in the ambient set theory. However, the embedding of a structure into its chase-completion still satisfies a conservativity property, which suffices for applications such as the completeness of regular logic with respect to Tarski (i.e. set) models.Unlike most constructive developments of predicate logic, we do not assume that equality between symbols in the signature is decidable. While in this setting, we also give a version of one classical lemma which is trivial over discrete signatures but more interesting here: the abstraction of constants in a proof to variables.
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| 7. |
- Forssell, Henrik, et al.
(författare)
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CONSTRUCTIVE REFLECTIVITY PRINCIPLES FOR REGULAR THEORIES
- 2019
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Ingår i: Journal of Symbolic Logic (JSL). - : Cambridge University Press (CUP). - 0022-4812 .- 1943-5886. ; 84:4, s. 1348-1367
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Tidskriftsartikel (refereegranskat)abstract
- Classically, any structure for a signature may be completed to a model of a desired regular theory by means of the chase construction or small object argument. Moreover, this exhibits as weakly reflective in .We investigate this in the constructive setting. The basic construction is unproblematic; however, it is no longer a weak reflection. Indeed, we show that various reflectivity principles for models of regular theories are equivalent to choice principles in the ambient set theory. However, the embedding of a structure into its chase-completion still satisfies a conservativity property, which suffices for applications such as the completeness of regular logic with respect to Tarski (i.e., set) models.Unlike most constructive developments of predicate logic, we do not assume that equality between symbols in the signature is decidable. While in this setting, we also give a version of one classical lemma which is trivial over discrete signatures but more interesting here: the abstraction of constants in a proof to variables.
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| 8. |
- Forssell, Henrik, et al.
(författare)
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Feature-Based Multi-User Authentication for Parallel Uplink Transmissions
- 2016
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Ingår i: 2016 9TH INTERNATIONAL SYMPOSIUM ON TURBO CODES AND ITERATIVE INFORMATION PROCESSING (ISTC). - : IEEE. - 9781509034017 ; , s. 355-359
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Konferensbidrag (refereegranskat)abstract
- We study a multi-user up-link scenario where an attacker tries to impersonate the legitimate transmitters. We present a new framework for deriving a posteriori attack probabilities from the channel observations at the access point, which enables fast intrusion detection and authentication at the physical layer and can be exploited to reduce the security overhead by offtoading higher-layer authentication schemes. This is highly relevant for delay-sensitive applications that are targeted in 5G where the security overhead may limit the real-time performance. We take a factor-graph approach that can easily be extended to take into account other features, channel models, and radio access schemes. While related works only consider single-link scenarios, the multi-user approach in this paper allows us to exploit the cross-channel correlation of the large-scale fading parameters that is due to the propagation environment for improving the detection performance. As numerical results show, especially for slowly changing channels with high correlation our approach provides significant performance gains.
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| 9. |
- Forssell, Henrik, et al.
(författare)
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On the Impact of Feature-Based Physical Layer Authentication on Network Delay Performance
- 2017
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Ingår i: Globecom 2017 - 2017 IEEE Global Communications Conference. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509050192
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Konferensbidrag (refereegranskat)abstract
- Feature-based authentication schemes that verify wireless transmitter identities based on physical-layer features allow for fast and efficient authentication with minimal overhead. Hence, they are interesting to consider for safety-critical applications where low latency and high reliability is required. However, as erroneous authentication decisions will introduce delays, we propose to study the impact of feature-based schemes on the system-level performance. In this paper, we therefore study the queuing performance of a line-of-sight wireless link that employs a feature-based authentication scheme based on the complex channel gain. Using stochastic networks calculus, we provide bounds on the delay performance which are validated by numerical simulations. The results show that the delay and authentication performance is highly dependent on the SNR and Rice factor. However, under good channel conditions, a missed-detection rate of 10(-8) can be achieved without introducing excessive delays in the system.
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| 10. |
- Forssell, Henrik, 1991-
(författare)
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Performance Guarantees for Physical Layer Authentication in Mission-Critical Communications
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As the application areas for wireless communications are expanding, we also see new security vulnerabilities arise due to the open nature of the wire- less medium. One particularly challenging problem is how to guarantee the security of emerging mission-critical communications, e.g., realized by fifth generation (5G) mobile networks, that will enable use-cases like industrial automation, vehicular communications, and smart grids. As the room for security overhead is limited in mission-critical communications, mainly due to the associated strict requirements on latency and reliability, new lightweight security techniques are researched within the area of physical layer security. In particular, feature-based physical layer authentication (PLA), exploiting transmitter-specific features extracted from received signals for device au- thentication, is considered a promising solution for lightweight authentication and intrusion detection in mission-critical communications. In this thesis, we provide mathematical tools for analyzing channel-based PLA schemes, and in particular, for deriving worst-case performance guarantees appropriate for mission-critical contexts. We consider worst-case performance guarantees for feature-based PLA from two perspectives: Firstly, we provide mathematical bounds on the delay-performance im- pacts that arise due to the unlikely but inevitable erroneous authentication decisions (i.e., false alarms and missed detections). We model the PLA scheme using queueing analysis, develop models for active impersonation attacks, and derive bounds on the queueing delay violation probability using tools from stochastic network calculus. We consider the performance for both single- and multiple-antenna receiver architectures, and furthermore, a distributed multiple-antenna system in which we analyze varying degrees of distributed processing. These results establish under which practical deployments and channel conditions feature-based PLA would constitute a viable option for mission-critical applications. For instance, we find that for low-mobility scenarios with line-of-sight conditions, as exemplified by an industrial automation scenario with fixed sensor deployment, PLA can be used for strongly enhanced security while simultaneously maintaining mission-critical latency deadlines with high reliability. Moreover, we discuss extensions that would allow analysis of scenarios without line-of-sight and with higher mobility. From the second perspective, we provide tools for deriving the worst-case detection performance under optimal attackers that are aware of the PLA scheme. First, we consider a distributed PLA setting where authentication is based on the channel-states observed at multiple distributed radio-heads. We derive the optimal single-antenna attack strategy and corresponding missed detection probability, and provide a heuristic method for finding the optimal spatial attack position with respect to a given deployment. We then extend the results by considering a multiple-antenna attacker, the correspond- ing optimal pre-coding strategies, and the detection performance under the worst-case attacker. Furthermore, we analyze the impacts of limited channel state information (CSI) and power budgets at the attacker and provide a counter-strategy that can be used by the PLA receiver. With the single- antenna attacker, our results show significant detection performance benefits from a distributed antenna setting, which argues for practical relevance of PLA within modern 5G technologies like coordinated multi-point (CoMP) and distributed multiple-input multiple-output (MIMO) systems. For the multiple-antenna attacker, we observe significant impacts given perfect CSI knowledge and favorable channel conditions at the attacker. However, under realistic assumptions on power budget, CSI imperfections, and through the proposed counter-strategy, we find that strict detection performance guarantees can be maintained.
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