Simultaneous integrated boost (SIB) radiation therapy of right sided breast cancer with and without flattening filter - A treatment planning study

Background: The aim of the study was to compare the two irradiation modes with (FF) and without flattening filter (FFF) for three different treatment techniques for simultaneous integrated boost radiation therapy of patients with right sided breast cancer. Methods: An Elekta Synergy linac with Agility collimating device is used to simulate the treatment of 10 patients. Six plans were generated in Monaco 5.0 for each patient treating the whole breast and a simultaneous integrated boost (SIB) volume: intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and a tangential arc VMAT (tVMAT), each with and without flattening filter. Plan quality was assessed considering target coverage, sparing of the contralateral breast, the lungs, the heart and the normal tissue. All plans were verified by a 2D-ionisation-chamber-array and delivery times were measured and compared. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Results: Significantly best target coverage and homogeneity was achieved using VMAT FFF with V95% = (98.7 +/- 0.8) % and HI = (8.2 +/- 0.9) % for the SIB and V95% = (98.3 +/- 0.7) % for the PTV, whereas tVMAT showed significantly lowest doses to the contralateral organs at risk with a D-mean of (0.7 +/- 0.1) Gy for the contralateral lung, (1.0 +/- 0.2) Gy for the contralateral breast and (1.4 +/- 0.2) Gy for the heart. All plans passed the gamma evaluation with a mean passing rate of (99.2 +/- 0.8) %. Delivery times were significantly reduced for VMAT and tVMAT but increased for IMRT, when FFF was used. Lowest delivery times were observed for tVMAT FFF with (1:20 +/- 0:07) min. Conclusion: Balancing target coverage, OAR sparing and delivery time, VMAT FFF and tVMAT FFF are considered the preferable of the investigated treatment options in simultaneous integrated boost irradiation of right sided breast cancer for the combination of an Elekta Synergy linac with Agility and the treatment planning system Monaco 5.0

Egg activation events are regulated by the duration of a sustained [Ca2+]cyt signal in the mouse

AbstractAlthough the dynamics of oscillations of cytosolic Ca2+ concentration ([Ca2+]cyt) play important roles in early mammalian development, the impact of the duration when [Ca2+]cyt is elevated is not known. To determine the sensitivity of fertilization-associated responses [i.e., cortical granule exocytosis, resumption of the cell cycle, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, recruitment of maternal mRNAs] and developmental competence of the parthenotes to the duration of a [Ca2+]cyt transient, unfertilized mouse eggs were subjected to a prolonged [Ca2+]cyt change for 15, 25, or 50 min by means of repetitive Ca2+ electropermeabilization at 2-min intervals. The initiation and completion of fertilization-associated responses are correlated with the duration of time in which the [Ca2+]cyt is elevated, with the exception that autonomous CaMKII activity is down-regulated with prolonged elevated [Ca2+]cyt. Activated eggs from 25- or 50-min treatments readily develop to the blastocyst stage with no sign of apoptosis or necrosis and some implant. Ca2+ influx into unfertilized eggs causes neither Ca2+ release from intracellular stores nor rapid removal of cytosolic Ca2+. Thus, the total Ca2+ signal input appears to be an important regulatory parameter that ensures completion of fertilization-associated events and oocytes have a surprising degree of tolerance for a prolonged change in [Ca2+]cyt

Differences in leukocyte profile, gene expression, and metabolite status of dairy cows with or without sole ulcers

peer-reviewedSole ulcers are one of the most severe pathologies causing lameness in dairy cows and are associated with abnormal behavior and impaired production performance. However, little is known about how or whether lameness caused by sole ulcers affects the cow systemically. This study compared hematology profile, leukocyte gene expression, and physiological responses [metabolite, cortisol, the endogenous steroid hormone dehydroepiandrosterone (DHEA), and haptoglobin concentrations] of cows with sole ulcers and healthy cows. Twelve clinically lame cows (lame) were identified as having at least one sole ulcer and no other disorder, and matched with a cow that had good locomotion and no disorders (sound), using days in milk, liveweight, body condition score, and diet. Blood samples were taken from all 24 cows within 24 h of sole ulcer diagnosis. Leukocyte counts were obtained using an automated cell counter, cortisol and DHEA concentration by ELISA, and plasma haptoglobin, urea, total protein, creatine kinase, and glucose were analyzed on an Olympus analyzer. Expression of 16 genes associated with lameness or stress were estimated using reverse transcription-PCR. Data were analyzed using the MIXED procedure in SAS software (version 9.3; SAS Institute Inc., Cary, NC). Lame cows had a higher neutrophil percentage, a numerically lower lymphocyte percentage, and tended to have a higher neutrophil:lymphocyte ratio than sound cows. Serum cortisol and DHEA concentrations were higher in lame than in sound cows. Lame cows also tended to have higher haptoglobin and glucose levels than sound, as well as higher protein yet lower urea levels. Sound cows tended to have higher relative expression of the gene coding for colony-stimulating factor 2 than lame, but in all other cases where differences were detected in cytokine gene expression (IL-1α, IL-1β, CXCL8, and IL-10), relative gene expression in sound cows tended to be, or was, lower than in lame. Relative expression of MMP-13, GR-α, Fas, haptoglobin, and CD62L were, or tended to be, higher in lame than sound cows. A high neutrophil:lymphocyte ratio in combination with higher cortisol levels in cows with ulcers is indicative of physiological stress. Moreover, increased DHEA and a higher cortisol:DHEA ratio, as well as a tendency for higher haptoglobin levels and increased haptoglobin mRNA expression, are indicative of systemic inflammation. Increased cytokine mRNA expression indicates activation of the immune system compared with healthy cows. Increased expression of MMP-13 mRNA has been found in cows with impaired locomotion and thus could be implicated in development of claw horn disorders.This study was funded by a Marie Curie Intra-European Fellowship (FP7-People 2009-IEF; grant agreement number: 252611) to Keelin O'Driscoll

Die Manifestation von Lokalrezidiven, Fernmetastasen und Zweittumoren und ihr Einfluss auf das Überleben von 600 Patienten mit malignen Tumoren der Kopf-Hals-Region - Eine retrospektive monoinstitutionale Analyse

Zielsetzung: Untersuchung der Inzidenz von Lokalrezidiven, Fernmetastasen und Zweittumoren und ihr Einfluss auf das Gesamtüberleben von 600 Patienten mit malignen Tumoren der Kopf-Hals-Region vor dem Hintergrund tumor- und therapieassoziierter Einflussparameter. Material/Methoden: Retrospektive Analyse von 600 Patienten mit malignen Kopf-Hals-Tumoren (medianes Alter bei Erstdiagnose: 56,7 Jahre, 73,0% mit einem Stadium IV), die zwischen 1993 und 2005 an der Klinik und Poliklinik für Strahlentherapie der Universität Regensburg behandelt worden waren (45% mit einer primären Radiatio, 55% im adjuvanten Behandlungskonzept). Mithilfe der Kaplan-Meier-Methode erfolgte eine Analyse hinsichtlich der medianen Zeit bis zum Auftreten des jeweiligen Endpunktes, des endpunktspezifischen Überlebens sowie des Gesamtüberlebens. Ergebnisse: Bei einem medianen Nachbeobachtungszeitraum von 45,9 Monaten zeigte sich ein medianes Gesamtüberleben von 37,9 Monaten. Nach einer medianen lokalrezidivfreien Zeit von 12,2 Monaten wurde bei 227 Patienten (37,8%) ein Lokalrezidiv diagnostiziert mit einem endpunktspezifischen Überleben von 7,3 Monaten. Das Gesamtüberleben mit Lokalrezidiv lag bei 27,2 Monaten. 193 Patienten (32,2%) entwickelten nach einer medianen metastasenfreien Zeit von 12,8 Monaten Fernmetastasen. Das endpunktspezifische Überleben lag bei sechs Monaten, mit einem Gesamtüberleben mit 20,7 Monaten. Nach einem medianen zweittumorfreien Intervall von 21,2 Monaten wurde bei 123 Patienten (20,5%) ein Zweitmalignom diagnostiziert (87 syn-/metachrone Tumore). Es zeigte sich ein endpunktspezifisches Überleben mit Zweitkarzinom von 17,3 Monaten, das Gesamtüberleben lag bei 45,3 Monaten. Fazit: Am stärksten überlebenslimitierend erwiesen sich Fernmetastasen mit einem Gesamtüberleben von 20,7 Monaten und einem medianen metastasenfreien Zeitraum von 12,8 Monaten. Dies unterstreicht die Notwendigkeit der Standardisierung von systemischen Staginguntersuchungen sowohl bei Erstdiagnose als auch in der Rezidivsituation zum Nachweis klinisch silenter Fernmetastasen

Second Cancer Risk after simultaneous integrated boost radiation therapy of right sided breast cancer with and without flattening filter

Background The aim of this study was to investigate if the flattening filter free mode (FFF) of a linear accelerator reduces the excess absolute risk (EAR) for second cancer as compared to the flat beam mode (FF) in simultaneous integrated boost (SIB) radiation therapy of right-sided breast cancer. Patients and methods Six plans were generated treating the whole breast to 50.4 Gy and a SIB volume to 63 Gy on CT data of 10 patients: intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and a tangential arc VMAT (tVMAT), each with flattening filter and without. The EAR was calculated for the contralateral breast and the lungs from dose-volume histograms (DVH) based on the linear-exponential, the plateau, and the full mechanistic dose-response model. Peripheral low-dose measurements were performed to compare the EAR in more distant regions as the thyroids and the uterus. Results FFF reduces the EAR significantly in the contralateral and peripheral organs for tVMAT and in the peripheral organs for VMAT. No reduction was found for IMRT. The lowest EAR for the contralateral breast and lung was achieved with tVMAT FFF, reducing the EAR by 25 % and 29 % as compared to tVMAT FF, and by 44 % to 58 % as compared to VMAT and IMRT in both irradiation modes. tVMAT FFF showed also the lowest peripheral dose corresponding to the lowest EAR in the thyroids and the uterus. Conclusion The use of FFF mode allows reducing the EAR significantly when tVMAT is used as the treatment technique. When second cancer risk is a major concern, tVMAT FFF is considered the preferred treatment option in SIB irradiation of right-sided breast cancer

“It’s an emotional roller coaster… But sometimes it’s fucking awesome” : Meaning and Motivation of Work for Peers in Overdose Response Environments in British Columbia

The province of British Columbia (BC), Canada is amid dual public health emergencies in which the overdose epidemic declared in 2016 has been exacerbated by restrictions imposed by the Coronavirus Disease of 2019 (COVID-19) pandemic. Experiential workers, commonly known as ‘peers’ (workers with past or present drug use experience) are at the forefront of overdose response initiatives and are essential in creating safe spaces for people who use drugs (PWUD) in harm reduction. Working in overdose response environments can be stressful, with lasting emotional and mental health effects. There is limited knowledge about the personal meaning that experiential workers derive from their work, which serve as motivators for them to take on these often stressful roles.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearche

Finding My Way: Protocol of a randomised controlled trial evaluating an internet self-help program for cancer-related distress

Background\ud \ud A cancer diagnosis elicits greater distress than any other medical diagnosis, and yet very few studies have evaluated the efficacy of structured online self-help therapeutic programs to alleviate this distress. This study aims to assess the efficacy over time of an internet Cognitive Behaviour Therapy (iCBT) intervention (‘Finding My Way’) in improving distress, coping and quality of life for individuals with a recent diagnosis of early stage cancer of any type.\ud \ud Methods/Design\ud \ud The study is a multi-site Randomised Controlled Trial (RCT) seeking to enrol 188 participants who will be randomised to either the Finding My Way Intervention or an attention-control condition. Both conditions are delivered online; with 6 modules released once per week, and an additional booster module released one month after program-completion. Participants complete online questionnaires on 4 occasions: at baseline (immediately prior to accessing the modules); post-treatment (immediately after program-completion); then three and six months later. Primary outcomes are general distress and cancer-specific distress, with secondary outcomes including Health-Related Quality of Life (HRQoL), coping, health service utilisation, intervention adherence, and user satisfaction. A range of baseline measures will be assessed as potential moderators of outcomes. Eligible participants are individuals recently diagnosed with any type of cancer, being treated with curative intent, aged over 18 years with sufficient English language literacy, internet access and an active email account and phone number. Participants are blinded to treatment group allocation. Randomisation is computer generated and stratified by gender.\ud \ud Discussion\ud \ud Compared to the few prior published studies, Finding My Way will be the first adequately powered trial to offer an iCBT intervention to curatively treated patients of heterogeneous cancer types in the immediate post-diagnosis/treatment period. If found efficacious, Finding My Way will assist with overcoming common barriers to face-to-face therapy in a cost-effective and accessible way, thus helping to reduce distress after cancer diagnosis and consequently decrease the cancer burden for individuals and the health system.\ud \ud Trial registration\ud \ud Australian New Zealand Clinical Trials Registry ACTRN12613000001​796 16.10.1