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• Two doses of 4CMenB are required in naïve adolescents to elicit sufficient bactericidal activity. • Impact of childhood vaccination with 4CMenB on response to a single boost at adolescence is unknown. • No safety concerns raised after administration of fourth to sixth doses of 4CMenB in adolescence. • A single dose induced better responses in previously vaccinated than in naïve adolescents. • Responses to the adolescent dose were better when a preschool boost had been administered. The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3–5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163. [ABSTRACT FROM AUTHOR]

Background We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)–vectored coronavirus disease 2019 (COVID-19) vaccine with homologous prime-boost regimens in healthy participants aged ≥6 years. Methods In this randomized, double-blind, placebo-controlled trial, participants received vaccine or placebo 56 days apart. Enzyme-linked immunosorbent assay (ELISA) antibodies to the receptor binding domain (RBD) and pseudovirus neutralizing antibodies were detected. Adverse events were monitored for 28 days following each vaccination. Results A total of 430 participants were enrolled in the study, with 30 participants aged 18–55 years (MID cohort), 250 aged ≥56 years (OLD cohort), and 150 aged 6–17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies that decreased with increasing age, with geometric mean titers (GMTs) of 1037.5 in the MIN cohort, 647.2 in the MID cohort, and 338.0 in the OLD cohort receiving 5 × 1010 viral particles on day 28 following boost vaccination. Pseudovirus neutralizing antibodies showed a similar pattern, with GMTs of 168.0 in the MIN cohort, 76.8 in the MID cohort, and 79.7 in the OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by 2 doses in adults, with GMTs of 1091.6 and 96.6 for ELISA antibody and neutralizing antibody, respectively. Homologous prime-boost vaccination was safe and tolerable. Conclusions Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6–17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine. Ad5-vectored COVID-19 vaccine with a single dose was safe and tolerated, and induced robust immune responses in children and adolescents aged 6-17 years. The boosting effect on immune responses of the homologous prime-boost regime given 56 days apart was limited. Clinical Trials Registration NCT04566770. [ABSTRACT FROM AUTHOR]

Increased high-power exigency in industries insists for high step-up converters. Boost topology of DC–DC converters is the simplest and most used structure in numerous applications. This paper proposes a non-isolating type novel cluster switched inductor Boost (CSIB) hybrid converter having elevated voltage adaptation ratio. The key attribute of the projected CSIB converter is it gives high gain ratio when compared to other Boost topologies. With the same equivalent inductance value (while transferring energy to the load) as that of conventional converters, the proposed CSIB converter furnishes high voltage conversion ratio and adds an additional feature of proposed CSIB Hybrid DC–DC converter. With high conduction losses at high duty ratio and high parasitic resistance, distributed inductor shows a prominent role in increasing the gain of the converter and is the case in proposed CSIB converter. Transformer-less operation of novel CSIB converter reduces the size and avoids EMI/EMC effects, which is an added advantage. The Novel Cluster Switched Inductor Boost (CSIB) hybrid DC–DC converter in CCM operation is compared with Hybrid Boost and Symmetrical Hybrid Switched Inductor converter (SH-SLC) topologies to validate its performance. Simulation analysis is presented using MATLAB/SIMULINK software. [ABSTRACT FROM AUTHOR]

This article presents an auto-polarity thermoelectric energy-harvesting interface circuit based on a single-inductor boost/buck–boost hybrid converter. The power stage is configured automatically as a boost converter for a positive input voltage or a buck–boost converter for a negative input voltage. A collaborative efficiency-improving scheme of frequency selection and maximum power point tracking (MPPT) is implemented for input power ranging from 1 to 800 $\mu \text{W}$. An improved digital zero-current detection (ZCD) technique with fast searching is proposed to turn off power switches accurately. Dual-polarity cold startup is realized with the aid of a pair of cross-coupled Dickson charge pumps. This work is fabricated with a 0.13- $\mu \text{m}$ CMOS process. From the measured results, the interface starts up from a 140- or −160-mV thermoelectric generator (TEG) voltage. It boosts input voltages ranging from 10 mV to 0.4 V and from −10 mV to −0.4 V to a 1.2-V output voltage. It achieves a peak end-to-end efficiency of 90% with a 0.3-V input voltage or 88% with a −0.4-V input voltage. Moreover, end-to-end efficiencies are higher than 80% for input voltages from 90 mV to 0.4 V and from −110 mV to −0.4 V. [ABSTRACT FROM AUTHOR]

The paper concentrates on a comparison between two DC/DC converters topologies, the conventional Boost and the Multi Level Boost Converter (MLBC), for connecting into PV systems. Several performance criteria are included as part of this comparison process for both converters under varying climatic conditions (irradiation and/or temperature). The DC/DC converters' function is to serve as an interface between PV generator and load. We apply MPPT (Maximum Power Point Tracking) control with duty cycle adjustment using PWM technique for extracting the highest achievable output power from PV generator. The multilevel boost converter (MLBC), which is capable of monitoring and maintaining an equal voltage on all N output levels, along with controlling the input current. MATLAB/Simulink simulation results highlight the performance of the Multi-Level Boost Converter (MLBC) converter topology, to match the GPV voltage to the load.

Summary: Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents. Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered). Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p

Waning antibodies and rapidly emerging variants are challenges for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine development. Adjusting existing immunization schedules and further boosting strategies are under consideration. Here, the immune responses induced by an alum‐adjuvanted inactivated SARS‐CoV‐2 vaccine in mice were compared among immunization schedules with two or three doses. For the two‐dose schedule, a 0–28‐day schedule induced 5‐fold stronger spike‐specific IgG responses than a 0–14‐day schedule, with only a slight elevation of spike‐specific cellular immunity 14 days after the last immunization. A third homologous boost 2 or 5 months after the second dose for the 0–28‐day schedule slightly strengthened humoral responses (1.3‐fold for the 0–1–3‐month schedule, and 1.8‐fold for the 0–1–6‐month schedule) 14 days after the last immunization. Additionally, a third homologous boost (especially with the 0–1–3‐month schedule) induced significantly stronger cell‐mediated immunity than both two‐dose immunization schedules for all indexes tested, with a response similar to that induced by a one‐dose heterologous boost with BNT162b2 in clinical trials, according to cellular immunity analysis (1.5‐fold). These T cell responses were Th2 oriented, with good CD4+ and CD8+ memory. These results may offer clues for applying a homologous boosting strategy for alum‐adjuvanted inactivated SARS‐CoV‐2 vaccines. [ABSTRACT FROM AUTHOR]

Purpose: To present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes. Materials and methods: Eighty patients treated with an Intrabeam® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits. Results: Thirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group. Conclusion: IORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Materials/Methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12–180) months, and age was 58 (27–86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6–20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08–0.47; p < 0.05). The 10-year estimated OS was 81.2%. Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings. [ABSTRACT FROM AUTHOR]

The CoronaVac vaccine is widely used in Thailand to combat the coronavirus disease 2019 (COVID-19) pandemic. The limited immunogenicity of this vaccine is a concern, especially because of expanding delta variant outbreaks. A third boost may enhance antiviral immune responses. This non-inferiority randomized controlled trial evaluated the immunogenicity and safety of an intradermal (ID) fractional third dose of AZD1222 vaccine compared with those of a standard intramuscular (IM) third dose. Participants were enrolled from August 9, 2021 to August 13, 2021 at Chulabhorn Hospital, Bangkok, Thailand. The eligibility criteria were age 18 years or older and prior two-dose Coronavac vaccination completed at least 2 months previously. Participants were randomly assigned to one of three groups by block randomization: (i) standard dose by IM administration (IM), (ii) 20% of the standard dose ID (ID1), or (iii) 40% of the standard dose ID (ID2). The primary endpoint was the geometric mean ratio of anti-receptor binding domain antibody in the ID1/ID2 vs. the IM groups 14 days post-vaccination. A total of 125 participants were randomized (IM, n = 41; ID1, n = 41; and ID2, n = 43). One participant was lost to follow-up by day 14 post-vaccination in the ID1 group. The geometric mean ratio (95% confidence interval) of anti-receptor binding domain antibody was 0.94 (0.80–1.09) in the ID1 group and 1.28 (0.95–1.74) in the ID2 group. Immunogenicity in both ID groups met the non-inferiority criteria. Local adverse events were more common in the ID groups than in the IM group but were mostly mild to moderate in severity. An ID fractional third dose of AZD1222 was non-inferior to a standard IM third dose among individuals previously vaccinated with CoronaVac. Adverse events associated with the ID fractional third dose included mild to moderate local site reactions. This vaccination strategy may help conserve vaccine supply. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative electron radiation therapy (IOERT) has repeatedly demonstrated its power to yield high local control rates in all risk constellation of patients with invasive breast cancer when given as tumor bed boost prior to conventional whole breast irradiation (WBI) after breast conserving surgery (BCS). Since the standard for WBI continuously moved towards hypofractionation, we initiated a prospective trial in 2011 where we combined a high precision IOERT boost with a "moderate" hypofractionation schedule (15 × 2.7 Gy), the HIOB-trial [NCT01343459], as clinical evidence for this combination was scarce. Our results demonstrated a low five-year local recurrence rate (overall two events in a population of 1119 patients), which undershot such best evidences in two age groups (41–50 y and >50 y). As acute and late toxicity were mild with no impaired cosmetic outcome, the HIOB-concept seems to be a viable treatment option for patients who underwent BCS and intended WBI. Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35–40 y and 41–50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7–104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41–50 and >50 y, respectively. For the youngest group (35–40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41–50 when compared to best published evidence until 2010. [ABSTRACT FROM AUTHOR]

To evaluate the role and technique of a vaginal cuff brachytherapy (VB) boost to adjuvant external beam (EB) radiation for endometrial cancer through a systematic review. Relevant trials were identified through a systematic search of the literature. A total of 21 prospective and retrospective studies which had a patient cohort undergoing EB + VB was identified to evaluate for rates of vaginal and pelvic recurrences, overall survival, and toxicity. Additional database studies were utilized to demonstrate differences in local control and overall survival between EB and EB + VB. While there is limited prospective evidence to guide the use of a VB boost after EB, the evidence suggests that patients with a higher risk of a vaginal recurrence such as those with cervical stromal involvement in select Stage III patients may derive local control and survival benefits from a VB boost. Additional individual risk factors such as grade, histology, extent of invasion, margin status, age, and the use of lower doses of EB should be considered when deciding when to add a VB boost. [ABSTRACT FROM AUTHOR]

This article studies the model predictive control (MPC) for a twisted buck–boost inverter based on unfolding circuit. The focus is on the practical implementation of the MPC algorithm for the microcontroller designed for application in power electronics. Selection of proper cost function parameters along with a continuous control set reduced prediction horizon, at the same time keeping good quality of the grid current. The results showed that simplified differential equations and a multicore microcontroller contribute to the sample time reduction, which in turn increases the sampling frequency with the corresponding increase in the output current quality. The simulation and experimental results confirmed theoretical predictions. In conclusion, the MPC technique suits for reducing zero-crossing distortion and in applications based on unfolding circuit. [ABSTRACT FROM AUTHOR]

Critical conduction mode (CRM) or discontinuous conduction mode (DCM) boost power factor correction (PFC) converter is widely used in low power applications for its advantages of zero-current turn-on of the switch, no reverse recovery in diode, and simple control. The input current of fixed switching frequency control CRM boost PFC converter and the input current of constant duty-cycle control DCM boost PFC converter mainly contain third harmonic. Moreover, the phase of the third harmonics is opposite. This article proposes a harmonic elimination parallel control to connect these two converters in parallel. The input current third harmonic of the parallel converter can be eliminated completely so as to improve the PF to nearly unity in the whole input voltage range. This parallel method is an interesting way to extend power, and is different from the existing method of parallel DCM boost PFC converter or parallel CRM boost PFC converter. The experimental results verify the accuracy of the theoretical analysis. [ABSTRACT FROM AUTHOR]

An IGBT/MOSFET driver circuit works at a low voltage, between 5-15 V of its gate voltage to drive power converter switching devices that work at higher voltages. If there is no isolation between the driver and power converter circuits, any damage that may occur to the power converter circuit at high voltage will damage the driver circuit as well. This paper presents a design of an isolated IGBT/MOSFET driver circuit for an interleaved DC/DC boost converter using a TL494 IC to generate the required pulses for the converter’s circuit. Isolation is done using optocouplers. An IC IR2117 driver is also used to produce smooth rise and fall times for the pulses for each IGBT. The designed driver circuit is modelled using a co-simulation employing Multisim and LabVIEW software and then implemented experimentally with the help of a NI PCI-DAQ 6259. A P-I controller is implemented to regulate the output voltage of the boost converter, as well at the desired set point.

Purpose: To compare treatment plans of two different rectal boost strategies: up-front versus adaptive boost at the 1.5 T MR-Linac. Methods: Patients with locally advanced rectal cancer (LARC) underwent standard neoadjuvant radiochemotherapy with 50.4 Gy in 28 fractions. T2-weighted MRI prior and after the treatment session were acquired to contour gross tumor volumes (GTVs) and organs at risk (OARs). The datasets were used to simulate four different boost strategies (all with 15 Gy/5 fractions in addition to 50.4 Gy): up-front boost (5 daily fractions in the first week of treatment) and an adaptive boost (one boost fraction per week). Both strategies were planned using standard and reduced PTV margins. Intra-fraction motion was assessed by pre- and post-treatment MRI-based contours. Results: Five patients were included and a total of 44 MRI sets were evaluated. The median PTV volumes of the adaptive boost were significantly smaller than for the up-front boost (81.4 cm3 vs 44.4 cm3 for PTV with standard margins; 31.2 cm3 vs 15 cm3 for PTV with reduced margins; p = 0.031). With reduced margins the rectum was significantly better spared with an adaptive boost rather than with an up-front boost: V60Gy and V65Gy were 41.2% and 24.8% compared with 59% and 29.9%, respectively (p = 0.031). Median GTV intra-fractional motion was 2 mm (range 0–8 mm). Conclusions: The data suggest that the adaptive boost strategy exploiting tumor-shrinkage and reduced margin might result in better sparing of rectum and anal canal. Individual margin assessment, motion management and real-time adaptive radiotherapy appear attractive applications of the 1.5 T MR-Linac for further testing of individualized and safe dose escalation in patients with rectal cancer.

The paper deals with disturbed transatmospheric motion of the first stage of an aerospace system. Deviations of atmospheric density and deviations of aerodynamic force coefficients from reference values are taken as disturbances. Optimal angle-of-attack schedules for the first stage are specified. Comparative analysis of optimal control programs for disturbed and undisturbed motion is carried out.

The aim of this study is to present a very simple, intuitive and feasible tool: the D-transform between converters. This new method proposes to find a control equation of any pre-defined control law from one converter to another power converter. The central goal is to take maximum advantage of the robustness offered by the originator nonlinear control law. Although there is the possibility of more than one conversion, some candidates show good performance in terms of transient overshoot, settling time and steady-state regulation. The stability proof is disposed individually for each generated equation. The performance of D-Controllers is verified through Hardware In the Loop (HIL) simulations. A small overshoot under input and load perturbations is achieved for the buck-boost example. Finally, a experimental validation using a buck converter is given to illustrate the application method and the nonlinear control design.

PurposeThe purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort.Materials/MethodsPatients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors.ResultsA total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12–180) months, and age was 58 (27–86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6–20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age

Purpose: Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. Methods: Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. Results: ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220–0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245–9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338–2.169, P = 0.743, and HR = 2.39, 95% CI 0.93–6.111, P = 0.067, respectively). Conclusion: Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Treating localized prostate cancer (PC) with combination radiotherapy consisting of external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has been proven to result in better disease outcome than EBRT only. We aimed to evaluate the incidence of toxicities due to combination therapy and identify parameters correlated to acute or late urinary, rectal, and erectile toxicities. Material and methods: Data on symptoms and tumor/treatment parameters were collected from 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) and HDR-BT (14.5 Gy in one fraction) for localized PC, at the Örebro University Hospital. Urinary, rectal, and erectile symptoms were presented descriptively, and bivariate analyses for correlation between grade = 2 toxicity and potential predictors were performed. To evaluate prognostic models, multivariable analyses were applied. Results: Urinary toxicity grade = 2 was observed in 154 patients (47% of patients without pre-existing symptoms grade = 2), of which 15 were grade 3. Rectal toxicity grade 2 was observed in 22 (6%) patients. Any grade erectile dysfunction was evident in all patients without pre-existing dysfunction (n = 103), whereas only 7 recovered completely. In bivariate analyses age was correlated with higher risk of acute urinary toxicity, and irradiated volume was associated with both urinary and rectal toxicities. However, we found no multivariable model of clinical and statistical significance to predict the risk of urinary or rectal toxicities. Conclusions: In our study cohort, the severity of toxicities was in general mild or moderate and temporary, whereas the incidence of severe toxicity was considerably low. Although we found no predictive models for toxicities, our findings are reassuring that this treatment approach as curative therapy for localized PC is well-tolerated. [ABSTRACT FROM AUTHOR]

This paper presents the development of a multi-input multi-output bi-directional power converter (MIMO-BDPC) with a digital pulse-width modulation (DPWM) controller for solar photovoltaic (SVP) application. The converter is operated in three modes such as buck, boost, and inverter. The converter uses a minimum number of active components and the DPWM controller controls the switching frequency or pulse period which are reconfigurable for effective synchronous and autonomous operation. The autonomous mode is selected by the controller based on the availability of the power source. The combination of high performance, low cost, and high reliability in a single controller is achieved via this intelligent digital approach. The controller is based on the power and load changes in multiple PWM modes. The Intel Altera Cyclone IV FPGA control will be used for digital PWM. The FPGA is scheduled for parallel data processing with multiple resource blocks. During control, this controller can be reprogrammed dynamically again. This makes the system extremely efficient in the check aspect, reducing time and cost. The proposed MIMO-BDPC is tested with the above-mentioned modes of operation using MATLAB software and also through hardware results. [ABSTRACT FROM AUTHOR]

Introduction: Hypofractionated whole breast irradiation (hWBI) and intraoperative radiotherapy (IORT) could be associated in breast cancer patients showing high-risk factors of local recurrence after breast conserving therapy (BSC). The aim of this trial was to evaluate, for the first time, the toxicity and cosmesis of hWBI after photon-IORT in high-risk patients treated by adjuvant chemotherapy. Materials and methods: Thirty-one high-risk localized breast cancer patients treated by BCS, IORT (20 Gy), and adjuvant chemotherapy were included from February 2019 to August 2020 in this prospective trial, of hWBI (40.5 Gy/2.67 Gy/15 fractions). Acute and late toxicity (CTCAEv5.0) and cosmesis (Harvard scale), were assessed after treatment. Results: All patients completed their treatment and were evaluable after treatment. No patients showed severe (G3) acute/late toxicity. Excellent/good cosmesis at least 6 months after completing the treatment, was present in 93.6% of the patients. Conclusion: hWBI in high-risk localized breast cancer patients treated by chemotherapy seems to have similar toxicity and cosmetic results than conventionally fractionated WBI in combination to photon-IORT after BCS. [ABSTRACT FROM AUTHOR]

Large-signal input characteristics of three DC–DC converter types: buck, boost and flyback working in the discontinuous conduction mode (DCM), obtained by precise large signal PSpice simulations, calculations based on averaged models and measurements are presented. The parasitic resistances of the converter components are included in the simulations. The specific features of the input characteristics in theDCMand the differences between the continuous conduction mode (CCM) and DCM are discussed.

Photovoltaic is an absolute device in the solar power plant system. A DC-DC converter with a maximum power point tracker (MPPT) algorithm is required to obtain the maximum power of photovoltaic. In general, solar power plant applications used a two-stage converter: the first stage is boosting DC-DC converter, and the second stage is the multilevel Inverter. Boost DC-DC converter is usually implemented singly, which causes many boost DC-DC converters to be implemented in a solar power plant application. The voltage doubler type boost DC-DC converter proposed in this paper is to simplify the circuit so that there is only one converter in a solar power plant application. This converter principle combines two conventional boost converters, which are integrated into one so that the power circuit and control circuit form become simpler. This proposal is verified through computation simulation and hardware design using the STM32F1038CT microcontroller for the final verification. The efficiency algorithm of the simulation is 99.7%, and the hardware experimental is 85.65%

Large-signal input characteristics of three DC–DC converter types: buck, boostand flyback working in the continuous conduction mode (CCM), obtained by simulationsand measurements are investigated. The results of investigations are presented in the formof the analytical formulas and the exemplary results of the measurements and two formsof simulations: based on the full description of the converter components and on theaveraged models. The parasitic resistances of the converter components are included in thesimulations and their influence on the simulation results is discussed.

A high gain three port converter with a unidirectional port for photovoltaic (PV) side and two bidirectional ports one each for the battery and the DC bus for PV integration to DC microgrid is presented. High gain is achieved by a coupled inductor with switched capacitor, whereas single stage conversion is used between the ports to achieve high efficiency. The proposed converter is modelled in PLECS/MATLAB and the simulated results for various operational modes are validated using a 500 W prototype. For main operating mode, i.e., single input single output (SISO), the efficiency is calculated to be as high as 96 %. Similarly, owing to the reduced number of components, the losses are reduced considerably for different operation modes.

Total skin electron beam therapy (TSEBT) in female patients with large or pendulous breasts is usually associated with shaded inframammary folds. In this analysis, 18 patients with cutaneous malignancy and pendulous breasts were irradiated with a radiation bra and five patients received TSEBT without bra. All patients had moderate or severe sagging of the breasts. The median inframammary dose in the radiation bra group was 89% of the prescription dose versus 4% in the group without bra. The usage of the radiation bra enables an adequate radiation dose for the inframammary folds during TSEBT with no additional local irradiation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Sequencing the tyrosine phosphoproteome using MS-based proteomics is challenging due to the low abundance of tyrosine phosphorylation in cells, a challenge compounded in scarce samples like primary cells or clinical samples. The broad-spectrum optimisation of selective triggering (BOOST) method was recently developed to increase phosphotyrosine sequencing in low protein input samples by leveraging tandem mass tags (TMT), phosphotyrosine enrichment, and a phosphotyrosine-loaded carrier channel. Here, we demonstrate the viability of BOOST in T cell receptor (TCR)-stimulated primary murine T cells by benchmarking the accuracy and precision of the BOOST method and discerning significant alterations in the phosphoproteome associated with receptor stimulation. Using 1 mg of protein input (about 20 million cells) and BOOST, we identify and precisely quantify more than 2000 unique pY sites compared to about 300 unique pY sites in non-BOOST control samples. We show that although replicate variation increases when using the BOOST method, BOOST does not jeopardise quantitative precision or the ability to determine statistical significance for peptides measured in triplicate. Many pY previously uncharacterised sites on important T cell signalling proteins are quantified using BOOST, and we identify new TCR responsive pY sites observable only with BOOST. Finally, we determine that the phase-spectrum deconvolution method on Orbitrap instruments can impair pY quantitation in BOOST experiments., (© 2024 Wiley‐VCH GmbH.)

• The role of an additional boost to the tumor bed in DCIS is still unknown. • Severity of acute skin toxicities is significantly increased by tumor bed boost. • Smoking history and large breast CTV are predictive factors of acute toxicities. • Dummy run before patients' inclusion reduced the risk of major TP deviations. To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities. [ABSTRACT FROM AUTHOR]

• First-in-human application of a weekly online adaptive MR-guided radiotherapy boost. • Rectal ultrasound gel filling facilitated excellent tumor visualization and sparing of healthy mucosa. • Treatment was very well tolerated with only minimal toxicity. Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation. [ABSTRACT FROM AUTHOR]

