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Purpose: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands., Methods: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results., Results: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC., Conclusions: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited., (© 2024. The Author(s).)

Importance: Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late local toxic effects after breast irradiation. Strong evidence of effectiveness is lacking., Objective: To assess effectiveness of HBOT for late local toxic effects in women who received adjuvant radiotherapy for breast cancer., Design, Setting, and Participants: This was a hospital-based, pragmatic, 2-arm, randomized clinical trial nested within the prospective UMBRELLA cohort following the trials within cohorts design in the Netherlands. Participants included 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction 12 months or longer after breast irradiation. Data analysis was performed from May to September 2023., Intervention: Receipt of 30 to 40 HBOT sessions over a period of 6 to 8 consecutive weeks., Main Outcomes and Measures: Breast, chest wall, and/or shoulder pain 6 months postrandomization measured by the European Organization for Research and Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were patient-reported fibrosis, edema, movement restriction, and overall quality of life. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles., Results: Between November 2019 and August 2022, 125 women (median [range] age at randomization, 56 [37-85] years) with late local toxic effects were offered to undergo HBOT (intervention arm), and 61 women (median [range] age at randomization, 60 [36-80] years) were randomized to the control arm. Of those offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity. In ITT, moderate or severe pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI, 0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75% (9.7 of 12.9) among control participants expected to complete HBOT if offered (adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49 (51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no significant differences in breast edema, movement restriction, and quality of life between groups in ITT and CACE., Conclusions and Relevance: In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller than anticipated proportion of women with late local toxic effects was prepared to undergo HBOT., Trial Registration: ClinicalTrials.gov Identifier: NCT04193722.

Background and Objective: Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo., Materials and Methods: DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study., Results: Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively., Conclusion: We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The success of radiofrequency (RF) ablation is limited by the inability to assess thermal tissue damage achieved during or immediately after the procedure. The goal of this proof-of-principle study was to investigate whether diffuse reflectance (DR) spectroscopy during and after RF ablation of liver tumours could aid in detecting complete tissue ablation., Material and Methods: DR spectra were acquired in vivo in eight patients undergoing RF ablation for unresectable colorectal liver metastases, using a disposable spectroscopy needle. Intraoperative ultrasound imaging was used for accurate positioning of the RF electrode and the spectroscopy needle. Spectral changes were quantified and correlated to tissue histopathology and follow-up CT imaging., Results: For the lesions in which ablation was monitored by DR spectroscopy (N = 8), median tumour size was 1.6 cm (range 0.8-3.3 cm). We found an excellent correlation (97-99%) between thermal damage suggested by spectral changes and histology. DR spectroscopy allowed discrimination between non-ablated and ablated tissue, regardless whether the needle was placed in tumour tissue or in surrounding liver tissue. Additional measurements performed continuously during ablation confirmed that the magnitude of spectral change correlates with the histochemical degree of thermal damage., Conclusions: Diffuse reflectance spectroscopy allows accurate quantification of thermal tissue damage during and after RF ablation. Real-time feedback by DR spectroscopy could improve the accuracy and quality of the RF procedures by lowering incomplete ablation rates., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers., Experimental Design: Tissues from 21 consented patients undergoing lung cancer surgery were measured intraoperatively using the fiber-optic platform capable of assessing various physical tissue properties highly correlated to tissue architecture and composition. In addition, the method was tested for clinical use by performing DRS tissue sensing during 11 routine biopsy procedures in patients with suspected lung cancer., Results: We found that water content and scattering amplitude are the primary discriminators for the transition from healthy lung tissue to tumor tissue and that the reliability of these parameters is not affected by the amount of blood at the needle tip. In the 21 patients measured intraoperatively, the water-to-scattering ratio yielded a 56% to 81% contrast difference between tumor and surrounding tissue. Analysis of the 11 image-guided lung biopsy procedures showed that the tissue diagnosis derived from DRS was diagnostically discriminant in each clinical case., Conclusions: DRS tissue sensing integrated into a biopsy needle may be a powerful new tool for biopsy guidance that can be readily used in routine diagnostic lung biopsy procedures. This approach may not only help to increase the successful biopsy yield for histopathologic analysis, but may also allow specific sampling of vital tumor tissue for genetic profiling., (©2015 American Association for Cancer Research.)

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real-time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy-eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery., (© 2015 Steunstichting ESOT.)

High-throughput DNA sequencing has considerably changed the possibilities for conducting biomedical research by measuring billions of short DNA or RNA fragments. A central computational problem, and for many applications a first step, consists of determining where the fragments came from in the original genome. In this article, we review the main techniques for generating the fragments, the main applications, and the main algorithmic ideas for computing a solution to the read alignment problem. In addition, we describe pitfalls and difficulties connected to determining the correct positions of reads.

Despite the widespread use of radio frequency (RF) ablation, an effective way to assess thermal tissue damage during and after the procedure is still lacking. We present a method for monitoring RF ablation efficacy based on thermally induced methemoglobin as a marker for full tissue ablation. Diffuse reflectance (DR) spectra were measured from human blood samples during gradual heating of the samples from 37 to 60, 70, and 85°C. Additionally, reflectance spectra were recorded real-time during RF ablation of human liver tissue ex vivo and in vivo. Specific spectral characteristics of methemoglobin were extracted from the spectral slopes using a custom optical ablation ratio. Thermal coagulation of blood caused significant changes in the spectral slopes, which is thought to be caused by the formation of methemoglobin. The time course of these changes was clearly dependent on the heating temperature. RF ablation of liver tissue essentially led to similar spectral alterations. In vivo DR measurements confirmed that the method could be used to assess the degree of thermal damage during RF ablation and long after the tissue cooled.

Introduction: Anatomic imaging alone is often inadequate for tuning systemic treatment for individual tumor response. Optically based techniques could potentially contribute to fast and objective response monitoring in personalized cancer therapy. In the present study, we evaluated the feasibility of dual-modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS) to monitor the effects of systemic treatment in a mouse model for hereditary breast cancer., Methods: Brca1(-/-); p53(-/-) mammary tumors were grown in 36 mice, half of which were treated with a single dose of cisplatin. Changes in the tumor physiology and morphology were measured for a period of 1 week using dual-modality DRS-AFS. Liver and muscle tissues were also measured to distinguish tumor-specific alterations from systemic changes. Model-based analyses were used to derive different optical parameters like the scattering and absorption coefficients, as well as sources of intrinsic fluorescence. Histopathologic analysis was performed for cross-validation with trends in optically based parameters., Results: Treated tumors showed a significant decrease in Mie-scattering slope and Mie-to-total scattering fraction and an increase in both fat volume fraction and tissue oxygenation after 2 days of follow-up. Additionally, significant tumor-specific changes in the fluorescence spectra were seen. These longitudinal trends were consistent with changes observed in the histopathologic analysis, such as vital tumor content and formation of fibrosis., Conclusions: This study demonstrates that dual-modality DRS-AFS provides quantitative functional information that corresponds well with the degree of pathologic response. DRS-AFS, in conjunction with other imaging modalities, could be used to optimize systemic cancer treatment on the basis of early individual tumor response., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: A significant number of transthoracic diagnostic biopsy procedures for lung lesions show indeterminate results. Such failures are potentially due to inadequate recognition of vital tumor tissue. The objective of this study was to evaluate whether optical spectroscopy at the tip of a biopsy needle device can improve the accuracy of transthoracic lung biopsies., Methods: Ex vivo optical measurements were performed on lung tissue from 13 patients who underwent either lobectomy or segmental resection for primary non-small cell lung cancer or pulmonary metastases from various origins. From Diffuse Reflectance Spectroscopy (DRS) and Fluorescence Spectroscopy (FS) measurements, different parameters were derived such as tissue composition as well as physiological and metabolic characteristics. Subsequently, a classification and regression trees (CART) algorithm was used to classify the type of tissue based on the derived parameters. Histology analysis was used as gold standard to report sensitivity and specificity of the tissue classification based on the present optical method., Results: Collective analysis of all DRS measurements showed an overall discrimination between lung parenchyma and tumor tissue with a sensitivity and specificity of 98 and 86%, respectively. When the data were analyzed per individual patient, eliminating inter-patient variation, 100% sensitivity and specificity was achieved. Furthermore, based on FS parameters, necrotic and non-necrotic tumor tissue could be distinguished with 91% sensitivity and specificity., Conclusion: This study demonstrates that DRS provides accurate diagnosis of malignant lung lesions, whereas FS enables identification of necrotic tissue. When both optical techniques are combined within a biopsy device, the diagnostic performance and the quality of transthoracic biopsies could significantly be enhanced., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Diffuse reflectance spectroscopy (DRS) is a promising new technique for breast cancer diagnosis. However, inter-patient variation due to breast tissue heterogeneity may interfere with the accuracy of this technique. To tackle this issue, we aim to determine the diagnostic accuracy of DRS in individual patients. With this approach, DRS measurements of normal breast tissue in every individual patient are directly compared with measurements of the suspected malignant tissue. Breast tissue from 47 female patients was analysed ex vivo by DRS. A total of 1,073 optical spectra were collected. These spectra were analyzed for each patient individually as well as for all patients collectively and results were compared to the pathology analyses. Collective patient data analysis for discrimination between normal and malignant breast tissue resulted in a sensitivity of 90 %, a specificity of 88 %, and an overall accuracy of 89 %. In the individual analyses all measurements per patient were categorized as either benign or malignant. The discriminative accuracy of these individual analyses was nearly 100 %. The diagnosis was classified as uncertain in only one patient. Based on the results presented in this study, we conclude that the analysis of optical characteristics of different tissue classes within the breast of a single patient is superior to an analysis using the results of a cohort data analysis. When integrated into a biopsy device, our results demonstrate that DRS may have the potential to improve the diagnostic workflow in breast cancer.

