Deploying Big Data To Crack The Genotype To Phenotype Code

Mechanistically connecting genotypes to phenotypes is a longstanding and central mission of biology. Deciphering these connections will unite questions and datasets across all scales from molecules to ecosystems. Although high-throughput sequencing has provided a rich platform on which to launch this effort, tools for deciphering mechanisms further along the genome to phenome pipeline remain limited. Machine learning approaches and other emerging computational tools hold the promise of augmenting human efforts to overcome these obstacles. This vision paper is the result of a Reintegrating Biology Workshop, bringing together the perspectives of integrative and comparative biologists to survey challenges and opportunities in cracking the genotype to phenotype code and thereby generating predictive frameworks across biological scales. Key recommendations include: promoting the development of minimum “best practices” for the experimental design and collection of data; fostering sustained and long-term data repositories; promoting programs that recruit, train, and retain a diversity of talent and providing funding to effectively support these highly cross-disciplinary efforts. We follow this discussion by highlighting a few specific transformative research opportunities that will be advanced by these efforts

SOILS Ammonium and Nitrate Nitrogen in Soil Profiles of Long-Term Winter Wheat Fertilization Experiments

ABSTRACT Accumulation of NH~ -N and NO3 -N in soils has not been thor. oughly evaluated in long-term continuous winter wheat (Triticum aes. tivum L.) production systems. The objectives of this study were to determine long-term response of winter wheat to N fertilization and to evaluate accumulation of NH~ -N and NO3 -N in the soil profile. Four long-term winter wheat soil fertility experiments on thermic Ustoll soils that received annual applications of N for > 18 yr at selected N rates were sampled. At each location, one soil core 4.4 cm in diameter was taken to a depth of 240 cm from plots receiving variable N rates. Cores were separated into 30-cm increments and analyzed for 2 M KCI-extractable NH~ -N and NO~-N. At all locations, NH~ -N levels were not significantly different from the check (no fertilizer N) when rates were applied at or below yield goal requirements (90 or45 kg N ha -~ vs. 0 N). At N rates >90 kg N ha -~, surface (0-15 cm) NH~ -N increased compared with the check, while subsurface NH~ -N did not. Similarly, when N rates were <90 kg N ha -~, no significant differences in either surface or subsurface NO 3 -N were found. At N rates >90 kg N ha -1, NO5 -N accumulated in the subsurface soil profile (>30 cm). Estimates of N rates determined from simultaneous solutions of NO5 -N accumulation minimums and yield maximums generated from quadratic regression were greater than N rates currently recommended to achieve yield goals at all locations. For these long-term continuous winter wheat experiments, no accumulation of NH~ -N and NO5 -N occurred at recommended N rates where near maximum yields were obtained. p AST AND PRESENT use of N fertilizers for winter wheat production has been related to the potential for NOA--N contamination of surface and subsurface water. Although N fertilizers are essential for economic grain production, long-term N accumulation as a result of excessive N rates has not been monitored closely. Work by Liang et al. (1991) found that residual soil NO~--N did not increase in the soil profile (0-60 cm) over a 4-yr period when comparing N rates of 170 and 400 kg ha -1 applied to corn. MacDonald et al. (1989) indicated that following harvest, unfertilized wheat plots had inorganic N contents equal to those where 234 kg N ha -1 had been applied. This work further suggested that almost all of the NO~--N at risk to leaching over the winter period comes from mineralization of organic N and not from unused fertilizer applied in the spring; therefore, even a drastic reduction in N fertilizer use would have little effect on NO~--N leaching. Lamb et al. (1985) reported that the addition of N fertilizer increased the amount of NO~-N accumulated but did not change the accumulation pattern. Tillage system (no-till, stubble mulch, and plow) did not affect the time at which the NOA--N started to accumulate during the fallow period nor the rate of accumulation (Lamb et al., 1985). Sharpley al. (1991) reported no evidence of N accumulation the soil profile (0--180 cm) after 5 yr for either no-till or reduced-till cultural practices with N fertilizer applied to sorghum at recommended rates (0--146 kg ha-1 yr-1), although annual total N in surface runoff . was 0.76 kg N ha -1 for no-till, 0.99 kg N ha -1 for reduced-till, and 7.28 kg N ha -1 for conventional till. Smika (1990) reported that time must be allowed for the equilibration of soil conditions before evaluating NO~--N accumulation, citing research that showed less NO~--N accumulation to 120 cm for reduced-till methods compared with conventional tillage for short-term studies, but more NO~--N accumulation for reducedtill methods in long-term studies. Tracy et al. (1990) noted that tillage method (conventional, no-till) did not affect NO~--N accumulation below 5 cm; differences in NO~--N in the topsoil were attributed to organic matter incorporation over 16 yr of winter wheat farming. Varvel and Peterson (1990) reported that high N application rates (180 kg N ha-1) resulted in greater residual soil NO~--N to 150 cm for continuous corn and grain sorghum systems than for other cropping systems. This same study found that all systems had similar NO~--N accumulation at lower N application rates. Work by Liang et al. (1991) found that under irrigation, 100 kg NOA--N ha -~ was lost from the rooting zone (0-60 cm) during four growing seasons, with the majority coming from the surface 40 cm. The effects of N fertilizer rate (90 and 180 kg ha -x) and nitrification inhibitors on urea lSN leaching and balance on a irrigated sandy loam were summarized by Waiters and Malzer (1990). The higher N application rate resulted in 3.4 times more N leached over a 3-yr period (206 vs. 88 kg ha -1 to 1.2 m depth). Nitrification inhibitors delayed N losses, but did not decrease the total N lost. Westerman and Tucker (1979) noted that the presence of organic residue can lower denitrification by increased immobilization of inorganic or mineralized N. Immobilization was thus considered to be an N conserving process competing with denitrification for nitrate. Nitrate studies in field microplots showed that 17% of applied 15N (120 kg N ha -~ equivalent) was still in the 45-cm soil profile after 1 yr (Kowalenko, 1989). Webster et al. (1986) evaluated the movement (92 and 102 kg NHnNO 3 ha -~) in clay and sandy loam field microplots and found that < 1% of the fertilizer was leached beyond 130 cm in the first winter following application. Response of wheat grain yields to N fertilization has been documented in numerous soil fertility experiments. However, very few of these experiments have included evaluation for more than 3 to 5 yr that also accounted for accumulation of NOA--N and NH~--N within the soil profile. The objectives of this study were to determine the long-term response of 9

Applying a User-centred Approach to Interactive Visualization Design

Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches

Treatment sequences and drug costs from diagnosis to death in multiple myeloma

Novel therapies for multiple myeloma (MM) have improved patient survival, but their high costs strain healthcare budgets. End-of-life phases of treatment are generally the most expensive, however, these high costs may be less justifiable in the context of a less pronounced clinical benefit. To manage drug expenses effectively, detailed information on end-of-life drug administration and costs are crucial. In this retrospective study, we analysed treatment sequences and drug costs from 96 MM patients in the Netherlands who died between January 2017 and July 2019. Patients received up to 16 lines of therapy (median overall survival: 56.5 months), with average lifetime costs of €209 871 (€3111/month; range: €3942–€776 185) for anti-MM drugs. About 85% of patients received anti-MM treatment in the last 3 months before death, incurring costs of €20 761 (range: €70–€50 122; 10% of total). Half of the patients received anti-MM treatment in the last 14 days, mainly fully oral regimens (66%). End-of-life treatment costs are substantial despite limited survival benefits. The use of expensive treatment options is expected to increase costs further. These data serve as a reference point for future cost studies, and further research is needed to identify factors predicting the efficacy and clinical benefit of continuing end-of-life therapy.</p

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

A systematic review of the literature on digital transformation: insights and implications for strategy and organizational change

In this article we provide a systematic review of the extensive yet diverse and fragmented literature on digital transformation (DT), with the goal of clarifying boundary conditions to investigate the phenomenon from the perspective of organizational change. On the basis of 279 articles, we provide a multi-dimensional framework synthesizing what is known about DT and discern two important thematical patterns: DT is moving firms to malleable organizational designs that enable continuous adaptation, and this move is embedded in and driven by digital business ecosystems. From these two patterns, we derive four perspectives on the phenomenon of DT: technology impact, compartmentalized adaptation, systemic shift and holistic co-evolution. Linking our findings and interpretations to existing work, we find that the nature of DT is only partially covered by conventional frameworks on organizational change. On the basis of this analysis, we derive a research agenda and provide managerial implications for strategy and organizational change.info:eu-repo/semantics/publishedVersio