"Functioning better is doing better": older adults' priorities for the evaluation of assistive technology.

Despite the benefits of assistive technology (AT), barriers to technology adoption still exist and are uniquely affecting older populations. Improving technology adoption can be achieved by involving end-users in the development and evaluation process. However, existing AT evaluation tools rarely take into account older adults' experiences. The goal of this study was to fill this gap by determining which AT evaluation criteria are important for older adults. We conducted 4 nominal group meetings with 21 participants aged 50+ in Vancouver, Canada. In the meetings, participants generated AT evaluation criteria and organized them in the order of importance. The content from the meetings was analyzed using qualitative content analysis. Final rankings were collated to reveal which criteria were the most important across the groups. We found that promotion of independence, affordability, ease of use and ethics are the most important AT evaluation criteria for older adults. Some aspects of ATs that older adults value, such as reliability, are not featured in AT evaluation tools. This study provides insight into older adults' priorities for AT evaluation criteria, and concerns that older adults have about AT use. The findings are supplemented with a comprehensive analysis of the group discussions that contextualizes the criteria.

Effective drug combinations in breast, colon and pancreatic cancer cells.

Combinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.

Influence of Haptoglobin Polymorphism on Stroke in Sickle Cell Disease Patients.

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions.

The clinicopathologic spectrum and genomic landscape of de-/trans-differentiated melanoma.

Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42-86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4-80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8-36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.

Teaching Intuitive Eating and Acceptance and Commitment Therapy Skills Via a Web-Based Intervention: A Pilot Single-Arm Intervention Study.

BACKGROUND: Middle-aged women are at risk of weight gain and associated comorbidities. Deliberate restriction of food intake (dieting) produces short-term weight loss but is largely unsuccessful for long-term weight management. Two promising approaches for the prevention of weight gain are intuitive eating (ie, eating in accordance with hunger and satiety signals) and the development of greater psychological flexibility (ie, the aim of acceptance and commitment therapy [ACT]). OBJECTIVES: This pilot study investigated the usage, acceptability, and feasibility of "Mind, Body, Food," a Web-based weight gain prevention intervention prototype that teaches intuitive eating and psychological flexibility skills. METHODS: Participants were 40 overweight women (mean age 44.8 [standard deviation, SD, 3.06] years, mean body mass index [BMI] 32.9 [SD 6.01] kg/m2, mean Intuitive Eating Scale [IES-1] total score 53.4 [SD 7.46], classified as below average) who were recruited from the general population in Dunedin, New Zealand. Module completion and study site metrics were assessed using Google Analytics. Use of an online self-monitoring tool was determined by entries saved to a secure online database. Intervention acceptability was assessed postintervention. BMI, intuitive eating, binge eating, psychological flexibility, and general mental and physical health were assessed pre- and postintervention and 3-months postintervention. RESULTS: Of the 40 women enrolled in the study, 12 (30%) completed all 12 modules (median 7.5 [interquartile range, IQR, 2-12] modules) and 4 (10%) used the self-monitoring tool for all 14 weeks of the intervention period (median 3 [IQR 1-9] weeks). Among 26 women who completed postintervention assessments, most women rated "Mind, Body, Food" as useful (20/26, 77%), easy to use (17/25, 68%) and liked the intervention (22/25, 88%). From pre- to postintervention, there were statistically significant within-group increases in intuitive eating (IES-2 total score P<.001; all IES-2 subscale scores: P ≤.01), psychological flexibility (P=.01), and general mental health (P<.001) as well as significant decreases in binge eating (P=.01). At the 3-month follow-up, IES-2 improvements were maintained, and there were further improvements in binge eating (P<.001) and general mental health (P=.03), and a marginal yet nonsignificant tendency for further improvement in psychological flexibility (P=.06). There were no significant within-group changes in BMI from pre- to postintervention and postintervention to 3-month follow-up (P=.46 and P=.93, respectively). CONCLUSIONS: The "Mind, Body, Food" prototype Web-based intervention is appealing to middle-aged women and may be a useful tool to help women learn intuitive eating and ACT skills, reduce binge eating, and maintain weight over 3 months. Further work to improve the user experience and engagement is required before testing the online intervention in a randomized controlled trial.