Background: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools., Methods: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis., Results: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86., Conclusions: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Failure to extinguish fear can lead to persevering anxiety and has been postulated as an important mechanism in the pathogenesis of human anxiety disorders. In animals, it is well documented that the endogenous cannabinoid system has a pivotal role in the successful extinction of fear, most importantly through the cannabinoid receptor 1. However, no human studies have reported a translation of this preclinical evidence yet. Healthy medication-free human subjects (N=150) underwent a fear conditioning and extinction procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex was measured to assess fear-conditioned responding, and subjective fear ratings were collected. Participants were genotyped for two polymorphisms located within the promoter region (rs2180619) and the coding region (rs1049353) of cannabinoid receptor 1. As predicted from the preclinical literature, acquisition and expression of conditioned fear did not differ between genotypes. Crucially, whereas both homozygote (G/G, N=23) and heterozygote (A/G, N=68) G-allele carriers of rs2180619 displayed robust extinction of fear, extinction of fear-potentiated startle was absent in A/A homozygotes (N=51). Additionally, this resistance to extinguish fear left A/A carriers of rs2180619 with significantly higher levels of fear-potentiated startle at the end of the extinction training. No effects of rs1049353 genotype were observed regarding fear acquisition and extinction. These results suggest for the first time involvement of the human endocannabinoid system in fear extinction. Implications are that genetic variability in this system may underlie individual differences in anxiety, rendering cannabinoid receptor 1 a potential target for novel pharmacological treatments of anxiety disorders.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Whole genome amplification by the multiple displacement amplification (MDA) method allows sequencing of DNA from single cells of bacteria that cannot be cultured. Assembling a genome is challenging, however, because MDA generates highly nonuniform coverage of the genome. Here we describe an algorithm tailored for short-read data from single cells that improves assembly through the use of a progressively increasing coverage cutoff. Assembly of reads from single Escherichia coli and Staphylococcus aureus cells captures >91% of genes within contigs, approaching the 95% captured from an assembly based on many E. coli cells. We apply this method to assemble a genome from a single cell of an uncultivated SAR324 clade of Deltaproteobacteria, a cosmopolitan bacterial lineage in the global ocean. Metabolic reconstruction suggests that SAR324 is aerobic, motile and chemotaxic. Our approach enables acquisition of genome assemblies for individual uncultivated bacteria using only short reads, providing cell-specific genetic information absent from metagenomic studies.

