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Purpose: The purpose of this research was to cocreate with patients and the public a set of evidence-informed guiding principles for their authentic, responsive, ongoing, and sustainable engagement in the mission, goals, curriculum, and delivery of medical education., Method: A set of guiding principles of relevance to medical education was identified from the literature. Eight focus groups with patients and community members representing a wide variety of perspectives were conducted in April and May 2022. Participants reviewed, prioritized, and discussed the principles and described successful engagement, resulting in 8 guiding principles in priority order. A summary report was circulated to participants for feedback. The principles were reviewed and endorsed by senior leaders in the medical school., Results: The 8 focus groups were attended by 38 people (age range, mid-20s to postretirement; 7 male, 27 female, and 4 unknown gender). Accountability (19%), inclusion (18%), reciprocity (17%), and partnership and shared decision-making (14%) were chosen as the most important principles. Participants want evidence that their contributions are valued and have made a difference. They want the medical school to include and support a diversity of perspectives that reflect the populations being served by the health care system. They want the medical school to invest in building trusting and respectful long-term relationships with patients and the public., Conclusions: The guiding principles could be used by medical schools as a starting point to build relationships with their local communities to increase the authentic and sustainable engagement of patients and the public in the educational mission of the medical school., (Copyright © 2024 the Association of American Medical Colleges.)

Objectives: Limited data are available comparing the efficacy of osi versus earlier generation TKIs for mNSCLC with atypical EGFR mutations (AMs) such as L861Q, G719X, S768I and exon20., Methods: We performed a single-institution retrospective analysis of patients with EGFR-mutated mNSCLC treated from 2007 to 2023 with 1L TKIs, comparing outcomes for AM patients treated with osi, afatinib, and erlotinib. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared between TKIs using independent sample t-tests and chi-square analyses. Median progression free survival (mPFS) and overall survival (mOS) were compared via Kaplan-Meier log-rank analysis and Cox multivariable regression., Results: Among 355 patients with EGFR-mutated mNSCLC, 36 (10 %) harbored AMs in G719X (N=21; 6 %), Exon 20 (N=11; 3 %), L861Q (N=7; 2 %), S768I (N=4; 1 %), C797S (N=1; 0.3 %); 6 patients had compound mutations. Patients with classical mutations (CMs) vs AMs had similar baseline demographic and disease characteristics and usage of TKIs (p = 0.124). Among AM patients, osi yielded superior mPFS (22 m) vs afatinib (12 m; p = 0.005) or erlotinib (9 m; p = 0.001). mOS was likewise superior for osi (32 m) vs afatinib (21 m; p = 0.032) or erlotinib (17 m; p = 0.011). Dose-reduction rates due to AEs were lower for osi (19 %) vs afatinib (24 %; p = 0.003) or erlotinib (23 %; p = 0.002). Discontinuation rates due to AEs were lower for osi vs afatinib (1 % vs 2 %; p < 0.001) or erlotinib (2 %; p = 0.004)., Conclusions: In a large real-world analysis, osi demonstrated superior progression-free and overall survival and improved tolerability compared to afatinib or erlotinib for atypical EGFR-mutated mNSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Patient/public involvement in health professional education is increasing but remains episodic, narrowly focused, reliant on individual enthusiasts, and lacks supportive institutional infrastructure. There is little evidence-informed practical guidance on how to take a more strategic and formal approach. We undertook a qualitative study to learn from patients and the public how medical schools could engage in an authentic and sustainable way., Methods: In 2022 we conducted eight focus groups with patients and members of community organizations. Participants were asked about experiences and perceptions of what needs to happen to enable and support them to participate in medical education, barriers to authentic engagement, and how they might be overcome. Recordings were transcribed and data coded inductively. A summary report was circulated to participants for validation of findings., Results: The focus groups were attended by 38 participants representing a wide variety of perspectives. Participants provided practical suggestions that we categorized into six major themes: inviting participation; preparing for participation; supporting participation; increasing and supporting diversity; recognizing participation; institutional buy-in and support., Conclusions: Individual instructors can enhance authentic patient engagement through recruitment, support and recognition practices. Institutional commitment is required to sustain and widen participation through funding, policies and infrastructure.

Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Combination chemotherapy is an established approach used to manage toxicities while eliciting an enhanced therapeutic response. Delivery of drug combinations at specific molar ratios has been considered a means to achieve synergistic effects resulting in improvements in efficacy while minimizing dose related adverse drug reactions. The benefits of this approach have been realized with the FDA approval of Vyxeos®, the first liposome formulation to deliver a synergistic drug combination leading to improved overall survival against standard of care. In the current study, we demonstrate the synergistic potential of the PARP inhibitor niraparib and doxorubicin for the treatment of ovarian cancer. Through in vitro screening in a panel of ovarian cancer cell lines, we find that niraparib and doxorubicin demonstrate consistent synergy/additivity at the majority of evaluated molar ratio combinations. Further to these findings, we report formulation of a nanoparticle encapsulating our identified synergistic combination. We describe a rational design process to achieve highly stable liposomes that are targeted with folate to folate-receptor-alpha, which is known to be overexpressed on the surface of ovarian cancer cells. With this approach, we aim to achieve targeted delivery of niraparib and doxorubicin at a pre-determined synergistic molar ratio via increased receptor-mediated endocytosis., (© 2023. The Author(s).)

Within the last decade, stakeholder engagement in research has become increasingly popular in childhood disability research; however, literature on the engagement of youth with neurodisabilities and their families in evidence syntheses is underdeveloped. Involving patients as partners in research has the potential to improve applicability and relevance of the research and benefit patient partners (e.g. enhanced self-esteem, increased research knowledge and skills); however, the methods, challenges, outcomes and recommendations of engaging youth with neurodisabilities and their families in evidence syntheses are unknown. Two parents of youth with complex disability needs were engaged as partners throughout this review. Following methods outlined by Arksey and O'Malley (2005), the primary research question in this scoping review is twofold: (i) what activities have youth with neurodisabilities and their families been engaged in as part of evidence syntheses and (ii) what were the outcomes of that engagement? After full text review of 369 articles, nine articles were included. Youth and families were engaged prior to the evidence synthesis and at every stage in the project, most often during data analysis where they contextualized the findings. Youth and family engagement were not formally evaluated; however, positive outcomes were reported by parents and researchers. Challenges such as increased time, sustaining engagement, and parents' dissatisfaction with their level of involvement were reported. Recommendations centred around providing partners with information, building relationships via social media, and openly communicating about roles, feedback and logistics. Childhood disability researchers should be aware of how they can increase engagement opportunities at all stages of evidence syntheses and how they might improve accessibility for youth with neurodisabilities and their families. Further research is needed to solidify a unified framework for conduct and reporting of youth and family engagement in evidence syntheses., (© 2022 John Wiley & Sons Ltd.)

Myoepithelial carcinoma (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. We report a case of MEC in a 22-year-old man, who presented with a 6.5 cm soft tissue mass on his right distal forearm that has been enlarging over the past 3 months. Ultrasound-guided fine-needle aspiration (FNA) revealed abundant isolated neoplastic cells ranging from spindled cells to epithelioid and plasmacytoid morphology in a myxoid background. These cells showed moderate cytologic atypia characterized by high-nuclear/cytoplasmic ratio, irregular nuclear contours, and prominent nucleoli. The cytoplasm varied from dense to vacuolated and occasionally rhabdoid with intracytoplasmic inclusions. Scattered bi- and multinucleated cells were identified. A diagnosis of high-grade malignancy was made with the differential diagnosis including rhabdomyosarcoma and melanoma. A subsequent core biopsy of the tumor showed immunoreactivity for pan-cytokeratins, calponin, p63, and smooth muscle actin. INI-1 was lost. SOX-10 and Melan-A were negative. Molecular studies showed loss of SMARCB1 (INI-1) and CDKN2A. Gene fusion studies did not detect any fusion. A diagnosis of soft tissue MEC was made which is a challenge on FNA due to several cytologic mimickers including rhabdomyosarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor, extra-axial chordoma and melanoma. Recognition of the biphasic cell population in a myxoid background and a battery of immunohistochemical stains are crucial for accurate diagnosis., (© 2022 Wiley Periodicals LLC.)

A key to longevity assurance is the nutrient-sensing mTOR pathway. Inhibition of mTOR extends lifespan in a variety of organisms. However, the downstream effectors of the mTOR pathway for lifespan regulation are elusive. In a recent report, we described the role of Maf1 as a critical lifespan regulator downstream of the mTOR pathway in fission yeast. Maf1 is the master negative regulator of RNA polymerase III-directed transcription (e.g. tRNAs and 5S rRNAs) and is regulated by mTOR-mediated phosphorylation. We demonstrated that Maf1 is required for lifespan extension under calorie restriction or when mTOR is inhibited. We also showed that Maf1 prevents DNA damage at tRNA genes, which appears to contribute to lifespan maintenance by Maf1. Here we highlight these observations and present additional results to discuss the role of the mTOR-Maf1-Pol III axis in promoting genomic integrity in the face of DNA replication-transcription conflicts in order to maintain normal lifespan.

The objective was to study the effects of microencapsulated organic acids (OA) and essential oils (EO) on growth performance, immune system, gut barrier function, nutrient digestion and absorption, and abundance of enterotoxigenic Escherichia coli F4 (ETEC F4) in the weaned piglets challenged with ETEC F4. Twenty-four ETEC F4 susceptible weaned piglets were randomly distributed to 4 treatments including (1) sham-challenged control (SSC; piglets fed a control diet and challenged with phosphate-buffered saline (PBS)); (2) challenged control (CC; piglets fed a control diet and challenged with ETEC F4); (3) antibiotic growth promoters (AGP; CC + 55 mg·kg-1 of Aureomycin); and (4) microencapsulated OA and EO [P(OA+EO); (CC + 2 g·kg-1 of microencapsulated OA and EO]. The ETEC F4 infection significantly induced diarrhea at 8, 28, 34, and 40 hr postinoculation (hpi) (P < 0.05) in the CC piglets. At 28 d postinoculation (dpi), piglets fed P(OA+EO) had a lower (P < 0.05) diarrhea score compared with those fed CC, but the P(OA+EO) piglets had a lower (P < 0.05) diarrhea score compared with those fed the AGP diets at 40 dpi. The ETEC F4 infection tended to increase in vivo gut permeability measured by the oral gavaging fluorescein isothiocyanate-dextran 70 kDa (FITC-D70) assay in the CC piglets compared with the SCC piglets (P = 0.09). The AGP piglets had higher FITC-D70 flux than P(OA+EO) piglets (P < 0.05). The ETEC F4 infection decreased mid-jejunal VH in the CC piglets compared with the SCC piglets (P < 0.05). The P(OA+EO) piglets had higher (P < 0.05) VH in the mid-jejunum than the CC piglets. The relative mRNA abundance of Na+-glucose cotransporter and B0AT1 was reduced (P < 0.05) by ETEC F4 inoculation when compared with the SCC piglets. The AGP piglets had a greater relative mRNA abundance of B0AT1 than the CC piglets (P < 0.05). The ETEC F4 inoculation increased the protein abundance of OCLN (P < 0.05), and the AGP piglets had the lowest relative protein abundance of OCLN among the challenged groups (P < 0.05). The supplementation of microencapsulated OA and EO enhanced intestinal morphology and showed anti-diarrhea effects in weaned piglets challenged with ETEC F4. Even if more future studies can be required for further validation, this study brings evidence that microencapsulated OA and EO combination can be useful within the tools to be implemented in strategies for alternatives to antibiotics in swine production., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Our goal was to identify the opportunities and challenges in analyzing data from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE), a multi-institutional database derived from clinically driven genomic testing, at both the inter- and the intra-institutional level. Inter-institutionally, we identified genotypic differences between primary and metastatic tumors across the 3 most represented cancers in GENIE. Intra-institutionally, we analyzed the clinical characteristics of the Vanderbilt-Ingram Cancer Center (VICC) subset of GENIE to inform the interpretation of GENIE as a whole., Methods: We performed overall cohort matching on the basis of age, ethnicity, and sex of 13,208 patients stratified by cancer type (breast, colon, or lung) and sample site (primary or metastatic). We then determined whether detected variants, at the gene level, were associated with primary or metastatic tumors. We extracted clinical data for the VICC subset from VICC's clinical data warehouse. Treatment exposures were mapped to a 13-class schema derived from the HemOnc ontology., Results: Across 756 genes, there were significant differences in all cancer types. In breast cancer, ESR1 variants were over-represented in metastatic samples (odds ratio, 5.91; q < 10 -6 ). TP53 mutations were over-represented in metastatic samples across all cancers. VICC had a significantly different cancer type distribution than that of GENIE but patients were well matched with respect to age, sex, and sample type. Treatment data from VICC was used for a bipartite network analysis, demonstrating clusters with a mix of histologies and others being more histology specific., Conclusion: This article demonstrates the feasibility of deriving meaningful insights from GENIE at the inter- and intra-institutional level and illuminates the opportunities and challenges of the data GENIE contains. The results should help guide future development of GENIE, with the goal of fully realizing its potential for accelerating precision medicine., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Michele Lenoue-NewtonEmployment: DaVita (I) Stock and Other Ownership Interests: DaVita (I) Travel, Accommodations, Expenses: GenomOncologyMia LevyEmployment: SeqTech Diagnostics (I) Leadership: Personalis Stock and Other Ownership Interests: Personalis, GenomOncology Honoraria: Roche Consulting or Advisory Role: Personalis, GenomOncology, Roche Research Funding: GenomOncology Patents, Royalties, Other Intellectual Property: Royalties from GenomOncology for licensing of MyCancerGenome content Travel, Accommodations, Expenses: RocheChristine MicheelConsulting or Advisory Role: Roche Research Funding: GenomOncology (Inst), GE Healthcare (Inst)Lester MackeyPatents, Royalties, Other Intellectual Property: Royalties from Stanford University Docket No. S15-106 Model for Predicting a Patient’s Future Healthcare CostsJeremy L. WarnerStock and Other Ownership Interests: HemOnc.org Consulting or Advisory Role: Westat, IBM Travel, Accommodations, Expenses: IBM No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

Melanoma represents the most serious type of skin cancer. Although recent years have seen advances using targeted and immunotherapies, most patients remain at high risk for tumor recurrence. Here we show that IRAK-M, a negative regulator of MyD88 signaling, is deficient or low in melanoma and expression levels correlate with patient survival. Inducing IRAK-M expression using genetic approaches or epigenetic modifiers initiates apoptosis by prompting its interaction with TRAF6 via IRAK-M's C-terminal domain. This complex recruits and degrades calpastatin which stimulates calpain activity and triggers caspase-3-dependent but caspase-8,-9-independent apoptosis. Using a drug screen, we identified compounds that induced IRAK-M expression. Administration of IRAK-M-inducing drugs reduced tumor growth in mice but was ineffective against IRAK-M knock-down tumors. These results uncover a previously uncharacterized apoptosis pathway, emphasize IRAK-M as a potential therapeutic target and suggest that the anticancer activity of certain drugs could do so through their ability to induce IRAK-M expression.

Objectives: To review the significance of MDM2 and cyclin D1 expression and loss of p16 expression in malignant and borderline Brenner tumors (BTs) of the ovary., Methods: We describe 2 new cases of ovarian BT, 1 malignant and 1 borderline. We studied MDM2, p16, and cyclin D1 expression by immunohistochemistry in the benign, borderline, and malignant components of these 2 cases and in 5 additional cases of benign BT. We also reviewed and summarized the literature on the clinical, immunohistochemical and molecular characteristics of borderline and malignant BTs (BdBTs and MBTs)., Results: Nuclear expression of MDM2 was seen only in the MBT. Loss of p16 expression was seen in both BdBT and MBT. Cyclin D1 expression was in proportion to the degree of malignancy. Amplification of MDM2, loss of CDKN2A (p16-encoding gene), and amplification of CCND1 (cyclin D1-encoding gene) were confirmed by commercial next-generation sequencing in the case of MBT., Conclusions: We are the first to report immunohistochemical expression of MDM2 in an MBT. Amplification of MDM2 and loss of p16 expression may have a role in malignant transformation of BT., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To evaluate the impact of blended learning using a combination of educational resources (flipped classroom and short videos) on medical students' (MSs) for radiology learning., Material and Methods: A cohort of 353 MSs from 2015 to 2018 was prospectively evaluated. MSs were assigned to four groups (high, high-intermediate, low-intermediate, and low achievers) based on their results to a 20-MCQs performance evaluation referred to as the pretest. MSs had then free access to a self-paced course totalizing 61 videos based on abdominal imaging over a period of 3 months. Performance was evaluated using the change between posttest (the same 20 MCQs as pretest) and pretest results. Satisfaction was measured using a satisfaction survey with directed and spontaneous feedbacks. Engagement was graded according to audience retention and attendance on a web content management system., Results: Performance change between pre and posttest was significantly different between the four categories (ANOVA, P = 10 -9 ): low pretest achievers demonstrated the highest improvement (mean ± SD, + 11.3 ± 22.8 points) while high pretest achievers showed a decrease in their posttest score (mean ± SD, - 3.6 ± 19 points). Directed feedback collected from 73.3% of participants showed a 99% of overall satisfaction. Spontaneous feedback showed that the concept of "pleasure in learning" was the most cited advantage, followed by "flexibility." Engagement increased over years and the number of views increased of 2.47-fold in 2 years., Conclusion: Learning formats including new pedagogical concepts as blended learning, and current technologies allow improvement in medical student's performance, satisfaction, and engagement.

Essential oils (EO) are defined as plant-derived natural bioactive compounds, which can have positive effects on animal growth and health due to their antimicrobial and antioxidative properties. However, EO are volatile, can evaporate quickly, and be rapidly absorbed in the upper gastrointestinal tract. Also, due to their labile nature, the stability of EO during feed processing is often questionable, leading to variations in the final concentration in feed. Encapsulation has become one of the most popular methods of stabilizing EO during feed processing, storage, and delivery into the lower gut. The objectives of the present study were to 1) evaluate the stability of thymol microencapsulated in combination with organic acids in commercially available lipid matrix microparticles during the feed pelleting process and storage; 2) validate and demonstrate the slow release of thymol from the lipid matrix microparticles in a simulated pig gastric fluid (SGF) and a simulated pig intestinal fluid (SIF); and 3) evaluate in vivo release of thymol from the lipid matrix microparticles along the pig gut. The results showed that thymol concentration was not significantly different in the mash and pelleted feeds ( P > 0.05). In the in vitro study, 26.04% thymol was released in SGF, and the rest of the thymol was progressively released in SIF until completion, which was achieved by 24 h. The in vivo study showed that 15.5% of thymol was released in the stomach, and 41.85% of thymol was delivered in the mid-jejunum section. Only 2.21% of thymol was recovered in feces. In conclusion, the lipid matrix microparticles were able to maintain the stability of thymol during a feed pelleting process and storage and allow a slow and progressive intestinal release of thymol in weaned pigs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Worldwide, around 600 million people are affected by foodborne illnesses each year which highlights the importance of food safety. It is important to ensure the cleanliness of the working surfaces in food processing facilities. Stainless steel is widely used in the food industry as a food contact surface. Endowing stainless steel with a potent rechargeable antibacterial function offers the prospect of a reusable and clean surface. In this study, a "clickable" coating for stainless steel was developed. Quaternized azido-hydantoin ( C1 ), quaternary ammonium compound ( C2 ), and azido-hydantoin ( C3 ) were bonded to stainless steel primed with the clickable coating to yield three samples: SSMC1, SSMC2, and SSMC3, respectively. The coating was stable during the chlorination process which was used to convert the immobilized C1 and C3 to their N -chloramine counterparts (SSMC1-Cl and SSMC3-Cl, respectively). It was shown that SSMC1-Cl had the best antibacterial activity with 100% reduction of E. coli and S. aureus after 1 and 2 h of contact, respectively. SSMC1-Cl also showed the best performance in high protein medium (HPM) against bacteria, demonstrating 100% and 99.9% bacterial reduction against E. coli and S. aureus , respectively, after 3 h of contact. After five cycles of chlorination-dechlorination, SSMC1-Cl sustained a kill efficiency of 100% for both E. coli and S. aureus within 2 h of contact. This result reveals that SSMC1-Cl has the ability to maintain its antibacterial activity after repetitive cycles, which emphasizes its rechargeable nature. Altogether, this study presents an effective quaternized N -chloramine-based biocidal coating on stainless steel (SSMC1-Cl) that is rechargeable, durable, and effective against Gram-positive and Gram-negative bacteria.

Successful translation of preclinical data relies on valid and comprehensive animal models. While high-grade serous ovarian cancer (HGSOC) is the most prevalent subtype, the most commonly used ovarian cancer cell lines are not representative of HGSOC. In addition, 50% of ovarian cancer patients present with dysfunctional BRCA1/2 , however currently there is a shortage of BRCA-deficient models. By utilizing the OVCAR8 cell line, which contains a hypermethylated BRCA1 promoter, the aim of the current study was to establish and characterize an animal model for BRCA-deficient HGSOC. Transfection of the luciferase gene to OVCAR8 cells enabled bioluminescent imaging for real-time, non-invasive monitoring of tumor growth. The resulting model was characterized by peritoneal metastasis and ascites formation at late stages of disease. Immunohistochemical staining revealed high-grade serous histology in all resected tumor nodules. Immunoblotting and qPCR analysis demonstrated BRCA1 deficiency was maintained in vivo. Moderate to strong correlations were observed between bioluminescent signal and tumor weight. Lastly, intraperitoneal administration of carboplatin significantly reduced tumor growth as measured by bioluminescence. The current model demonstrated BRCA1 deficiency and a high resemblance of the clinical features of HGSOC. This model may be well-suited for evaluation of therapeutic efficacy in BRCA-deficient HGSOC.

Objectives: While obesity has been linked with lower quality of life in the general adult population, the prospective effects of present obesity on future quality of life amongst the elderly is unclear. This article investigates the cross-sectional and longitudinal relationships between obesity and aspects of quality of life in community-dwelling older Australians., Method: A 2-year longitudinal sample of community dwellers aged 70-90 years at baseline, derived from the Sydney Memory and Ageing Study (MAS), was chosen for the study. Of the 1037 participants in the original MAS sample, a baseline (Wave 1) sample of 926 and a 2-year follow-up (Wave 2) sample of 751 subjects were retained for these analyses. Adiposity was measured using body mass index (BMI) and waist circumference (WC). Quality of life was measured using the Assessment of Quality of Life (6 dimensions) questionnaire (AQoL-6D) as well as the Satisfaction with Life Scale (SWLS). Linear regression and analysis of covariance (ANCOVA) were used to examine linear and non-linear relationships between BMI and WC and measures of health-related quality of life (HRQoL) and satisfaction with life, adjusting for age, sex, education, asthma, osteoporosis, depression, hearing and visual impairment, mild cognitive impairment, physical activity, and general health. Where a non-linear relationship was found, established BMI or WC categories were used in ANCOVA., Results: Greater adiposity was associated with lower HRQoL but not life satisfaction. Regression modelling in cross-sectional analyses showed that higher BMI and greater WC were associated with lower scores for independent living, relationships, and pain (i.e. worse pain) on the AQoL-6D. In planned contrasts within a series of univariate analyses, obese participants scored lower in independent living and relationships, compared to normal weight and overweight participants. Longitudinal analyses found that higher baseline BMI and WC were associated with lower independent living scores at Wave 2., Conclusions: Obesity is associated with and predicts lower quality of life in elderly adults aged 70-90 years, and the areas most affected are independent living, social relationships, and the experience of pain.

Background: As targeted cancer therapies and molecular profiling become widespread, the era of "precision oncology" is at hand. However, cancer genomes are complex, making mutation-specific outcomes difficult to track. We created a proof-of-principle, CUSTOM-SEQ: Continuously Updating System for Tracking Outcome by Mutation, to Support Evidence-based Querying, to automatically calculate and display mutation-specific survival statistics from electronic health record data., Methods: Patients with cancer genotyping were included, and clinical data was extracted through a variety of algorithms. Results were refreshed regularly and injected into a standard reporting platform. Significant results were highlighted for visual cueing. A subset was additionally stratified by stage, smoking status, and treatment exposure., Results: By August 2015, 4310 patients with a median follow-up of 17 months had sufficient data for survival calculation. As expected, epidermal growth factor receptor (EGFR) mutations in lung cancer were associated with superior overall survival, hazard ratio (HR) = 0.53 (P < .001), validating the approach. Guanine nucleotide binding protein (G protein), q polypeptide (GNAQ) mutations in melanoma were associated with inferior overall survival, a novel finding (HR = 3.42, P < .001). Smoking status was not prognostic for epidermal growth factor receptor-mutated lung cancer patients, who also lived significantly longer than their counterparts, even with advanced disease (HR = 0.54, P = .001)., Interpretation: CUSTOM-SEQ represents a novel rapid learning system for a precision oncology environment. Retrospective studies are often limited by study of specific time periods and can lead to incomplete conclusions. Because data is continuously updated in CUSTOM-SEQ, the evidence base is constantly growing. Future work will allow users to interactively explore populations by demographics and treatment exposure, in order to further investigate significant mutation-specific signals., (© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Precision cancer medicine (PCM) will require ready access to genomic data within the clinical workflow and tools to assist clinical interpretation and enable decisions. Since most electronic health record (EHR) systems do not yet provide such functionality, we developed an EHR-agnostic, clinico-genomic mobile app to demonstrate several features that will be needed for point-of-care conversations., Methods: Our prototype, called Substitutable Medical Applications and Reusable Technology (SMART)® PCM, visualizes genomic information in real time, comparing a patient's diagnosis-specific somatic gene mutations detected by PCR-based hotspot testing to a population-level set of comparable data. The initial prototype works for patient specimens with 0 or 1 detected mutation. Genomics extensions were created for the Health Level Seven® Fast Healthcare Interoperability Resources (FHIR)® standard; otherwise, the prototype is a normal SMART on FHIR app., Results: The PCM prototype can rapidly present a visualization that compares a patient's somatic genomic alterations against a distribution built from more than 3000 patients, along with context-specific links to external knowledge bases. Initial evaluation by oncologists provided important feedback about the prototype's strengths and weaknesses. We added several requested enhancements and successfully demonstrated the app at the inaugural American Society of Clinical Oncology Interoperability Demonstration; we have also begun to expand visualization capabilities to include cancer specimens with multiple mutations., Discussion: PCM is open-source software for clinicians to present the individual patient within the population-level spectrum of cancer somatic mutations. The app can be implemented on any SMART on FHIR-enabled EHRs, and future versions of PCM should be able to evolve in parallel with external knowledge bases., (© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Citric acid is used in cough reflex testing in clinical and research settings to assess reflexive cough in patients at risk of swallowing disorders. To address a lack of knowledge in this area, this study investigated the stability and sterility of citric acid solutions. Triplicate solutions of citric acid (0.8 M) in isotonic saline were stored at 4 ± 2 °C for up to 28 days and analysed by high-performance liquid chromatography. Microbiological sterility of freshly prepared samples and bulk samples previously used for 2 weeks within the hospital was determined using a pour plate technique. Microbial survival in citric acid was determined by inoculating Staphylococcus aureus, Escherichia coli, or Candida albicans into citric acid solution and monitoring the number of colony-forming units/mL over 40 min. Citric acid solutions remained stable at 4 °C for 28 days (98.4 ± 1.8 % remained). The freshly prepared and clinical samples tested were sterile. However, viability studies revealed that citric acid solution allows for the survival of C. albicans but not for S. aureus or E. coli. The microbial survival study showed that citric acid kills S. aureus and E. coli but has no marked effect on C. albicans after 40 min. Citric acid samples at 0.8 M remained stable over the 4-week testing period, with viable microbial cells absent from samples tested. However, C. albicans has the ability to survive in citric acid solution if inadvertently introduced in practice. For this reason, in clinical and research practice it is suggested to use single-use aliquots prepared aseptically which can be stored for up to 28 days at 4 °C.

Objective: With the reduction of resident work hours and the increasing focus on patient safety, it has become evident that simulation has a growing role to play in surgical education. We surveyed the program directors of 99 U.S. Neurosurgery programs in an effort to better understand how simulation can be implemented in Neurosurgery and to gain insight into key issues that are currently being discussed amongst Neurosurgical educators., Methods: A 14-item questionnaire was emailed to 99 Neurosurgery residency program directors. Questions assessed the clinical impact of simulation, the role of simulation in academia, the investments required in time and money, and the model best suited for simulation., Results: The survey response rate was 53.5%. Seventy-two percent of respondents believed that simulation would improve patient outcome, 74% that it could supplement conventional training, but only 25% that it could replace it. The majority strongly believed that it could help preparing complex cases and could be of use to attending faculty. Forty-five percent thought that residents should achieve pre-defined levels of proficiency on simulators before working on patients. Seventy-four percent of respondents declared they would make simulator practice mandatory if available, and the majority was willing to invest daily time and considerable funds on simulators. Cadavers were the least preferred models to use compared to virtual simulation and noncadaveric physical models., Conclusions: Simulation should be integrated in Neurosurgery training curricula. The validation of available tools is the next step that will enable the training, acquisition, and testing of neurosurgical skills., (Copyright © 2013 Elsevier Inc. All rights reserved.)