This article proposes a unified pulsewidth-cycle (UPWC) control strategy to achieve mixed-mode operation and consistent valley switching (VS) for boost power factor correction converter. Compared with conventional single-mode controllers, it has a unified scheme to achieve single discontinuous conduction mode (DCM), single critical conduction mode (CRM), or mixed DCM/CRM operations in each half-line cycle. To regulate the input current as a sinusoid, the UPWC controller adopts a variable pulsewidth and a near-constant switching cycle under DCM, while adopts a constant pulsewidth and a variable switching cycle under CRM. To facilitate analysis, normalized mapping of operation modes is provided, along with the final pulsewidth and switching cycle. Furthermore, to ensure consistent VS, a controlled zero current detection method is proposed to fix the turn-on point of the power switch. No matter in DCM or CRM, consistent VS reduces both the switching loss and current distortion caused by parasitic resonance. To further reduce the current distortion caused by fixing the turn-on point, a compensation gain is provided that reshapes the input current as a sinusoid. Finally, through mixed DCM/CRM operation and consistent VS, the proposed UPWC controller achieves preferable performances in the power range, efficiency, power factor, and current distortion. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime–boost vaccination with different vaccines remain largely unclear. Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination. As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2). Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals. [ABSTRACT FROM AUTHOR]

Background: There are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center. Methods: From 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3–6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS). Results: Median follow-up for the 214 patients was 28 (range 2–59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4–50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event. Conclusion: This investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT‑B. [ABSTRACT FROM AUTHOR]

Abstract Background Intraoperative electron radiotherapy (IOERT) followed by hypofractionated whole breast irradiation (HWBI) provides the shortest possible time of adjuvant breast irradiation. The efficacy of either method has been described in previous reports; however, to our knowledge, the efficacy of combined therapy has not been reported. Aim To compare the toxicity and cosmetic outcome of IOERT as a tumor bed boost followed by HWBI with conventional whole breast irradiation (CWBI) followed by external electron tumor bed boost (EETBB) after breast conserving surgery (BCS) in patients with invasive breast cancer. Methods In 2019, a prospective noninferiority trial (IRCT20180919041070N2) was started. After BCS, early‐stage breast cancer patients were treated by IOERT (10 Gy) and HWBI (42.56 Gy in 16 fractions) or CWBI (50 Gy in 25 fraction) and EETBB (10 Gy in 5) in a double‐arm design. Acute/late toxicity and cosmetic outcome were evaluated by common toxicity criteria (CTC) after 1‐year follow‐up (FUP) at the level of p

This paper presents a triple-mode average current control (TACC) strategy to achieve unity power factor and reduce the current stress for a boost PFC converter. The controller switches among different modes in each half-line cycle, and smooth transition is ensured by mapping of the operation region. By adaptive mode shifting, it reduces the current stress and current distortion caused by non-linear effects. With valley current shaping and comparisons, the TACC controller accordingly incorporates three control laws to adapt different modes. In discontinuous conduction mode (DCM), a variable on-time is calculated while the modulation is equivalent to PWM. In critical conduction mode (CRM), a constant on-time is derived, while the switching cycle is modified to regulate the current average value. For both DCM and CRM, the switching cycle is slightly extended to realize valley switching. Furthermore, with valley current shaping, the proposed controller reuses the CRM calculation to form continuous conduction mode (CCM) control law. To make the control laws compatible, normalized mapping and design rules are provided with respect to mode boundaries. This allows the TACC controller to automatically switch among different modes. Finally, experimental results prove the effectiveness of the controller in reducing the current stress and enlarging the preferable power range.

Maximizing the efficiency and power density of dc–dc converters demands parallel optimizations in design and control, especially for variable-frequency converters operating over wide frequency ranges. This letter presents the full-scale optimization of a kilowatt-range megahertz-class boost converter based on the impulse rectification. To maximize the heat extraction from the converter and increase its power density, the entire power stage is implemented on a single-layer insulated-metal substrate. For high efficiencies over wide frequency ranges, high-performance gallium nitride transistors are employed and various high-frequency materials (MnZn, NiZn, and air) with different geometries are compared to realize a wide-bandwidth inductor. Silicon carbide Schottky diodes with a zero reverse recovery are utilized for efficient high-frequency rectification, and the impact of the device's current rating on its generated reactive power and the overall system efficiency are investigated at different power levels up to 1 kW. The proposed optimum duty cycle control maximizes the conversion efficiency at different gains and powers and prevents fatal device hard switching at high frequencies. The optimized converter enables a peak efficiency of 98.6% along with an ultrahigh power density of 52 kW/l (850 W/in3). A loss breakdown summarizes major efficiency bottlenecks to be overcome by future advances in power electronics. [ABSTRACT FROM AUTHOR]