We report on the use of diffuse optical spectroscopy analysis of breast spectra acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A total of 102 ex vivo samples of five different breast tissue types, namely adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ from 52 patients were measured. A model deriving from the diffusion theory was applied to the measured spectra in order to extract clinically relevant parameters such as blood, water, lipid, and collagen volume fractions, β-carotene concentration, average vessels radius, reduced scattering amplitude, Mie slope, and Mie-to-total scattering fraction. Based on a classification and regression tree algorithm applied to the derived parameters, a sensitivity-specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic performance of 94%. Sensitivity-specificity values obtained for discriminating malignant from nonmalignant tissue were compared to existing reported studies by applying the different classification methods that were used in each of these studies. Furthermore, in these reported studies, either lipid or β-carotene was considered as adipose tissue precursors. We estimate both chromophore concentrations and demonstrate that lipid is a better discriminator for adipose tissue than β-carotene.

We investigated differences between healthy tissue and metastatic tumor from ex vivo human partial liver resections using diffuse optical spectroscopy with a fiber optic probe. We extracted various physiological and morphological parameters from the spectra. During evaluation of the residual between the measurements and a fit model based on diffusion theory, we found that bile is an additional chromophore absorbing in the visible wavelength range that was missing in our model. Consistency of the residual with the absorption spectrum of bile was noticed. An accurate measurement of the absorption coefficient of bile from various human bile samples was performed and implemented into the fit model. Having the absorption coefficient of bile as a priori knowledge in the model showed a clear improvement in terms of reducing the fitting discrepancies. The addition of this chromophore yields significantly different estimates of the amount of blood. Furthermore, the estimated bile volume fraction and reduced scattering amplitude turned out to be two main relevant discriminators between normal and metastatic liver tissues.

Background: The incidence of ovarian metastases at the time of peritoneal carcinomatosis, and the influence of such metastases on survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), are unknown., Methods: This retrospective analysis included 194 women subjected to CRS and HIPEC since 2001. The incidence of ovarian metastases, disease-free survival and disease-specific survival were analysed., Results: The histological diagnosis was colorectal cancer carcinomatosis in 108 patients, peritoneal mucinous carcinomatosis (PMCA) in 23 and disseminated peritoneal adenomucinosis (DPAM) in 63. Ninety-nine patients underwent oophorectomy during the HIPEC procedure. Ovarian metastases were confirmed in at least 52 per cent of the patients. There was a significant difference in disease-free survival between women with or without ovarian metastases in both PMCA and DPAM groups (P = 0·044 and P = 0·010 respectively). No significant differences in survival were found in the group with colorectal cancer carcinomatosis., Conclusion: When peritoneal carcinomatosis of colorectal or appendiceal origin is confirmed, at least 52 per cent of ovaries will have synchronous metastases. Disease-free survival after a HIPEC procedure for PMCA or DPAM is significantly lower in women with ovarian metastases. Oophorectomy during CRS for peritoneal carcinomatosis should be strongly considered.

