Paging: a Collection of Short Stories

Introduction: Paging is a series of thematically interconnected short stories that take place at a single fictional urban hospital center. The guiding questions that the stories explore are twofold: other than doctors and patients, what kinds of people spend their time in a hospital? And, what kind of place is the hospital for these people? Methods: The background research for Paging began by exploring written works of fiction, nonfiction, and memoir set in hospitals. After I had developed a set of guiding research questions, I spent the summer at a major hospital in New York City, where I was able to observe the people and employees that comprised the environment of an urban medical center. These observations were used draft fiction about the kinds of dilemmas various characters in a hospital might grapple with on a daily basis. Results: Paging is a series of three short stories that explore the lives of three different hospital employees at the same hospital center. The first story is about a medical assistant at an outpatient clinic who encounters an ethical dilemma that brings his personal life to work. The second is about a custodian who gets to know the patients of a hospital in a very different, but equally intimate, manner to the doctors and nurses who take care of the patients’ medical needs. The third is about a woman who assists in the distribution of organs that have been harvested for transplant. Discussion: We often think of the hospital as a place where patients go to seek care from doctors. In reality, the hospital is a far richer environment than this. Paging explores the other inhabitants of a hospital that allow it to be a bustling ecosystem, and offers stories from perspectives that are often overlooked

Stop Requested: A Collection of ALS Poetry

Introduction: This project aims to use poetry to convey the lessons, challenges, and experiences encountered by patients in the Jefferson Weinberg ALS Center diagnosed with Amyotrophic Lateral Sclerosis (ALS). This will not only allow for individual patients to freely discuss, reminisce, and reflect on their journey with this disease, but distributing the collection to our community will aid in a better understanding of ALS patients, serve to humanize ALS, and deepen the empathic beyond between community members and patients. Additionally, it will create an environment in which both myself and physicians can reflect on the human experience and how disease affects a patient holistically. Methods: A questionnaire was drafted and used to guide conversations with patients about their experiences living with ALS. After the interview, the conversation was analyzed for themes and a first draft of a poem inspired by their story was created. Edits were obtained from advisors and peers, and poems were then organized into a final collection, to be printed and distributed to clinic patients and the Jefferson community. Results: This project resulted in a printed collection of poetry titled Stop Requested: A Collection of ALS Poetry. The final product is to be distributed to each patient at the Jefferson Weinberg ALS Center and more broadly to the ALS and Jefferson communities. This collection details intimate accounts of confusion, suffering, fight, hope, and change that ALS patients experience during their disease progression. Discussion: By using poetry to portray the human experience specific to ALS, this collection helps to connect patients to each other, providers to patients, and community members to patients. The experiences outlined in this collection help to build compassion within the medical field and community for those experiencing ALS and offers a unique perspective of the spectrum of suffering, and triumph in neurodegenerative disease

What It’s Like to Study the Brain: A Creative Exploration

Introduction: In recent years, medicine and the humanities have evolved to be adopted synergistically in dual practice. Employing principles of narrative medicine, this multimodal piece explores the experience of hunger to draw parallels between creativity in art and creativity in medicine. By stimulating reading, writing, listening, and seeing, this account aims to represent these faculties as necessary to both art and medicine and to exemplify synergy between the two. Methods: As codified by the field of narrative medicine, methods consisted of a repetitive practice of close reading, writing, and reflecting. In viewing medicine as interconnected provider-patient narrative, scholars of narrative medicine write to contribute to these accounts of “self”. This engages them in healing, intersubjective contact that enhances empathy, self-awareness, and ethical consideration. This project serves a dual function: first, as an account of the enrichment of skills of observation, interpretation, and reflection that result from a purposeful practice of narrative medicine and second, as a platform for engagement for those who wish to develop their own practice. Results: Reflection on the neuroscience and psychology inherent to medical education has yielded six (6) chapters of topical creative writing consisting of short story, prose, and poetry: hunger (1) for knowledge, (2) for meaning, (3) for food, (4) as ambition, (5) as struggle, and (6) for wellness. Each chapter consists of original writing resulting from subjective and objective experience in medicine such as neurosurgical research and patient interaction at needle exchange clinics. Discussion: This project serves as a tangible representation of the multimodality of both art and medicine. It underscores the importance of narrative in the enrichment of empathy within medical practice and enhances accessibility to narrative medicine by inviting active engagement. Further extrapolations would facilitate more opportunities for narrative training based on this project, such as workshops or interactive exhibitions

Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

Background: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.Results: We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.Conclusion: This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study.

Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson's study, 424 had young-onset Parkinson's disease (age at onset ≤ 50) and 1799 had late onset Parkinson's disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 'Kompetitive' allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson's disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson's disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors.Only competing interests included in the manuscript

Depressive Symptoms, Bone Loss, and Fractures in Postmenopausal Women

BackgroundOsteoporosis and depression may be associated through common physiologic systems or risk factors.ObjectiveTo assess the associations between depressive symptoms (Burnam's scale) or antidepressant use and bone outcomes.DesignProspective cohort study.ParticipantsA total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women's Health Initiative Observational Study.MeasurementsSelf-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and "other"). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites.ResultsOverall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at "other" anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture.ConclusionIn this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and "other " anatomic sites