The impact of surgery for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of treatment: A longitudinal, mixed methods study

© 2015 The Authors.Objective: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. Methods: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. Results: Mean age was 59.9 years (SD=15.3; range=23.8-86.6 yrs). Mean BMI was 30.0 (SD=4.5; range=24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p=< 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p=0.037). Conclusions: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications

The effect of pressure on DNA deposition by touch

Casework exhibits are routinely examined for DNA that might have been deposited by touch, although the success of downstream profiling can vary. Many variables affect DNA deposition by touch, such as ‘shedder status’, surface type, and nature of contact. This may include pressure, which has been shown to increase the transfer of DNA between two surfaces, although whether pressure can impact DNA deposition directly from skin has yet to be examined. Therefore, this study uses a novel method to investigate whether pressure can affect the amount and quality of DNA directly deposited by touch. With the fingertips of one hand, volunteers exerted pressure for one minute onto a DNA-free polycarbonate board placed on top of a balance; all five fingermarks were then swabbed and combined as one sample for DNA extraction, quantification and profiling. For each hand, the area of the combined fingertips was used to determine the weight value to which to push the balance to give pressures of 4, 21 or 37 kPa. Volunteers used both their right and left hands at each pressure in a randomised order on each day of three non-consecutive days. Increasing the pressure between skin and surface significantly increased the amount of DNA deposited, which resulted in the detection of more alleles, from both the donor and unknown sources. No significant differences were observed in the amounts of DNA deposited between hands and among different days for each volunteer. DNA amounts significantly varied between individuals at 21 and 37 kPa, but not at 4 kPa. These findings provide insights into the impact of pressure on touch DNA deposition, and suggest that pressure is a key variable for crime scene investigators and forensic examiners to consider when prioritising items/surfaces that are likely to produce successful touch DNA results during a criminal investigation

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: The Cancer, Fertility and Me research protocol

Introduction: Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services whilst undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women’s fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the ‘Cancer, Fertility and Me’ study is to develop and evaluate a new evidence-based patient decision aid (ptDA) for women with any cancer considering fertility preservation to address this unmet need. Methods and analysis: This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In Stage 1 the aim is to develop the ptDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In Stage 2, the aim is to assess the face validity of the ptDA. Feedback on its content and format will be ascertained using both questionnaires and interviews with patients, user groups and key stakeholders. Finally, in Stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the ptDA in clinical practice. Measures chosen include using count data of the ptDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t tests and confidence intervals; interviews will be analysed using thematic analysis. Ethics and dissemination: Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me ptDA will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of ptDAs and other relevant professional organisations e.g. the British Fertility Society. Trial registration number: NCT02753296 (www.clinicaltrials.gov); pre-results

The impact of image dynamic range on texture classification of brain white matter

<p>Abstract</p> <p>Background</p> <p>The Greylevel Cooccurrence Matrix method (COM) is one of the most promising methods used in Texture Analysis of Magnetic Resonance Images. This method provides statistical information about the spatial distribution of greylevels in the image which can be used for classification of different tissue regions. Optimizing the size and complexity of the COM has the potential to enhance the reliability of Texture Analysis results. In this paper we investigate the effect of matrix size and calculation approach on the ability of COM to discriminate between peritumoral white matter and other white matter regions.</p> <p>Method</p> <p>MR images were obtained from patients with histologically confirmed brain glioblastoma using MRI at 3-T giving isotropic resolution of 1 mm³. Three Regions of Interest (ROI) were outlined in visually normal white matter on three image slices based on relative distance from the tumor: one peritumoral white matter region and two distant white matter regions on both hemispheres. Volumes of Interest (VOI) were composed from the three slices. Two different calculation approaches for COM were used: i) Classical approach (CCOM) on each individual ROI, and ii) Three Dimensional approach (3DCOM) calculated on VOIs. For, each calculation approach five dynamic ranges (number of greylevels N) were investigated (N = 16, 32, 64, 128, and 256).</p> <p>Results</p> <p>Classification showed that peritumoral white matter always represents a homogenous class, separate from other white matter, regardless of the value of N or the calculation approach used. The best test measures (sensitivity and specificity) for average CCOM were obtained for N = 128. These measures were also optimal for 3DCOM with N = 128, which additionally showed a balanced tradeoff between the measures.</p> <p>Conclusion</p> <p>We conclude that the dynamic range used for COM calculation significantly influences the classification results for identical samples. In order to obtain more reliable classification results with COM, the dynamic range must be optimized to avoid too small or sparse matrices. Larger dynamic ranges for COM calculations do not necessarily give better texture results; they might increase the computation costs and limit the method performance.</p

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt

QiSampler: evaluation of scoring schemes for high-throughput datasets using a repetitive sampling strategy on gold standards

<p>Abstract</p> <p>Background</p> <p>High-throughput biological experiments can produce a large amount of data showing little overlap with current knowledge. This may be a problem when evaluating alternative scoring mechanisms for such data according to a gold standard dataset because standard statistical tests may not be appropriate.</p> <p>Findings</p> <p>To address this problem we have implemented the QiSampler tool that uses a repetitive sampling strategy to evaluate several scoring schemes or experimental parameters for any type of high-throughput data given a gold standard. We provide two example applications of the tool: selection of the best scoring scheme for a high-throughput protein-protein interaction dataset by comparison to a dataset derived from the literature, and evaluation of functional enrichment in a set of tumour-related differentially expressed genes from a thyroid microarray dataset.</p> <p>Conclusions</p> <p>QiSampler is implemented as an open source R script and a web server, which can be accessed at <url>http://cbdm.mdc-berlin.de/tools/sampler/</url>.</p

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes

Aims: Biomarker‐driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub‐classify iMB, and proffer strategies for personalized, risk‐adapted therapies. Methods: We characterized the iMB molecular landscape, including second‐generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). Results: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second‐generation subtypes II/III/IV. Subtype II strongly associated with large‐cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very‐high‐risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4) and subtype IV tumours were standard risk (80% OS) using upfront CSI‐based therapies; randomized‐controlled trials of upfront radiation‐sparing and/or second‐line radiotherapy should be considered. Seventy‐five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non‐DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH. iMBSHH harboured two distinct subtypes (iMBSHH‐I/II). Within the discriminated favourable‐risk iMBSHH DN/MBEN patient group, iMBSHH‐II had significantly better progression‐free survival than iMBSHH‐I, offering opportunities for risk‐adapted stratification of upfront therapies. Both iMBSHH‐I and iMBSHH‐II showed notable rescue rates (56% combined post‐relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. Conclusions: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup‐dependent survival models highlight opportunities for biomarker‐directed therapies

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered