Interpretation of ambiguous TP53 test results: Mosaicism, clonal hematopoiesis, and variants of uncertain significance.

The increased use of next-generation sequencing has led to the detection of pathogenic TP53 variants in the germline setting in patients without a personal or family history consistent with Li-Fraumeni syndrome (LFS). These variants can represent low-penetrance LFS, mosaic LFS, or clonal hematopoiesis of indeterminate potential. Additionally, TP53 variants of uncertain significance can be detected in patients with a history suspicious for LFS. The interpretation of the significance of these variants can be challenging but is crucial for an accurate diagnosis and appropriate medical management. This retrospective case review provides illustrative examples of the interpretation of challenging TP53 results through multidisciplinary expertise and use of a flowchart. The authors describe eight patients with TP53 variants associated with ambiguous diagnoses and, for each case, describe how the results were interpreted and the medical care that was implemented. This report presents illustrative cases to help guide clinicians to reach definitive diagnoses for patients when confronted with TP53 variants that are inconsistent with the clinical picture and to add to the body of literature regarding interpretation and medical management of TP53 variants discovered on germline testing.

"I think that a brief conversation from their provider can go a very long way": Patient and provider perspectives on barriers and facilitators of genetic testing after ovarian cancer.

OBJECTIVE: Identify predisposing, enabling, and reinforcing factors impacting genetic counseling/testing among ovarian cancer patients guided by Green and Kreuter's PRECEDE-PROCEED model. METHODS: Gynecologic oncology providers (N = 4), genetic counselors (N = 4), and ovarian cancer patients (N = 9) completed semi-structured qualitative interviews exploring participants' knowledge of and experiences with genetic counseling/testing. Interviews were audio recorded, transcribed verbatim, and analyzed using inductive content analysis by two independent raters. RESULTS: Thematic analysis identified predisposing, enabling, and reinforcing factors impacting referral for and uptake of genetic counseling/testing. Predisposing factors included participant's knowledge, beliefs, and attitudes related to genetic counseling/testing. Both patients and providers also cited that insurance coverage and out-of-pocket cost are major concerns for ovarian cancer patients considering genetic testing. Finally, both patients and providers emphasized that genetic counseling/testing would provide additional information to an ovarian cancer patient. While providers emphasized that genetic testing results were useful for informing a patient's personal treatment plan, patients emphasized that this knowledge would be beneficial for their family members. CONCLUSION: Barriers to genetic testing for ovarian cancer patients exist at multiple levels, including the patient (e.g., knowledge, attitudes), the provider (e.g., workload, availability of services), the institution (e.g., difficulty with referrals/scheduling), and the healthcare system (e.g., insurance/cost). Interventions aiming to increase genetic testing among ovarian cancer patients will likely need to target multiple levels of influence. Future quantitative studies are needed to replicate these results. This line of work will inform specific multilevel intervention strategies that are adaptable to different practice settings, ultimately improving guideline concordant care.

What do mathematics lessons look like? Analyses of primary students' drawings.

The use of student drawings to assess their experiences and beliefs about teaching and learning of mathematics has become almost a regular research method - especially when working with young students who may not express themselves well, for example, in self-report questionnaires. These methods, nevertheless, need to be improved regarding their objectivity and validity. By building on the existing research, in this study, we focus on objectivity and validity issues in drawing-based methods. We use a drawing-based instrument: Draw A Mathematics Classroom (DAMC) and present 104 fourth-grade students to draw a picture of their regular mathematics lessons. We especially aim to develop and validate a data coding manual with low-inferent categories; that is, well-operationalizable categories that can be used with high interrater-reliability like the presence of teachers, the arrangement of student desks, and teacher-student interactions. The results reveal that almost half of the participating students perceive their lessons as teacher-centered. The results also confirm the reliability and validity of the methodological approach. For example, in pictures where the teacher is depicted larger than the students, the teacher is also depicted in the center, and students are pictured working alone. Classroom observations support students' perceptions, and all these show that the manual used in this study is useful to getting insights into young students' perceptions of their mathematics classroom.

Survey-based personas for a target-group-specific consideration of elderly end users of information and communication systems in the German health-care sector.

BACKGROUND: In many countries, including Germany, older people are increasing in numbers, while fewer caregivers are available. A way to address the problem is to develop new medical assistance and monitoring systems that are operated by the elderly on their own, e.g. in-home aftercare systems. OBJECTIVE: The development of a set of eight data-based personas in terms of a best practice approach is presented. METHOD: "Personas" are an integral method of the user-centered design approach. They address the problem of incomplete knowledge of individual user behaviour by introducing archetypal user groups. Thus, personas can be used at an early stage of development to raise the awareness of developers to the needs, skills, and abilities of the elderly. Personas are also a cost-effective method and quickly and easily accessible. In order to guarantee representativeness the development of personas needs to occur based on a robust data set of a certain user group. RESULTS: This article presents the data-driven development of eight personas. The applied data set results from a nationwide questionnaire study on the elderly's use of information and communication technology, out of elderly people in Germany. The results will be presented in terms of best practice. CONCLUSION: To conclude, survey-based personas of older end users can play an important role in the research and development of innovative devices. APPLICATION: The personas presented in this paper can be used in research and development to raise awareness of the needs and demands of end users.

Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome.

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder associated with intellectual disability, sleep disturbances, early onset obesity and vast behavioral deficits. We used the Behavior Problems Inventory-01 to categorize the frequency and severity of behavioral abnormalities in a SMS cohort relative to individuals with intellectual disability of heterogeneous etiology. Self-injurious, stereotyped, and aggressive/destructive behavioral scores indicated that both frequency and severity were significantly higher among individuals with SMS relative to those with intellectual disability. Next, we categorized food behaviors in our SMS cohort across age using the Food Related Problems Questionnaire (FRPQ) and found that problems began to occur in SMS children as early as 5-11 years old, but children 12-18 years old and adults manifested the most severe problems. Furthermore, we evaluated the similarities of SMS adult food-related behaviors to those with intellectual disability and found that SMS adults had more severe behavioral problems. Many neurodevelopmental disorders exhibit syndromic obesity including SMS. Prader-Willi syndrome (PWS) is the most frequent neurodevelopmental disorder with syndromic obesity and has a well-established management and treatment plan. Using the FRPQ we found that SMS adults had similar scores relative to PWS adults. Both syndromes manifest weight gain early in development, and the FRPQ scores highlight specific areas in which behavioral similarities exist, including preoccupation with food, impaired satiety, and negative behavioral responses. SMS food-related behavior treatment paradigms are not as refined as PWS, suggesting that current PWS treatments for prevention of obesity may be beneficial for individuals with SMS.