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Heme oxygenase-1 (HO-1, HMOX1) degrades heme protecting cells from heme-induced oxidative damage. Beyond its well-established cellular functions, heme has emerged as a stabilizer of G-quadruplexes. These secondary DNA structures interfere with DNA replication. We recently revealed that nuclear HO-1 colocalizes with DNA G-quadruplexes and promotes their removal. Here, we investigate whether HO-1 safeguards cells against replication stress.Experiments were conducted in control and HMOX1-deficient HEK293T cell lines. Immunostaining unveiled that DNA G-quadruplexes accumulated in the absence of HO-1, the effect that was further enhanced in response to δ-aminolevulinic acid (ALA), a substrate in heme synthesis. This was associated with replication stress, as evidenced by an elevated proportion of stalled forks analyzed by fiber assay. We observed the same effects in hematopoietic stem cells isolated from Hmox1 knockout mice and in a lymphoblastoid cell line from an HMOX1-deficient patient. Interestingly, in the absence of HO-1, the speed of fork progression was higher, and the response to DNA conformational hindrance less stringent, indicating dysfunction of the PARP1-p53-p21 axis. PARP1 activity was not decreased in the absence of HO-1. Instead, we observed that HO-1 deficiency impairs the nuclear import and accumulation of p53, an effect dependent on the removal of excess heme. We also demonstrated that administering ALA is a more specific method for increasing intracellular free heme compared to treatment with hemin, which in turn induces strong lipid peroxidation.Our results indicate that protection against replication stress is a universal feature of HO-1, presumably contributing to its widely recognized cytoprotective activity.

Purpose: The aim of our study was to compare dosimetric aspects of three radioablation modalities – direct high-dose-rate brachytherapy (HDR-BT) and virtually planned stereotactic body radiation therapy performed on CyberKnife (SBRTck) and Elekta Versa HD LINAC (SBRTe) applied in patients with liver metastases. Material and methods: We selected 30 patients with liver metastases, who received liver interstitial HDR-BT and virtually prepared plans for SBRTck and SBRTe. In all the cases, the prescribed dose was a single fraction of 25 Gy. Treatment delivery time, doses delivered to PTV and organs at risk, as well as conformity indices, were calculated and compared. Results: The longest median treatment delivery time was observed in SBRTck in contrast to HDR-BT and SBRTe which were significantly shorter and comparable. HDR-BT plans achieved better coverage of PTV (except for D98%) in contrast to SBRT modalities. Between both SBRT modalities, SBRTck plans resulted in better dose coverage in Dmean, D50%, and D90% values compared to SBRTe without difference in D98%. The SBRTe was the most advantageous considering the PCI and R100%. SBRTck plans achieved the best HI, while R50% value was comparable between SBRTe and SBRTck. The lowest median doses delivered to uninvolved liver volume (V5Gy, V9.1Gy) were achieved with HDR-BT, while the difference between SBRT modalities was insignificant. SBRT plans were better regarding more favourable dose distribution in the duodenum and right kidney, while HDR-BT achieved lower doses in the stomach, heart, great vessels, ribs, skin and spinal cord. There were no significant differences in bowel and biliary tract dose distribution between all selected modalities. Conclusions: HDR-BT resulted in more favourable dose distribution within PTVs and lower doses in organs at risk, which suggests that this treatment modality could be regarded as an alternative to other local ablative therapies in carefully selected patients’ with liver malignancies. Future studies should further address the issue of comparing treatment modalities in different liver locations and clinical scenarios.

Autism spectrum disorder is a complex neurodevelopmental disorder. The available medical treatment options for autism spectrum disorder are very limited. While the etiology and pathophysiology of autism spectrum disorder are still not fully understood, recent studies have suggested that wide alterations in the GABAergic, glutamatergic, cholinergic, and serotonergic systems play a key role in its development and progression. Histamine neurotransmission is known to have complex interactions with other neurotransmitters that fit perfectly into the complex etiology of this disease. Multitarget-directed compounds with an affinity for the histamine H3 receptor indicate an interesting profile of activity against autism spectrum disorder in animal models. Here, we present the results of our research on the properties of (4-piperazin-1-ylbutyl)guanidine derivatives acting on histamine H3 receptors as potential multitarget ligands. Through the virtual screening approach, we identified promising ligands among 32 non-imidazole histamine H3 receptor antagonists/inverse agonists with potential additional activity against the dopamine D2 receptor and/or cholinesterases. The virtual screening protocol integrated predictions from SwissTargetPrediction, SEA, and PPB2 tools, along with molecular docking simulations conducted using GOLD 5.3 and Glide 7.5 software. Among the selected ligands, compounds 25 and 30 blocked radioligand binding to the D2 receptor at over 50% at a screening concentration of 1 µM. Further experiments allowed us to determine the pKi value at the D2 receptor of 6.22 and 6.12 for compounds 25 and 30, respectively. Our findings suggest that some of the tested compounds could be promising multitarget-directed ligands for the further research and development of more effective treatments for autism spectrum disorder.

Background and purposeThe optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens.Materials and methodsIn 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS).ResultsMedian follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p

Workwear dedicated for motor impaired employees was designed. The woven fabrics used meet the requirements for light to moderate effort according to PN-P-08525:1998, reaching suitable level of water vapor resistance meanwhile. The workwear’s design was carefully chosen to meet the requirements of motor impaired employees during their work activities. The analysis of microclimate was carried out to investigate the garment’s ability to transport water vapor outside from gaps between body part and item of clothing. Two sets of workwear were tested, showing that both garments’ construction and woven fabrics properties influence thereon.

Autism spectrum disorder is a complex neurodevelopmental disorder. The available medical treatment options for autism spectrum disorder are very limited. While the etiology and pathophysiology of autism spectrum disorder are still not fully understood, recent studies have suggested that wide alterations in the GABAergic, glutamatergic, cholinergic, and serotonergic systems play a key role in its development and progression. Histamine neurotransmission is known to have complex interactions with other neurotransmitters that fit perfectly into the complex etiology of this disease. Multitarget-directed compounds with an affinity for the histamine H3 receptor indicate an interesting profile of activity against autism spectrum disorder in animal models. Here, we present the results of our research on the properties of (4-piperazin-1-ylbutyl)guanidine derivatives acting on histamine H3 receptors as potential multitarget ligands. Through the virtual screening approach, we identified promising ligands among 32 non-imidazole histamine H3 receptor antagonists/inverse agonists with potential additional activity against the dopamine D2 receptor and/or cholinesterases. The virtual screening protocol integrated predictions from SwissTargetPrediction, SEA, and PPB2 tools, along with molecular docking simulations conducted using GOLD 5.3 and Glide 7.5 software. Among the selected ligands, compounds 25 and 30 blocked radioligand binding to the D2 receptor at over 50% at a screening concentration of 1 µM. Further experiments allowed us to determine the pKi value at the D2 receptor of 6.22 and 6.12 for compounds 25 and 30, respectively. Our findings suggest that some of the tested compounds could be promising multitarget-directed ligands for the further research and development of more effective treatments for autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Objectives: Celem niniejszego artykułu było przedstawienie przedstawienie przez autora wieloletniej działalności Rosji w aspekcie produkcji zarówno broni biologicznej jak również chemicznej, a także prowadzeniu przez nią badań nad skutkami wynikającymi z potencjalnego jej użycia. W świetle tak określonego celu ustanowiono następujący problem badawczy, który sformułowano w postaci niżej przedstawionego pytania: czy istnieje prawdopodobieństwo wykorzystania przez Rosję broni biologicznej lub chemicznej podczas trwającej obecnie wojny z Ukrainą? Methods: Metody badań zastosowane w procesie badawczym obejmowały przede wszystkim dogłębną analizę materiałów źródłowych – aktów prawnych, pozycji zwartych oraz artykułów naukowych dotyczących funkcjonowania na terenie Rosji zakładów produkujących broń masowego rażenia. Results: Wyniki badań potwierdziły przyjętą hipotezę, że Rosja dysponuje zarówno bronią biologiczną jak i chemiczną, oraz możliwościami do jej wykorzystania. Od dnia napaści zbrojnej na Ukrainę, Rosja dopuszcza się rozmaitych prowokacji, mających na celu usprawiedliwienie ewentualnego użycia tej śmiercionośnej broni. Zweryfikowanie postawionej wcześniej hipotezy wymagało dogłębnej analizy wcześniejszych działań Rosji ukierunkowanych na produkcję oraz badania broni masowego rażenia oraz obserwacji przebiegu toczącej się wojny. Conclusions: Wnioski z przeprowadzonych badań wskazują na prawdopodobieństwo użycia przez Rosję broni biologicznej lub chemicznej w trwającym obecnie konflikcie zbrojnym z Ukrainą, będące skutkiem dynamiki wojny, pogarszającej się sytuacji ekonomicznej Rosji oraz zastosowania względem niej coraz większych sankcji.

The aim of this study was to evaluate the quantitative and qualitative changes in the proteome of the hemolymph of female Steatoda grossa spiders (Theridiidae) that were chronically exposed to cadmium and copper in food and were additionally immunostimulated (phorbol 12–myristate 13–acetate (PMA); bacterial suspensions: Staphylococcus aureus (G+), Pseudomonas fluorescens (G–). It was found that the expression of nearly 90 proteins was altered in cadmium–intoxicated spiders and more than 60 in copper–exposed individuals. Regardless of the type of metal used, these proteins were mainly overexpressed in the hemolymph of the exposed spiders. On the other hand, immunostimulation did not significantly change the number of proteins with altered expression in metal–intoxicated individuals. Hemocyanin (Hc) was found to be the most abundant of the proteins identified with altered expression. In copper–intoxicated spiders, immunostimulation increased the expression of A-, E–, F–, and G–chain–containing proteins, while in the case of cadmium–intoxicates spiders, it decreased the expression of E– and A–chain–containing Hc and increased the expression of G–chain–containing Hc. Regardless of the type of metal and immunostimulant used, there was an increase in the expression of actin. In addition, cadmium increased the expression of cullin, vimentin, and ceruloplasmin. The changes observed in the expression of hemolymph proteins indicate their protective function in S. grossa (Theridiidae) spiders under conditions of metal exposure.

Thymomas are very rare neoplasms in children and they represent less than 1% of mediastinal tumours in the paediatric population. The aim of our study was to assess the long-term treatment results of children with thymic tumours. A total number of eight children (four boys and four girls) with thymic tumours were identified. Median age at diagnosis was 7 years. In seven of them, thymoma was diagnosed; in one, a thymic carcinoma was diagnosed. In five of them, the WHO type was assessed: in two of them, the B1 type was found; in one, B2 was found; in one, AB was found, and in one, C was found. In all but one, surgery was the first-line treatment, but six patients had only partial resection. One patient started treatment with chemotherapy and four others received chemotherapy after the surgery. Radiotherapy was applied in six patients, with a median total dose of 37.5 Gy. Follow-up ranged from 8.5 to 273.5 months, with a median of 6.1 years. During this time, four patients died: one due to progression of the disease, and in the other three, the reason for death was unknown. In all evaluated patients, complete regression was observed (100% local control). Two-, 5- and 10-year OS and PFS were 85% and 72%, 51% and 54%, 51% and 54%, respectively. Combined treatment could provide satisfactory results in thymoma patients. There is a need for further, larger studies, which could help to establish optimal management strategies.

An analysis of patients below 21 years old treated due to craniopharyngioma in the years 1979–2022 was performed with the aim of evaluating the long-term outcome and treatment side-effects. The standard statistical tests were used, and 56 patients with a median age of 11 years were evaluated. Surgery was the primary treatment in 55 patients; however, in only 29 it was the only neurosurgical intervention. Eighteen children were treated with radiotherapy (RTH) in primary treatment. The most common neurosurgical side effects observed were visual and endocrine deficits and obesity, which were diagnosed in 27 (49%), 50 (91%), and 25 (52%) patients, respectively. Complications after RTH were diagnosed in 14 cases (32%). During the median follow-up of 8.4 years (range: 0.4–39.8 years), six patients died and the 5- and 10-year overall survival was 97% and 93%, respectively. Five-year progression-free survival for gross total resection, resection with adjuvant RTH, and non-radical resection alone was 83%, 68%, and 23%, respectively (p = 0.0006). Surgery combined with RTH provides comparable results to gross tumor resection in terms of oncologic outcome in craniopharyngioma patients. Adjuvant irradiation applied in primary or salvage treatment improves disease control. The rate of complications is high irrespective of improved surgical and radiotherapeutic management.

The high electrical stresses in the Electrical Insulation Systems of machines fed by pulse width modulation (PWM) inverters remain a limitation of the lifetime. The stress is caused by repetitive over voltages caused by the short switching times of the PWM inverter power electronic circuit. This paper provides measurements made on an industrial drive connected to the grid with standard cables that include a ground connection wire, following the current standards. The phase-to-phase, phase-to-neutral, and neutral-to-ground voltages are measured focusing on short and repetitive voltage spikes. The causes of these voltage spikes are analyzed using a high frequency equivalent circuit of the whole drive, including the earthing system. The simulations are made with the well-known SPICE circuit simulator. This study focuses on the common-mode currents flowing in the earthing connections and its influence on voltage spikes. A solution that can reduce significantly the phase-to-neutral voltage spikes is proposed.

The article proposes an analysis of the possible architectures of synchronous machines with an ability to operate at high temperatures of over 200°C in their environment. Two machine principles have been considered: the permanent magnet synchronous machine and the synchronous reluctance machine. The numerical analyses are carried out with 3D-coupled electromagnetic-fluid-thermal models; the electromagnetic one provides the local losses that give the input data to the coupled thermal-fluid analysis model for computing the temperatures inside the machines. The simulation results are used for estimating the temperature limit of each machine architecture, considering the characteristics of their critical parts.

Purpose/ObjectivesThe debate on whether radiotherapy (RT) is an essential part of primary treatment in patients with grade II ependymoma (G2E) is still ongoing, and this study aimed to evaluate its role.Materials/MethodsA retrospective analysis of all the consecutive patients treated due to G2E in years 1985–2019 was performed. The group consisted of 116 patients with a small predominance of woman (55% vs. 45%) and the location of the tumor in the brain (58% vs. 42%). All had surgery as the primary treatment with 47% R0 resection. Radical RT was applied in 81 patients. In majority of cases (91%), patients received local irradiation.ResultsMedian follow-up was 65 months, and during that time, 17 patients died. Five- and 10-year overall survival (OS) of the whole group was 87% and 83%. Radical surgery (R0 vs. R1/2) improved OS (p = 0.004), but the difference was observed only in patients with brain lesions (p = 0.01). Five- and 10-year progression-free survival (PFS) was 68% and 51%, respectively. Looking at the treatment of recurrence, those who received RT as a part of the treatment of the recurrent tumor had better OS (p = 0.048)—5- and 10-year OS of 85% and 78% vs. 66% and 57%. In the multivariate analysis, radical surgery (R0 vs. R1/2) and the use of RT in the primary treatment improved PFS (p = 0.006 and 0.007). Based on the location of the tumor, the positive influence of RT on PFS was observed only in the case of patients with brain tumors (p = 0.01). Also, comparing R1/2 surgery with R0 resection—the benefit of RT was only observed in R1/2 group (0.02).ConclusionsRT in the case of patients with G2E is a valuable treatment of the recurrent disease. Patients with brain lesions after nonradical surgery might benefit from the local irradiation in terms of PFS.

Background: A retrospective evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients (pts) with unresectable rectal cancer: radiochemotherapy (CRT) and radiotherapy (RT), including conventional and accelerated hyperfractionation. Material and Method: A total of 145 consecutive pts with unresectable, locally advanced rectal cancer. The schemes used are RT in 73 (50%) or CRT in 72 (50%). In CRT, 54 Gy in 1.8 Gy fractions was given with chemotherapy, In the RT group, conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). HART was introduced at first as an alternative to CFRT, after radiobiological studies suggesting a therapeutic gain of hyperfractionation in other cancers, and second to administer relatively high dose needed in unresectable cancer, which is not feasible in hypofractionation because of critical organs sensitivity to high fraction doses (fd). HART was an alternative option in pts with medical contraindications to chemotherapy and to shorten overall treatment time with greater radiobiological effectiveness than CFRT. Results: Objective response (OR) in the RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status (PS), tumor mobility, and neoadjuvant treatment method were significant for RR.

Frame-based stereotactic radiosurgery (SRS) has an established role in the treatment of tremor in patients with Parkinson’s disease (PD). The low numbers of studies of frameless approaches led to our prospective phase 2 open-label single-arm clinical trial (NCT02406105), which aimed to evaluate the safety and efficacy of CyberKnife frameless SRS. Twenty-three PD patients were irradiated on the area of the thalamic ventral nuclei complex with gradually increasing doses of 70 to 105 Gy delivered in a single fraction. After SRS, patients were monitored for tremor severity and the toxicity of the treatment. Both subjective improvement and dose-dependent efficacy were analysed using standard statistical tests. The median follow-up was 23 months, and one patient died after COVID-19 infection. Another two patients were lost from follow-up. Hyper-response resulting in vascular toxicity and neurologic complications was observed in two patients irradiated with doses of 95 and 100 Gy, respectively. A reduction in tremor severity was observed in fifteen patients, and six experienced stagnation. A constant response during the whole follow-up was observed in 67% patients. A longer median response time was achieved in patients irradiated with doses equal to or less than 85 Gy. Only two patients declared no improvement after SRS. The efficacy of frameless SRS is high and could improve tremor control in a majority of patients. The complication rate is low, especially when doses below 90 Gy are applied. Frameless SRS could be offered as an alternative for patients ineligible for deep brain stimulation; however, studies regarding optimal dose are required.

IntroductionLung diseases are an increasing global health burden affecting millions of people worldwide. Only a few new inhaled medicines have reached the market in the last 30 years, in part due to foamy alveolar macrophage (FAM) responses observed in pre-clinical rat studies. The induction mechanism and signaling pathways involved in the development of highly vacuolated ‘foamy’ phenotype is not known. Furthermore, it has not been determined if these observations are adaptive or adverse responses.AimTo determine if high content image analysis techniques can distinguish between alveolar macrophage activation (LPS/IFN-γ activated and IL-4 activated macrophages) and if this could be applied to understanding the generation of ‘foamy’ macrophage phenotypes.MethodsNR8383 rat alveolar macrophages were stimulated with a mix of cytokines (LPS/IFN-γ or IL-4) for 24 h. The cells were further exposed to FAM inducing-compounds amiodarone and staurosporine. Following 24 h incubation, phagocytosis and lipid accumulation were measured using flow cytometry and high content image analysis techniques. The alveolar macrophages responses after exposure to cytokines were assessed by evaluation: (i) cell surface and biochemical markers such as: nitric oxide production, arginase-1 activity and MRC-1 receptor expression (ii) cellular morphology (iii) cellular functionality (phagocytic activity and lipids accumulation).ResultsMacrophages activated with LPS/IFN-γ showed distinct morphological (increased vacuolation) features and functionality (increased lipidosis, decreased phagocytic activity). Foamy macrophage phenotypes induced by amiodarone also displayed characteristics of proinflammatory macrophages (significantly increased nitric oxide production, increased vacuolation and lipidosis and decreased phagocytosis). In contrast, staurosporine treatment resulted in increased NO production, as well as arginase-1 activity.ConclusionHigh content image analysis was able to determine distinct differences in morphology between non-activated and LPS/IFN-γ activated macrophages, characterized by increased vacuolation and lipidosis. When exposed to compounds that induce a FAM phenotype, healthy non-activated macrophages displayed proinflammatory (amiodarone) or pro-apoptotic (staurosporine) characteristics but these responses were independent of a change in activation status. This technique could be applied in early drug discovery safety assessment to identify immune responses earlier and increase the understanding of alveolar macrophage responses to new molecules challenge in development of new inhalation therapies, which in turn will enhance decision-making in an early safety assessment of novel drug candidates.

The paper presents the design of a machine that can work at high temperature. The impact of various topologies and materials on electromagnetic field distribution and losses was analyzed. Two and three-dimensional simulations were carried out. The results obtained were discussed.

The subject of the paper is a three-dimensional analysis of a coupled fluid-thermal and electromagnetic field in permanent magnet synchronous machine that can work at very high temperatures. To obtain the distribution of the airflow and temperature we employed the coupled fluid-thermal model of the machine. This allowed us to check whether the temperature in sensitive elements does not exceed the permissible limits. The analysis took into account the effect of the color and the smoothness of the machine housing on the temperature distribution in its interior. The influence of design on the temperature distribution and distribution of hot spots was tested. Two topologies are studied considering magnet mounted on the rotor surface or buried in the rotor soft magnetic core. The simulation results were compared with measurements made on a prototype.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan–Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local–regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07–1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19–6.15). Definitive local salvage therapies were feasible in the majority of the patients with local–regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients’ survival compared to primary disease recurrence.

Abstract Background and purpose To compare the clinical outcome in prostate cancer patients treated with radiotherapy using two forms of image guidance: bone-based (BB) or fiducial-based (FB). Material and methods This retrospective study consisted of 180 patients treated with kV-kV image-guided radiotherapy (IGRT) between the years 2008 and 2011. A total of 89 patients were aligned to pelvic bone (Group BB) and 91 patients to the fiducial implanted into prostate for image guidance (Group FB). Patients were treated to a total dose of 76 Gy in 38 fractions. The Cox Regression Model was used to evaluate the influence of clinical and treatment-related parameters on overall survival, biochemical progression and progression-free survival. Acute and late toxicity were evaluated based on the RTOG/EORTC criteria. Sexual function was assessed with QLQ PR-25 (EORTC QLQ forms). An assessment of the differences in patient daily set-up from the time of simulation was performed. Results The incidence of acute G2/G3 genitourinary (GU) and gastrointestinal (GI) toxicity was similar between groups. In the BB group, 34 patients had G2 and 5 had G3 GU acute toxicity - compared to 40 patients with G2 and 2 with G3 in the FB group. G2 and G3 GI acute toxicity was observed respectively in 24 patients and in 1 patient in the BB group compared to 18 patients with G2 and 1 patient with G3 toxicity in the FB group. The five-year incidence of late ≥G2 GU toxicity was 12% in both groups (p = 0.98) and ≥ G2 GI toxicity 19% (BB) vs 15% (FB, p = 0.55), respectively. The five-year progression-free survival rate was 87% in BB and 81% in the FB Group (p = 0.15). The 5-year Overall Survival rate (OS) was 80% (BB) vs 91% % (FB, p = 0.20), but the difference was most pronounced in the intermediate-risk group: 5-year OS of 93% (FB) and 75% (BB), respectively (p = 0.06). No significant changes were observed in sexual or erectile functioning as compared to that specified at the beginning of radiotherapy and between the FB and BB Groups. Conclusion When comparing bone-based to fiducial-based techniques, no differences in clinical outcomes or late toxicity were seen in this population. However, intermediate risk prostate cancer patients are those who might benefit most from implementation of fiducial-based IGRT.

A new approach for designing ac motor windings free of partial discharges (PD) is proposed. The method consists of adding a thin conducting layer on the outer surface of the enameled wire used for building the machine winding. With this additional layer, PDs occur only in critical zones localized near the wire connections rather than randomly in the residual voids between turns. With such deterministic localizations, it is possible to reduce strongly the PD activity by adding small quantities of varnish in the determined critical zones. After studying the validity of the Paschen’s hypotheses for this application, the Paschen’s law is coupled to an electrostatic finite element analysis, for predicting the Partial Discharge Inception Voltage (PDIV), which corresponds to the electronic avalanche ignition in the air of critical zones.