Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts.

An Evaluation of Atlas Selection Methods for Atlas-Based Automatic Segmentation in Radiotherapy Treatment Planning.

Atlas-based automatic segmentation is used in radiotherapy planning to accelerate the delineation of organs at risk (OARs). Atlas selection has been proposed as a way to improve the accuracy and execution time of segmentation, assuming that, the more similar the atlas is to the patient, the better the results will be. This paper presents an analysis of atlas selection methods in the context of radiotherapy treatment planning.

Uncovering Female Child Sexual Offenders-Needs and Challenges for Practice and Research.

This article provides a short literature overview on female child sexual offenders (FCSO) focusing on the discrepancy between prevalence rates from different sources, characteristics of FCSO and their victims, as well as the societal "culture of denial" surrounding these women. FCSO are a powerful social taboo. Even professionals in the healthcare or justice system were shown to respond inappropriately in cases of child sexual abuse committed by women.

Paving the Way for Therapy: The Second International Conference of the Trisomy 21 Research Society.

In the last decade, a number of important research advances in different fields have allowed Down syndrome (DS) research to flourish, creating a time of both unparalleled opportunity and considerable challenge. Building a scientific framework that distills mechanisms involved in the developmental intellectual disability of DS as well as the early-onset component of Alzheimer disease and the several other comorbidities associated with the condition is a challenge that scientists are now tackling using novel technologies and multidisciplinary approaches. The Trisomy 21 Research Society (T21RS) was founded in 2014 to address these evolving needs and challenges.

The Benefits and Challenges of Using Patient Decision Aids to Support Shared Decision Making in Health Care.

Shared decision making (SDM) and patient-centered care require patients to actively participate in the decision-making process. Yet with the increasing number and complexity of cancer treatment options, it can be a challenge for patients to evaluate clinical information and make risk-benefit trade-offs to choose the most appropriate treatment. Clinicians face time constraints and communication challenges, which can further hamper the SDM process.

Multicenter CT phantoms public dataset for radiomics reproducibility tests.

Purpose: The aim of this paper is to describe a public, open-access, computed tomography (CT) phantom image set acquired at three centers and collected especially for radiomics reproducibility research. The dataset is useful to test radiomic features reproducibility with respect to various parameters, such as acquisition settings, scanners, and reconstruction algorithms.

Acquisition And Validation Methods: Three phantoms were scanned in three independent institutions.

Pornographic Content and Real-Life Sexual Experiences: Findings From a Survey of German University Students.

The aim of this study was to explore liked pornographic content and real-life experience with the depicted sexual activities in a nationwide sample of 1,197 German university students. The results indicate that there is a positive, content-specific association. Generally, the link was stronger for less conventional (less widespread) practices.

Cost-effectiveness analysis of a GP- and parent-directed intervention to reduce antibiotic prescribing for children with respiratory tract infections in primary care.

Objectives: We evaluated costs and effects of the RAAK (RAtional Antibiotic use Kids) intervention (GP online training and information booklets for parents), aiming to reduce antibiotic prescribing for children with respiratory tract infection (RTI).

Methods: We conducted a trial-based cost-effectiveness analysis from a societal perspective. We included children consulting the GP with RTI for whom parents kept a 2 week (cost) diary.

Parents' attitudes and views regarding antibiotics in the management of respiratory tract infections in children: a qualitative study of the influence of an information booklet.

Background: Respiratory tract infection (RTI) is the most common reason to consult a GP during childhood, and often results in unnecessary prescribing of antibiotics. Using an information booklet during the consultation has been shown to be a promising tool to reduce antibiotic prescribing. The influence of such information on parents' views, knowledge, and expectations has not been investigated yet.

Phenology of Trichodesmium spp. blooms in the Great Barrier Reef lagoon, Australia, from the ESA-MERIS 10-year mission.

Trichodesmium, a filamentous bloom-forming marine cyanobacterium, plays a key role in the biogeochemistry of oligotrophic ocean regions because of the ability to fix nitrogen. Naturally occurring in the Great Barrier Reef (GBR), the contribution of Trichodesmium to the nutrient budget may be of the same order as that entering the system via catchment runoff. However, the cyclicity of Trichodesmium in the GBR is poorly understood and sparsely documented because of the lack of sufficient observations.

OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer.

Background: Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.

Patients And Methods: Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.

External validation of a prognostic model incorporating quantitative PET image features in oesophageal cancer.

Aim: Enhanced prognostic models are required to improve risk stratification of patients with oesophageal cancer so treatment decisions can be optimised. The primary aim was to externally validate a published prognostic model incorporating PET image features. Transferability of the model was compared using only clinical variables.

Vulnerabilities of radiomic signature development: The need for safeguards.

Purpose: Refinement of radiomic results and methodologies is required to ensure progression of the field. In this work, we establish a set of safeguards designed to improve and support current radiomic methodologies through detailed analysis of a radiomic signature.

Methods: A radiomic model (MW2018) was fitted and externally validated using features extracted from previously reported lung and head and neck (H&N) cancer datasets using gross-tumour-volume contours, as well as from images with randomly permuted voxel index values; i.

Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort.

NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports.

Towards a modular decision support system for radiomics: A case study on rectal cancer.

Following the personalized medicine paradigm, there is a growing interest in medical agents capable of predicting the effect of therapies on patients, by exploiting the amount of data that is now available for each patient. In disciplines like oncology, where images and scans are available, the exploitation of medical images can provide an additional source of potentially useful information. The study and analysis of features extracted by medical images, exploited for predictive purposes, is termed radiomics.

External validation of an NTCP model for acute esophageal toxicity in locally advanced NSCLC patients treated with intensity-modulated (chemo-)radiotherapy.

Background And Purpose: We externally validated a previously established multivariable normal-tissue complication probability (NTCP) model for Grade ≥2 acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or volumetric-modulated arc therapy for locally advanced non-small cell lung cancer.

Materials And Methods: A total of 603 patients from five cohorts (A-E) within four different Dutch institutes were included. Using the NTCP model, containing predictors concurrent chemoradiotherapy, mean esophageal dose, gender and clinical tumor stage, the risk of Grade ≥2 AET was estimated per patient and model discrimination and (re)calibration performance were evaluated.

[The behavioral and psychological symptoms of dementia in down syndrome (BPSD-DS) scale: comprehensive assessment of psychopathology in down syndrome].

Behavioral and psychological symptoms of dementia (BPSD) have not been comprehensively studied in people with Down syndrome, despite their high risk on dementia. A novel evaluation scale was developed to identify the nature, frequency and severity of behavioral changes (83 behavioral items in 12 clinically defined sections). Central aim was to identify items that change in relation to the dementia status.

Comparative evaluation of autocontouring in clinical practice: A practical method using the Turing test.

Purpose: Automated techniques for estimating the contours of organs and structures in medical images have become more widespread and a variety of measures are available for assessing their quality. Quantitative measures of geometric agreement, for example, overlap with a gold-standard delineation, are popular but may not predict the level of clinical acceptance for the contouring method. Therefore, surrogate measures that relate more directly to the clinical judgment of contours, and to the way they are used in routine workflows, need to be developed.

Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice.

Repeatability and Reproducibility of Radiomic Features: A Systematic Review.

Purpose: An ever-growing number of predictive models used to inform clinical decision making have included quantitative, computer-extracted imaging biomarkers, or "radiomic features." Broadly generalizable validity of radiomics-assisted models may be impeded by concerns about reproducibility. We offer a qualitative synthesis of 41 studies that specifically investigated the repeatability and reproducibility of radiomic features, derived from a systematic review of published peer-reviewed literature.

Autosegmentation for thoracic radiation treatment planning: A grand challenge at AAPM 2017.

Purpose: This report presents the methods and results of the Thoracic Auto-Segmentation Challenge organized at the 2017 Annual Meeting of American Association of Physicists in Medicine. The purpose of the challenge was to provide a benchmark dataset and platform for evaluating performance of autosegmentation methods of organs at risk (OARs) in thoracic CT images.

Methods: Sixty thoracic CT scans provided by three different institutions were separated into 36 training, 12 offline testing, and 12 online testing scans.