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Eurasian badgers, Meles meles, have been shown to possess limited genetic population structure within Europe; however, field studies have detected high levels of philopatry, which are expected to increase population structure. Population structure will be a consequence of both contemporary dispersal and historical processes, each of which is expected to be evident at a different scale. Therefore, to gain a greater understanding of gene flow in the badger, we examined microsatellite diversity both among and within badger populations, focusing on populations from the British Isles and western Europe. We found that while populations differed in their allelic diversity, the British Isles displayed a similar degree of diversity to the rest of western Europe. The lower genetic diversity occurring in Ireland, Norway and Scotland was more likely to have resulted from founder effects rather than contemporary population density. While there was significant population structure ( FST = 0.19), divergence among populations was generally well explained by geographic distance ( P<0.0001) across the entire range studied of more than 3000 km. Transient effects from the Pleistocene appear to have been replaced by a strong pattern of genetic isolation by distance across western Europe, suggestive of colonization from a single refugium. Analysis of individuals within British populations through Mantel tests and spatial autocorrelation demonstrated that there was significant local population structure across 3–30 km, confirming that dispersal is indeed restricted. The isolation by distance observed among badger populations across western Europe is likely to be a consequence of this restricted local dispersal. [ABSTRACT FROM AUTHOR]

The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of three previously undescribed compounds: O -demethyl-norlycoramine ( 1 ), (-)-2- epi -pseudolycorine ( 2 ) and (+)-2- epi -pseudolycorine ( 3 ), together with eight known compounds: 6α-hydroxyhippeastidine ( 4 ), 6β-hydroxyhippeastidine ( 5 ), lycorine ( 6 ), 2- epi -lycorine ( 7 ), zephyranthine ( 8 ), ungeremine ( 9 ), pancratistatin ( 10 ) and 9- O -demethyl-7- O -methyllycorenine ( 11 ). Among the eight previously reported compounds, five were isolated from H. littoralis for the first time (compounds 4 , 5 , 7 , 8, and 9 ). Compounds 1 , 4 , 5 , 7 , 8 , and 11 exhibited weak anti-SARS-CoV-2 activity (EC 50 = 40-77 µM) at non-cytotoxic concentrations. Assessment of cytotoxicity on the Vero-E6 cell line revealed lycorine and pancratistatin as cytotoxic substances with CC 50 values of 1.2 µM and 0.13 µM, respectively. The preliminary structure-activity relationship for the lycorine-type alkaloids in this study was further investigated, and as a result ring C appears to play a crucial role in their anti-SARS-CoV-2 activity.

Advantages of using intraoperative radiotherapy with electrons (IOERT) as a boosting modality in breast-conserving therapy include the direct visualization of the tumor bed, a reduced skin dose, and patient convenience. We report oncological outcome, postoperative complication rate, and mammographic changes on follow-up imaging in women treated at our institution with IOERT as a boost modality in breast-conserving therapy for early-stage breast carcinoma. Between January 2007 and June 2018, 763 consecutive patients were enrolled. During breast-conserving surgery, an IOERT boost of 9 Gy was applied, followed by whole breast irradiation (WBI). At a median follow-up of 62.2 months (range: 0.5-135), 13 in-breast recurrences were observed, yielding a local tumor control rate of 98.4% at 5 years. In multivariable analysis, high tumor grading was predictive for local recurrence (HR = 5.6; 95%CI: 1.19-26.2). A total of 27 (3.5%) patients developed any kind of postoperative complication. None of the tumor characteristics nor any of the IOERT technical parameters were predictive for development of a postoperative complication. On follow-up imaging, 145 patients with mammographic changes BIRADS score ≥3 were found of which 50.3% required a biopsy. Only 17 patients had positive biopsies; none of the IOERT parameters were predictive for false-positive imaging. A 9 Gy IOERT boost combined with postoperative WBI provided outstanding local control rates, was well-tolerated, with limited postoperative complications. However, radiologists must be aware of a presumable higher prevalence of mammographic changes after IORT as a boost., (© 2020 Wiley Periodicals, Inc.)

