Prevalence and impact of childhood adversities and post-traumatic stress disorder in women with fibromyalgia and chronic widespread pain.

OBJECTIVE: This study investigates the prevalence of different types of childhood adversities (CA) and posttraumatic stress disorder (PTSD) in female patients with Fibromyalgia or Chronic Widespread Pain (FM/CWP) compared to patients with Functional Dyspepsia (FD) and achalasia. In FM/CWP, we also investigated the association between CA and PTSD on the one hand and pain severity on the other. METHODS: Patient samples consisted of 154 female FM/CWP, 83 female FD and 53 female achalasia patients consecutively recruited from a tertiary care hospital. Well-validated self-report questionnaires were used to investigate CA and PTSD. RESULTS: Forty-nine per cent of FM/CWP patients reported at least 1 type of CA, compared to 39.7% of FD patients and 23.4% of achalasia patients (p < 0.01). The prevalence of CA did not differ significantly between FM/CWP and FD, but both groups had a higher prevalence of CA compared to both achalasia and healthy controls (p < 0.01). FM/CWP patients were six times more likely to report PTSD than both FD (p < 0.001) and achalasia (p < 0.001) patients. CONCLUSION: In FM/CWP, PTSD comorbidity, but not CA, was associated with self-reported pain severity and PTSD severity mediated the relationship between CA and pain severity. In summary, the prevalence of CA is higher in FM/CWP compared to achalasia, but similar to FD. However, PTSD is more prevalent in FM/CWP compared to FD and associated with higher pain intensity in FM/CWP. SIGNIFICANCE: As expected and has been shown in other functional disorders, we found elevated levels of childhood adversity in FM/CWP patients. Results of this study however suggest that the impact of childhood adversity (i.e. whether such events have led to the development of PTSD symptoms), rather than the mere presence of such adversity, is of crucial importance in FM/CWP patients. Screening for PTSD symptoms should be an essential part of the assessment process in patients suffering from FM/CWP, and both prevention and intervention efforts should take into account PTSD symptoms and their impact on pain severity and general functioning

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

<p>Abstract</p> <p>Background</p> <p>To assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.</p> <p>Methods</p> <p>We quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.</p> <p>Results</p> <p>The median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm³(range, 7.17 - 14.3 cm³) and 1.99 for pituitary adenoma, and 6.86 cm³(range 6.05 - 14.6 cm³) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm³for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm³(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm³) than group 2 (6.91 ± 0.7 cm³, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.</p> <p>Conclusion</p> <p>Quality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.</p

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors

Abstract Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images

Integrated-boost IMRT or 3-D-CRT using FET-PET based auto-contoured target volume delineation for glioblastoma multiforme - a dosimetric comparison

<p>Abstract</p> <p>Background</p> <p>Biological brain tumor imaging using O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET)-PET combined with inverse treatment planning for locally restricted dose escalation in patients with glioblastoma multiforme seems to be a promising approach.</p> <p>The aim of this study was to compare inverse with forward treatment planning for an integrated boost dose application in patients suffering from a glioblastoma multiforme, while biological target volumes are based on FET-PET and MRI data sets.</p> <p>Methods</p> <p>In 16 glioblastoma patients an intensity-modulated radiotherapy technique comprising an integrated boost (IB-IMRT) and a 3-dimensional conventional radiotherapy (3D-CRT) technique were generated for dosimetric comparison. FET-PET, MRI and treatment planning CT (P-CT) were co-registrated. The integrated boost volume (PTV1) was auto-contoured using a cut-off tumor-to-brain ratio (TBR) of ≥ 1.6 from FET-PET. PTV2 delineation was MRI-based. The total dose was prescribed to 72 and 60 Gy for PTV1 and PTV2, using daily fractions of 2.4 and 2 Gy.</p> <p>Results</p> <p>After auto-contouring of PTV1 a marked target shape complexity had an impact on the dosimetric outcome. Patients with 3-4 PTV1 subvolumes vs. a single volume revealed a significant decrease in mean dose (67.7 vs. 70.6 Gy). From convex to complex shaped PTV1 mean doses decreased from 71.3 Gy to 67.7 Gy. The homogeneity and conformity for PTV1 and PTV2 was significantly improved with IB-IMRT. With the use of IB-IMRT the minimum dose within PTV1 (61.1 vs. 57.4 Gy) and PTV2 (51.4 vs. 40.9 Gy) increased significantly, and the mean EUD for PTV2 was improved (59.9 vs. 55.3 Gy, p < 0.01). The EUD for PTV1 was only slightly improved (68.3 vs. 67.3 Gy). The EUD for the brain was equal with both planning techniques.</p> <p>Conclusion</p> <p>In the presented planning study the integrated boost concept based on inversely planned IB-IMRT is feasible. The FET-PET-based automatically contoured PTV1 can lead to very complex geometric configurations, limiting the achievable mean dose in the boost volume. With IB-IMRT a better homogeneity and conformity, compared to 3D-CRT, could be achieved.</p

Second Language Processing Shows Increased Native-Like Neural Responses after Months of No Exposure

Although learning a second language (L2) as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2—particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP) study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes—including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research program with potentially important consequences for second language acquisition and related fields

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer