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Abstract When BRCA1/2 genetic susceptibility testing was introduced in the clinic in the mid-nineties, the "Huntington protocol" was used in the counselling of individuals applying for genetic testing. This protocol includes at least three sessions with a certain reflection period before blood sampling. Evidence on the psychological impact of BRCA1/2 genetic susceptibility testing has been accumulating in the last years. We will give a short overview of these psychological studies in order to reflect the need of using the extensive Huntington protocol in the counselling of individuals applying for BRCA1/2 genetic susceptibility testing. A shortened and more flexible BRCA1/2 counselling protocol is delineated, in which the attention is focused on the needs and strengths of the individual.

Abstract Background Counseling for whole‐exome sequencing (WES) could benefit from aligning parents' pre‐ and post‐disclosure attitudes. A few studies have qualitatively compared parents' pre‐ and post‐disclosure attitudes toward receiving WES results for their child in a diagnostic setting. This study explored these attitudes in the context of children with a developmental delay. Methods Semi‐structured interviews were conducted with parents (n = 27) of 16 children undergoing diagnostic WES in trio‐analysis, both before and after receiving results. Results Three key insights emerged. First, the distinction between hoping and expecting was relevant for shaping parents' experiences with receiving results related to the primary indication. Second, parents of young children whose development of autonomous capacities was uncertain sometimes found themselves in a situation resembling a Catch‐22 when confronted with decisions about unsolicited findings (UFs): an important reason for consenting to WES was to gain a better picture of how the child might develop, but in order to make responsible choices about UFs, some ideas of their child's development is needed. Third, default opt‐ins and opt‐outs helped parents fathom new kinds of considerations for accepting or declining UFs in different categories, thereby aiding decision‐making. Conclusion Results from this study are relevant for counseling and policy development.

This project's main objective is to create an open-source database containing a sizeable number of high-quality images of shoe impressions. The Center for Statistics and Applications in Forensic Evidence (CSAFE) team collected images that represented those found at crime scenes and constructed a database that is publicly available to forensic science and research communities. The database includes images obtained from mixed impression types: full blood impression, partial blood impression, and dust impression. The impressions are made on different flooring (vinyl and tile), and captured via various lift techniques: gel lifts and handiprints (exemplar prints with high definition using graphite powder and clear sticky vinyl, backed by a white sheet), and saved in multiple digital file types (TIF, XMP, CR3, and JPG). Our data were collected to ensure reproducibility, using simple but well-described protocols and easily accessible materials.The complete dataset includes 936 unique shoeprint images saved in 3,275 digital files.Data were collected by trained volunteers making shoe impressions on flooring with the two mediums: spatter blood and graphite powder. To make an impression, volunteers wearing a shoe stepped into the material and then walked on the flooring. A separate “lighter” step was taken to create a partial print for the blood prints. The blood prints were brought to the photography station, where researchers labeled and photographed them. Graphite prints were covered with a gel lifter before being moved to the photography room. There, the researchers removed the lift, labeled, and then photographed them.Our data will be of significant use to researchers, examiners, and anyone who could benefit from using a large dataset like this. Footwear datasets are often difficult to find, especially ones that resemble crime scenes, so our data can help fill that gap.

Pre-symptomatic frontotemporal dementia (FTD) mutation carriers and first-degree family members that are 50% at-risk for FTD may experience symptoms of anxiety and depression as a result of the ambiguity of when or if symptoms of the disease will manifest. We conducted a pilot study to investigate the use of an online mindfulness-based stress reduction (MBSR) course to reduce symptoms of anxiety and depression in presymptomatic frontotemporal dementia (FTD) mutation carriers and individuals 50% at-risk. Seven known mutation carriers and six individuals 50% at-risk completed a standardized 8-week MBSR course, and filled out pre- and post and two-month follow-up questionnaires. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS). Measures of psychological distress (SCL-90-R), coping style (UCL), quality of life (SF-36) and mindfulness skills (FFMQ) were administered as secondary outcome. Group effects were analyzed with repeated measures ANOVA or Friedman's test, and the individual reliability change index (RCI) was calculated per participant for each outcome measure. Semi-quantitative data included an evaluation and process measure post-intervention. Significant decline was found on the HADS-A post-intervention and after 2 months (p = 0.01), with 54% and 62% of participants demonstrating a clinically significant RCI, respectively. On the HADS-D, significant decline was found 2 months post-intervention (p = 0.04), which was driven by 23% of participants whom had a clinically significant RCI. Additional changes were found between baseline and post-intervention on the seeking distraction and reassuring thoughts subscales of the UCL, the depression and interpersonal sensitivity subscales of the SCL, the observe subscale of the FFMQ, and on physical role limitations of the SF-36 (all p < 0.05). The process evaluation form indicated that the course was found beneficial by participants, and that they applied it in a wide range of everyday situations. This exploratory pilot study indicates the feasibility of MBSR in reducing anxiety and depression in presymptomatic FTD mutation carriers and 50% at-risk individuals. A randomized controlled trial is necessary to replicate these results.

Abstract Background Patient and public involvement for co-creation is increasingly recognized as a valuable strategy to develop healthcare research targeting patients’ real needs. However, its practical implementation is not as advanced and unanimously accepted as it could be, due to cultural differences and complexities of managing healthcare programs and clinical studies, especially in the rare disease field. Main body The European Neuromuscular Centre, a European foundation of patient organizations, involved its key stakeholders in a special workshop to investigate the position of the neuromuscular patient community with respect to healthcare and medical research to identify and address gaps and bottlenecks. The workshop took place in Milan (Italy) on January 19–20, 2018, involving 45 participants who were mainly representatives of the patient community, but also included experts from clinical centers, industry and regulatory bodies. In order to provide practical examples and constructive suggestions, specific topics were identified upfront. The first set of issues concerned the quality of life at specific phases of a patient’s life, such as at the time of diagnosis or during pediatric to adult transition, and patient involvement in medical research on activities in daily living including patient reported outcome measures. The second set of issues concerned the involvement of patients in the management of clinical research tools, such as registries and biobanks, and their participation in study design or marketing authorization processes. Introductory presentations were followed by parallel working group sessions, to gain constructive contributions from all participants. The concept of shared decision making was used to ensure, in discussions, a partnership-based identification of the wishes and needs of all stakeholders involved, and the “ladder of participation” tool served as a model to evaluate the actual and the desired level of patients’ involvement in all topics addressed. A general consensus on the outcome of the meeting was collected during the final plenary session. This paper reports the outcome of the workshop and the specific suggestions derived from the analysis of the first set of topics, related to quality of life. The outcomes of the second set of topics are reported elsewhere and are only briefly summarized herein for the sake of completeness. Conclusions The neuromuscular community proved to be very active and engaged at different levels in the healthcare initiatives of interest. The workshop participants critically discussed several topics, providing practical examples where different stakeholders could play a role in making a change and bridging gaps. Overall, they indicated the need for education of all stakeholders for better communication, where everyone should become an ambassador to promote real change. Support should also come from institutions and healthcare bodies both at structural and economic level.

Ammonium is a fundamental nutrient for phytoplankton growth in seawater and is a key component of the microbial loop. Ammonium measured in parallel with other nutrients is crucial in understanding the small temporal scale changes in oceanographic ecology. Despite the importance of measuring ammonium at sea, owing to its lability, there is no consensus on the best method. The lack of availability of certified reference materials for ammonium in seawater also makes it difficult to assess the accuracy and reproducibility of ammonium measurements. In this study we present a modified segmented flow analysis method using ortho-phthaldialdehyde (OPA) with fluorescence detection to measure ammonium at sea together with four other macro-nutrients (nitrate, nitrite, silicate and phosphate) in near real time. An in-house ammonium quality control (QC) material was produced to improve the accuracy and repeatability of the measurement at sea. The QC was prepared following two different methods and stored in two types of containers. The suitability of the in-house QC’s as a reference material were assessed onboard the RV Investigator in 2018 during two oceanographic voyages, including one on the repeat SR03 CLIVAR transect. This paper describes the production and assessment of the in-house QC for ammonium in seawater, providing groundwork for creating a short-term stable ammonium reference material for sea going voyages. The uncertainty of this method of ammonium measurement was found to be 0.10 μmol/L at ammonium concentration of 1.0 μmol/L. Results show that preparation of the QC inside a laminar flow cabinet and directly into 10 mL polypropylene sample tubes just prior to the commencement of the voyage improved its stability.

We highlight a specific and hitherto poorly characterised phenotype of functional gait impairments: functional freezing of gait. Unique to the presented case is the use of compensation strategies, many of which at first sight might appear to hint towards the presence of freezing of gait typical of Parkinson's disease or another form of Parkinsonism. Importantly, however, this patient's compensation strategies involved various inconsistent and incongruent elements, supporting the diagnosis of a functional neurological disorder. Recognising the features of functional freezing also helps to appreciate better the classical manifestations of freezing of gait in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Counseling for whole‐exome sequencing (WES) could benefit from aligning parents' pre‐ and post‐disclosure attitudes. A few studies have qualitatively compared parents' pre‐ and post‐disclosure attitudes toward receiving WES results for their child in a diagnostic setting. This study explored these attitudes in the context of children with a developmental delay. Methods: Semi‐structured interviews were conducted with parents (n = 27) of 16 children undergoing diagnostic WES in trio‐analysis, both before and after receiving results. Results: Three key insights emerged. First, the distinction between hoping and expecting was relevant for shaping parents' experiences with receiving results related to the primary indication. Second, parents of young children whose development of autonomous capacities was uncertain sometimes found themselves in a situation resembling a Catch‐22 when confronted with decisions about unsolicited findings (UFs): an important reason for consenting to WES was to gain a better picture of how the child might develop, but in order to make responsible choices about UFs, some ideas of their child's development is needed. Third, default opt‐ins and opt‐outs helped parents fathom new kinds of considerations for accepting or declining UFs in different categories, thereby aiding decision‐making. Conclusion: Results from this study are relevant for counseling and policy development. [ABSTRACT FROM AUTHOR]

Background: Patients with Functional Neurological Disorder (FND) experience complex patterns of motor and/or sensory symptoms. Treatment studies of psychological interventions are promising but limited. Objectives: The aim of the current pilot study is to investigate the effect of treatment consisting of a combination of hypnosis and catalepsy induction on FND symptom severity. Methods: A within‐subject waiting list‐control design was used with 46 patients diagnosed with FND. The treatment consisted of 10 sessions. The primary outcome measure was FND symptom severity (The Psychogenic Movement Disorder Rating Scale; PMDRS). The secondary outcome measures were psychological distress and quality of life. Results: The repeated measures (RM) ANOVA for the PMDRS as outcome measure revealed a significant effect for time with a large effect size (η2 = 0.679). Pairwise comparisons indicated that the effect of time in the treatment period was significant for the measure of FND symptom severity, whereas the waiting list period was not. The effect remained stable even at 8 weeks post treatment. As for the additional measurement, general psychological distress and quality of life, no statistically significant differences between individual time points were found. Conclusions: This pilot study showed that eight sessions of treatment consisting of a combination of hypnosis and catalepsy induction was effective in reducing FND symptom severity. Some explanations and limitations are provided in the paper as well as several avenues of future research. [ABSTRACT FROM AUTHOR]

Patients with prostate cancer (PCa) have a lower docetaxel exposure for both intravenous (1.8‐fold) and oral administration (2.4‐fold) than patients with other solid cancers, which could influence efficacy and toxicity. An altered metabolism by cytochrome P450 3A (CYP3A) due to castration status might explain the observed difference in docetaxel pharmacokinetics. In this in vivo phenotyping, pharmacokinetic study, CYP3A activity defined by midazolam clearance (CL) was compared between patients with PCa and male patients with other solid tumors. All patients with solid tumors who did not use CYP3A‐modulating drugs were eligible for participation. Patients received 2 mg midazolam orally and 1 mg midazolam intravenously on 2 consecutive days. Plasma concentrations were measured with a validated liquid chromatography–tandem mass spectrometry method. Genotyping was performed for CYP3A4 and CYP3A5. Nine patients were included in each group. Oral midazolam CL was 1.26‐fold higher in patients with PCa compared to patients with other solid tumors (geometric mean [coefficient of variation], 94.1 [33.5%] L/h vs 74.4 [39.1%] L/h, respectively; P =.08). Intravenous midazolam CL did not significantly differ between the 2 groups (P =.93). Moreover, the metabolic ratio of midazolam to 1′‐hydroxy midazolam did not differ between the 2 groups for both oral administration (P =.67) and intravenous administration (P =.26). CYP3A4 and CYP3A5 genotypes did not influence midazolam pharmacokinetics. The observed difference in docetaxel pharmacokinetics between both patient groups therefore appears to be explained neither by a difference in midazolam CL nor by a difference in metabolic conversion rate of midazolam. [ABSTRACT FROM AUTHOR]

Information and communication technologies (ICTs) have been associated with development programmes for many decades. A theme of Lamberton's commentary on such initiatives focuses on the lack of attention given to information as a key factor in the development process. His writing reiterated a number of arguments that he saw as being fundamental to the application of an information perspective to development issues. With a focus on agricultural development policy in the Pacific region, the paper uses a number of propositions that are suggested by Lamberton to analyse contemporary development initiatives in Pacific Island agriculture. These propositions focus attention on information costs that can influence the transfer of information and development of knowledge. Document analysis of selected published sources from a Pacific Island development programme are reviewed to illustrate the significance of information costs for development processes. The paper addresses the contention between traditional authority and knowledge and its significance for development.

Research into strong light–matter interactions continues to fascinate, being spurred on by unforeseen and often spectacular experimental observations. Properties that were considered to depend exclusively on material composition have been found to be drastically altered when a material is placed inside a resonant optical cavity. This is nowhere more the case than in the field of intermolecular energy transfer, where polaritonic states formed as a result of strong light–matter interactions have been shown to promote energy transfer over distances vastly exceeding conventional limits. In this review, we provide the reader with a succinct account of the fundamental concepts of intermolecular energy transfer, and how they are modified by strong light–matter interactions. We also summarize recent experimental advances in the area, including in optoelectronic device contexts, and highlight both the potential and challenges that remain in this exciting field of research going forward. [ABSTRACT FROM AUTHOR]

Introduction: Aprepitant is used for the treatment of chemotherapy induced nausea and vomiting. A liquid formulation is needed for treatment of young children. However, the commercial (powder for) suspension was not available worldwide for a prolonged period of time and, therefore, a 10 mg/mL aprepitant oral suspension was extemporarily prepared to prevent suboptimal antiemetic treatment. The current pharmacokinetic study was developed to investigate whether this extemporaneous oral suspension offers an appropriate treatment option. Methods: From 49 pediatric patients (0.7–17.9 years) 235 plasma concentrations were collected. Patients were either treated with our extemporaneous oral suspension (n = 26; 53%), commercially available capsules (n = 18; 37%), or the intravenous prodrug formulation of aprepitant (fosaprepitant, n = 5; 10%). Pharmacokinetic analyses were performed using nonlinear mixed effects modelling. Results: A one-compartment model adequately described the pharmacokinetics of aprepitant in children. The bioavailability of the extemporaneous oral suspension was not significantly different to that of the capsules (P = 0.26). The observed bioavailability throughout the total population was 83% (95% CI 69%-97%). The absorption of the extemporaneous oral suspension was 39.4% (95%CI 19.5–57.4%) faster than that of capsules (mean absorption time of 1.78 h (95%CI 1.32–2.35), but was comparable to that of the commercial oral suspension. The median area under the curve after (fos)aprepitant was 22.2 mg/L*h (range 8.9–50.3 mg/L*h) on day 1. Conclusion: Our extemporaneous oral suspension is an adequate alternative for the commercially (un)available oral suspension in young children. An adequate exposure to aprepitant in children was yielded and the bioavailability of the extemporaneous suspension was comparable to capsules. [ABSTRACT FROM AUTHOR]