Purpose: To determine whether the use of a preoperative (preop) computed tomography (CT) reduces (1) the clinical target volume boost (CTV boost ) and (2) the interobserver variability (IOV) of the delineated CTV boost in breast radiation therapy., Methods and Materials: In patients treated with breast-conserving therapy, 3 CT scans in treatment position were performed: (1) preop; (2) after surgery, prechemotherapy (postop); and (3) postchemotherapy (postchemo). Six radiation-oncologists delineated the tumor bed and CTV boost before and after fusion of the preop CT. To assess the IOV, the Jaccard index was used. Linear mixed models were performedfor all analyses., Results: Eighty-two lumpectomy cavities were evaluated in 22 patients. No difference in CTV boost using the fusion of the preop CT (50.0 cm 3 ; 95% confidence interval [CI], 35.6-64.4) compared with no fusion (49.0 cm 3 ; 95% CI, 34.6-63.4) (P = .6) was observed. A significant increase in IOV was shown with the fusion of the preop CT; the mean Jaccard index of the CTV boost delineation of postop and postchemo CT together without the fusion of the preop CT was 0.53 (95% CI, 0.49-0.57) versus 0.50 (95% CI, 0.46-0.53) with fusion (P < .0001)., Conclusions: There is no benefit of using a preop CT to reduce the volume or the interobserver variability of the delineated CTV boost for breast radiation therapy., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this article is to compare isotropic and anisotropic margin expansion with regard to the size of the clinical target volume boost (CTV boost ) and the interobserver variability (IOV)., Methods and Materials: Lumpectomy cavities marked with 3 or more surgical clips were delineated by 6 radiation oncologists who specialized in breast radiation therapy. CTV boost anisotropic was created by manually expanding the tumor bed with an anisotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the surgical free margins in 6 directions (anteroposterior, craniocaudal, and superoinferior). For the CTV boost isotropic , the tumor bed was enlarged with an isotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the minimal surgical free margin. The volumes of the delineated CTV boost (cm 3 ) were measured. To assess the IOV, the Jaccard index (JI), defined as the intersection divided by the size of the union of the sample sets, was used (ideal value = 1). The JI was calculated for each case and each observer pair. Linear mixed models were used for all analyses., Results: A total of 444 delineated tumor beds were evaluated. The mean volume of the CTV boost almost doubled by expanding the tumor bed with an isotropic margin compared with anisotropic margins (CTV boost isotropic 94 mL [12.5-331.0] vs CTV boost anisotropic 50 mL [3.2-332.7]; P = .0006). The IOV, assessed by the JI, significantly decreased by using isotropic versus anisotropic margin expansion (JI CTV boost isotropic 0.73 [0.02-0.92] vs JI CTV boost anisotropic 0.51 [0.0-0.8]; P< .0001). Because of the known positive correlation of the IOV and larger volumes, we corrected for CTV boost volumes. With this correction, the difference in IOV remains highly significant (P < .0001) in favor of isotropic margin expansion., Conclusions: The use of anisotropic margin expansion from tumorbed to CTV boost isotropic significantly reduced the volume of the delineated CTV boost with a factor of 1.9 compared with isotropic margin expansion, but it substantially increased the interobserver variability., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients., Methods and Materials: This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT., Results: Mean heart and left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (-17.5% ± 1.9% immediately after RT, -16.6% ± 1.4% at 8 months, and -17.7% ± 1.9% at 14 months vs -19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (-16.6% ± 2.3% immediately after RT, -16% ± 2.6% at 8 months, and -16.8% ± 3% at 14 months vs -19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected., Conclusions: In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical outcome. In the meantime, we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the long-term impact of locoregional breast radiotherapy (RT) on pulmonary function tests (PFTs)., Methods and Materials: This study included 75 women who underwent postoperative locoregional breast RT. PFTs were performed before RT and 3, 6, and 12 months and 8 to 10 years after RT. By use of univariate and multivariate analyses, the impact of treatment- and patient-related factors on late changes in PFTs was evaluated., Results: During the first year after RT, all PFTs significantly worsened at 3 to 6 months after RT (p < 0.05). At 12 months, forced vital capacity (FVC), vital capacity (VC), and forced expiratory volume in 1 second (FEV(1)) recovered almost to baseline values, whereas total lung capacity (TLC) and diffusion capacity of carbon monoxide (DL(CO)) recovered only slightly and were still found to be decreased compared with baseline (p < 0.05). At 8 to 10 years after RT, mean reductions in FEV(1) of 4% (p = 0.03) and in VC, DL(CO), and TLC of 5%, 9%, and 11% (all p < 0.0001), respectively, were observed compared with pre-RT values. On multivariate analysis, tamoxifen use negatively affected TLC at 8 to 10 years after RT (p = 0.033), whereas right-sided irradiation was associated with a late reduction in FEV(1) (p = 0.027). For FEV(1) and DL(CO), an early decrease was predictive for a late decrease (p = 0.003 and p = 0.0009, respectively)., Conclusions: The time course of PFT changes after locoregional RT for breast cancer follows a biphasic pattern. An early reduction in PFTs at 3 to 6 months with a partial recovery at 12 months after RT is followed by a late, more important PFT reduction up to 8 to 10 years after RT. Tamoxifen use may have an impact on this late decline in PFTs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography., Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose., Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S(post-RT): -17.6 ± 1.5%, and S(FUP): -17.4 ± 2.3%, vs. S(baseline): -19.5 ± 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S(post-RT): -15.3 ± 2.5%, and S(FUP): -14.3 ± 3.7%, vs. S(baseline): -19.3 ± 3.0%, p < 0.01; and SR(post-RT): -1.06 ± 0.15 s(-1), and SR(FUP): -1.16 ± 0.28 s(-1), vs. SR(baseline): -1.29 ± 0.27 s(-1), p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S(post-RT): -16.1 ± 1.6%, and S(FUP): -15.8 ± 3.4%, vs. S(baseline): -18.9 ± 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy., Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We evaluated an isocentric technique for conformal irradiation of the breast, internal mammary, and medial supra-clavicular lymph nodes (IM-MS LN) using the oblique parasternal photon (OPP) technique. For 20 breast cancer patients, the OPP technique was compared with a conventional mixed-beam technique (2D) and a conformal partly wide tangential (PWT) technique, using dose-volume histogram analysis and normal tissue complication probabilities (NTCPs). The 3D techniques resulted in a better target coverage and homogeneity than did the 2D technique. The homogeneity index for the IM-MS PTV increased from 0.57 for 2D to 0.90 for PWT and 0.91 for OPP (both p < 0.001). The OPP technique was able to reduce the volume of heart receiving more than 30 Gy (V(30)), the cardiac NTCP, and the volume of contralateral breast receiving 5 Gy (V(5)) compared with the PWT plans (all p < 0.05). There is no significant difference in mean lung dose or lung NTCP between both 3D techniques. Compared with the PWT technique, the volume of lung receiving more than 20 Gy (V(20)) was increased with the OPP technique, whereas the volume of lung receiving more than 40 Gy (V(40)) was decreased (both p < 0.05). Compared with the PWT technique, the OPP technique can reduce doses to the contralateral breast and heart at the expense of an increased lung V(20)., (Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

The Eurasian badger (Meles meles) has been implicated in the transmission of bovine tuberculosis (TB, caused by Mycobacterium bovis) to cattle. However, evidence suggests that attempts to reduce the spread of TB among cattle in Britain by culling badgers have mixed effects. A large-scale field experiment (the randomized badger culling trial, RBCT) showed that widespread proactive badger culling reduced the incidence of TB in cattle within culled areas but that TB incidence increased in adjoining areas. Additionally, localized reactive badger culling increased the incidence of TB in cattle. It has been suggested that culling-induced perturbation of badger social structure may increase individual movements and elevate the risk of disease transmission between badgers and cattle. Field studies support this hypothesis, by demonstrating increases in badger group ranges and the prevalence of TB infection in badgers following culling. However, more evidence on the effect of culling on badger movements is needed in order to predict the epidemiological consequences of this control strategy. Here, analysis of the genetic signatures of badger populations in the RBCT revealed increased dispersal following culling. While standard tests provided evidence for greater dispersal after culling, a novel method indicated that this was due to medium- and long-distance dispersal, in addition to previously reported increases in home-range size. Our results also indicated that, on average, badgers infected with M. bovis moved significantly farther than did uninfected badgers. A disease control strategy that included culling would need to take account of the potentially negative epidemiological consequences of increased badger dispersal.

A recent meta-analysis, published by the Early Breast Cancer Trialists' Collaborative Group, demonstrated a clear survival advantage of post-operative radiotherapy on the breast, chest wall and regional lymphatics in node-positive disease. The extensive target volume in locoregional irradiation of breast cancer, in close proximity to the heart and lungs, complicates treatment planning. The breast or chest wall fields need to match the supraclavicular/axillary and parasternal fields, at the subclavicular and parasternal matchline, respectively. Dose distribution near the junction area is often inhomogeneous, and under- and over-dosage can occur, which can lead to recurrences and complications. This paper describes briefly the indications, complications and target localization concerning regional lymph node radiotherapy and discusses more extensively the advantages and disadvantages of the most frequently used treatment techniques.

Badgers are facultatively social, forming large groups at high density. Group-living appears to have high reproductive costs for females, and may lead to increased levels of inbreeding. The extent of female competition for reproduction has been estimated from field data, but knowledge of male reproductive success and the extent of extra-group paternity remains limited. Combining field data with genetic data (16 microsatellite loci), we studied the mating system of 10 badger social groups across 14 years in a high-density population. From 923 badgers, including 425 cubs, we were able to assign maternity to 307 cubs, with both parents assigned to 199 cubs (47%) with 80% confidence, and 14% with 95% confidence. Age had a significant effect on the probability of reproduction, seemingly as a result of a deficit of individuals aged two years and greater than eight years attaining parentage. We estimate that approximately 30% of the female population successfully reproduced in any given year, with a similar proportion of the male population gaining paternity across the same area. While it was known there was a cost to female reproduction in high density populations, it appears that males suffer similar, but not greater, costs. Roughly half of assigned paternity was attributed to extra-group males, the majority of which were from neighbouring social groups. Few successful matings occurred between individuals born in the same social group (22%). The high rate of extra-group mating, previously unquantified, may help reduce inbreeding, potentially making philopatry a less costly strategy.

Background and Purpose: To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients., Patients and Methods: Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated., Results: Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value<0.0001). A significant difference in loss of salivary excretion fraction (dSEF) was also observed between both parotid glands (P<0.0001) as a result of the parotid-sparing technique. When plotting the dSEF of a slice versus the dose given to that slice, doses as low as 10-15 Gy could result in a serious loss of function (dSEF>50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50., Conclusions: Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy.