A lung function information system

Abstract A lung function information system (LFIS) was developed for the data analysis of pulmonary function tests at different locations. This system was connected to the hospital information system (HIS) for the retrieval of patient data and the storage of the lung function variables of patients to generate follow-up reports and to support financial and administrative management. The application programs were developed in such a way that high flexibility was obtained with respect to the patient-computer-technician interaction. The sampled data are stored on a disc to correct earlier decisions, perform recalculations and reanalyse the data for research purposes. When the measurements performed on a patient are authorized, the sampled data are deleted, except for when they are needed for future research. A distributed computer system was chosen to combine the benefits of a centralized system with those of several stand-alone systems. The main tasks of the central unit are to store collected data and computer programs, generate a final lung function report on laser printer and provide a connection to the HIS. In the satellite computers, which are located close to the lung function equipment, the signals and raw data are processed. Furthermore, the satellite computers were in use for program development and several research projects, and for the offline data processing of the lung function measurements from two other hospitals by means of a modem connection. The LFIS improved the quantity and quality of data acquisition. It resulted in an increased capacity of about 50% concerning spirometry, and facilitated time-consuming complex analyses. It also avoided miscalculations and mistakes in reports previously experienced with hand calculations

Frailty and restrictions in geriatric domains are associated with surgical complications but not with radiation-induced acute toxicity in head and neck cancer patients:A prospective study

OBJECTIVES: We aimed to evaluate the association between frailty screening and geriatric assessment (GA) on short term adverse events in patients treated for head and neck cancer (HNC) for the first time in a prospective study. MATERIALS AND METHODS: Newly diagnosed HNC patients undergoing curative treatment were prospectively included in OncoLifeS, a data biobank. Prior to the start of treatment, frailty was assessed with a GA, Groningen Frailty Indicator (GFI) and Geriatric-8 (G8). The GA included comorbidity (Adult Comorbidity Evaluation - 27), nutritional status (Malnutrition Universal Screening Tool), functional status ((instrumental) Activities of Daily Living), mobility (Timed Up & Go), psychological (Geriatric Depression Scale 15) and cognitive (Mini Mental State Examination) measures. Clinically relevant postoperative complications (Clavien-Dindo ≥ grade 2) and acute radiation-induced toxicity (Common Terminology Criteria for Adverse Events version 4.0 ≥ grade 2) were defined as outcome measures. Univariable and multivariable logistic regression analyses were performed, yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: Of the 369 included patients, 259 patients were eligible for analysis. Postoperative complications occurred in 41/148 (27.7%) patients and acute radiation-induced toxicity was present in 86/160 (53.7%) patients. Number of deficit domains of GA (OR = 1.71, 95%CI = 1.14-2.56), GFI (OR = 2.54, 95%CI = 1.02-6.31) and G8 (OR5.59, 95%CI = 2.14-14.60) were associated with postoperative complications, but not with radiation-induced toxicity. CONCLUSION: Frailty and restrictions in geriatric domains were associated with postoperative complications, but not with radiation-induced acute toxicity in curatively treated HNC patients. The results of this prospective study further emphasizes the importance of geriatric evaluation, particularly before surgery

Frailty is associated with decline in health-related quality of life of patients treated for head and neck cancer

Objective: To determine the effect of frailty on Health Related Quality of Life (HRQoL) after treatment for Head and Neck Cancer (HNC). Materials and methods: Patients were prospectively included in OncoLifeS, a data-biobank. Before treatment, patients underwent geriatric screening, including the Groningen Frailty Indicator (GFI) and Geriatric 8 (G8). Patients' HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at three, six, twelve and twenty four months after treatment. Linear mixed models were used for statistical analysis. All models were adjusted for baseline HRQoL values, relevant confounders at baseline and yielded estimates (beta), 95% confidence intervals and p-values. Results: 288 patients were included. The mean age was 68.4 years and 68.8% were male. During follow-up, 84 patients had tumor recurrence and 66 died. Response to EORTC-QLQ-C30 ranged from 77.3% to 87.8%. Frail patients, defined by GFI, had significantly worse Global Health Status/Quality of Life (GHS/QoL) (beta = -8.70(-13.54;-3.86), p <0.001), physical functioning (beta = -4.55(-8.70;-0.40), p <0.032), emotional functioning (beta = -20.06(-25.65;-15.86), p <0.001), and social functioning (beta = -8.44(-13.91;-2.98), p <0.003) three months after treatment compared to non-frail patients. Furthermore, frail patients had a significantly worse course of GHS/QoL (j3 = -7.47(-11.23;-3.70), p = 0.001), physical functioning (beta = -3.28(-6.26;-0.31), p = 0.031) and role functioning (beta = -7.27(-12.26;-2.28), p = 0.005) over time, compared to non-frail patients. When frailty was determined by G8, frailty was significantly associated with worse GHS/QoL (beta = -6.68(-11.00;-2.37), p = 0.003) and emotional functioning (beta = -5.08(-9.43;-0.73), p = 0.022) three months after treatment. Conclusion: Frail patients are at increased risk for decline in HRQoL, and further deterioration during follow-up after treatment for HNC

Association of Deficits Identified by Geriatric Assessment With Deterioration of Health-Related Quality of Life in Patients Treated for Head and Neck Cancer

This cohort study assesses the association of single and accumulated geriatric deficits with health-related quality of life decline after treatment for head and neck cancer. Question Are pretreatment geriatric deficits associated with quality of life after treatment for head and neck cancer? Findings In this cohort study including 283 patients, items of geriatric assessment within all domains (physical, functional, psychological, social) were associated with decline of quality of life after treatment. The accumulation of domains with geriatric deficits was a major significant factor for deterioration at both short- and long-term follow-up after treatment. Meaning Deficits in individual and accumulated geriatric domains are associated with decline in quality of life; this knowledge may aid decision-making, indicate interventions, and reduce loss of quality of life. Importance Accumulation of geriatric deficits, leading to an increased frailty state, makes patients susceptible for decline in health-related quality of life (HRQOL) after treatment for head and neck cancer (HNC). Objective To assess the association of single and accumulated geriatric deficits with HRQOL decline in patients after treatment for HNC. Design, Setting, and Participants Between October 2014 and May 2016, patients at a tertiary referral center were included in the Oncological Life Study (OncoLifeS), a prospective data biobank, and followed up for 2 years. A consecutive series of 369 patients with HNC underwent geriatric assessment at baseline; a cohort of 283 patients remained eligible for analysis, and after 2 years, 189 patients remained in the study. Analysis was performed between March and November 2020. Interventions or Exposures Geriatric assessment included scoring of the Adult Comorbidity Evaluation 27, polypharmacy, Malnutrition Universal Screening Tool, Activities of Daily Living, Instrumental Activities of Daily Living (IADL), Timed Up & Go, Mini-Mental State Examination, 15-item Geriatric Depression Scale, marital status, and living situation. Main Outcomes and Measures The primary outcome measure was the Global Health Status/Quality of Life (GHS/QOL) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Differences between patients were evaluated using linear mixed models at 3 months after treatment (main effects, beta [95% CI]) and declining course per year during follow-up (interaction x time, beta [95% CI]), adjusted for baseline GHS/QOL scores, and age, sex, stage, and treatment modality. Results Among the 283 patients eligible for analysis, the mean (SD) age was 68.3 (10.9) years, and 193 (68.2%) were male. Severe comorbidity (beta = -7.00 [-12.43 to 1.56]), risk of malnutrition (beta = -6.18 [-11.55 to -0.81]), and IADL restrictions (beta = -10.48 [-16.39 to -4.57]) were associated with increased GHS/QOL decline at 3 months after treatment. Severe comorbidity (beta = -4.90 [-9.70 to -0.10]), IADL restrictions (beta = -5.36 [-10.50 to -0.22]), restricted mobility (beta = -6.78 [-12.81 to -0.75]), signs of depression (beta = -7.08 [-13.10 to -1.06]), and living with assistance or in a nursing home (beta = -8.74 [-15.75 to -1.73]) were associated with further GHS/QOL decline during follow-up. Accumulation of domains with geriatric deficits was a major significant factor for GHS/QOL decline at 3 months after treatment (per deficient domain beta = -3.17 [-5.04 to -1.30]) and deterioration during follow-up (per domain per year beta = -2.74 [-4.28 to -1.20]). Conclusions and Relevance In this prospective cohort study, geriatric deficits were significantly associated with HRQOL decline after treatment for HNC. Therefore, geriatric assessment may aid decision-making, indicate interventions, and reduce loss of HRQOL

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health-related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. METHODS: Patients with mucosal HNSCC were prospectively included. HRQOL and 2-year overall survival were analysed using linear mixed-model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. RESULTS: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL-scores (indicating better HRQOL) during 2-year follow-up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score-β: 2.62, 95% CI: 0.57-4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65-15.76, p = 0.005) and stage-IV tumours (HR: 12.37, 95% CI: 2.81-54.39, p = 0.001). Delay was not associated with worse overall survival. CONCLUSION: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL-scores or decreased overall survival during 2-year follow-up

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Genomes of multicellular algal sisters to land plants illuminate signaling network evolution

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution

Identification of constrained sequence elements across 239 primate genomes

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs