Search

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.

The number of undergraduates in the United States has increased by more than 30 percent since 2000, with two-year institutions absorbing the majority of new students. At the same time, outstanding student-loan debt has grown nationwide, reaching $1.4 trillion in 2018. Although the federal student-loan program exists to provide such resources, the growth in student loan debt is often described as a "crisis," and many colleges and universities have implemented policies designed to reduce student borrowing. However, there is little rigorous evidence on the causal effect of loans on educational outcomes. As a result, it is not clear whether efforts to reduce borrowing will benefit or harm students. The authors address this question through a randomized experiment at a large community college. Colleges that participate in the federal student-loan program must make loans available to all of their students, and the amount that each student can borrow is determined by his or her class standing and dependence on parental support. However, colleges have discretion over how much loan aid, if any, to list on students' annual financial-aid award letters. Depending on the school's approach, a letter might provide a loan "offer" equal to the maximum dollar amount a student could borrow, zero, or anything in between. The authors designed their experiment to test whether the decision of the amount of loan aid to list--a choice being made every year by most community colleges--has meaningful effects on borrowing and student attainment. Specifically, the experiment varied whether students were offered a nonzero loan amount in their financial-aid award letters. This study provides the first rigorous evidence of the effect of loan offers on both borrowing and academic performance. The authors find that students whose aid letters offered nonzero loans were more likely to borrow, and those who borrowed did better in school. Students who received nonzero loan offers were 7 percentage points more likely to take out a loan (a 30 percent increase) and borrowed $280 more than students whose letters offered $0 in loans. Students who borrowed as a result of receiving a nonzero loan offer earned 3.7 additional credits and raised their grade point averages (GPAs) by more than half a grade on a four-point scale, both representing increases of roughly 30 percent. One year after the intervention, borrowers were 11 percentage points more likely to have transferred to a four-year public institution. Based on these results and past research on the earnings gains from college persistence and attainment, the authors estimate that borrowers are likely to see an increase in their future earnings of at least $370 per year.

Background: Resources including Patient Decision Aids (PtDA) are useful and valued by patients and clinicians to provide information and complement shared decision‐making. Despite their promise, few PtDA exist for patients with genetic cancer susceptibility facing difficult decisions about risk management. We aimed to fill this gap, partnering with patients to codesign Lynch ChoicesTM, a PtDA website for families with Lynch Syndrome. In addition to a Patient Reference Panel, we purposively invited an international stakeholder panel including charities, public bodies, clinical and academic experts. Implementation strategies and frameworks were employed to optimise translation of research findings to improve care. Methods: Patient/stakeholder suggestions were incorporated in a transparent Table of Changes and prioritised using the Person‐Based Approach throughout planning and codesign of Lynch ChoicesTM. An interactive stakeholder meeting was convened to identify barriers and facilitators to clinical implementation of the PtDA. Results: Patient and stakeholder partnerships drove the direction of the research throughout codesign, resulting in several iterative refinements to the PtDA prior to roll out including the addition of illustrations/videos, clearer presentation of cancer risks and increased accessibility for lower literacy. Barriers and facilitators identified from stakeholders were used to create an implementation process map. Conclusions: Creating an effective, engaging PtDA is not enough. Systematic uptake in real world clinical practice, with its resource limitations, is needed to optimise benefit to patients and clinicians. Assessment of speed and breadth of dissemination and usage will be collected to further evidence the benefit of embedding implementation science methods from the outset to translate research findings into clinical practice. [ABSTRACT FROM AUTHOR]

Background Testing for germline pathogenic variants (GPVs) in cancer predisposition genes is increasingly offered as part of routine care for patients with cancer. This is often urgent in oncology clinics due to potential implications on treatment and surgical decisions. This also allows identification of family members who should be offered predictive genetic testing. In the UK, it is common practice for healthcare professionals to provide a patient information leaflet (PIL) at point of care for diagnostic genetic testing in patients with cancer, after results disclosure when a GPV is identified, and for predictive testing of at-risk relatives. Services usually create their own PIL, resulting in duplication of effort and wide variability regarding format, content, signposting and patient input in co-design and evaluation. Methods Representatives from UK Cancer Genetics Group (UKCGG), Cancer Research UK (CRUK) funded CanGene-CanVar programme and Association of Genetic Nurse Counsellors (AGNC) held a 2-day meeting with the aim of making recommendations for clinical practice regarding co-design of PIL for germline cancer susceptibility genetic testing. Lynch syndrome and haematological malignancies were chosen as exemplar conditions. Results Meeting participants included patient representatives including as co-chair, multidisciplinary clinicians and other experts from across the UK. High-level consensus for UK recommendations for clinical practice was reached on several aspects of PIL using digital polling, including that PIL should be offered, accessible, co-designed and evaluated with patients. Conclusions Recommendations from the meeting are likely to be applicable for PIL co-design for a wide range of germline genetic testing scenarios. [ABSTRACT FROM AUTHOR]

Introduction: Patient decision aids (PtDA) complement shared decision‐making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision‐making. Methods: Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small‐group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis. Results: The overarching theme was: It's personal. Contextual factors important for decision‐making were varied and changed over time. There was no one 'best fit' theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback. Conclusion: Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision‐making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care. Patient Contribution: Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi‐structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA. [ABSTRACT FROM AUTHOR]