Background: Delayed gastric emptying (DGE) is a main complication with unknown origin after a cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC). The aim of this study was to investigate if preservation of the right gastro-epiploic artery (GEA) during standard omentectomy would have a positive effect on gastric emptying after CRS-HIPEC., Methods: Forty-two patients subjected to a CRS-HIPEC were randomized into two groups perioperatively before performing an omentectomy: in Group I (N = 21) omentectomy was performed with preservation of the GEA; in Group II (N = 21) omentectomy was performed with resection of the GEA. The primary endpoint was the number of days to full oral intake of solid food. Secondary endpoints were number of days to intended occlusion of gastrostomy catheter and total hospital admission time., Results: No significant differences were discovered between both groups in any of the study endpoints after CRS-HIPEC. No significant differences were observed in patient or operation characteristics between the randomized groups., Conclusions: No association was demonstrated between preservation of the gastro-epiploic artery during omentectomy and gastric emptying after CRS-HIPEC. The extensive intestinal manipulation or the heated intra-peritoneal chemotherapy during surgery are more plausible causes of this phenomenon. This clinical trial was registered in the Netherlands at the Central Committee on Research involving Human Subjects (CCMO) under registration number P06.0301L., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Motivation: Copy number abnormalities (CNAs) represent an important type of genetic mutation that can lead to abnormal cell growth and proliferation. New high-throughput sequencing technologies promise comprehensive characterization of CNAs. In contrast to microarrays, where probe design follows a carefully developed protocol, reads represent a random sample from a library and may be prone to representation biases due to GC content and other factors. The discrimination between true and false positive CNAs becomes an important issue., Results: We present a novel approach, called CNAseg, to identify CNAs from second-generation sequencing data. It uses depth of coverage to estimate copy number states and flowcell-to-flowcell variability in cancer and normal samples to control the false positive rate. We tested the method using the COLO-829 melanoma cell line sequenced to 40-fold coverage. An extensive simulation scheme was developed to recreate different scenarios of copy number changes and depth of coverage by altering a real dataset with spiked-in CNAs. Comparison to alternative approaches using both real and simulated datasets showed that CNAseg achieves superior precision and improved sensitivity estimates., Availability: The CNAseg package and test data are available at http://www.compbio.group.cam.ac.uk/software.html.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.

A 66-year old woman was admitted with an acute symptomatic abdominal aortic aneurysm. After preoperative assessment, she was directly operated on via transperitoneal approach. Intraoperatively, a left-sided inferior vena cava was diagnosed. The preoperative study of the abdominal computed tomography had not revealed this venous malformation. Retroperitoneal venous anomalies are a major source of unexpected haemorrhage during aortic reconstruction. Thus, for optimal preoperative preparation, a systematic close examination of the preoperative contrast enhanced CT scan of the abdomen is advised.

RNA Movies is a simple, yet powerful visualization tool in likeness to a media player application, which enables to browse sequential paths through RNA secondary structure landscapes. It can be used to visualize structural rearrangement processes of RNA, such as folding pathways and conformational switches, or to browse lists of alternative structure candidates. Besides extending the feature set, retaining and improving usability and availability in the web is the main aim of this new version. RNA Movies now supports the DCSE and RNAStructML input formats besides its own RNM format. Pseudoknots and 'entangled helices' can be superimposed on the RNA secondary structure layout. Publication quality output is provided through the Scalable Vector Graphics output format understood by most current drawing programs. The software has been completely re-implemented in Java to enable pure client-side operation as applet and web-start application available at the Bielefeld Bioinformatics Server http://bibiserv.techfak.uni-bielefeld.de/rnamovies.

Background: Although mental stress is commonly considered to be an important trigger factor for migraine, experimental evidence for this belief is yet lacking., Objective: To study the temporal relationship between changes in stress-related parameters (both subjective and objective) and the onset of a migraine attack., Methods: This was a prospective, ambulatory study in 17 migraine patients. We assessed changes in perceived stress and objective biological measures for stress (saliva cortisol, heart rate average [HRA], and heart rate variability [low-frequency power and high-frequency power]) over 4 days prior to the onset of spontaneous migraine attacks. Analyses were repeated for subgroups of patients according to whether or not they felt their migraine to be triggered by stress., Results: There were no significant temporal changes over time for the whole group in perceived stress (p=0.50), morning cortisol (p=0.73), evening cortisol (p=0.55), HRA (p=0.83), low-frequency power (p=0.99) and high-frequency power (p=0.97) prior to or during an attack. Post hoc analysis of the subgroup of nine stress-sensitive patients who felt that >2/3 of their migraine attacks were triggered by psychosocial stress, revealed an increase for perceived stress (p=0.04) but no changes in objective stress response measures. At baseline, this group also showed higher scores on the Penn State Worry Questionnaire (p=0.003) and the Cohen Perceived Stress Scale (p=0.001) compared to non-stress-sensitive patients., Conclusions: Although stress-sensitive patients, in contrast to non-stress-sensitive patients, may perceive more stress in the days before an impending migraine attack, we failed to detect any objective evidence for a biological stress response before or during migraine attacks.