Patient perspectives on home-spirometry in interstitial lung disease: a qualitative co-designed study.

BACKGROUND: Opportunities for home-monitoring are increasing exponentially. Home- spirometry is reproducible and reliable in interstitial lung disease (ILD), yet patients' experiences are not reported. Given the morbidity and mortality associated with ILDs, maintaining health-related quality-of-life is vital. We report our findings from a codesigned, qualitative study capturing the perspectives and experiences of patients using home-spirometry in a UK regional ILD National Health Service England (NHSE) commissioned service. METHODS: Patients eligible for home-spirometry as routine clinical care, able to give consent and able to access a smart phone were invited to participate. In-depth, semistructured interviews were conducted at serial time points (baseline, 1, 3 and 6 months), recorded, transcribed and analysed thematically. RESULTS: We report on the experiences of 10 recruited patients (8 males; median age 66 years, range 50-82 years; 7 diagnosed with idiopathic pulmonary fibrosis, 3 other ILDs) who generally found spirometry convenient and easy to use, but their relationships with forced vital capacity results were complex. Main themes emerging were: (1) anticipated benefits-to identify change, trigger action and aid understanding of condition; (2) needs-clinical oversight and feedback, understanding of results, ownership, need for data and a need 'to know'; (3) emotional impact-worry, reassurance, ambivalence/conflicting feelings, reminder of health issues, indifference; (4) ease of home-spirometry-simplicity, convenience and (5) difficulties with home-spirometry-technical issues, technique, physical effort. CONCLUSION: Home-spirometry has many benefits, but in view of the potential risks to psychological well-being, must be considered on an individual basis. Informed consent and decision-making are essential and should be ongoing, acknowledging potential limitations as well as benefits. Healthcare support is vital.

Sarcoidosis Illuminations on Living During COVID-19: Patient Experiences of Diagnosis, Management, and Survival Before and During the Pandemic.

Background: Inspired by intense challenges encountered by patients and clinicians, we examined the experiences of living with sarcoidosis in three of the hardest impacted English-speaking cities during the early COVID-19 pandemic: London, New Orleans, and New York. Methods: A multi-disciplinary, multi-national research team including 6 patient leaders conducted qualitative investigations with analyses rooted in grounded theory. Recruitment occurred by self-referral through patient advocacy groups. Results: A total of 28 people living with sarcoidosis participated. The majority of patients had multi-system and severe sarcoidosis. Dominant themes were consistent across groups with differences expressed in spirituality and government and health systems. Racial, gender, and able-bodied inequity were voiced regarding healthcare access and intervention, societal interactions, and COVID-19 exposure and contraction. Agreement regarding extreme disruption in care and communication created concern for disability and survival. Concerns of COVID-19 exposure triggering new sarcoidosis cases or exacerbating established sarcoidosis were expressed. Pre-COVID-19 impediments in sarcoidosis healthcare delivery, medical knowledge, and societal burdens were intensified during the pandemic. Conversely, living with sarcoidosis cultivated personal and operational preparedness for navigating the practicalities and uncertainties of the pandemic. Optimism prevailed that knowledge of sarcoidosis, respiratory, and multi-organ diseases could provide pathways for COVID-19-related therapy and support; however, remorse was expressed regarding pandemic circumstances to draw long-awaited attention to multi-organ system and respiratory conditions. Conclusion: Participants expressed concepts warranting infrastructural and scientific attention. This framework reflects pre- and intra-pandemic voiced needs in sarcoidosis and may be an agent of sensitization and strategy for other serious health conditions. A global query into sarcoidosis will be undertaken.

DNA damage checkpoint activation impairs chromatin homeostasis and promotes mitotic catastrophe during aging.

Genome instability is a hallmark of aging and contributes to age-related disorders such as cancer and Alzheimer's disease. The accumulation of DNA damage during aging has been linked to altered cell cycle dynamics and the failure of cell cycle checkpoints. Here, we use single cell imaging to study the consequences of increased genomic instability during aging in budding yeast and identify striking age-associated genome missegregation events. This breakdown in mitotic fidelity results from the age-related activation of the DNA damage checkpoint and the resulting degradation of histone proteins. Disrupting the ability of cells to degrade histones in response to DNA damage increases replicative lifespan and reduces genomic missegregations. We present several lines of evidence supporting a model of antagonistic pleiotropy in the DNA damage response where histone degradation, and limited histone transcription are beneficial to respond rapidly to damage but reduce lifespan and genomic stability in the long term.

An inexpensive microscopy system for microfluidic studies in budding yeast.

Recently, microfluidic technologies have been developed to allow higher throughput collection of yeast replicative lifespan data. Adoption of these devices has been limited, in part, due to the high cost of the motorized microscopy instrumentation from mainline manufacturers. Inspired by recent development of open source microscopy hardware and software, we developed minimal-cost hardware attachments to provide long-term focus stabilization for lower-cost microscopes and open source software to manage concurrent time-lapse image acquisition from multiple microscopes. We hope that these tools will help spur the wider adoption of microfluidic technologies for the study of aging in yeast.

Human Performance Optimization and Precision Performance: The Future of Special Operations Human Performance Efforts.

The Precision Medicine Initiative (PMI) was launched by the White House to promote individualized medicine. Although the focus of the PMI is on curing disease, we introduce the concept of Precision Performance (P2)- advances that might "enable a new era of human performance optimization through research, technology, and policies that empower warfighters and those who support them to work together toward development of individually optimized performance" (The White House, 2015). We provide a limited review of the current state of the science in human performance optimization (HPO) and show that averages among individuals can be both misleading and potentially counterproductive. Several examples where individual differences have historically presented challenges to HPO research and application are provided, as are ideas on how such differences might be leveraged to enable new opportunities to approach the goal of individually optimized human performance. We end with a few questions likely to be of increasing importance if the notion of P2 continues to evolve and mature; we also provide limited recommendations, given this is a nascent concept. The Special Operations Forces human performance programs can move the science forward by considering and then implementing the infrastructures, processes, and approaches to best identify and exploit emerging tools for ever greater and faster P2 data collection, analyses, sharing, and applications.

Contraction and expansion of the silicon scaffold of stable Si6R6 isomers.

The reactivity of two stable Si(6)R(6) clusters (4 and 5, R = 2,4,6-(i)Pr(3)C(6)H(2)) with unsymmetrical substitution patterns (including Si, SiR, and SiR(2) vertices) is reported. In order to account for the importance of such clusters as model systems for transient intermediates in the deposition of elemental silicon, we here propose the term "siliconoids" for silicon clusters with unsaturated valencies. With the hexasilaprismane 8a, a saturated-i.e., non-siliconoid-Si(6)R(6) isomer is accessible from a suitable Si(3) precursor. Thermal redistribution of the substituents converts 1,1,2-trichlorocyclotrisilane 6 into the corresponding 1,2,3-derivative 7 prior to the requisite reductive coupling step leading to 8a. On the other hand, a stable expanded Si(11)-siliconoid 9 was isolated as a minor side product of the thermal isomerization of 4 to 5, thus providing a first example of siliconoid cluster expansion in the condensed phase. In the solid-state structure, the two unsubstituted vertices of 9 strongly interact in a staggered propellane-like fashion. Oxidative cluster contraction of a siliconoid scaffold is observed upon treatment of siliconoid 5 with a large excess of iodine in refluxing toluene, thus providing access to a highly functionalized hexaiodocyclopentasilane 11 in high yield. Conversely, chlorination of the isomeric 4 with BiCl(3) as a mild source of Cl(2) results in a complex mixture of products from chlorination of the unsubstituted vertices as well as σ-bonds of the cluster framework of 4. The main product, 1,2-dichlorotricyclo[2.2.0.0(2,5)]hexasilane 12, undergoes thermal cluster contraction to give tricyclo[2.1.0.0(2,5)]pentasilane 14 with an exohedral chlorosilyl group.