Precision-based Approach Research Articles

A Multivariate Phenotypical Approach of Sepsis and Septic Shock—A Comprehensive Narrative Literature Review

Despite medical advances, sepsis and septic shock remain some of the leading causes of mortality worldwide, with a high inter-individual variability in prognosis, clinical manifestations and response to treatment. Evidence suggests that pulmonary sepsis is one of the most severe forms of sepsis, while liver dysfunction, left ventricular dysfunction, and coagulopathy impact the prognostic. Sepsis-related hypothermia and a hypoinflammatory state are related to a poor outcome. Given the heterogeneity of sepsis and recent technological progress amongst machine learning analysis techniques, a new, personalized approach to sepsis is being intensively studied. Despite the difficulties when tailoring a targeted approach, with the use of artificial intelligence-based pattern recognition, more and more publications are becoming available, highlighting novel factors that may intervene in the high heterogenicity of sepsis. This has led to the devise of a phenotypical approach in sepsis, further dividing patients based on host and trigger-related factors, clinical manifestations and progression towards organ deficiencies, dynamic prognosis algorithms, and patient trajectory in the Intensive Care Unit (ICU). Host and trigger-related factors refer to patients’ comorbidities, body mass index, age, temperature, immune response, type of bacteria and infection site. The progression to organ deficiencies refers to the individual particularities of sepsis-related multi-organ failure. Finally, the patient’s trajectory in the ICU points out the need for a better understanding of interindividual responses to various supportive therapies. This review aims to identify the main sources of variability in clustering septic patients in various clinical phenotypes as a useful clinical tool for a precision-based approach in sepsis and septic shock.

Unveiling the pathogenesis and therapeutic approaches for diabetic nephropathy: insights from panvascular diseases.

Diabetic nephropathy (DN) represents a significant microvascular complication in diabetes, entailing intricate molecular pathways and mechanisms associated with cardiorenal vascular diseases. Prolonged hyperglycemia induces renal endothelial dysfunction and damage via metabolic abnormalities, inflammation, and oxidative stress, thereby compromising hemodynamics. Concurrently, fibrotic and sclerotic alterations exacerbate glomerular and tubular injuries. At a macro level, reciprocal communication between the renal microvasculature and systemic circulation establishes a pernicious cycle propelling disease progression. The current management approach emphasizes rigorous control of glycemic levels and blood pressure, with renin-angiotensin system blockade conferring renoprotection. Novel antidiabetic agents exhibit renoprotective effects, potentially mediated through endothelial modulation. Nonetheless, emerging therapies present novel avenues for enhancing patient outcomes and alleviating the disease burden. A precision-based approach, coupled with a comprehensive strategy addressing global vascular risk, will be pivotal in mitigating the cardiorenal burden associated with diabetes.

Achieving Sharp Upper Bounds on the Expressive Power of Neural Networks via Tropical Polynomials.

The expressive power of neural networks describes the ability to represent or approximate complex functions. The number of linear regions is the standard and most natural measure of expressive power. However, a major challenge in utilizing the number of linear regions as a measure of expressive power is the exponential gap between the theoretical upper and lower bounds, which becomes more pronounced as the neural network capacity increases. In this article, we aim to derive a sharp upper bound on piecewise linear neural networks (PLNNs) to bridge this gap. Specifically, we first establish the relationship between tropical polynomials and PLNNs. In the unexpanded tropical polynomials form, we make the proposition that hyperplanes are not all in the general positions, thereby reducing the number of intersecting hyperplanes. We propose a rank-based approach and present the empirical analysis that this approach outperforms previous Zaslavsky's theorem-based methods. In the expanded tropical polynomials form, accounting for limitations in weight initialization and model computational precision, we raise the concept that the values range of each term is bounded. We propose a precision-based approach that transforms the approximate exponential growth of the number of linear regions into polynomial growth with width, which is effective at larger layer widths. Finally, we compare the number of linear regions that can be represented by each hidden layer in both forms and derive a sharp upper bound for PLNNs. Empirical analysis and experimental results provide compelling evidence for the efficacy and feasibility of this sharp upper bound on both simulated experiments and real datasets.

Endogenous Retroviral Elements Constitute a Promising Vaccine Antigen Source for Haematological Malignancies

Introduction Immunotherapy has revolutionized modern cancer treatment, both within the fields of solid and haematology malignancies. The recent success of checkpoint inhibitor (CPI) therapies (e.g., aPD-1, aCTLA-4) in so called “high” tumour mutational burden (TMB) cancers, such as melanoma and lung cancer (Alexandrov et al. Nature 2013), have found only limited transferability to the haematological setting outside classical Hodgkins lymphoma (Pianko et al. Cancer J. 2018). Recently, the effect of CPIs in high TMB cancers has been further augmented by the combination of CPIs with personalized cancer vaccines (PCVs) in patients with resectable melanoma (NCT03897881). However, recent progress in the identification of novel alternative antigen targets, besides classical missense mutations targeted by PCVs, provides hope for the targeting of haematological cancers with low TMB by immunotherapy-based treatments such as PCVs or even precision-based cancer vaccines. Such sources include endogenous retroviral elements (ERVs) (Saini et al. Nat Commun. 2020), structural rearrangements (Robbe et al. Nat Gen 2022), or activation of transposon elements (Wolf et al. Nat Rev Nephrol. 2023). To investigate the applicability of such approaches in a haematological setting, prospective datasets curated from the database of Genotypes and Phenotypes (dbGaP) and in-house developed antigen prediction platforms, were employed. Methods Data was downloaded from dbGAP and missense mutations (SNVs, INDELs) were determined either from datasets (firehose, TCGA), when available, or through GATK-Mutect2. ERVs were identified using an in-house developed platform (ObsERV), as previously described (Garde et al. BioRxiv 2023). Simulated PCVs were designed for seven selected patients covering high/low TMB and ERV burdens from datasets pertaining to Acute Myeloid Leukaemia (AML), Acute Lymphoblastic Leukaemia (ALL), Multiple Myeloma (MM), Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukaemia (CLL) using in-house platforms PIONEER (neo-epitope identification and ranking for PCV design) and/or ObsERV. PIONEER ranking was based on MHC class I and II ligand propensity, epitope expression level, clonality and tumour specificity Cut-off for inclusion of “efficacious” neoepitopes were based on PIONEER ranking from a recent Phase 1 clinical trial (Mørk et al. ASCO 2023-9551). Due to the high degree of ERV conservation amongst patients within each haematological indications, a precision-based approach was attempted relying on MHC I/II ligand propensity prediction and epitope combination for optimal patient coverage (HLA haplotype) - a similar machine learning approach was proven useful for viral vaccine design (Persson et al Front. Immunol. 2023). Shared vaccines were designed based on HLA frequencies in the human population, which was then applied to the dataset of each patient. The resulting patient specific coverage was then used to compute the total coverage for a given indication. Results and Discussion We found a high presence of ERVs in several haematological malignancies suggesting the potential application of PCVs in these indications, relying on this antigen source (Fig 1A). The combination of missense mutations and ERV sources allowed PCVs to be designed for six of seven patients on average for AML, CLL, and MM compared to only three of seven on average with missense mutations alone. The high level of ERV expression in AML, CLL, and ALL allowed for the generation of vaccines based on shared antigens within each indication. The resulting vaccines had an average coverage, with at least three epitopes, for 84% of AML, 45% of ALL and 35% of CLL patients. In comparison, a missense mutation approach, for the highest TMB cancer (melanoma) would result in only 2.6 % patient coverage with three epitopes. We believe that these findings suggest a novel approach to the treatment of haematological malignancies, either through a PCVs approach, combining multiple sources of antigens, or a precision-based approach with “warehouse” HLA haplotype-specific vaccines for a given indication. This may allow for treatment regimens with greater treatment effect, more durable response, and improved quality of life in indications with a high unmet medical need such as AML and CLL.

CTNI-69. REAL-TIME DRUG SCREENING AND GENOMIC TESTING TO DETERMINE INDIVIDUALIZED TREATMENT PLANS IN CHILDREN AND YOUNG ADULTS WITH RELAPSED MEDULLOBLASTOMA: PRELIMINARY REPORT OF PNOC027

Abstract While current upfront multi-modal treatment for medulloblastoma is effective in many cases, for patients who relapse or don’t respond to initial therapy, effective treatment options are limited and novel therapeutic approaches are needed. The Pacific Pediatric Neuro-Oncology Consortium (PNOC) PNOC027 clinical trial investigates a precision medicine approach that combines real-time drug screening with whole exome and RNA sequencing of fresh tumor tissue to inform individualized treatment recommendations for children and young adults with relapsed medulloblastoma. The primary endpoint is to determine the feasibility of incorporating real time drug screening with DNA/RNA sequencing of tumor to develop a treatment regimen of up to 4-drug of FDA approved agents within 21 business days of tumor acquisition. To this end, freshly isolated cells from relapsed medulloblastoma tumor tissue undergo high-throughput drug screening using a platform of 232 clinically available compounds in parallel with multi-omic genomic analyses to predict individualized tumor response to treatment. Drug responses are assessed after 72 hours of drug exposure and the results yield drug prioritizations based on cytotoxicity and predicted blood-brain barrier permeability. Drugs from different classes are selected based on results from drug screening and molecular analyses combined with patient age, prior treatments, and other medical conditions. Four patients have been enrolled to date and viable tissue samples have been successfully collected and analyzed with treatment recommendations rendered within 21 business days for all patients. The five drug classes with the highest in vitro responses on the drug screen are HDAC inhibitors, proteosome inhibitors, anthracyclines, DNA crosslinkers and kinase inhibitors. PNOC027 demonstrates preliminary feasibility of real-time drug screening combined with DNA/RNA sequencing to inform targeted therapy selection for patients with relapsed medulloblastoma in clinically relevant timeframes. The trial is informing an expanded precision-based approach for relapsed medulloblastoma and the impact of genetic and epigenetic alterations on treatment response.

A precision-based approach to implement evidence-based interventions for students with externalizing behaviors in developing countries: A single case experimental study in China.

The prevalence of externalizing behaviors imposes a far-reaching negative impact on students' social, behavioral, and academic outcomes, which constitute a public health issue in low-resource and populous developing countries (e.g., China). Compared to the "one-size-fits-all" approach (OSFA; forcing a single evidence-based intervention [EBI] on any struggling students) that is prevalent in many countries, a precision-based approach (e.g., Student Intervention Matching System; SIMS) to intervention programming can better meet students' heterogeneous needs by matching individual characteristics to active components of EBIs. But precision-based approaches cannot fulfill their potential in developing countries unless the contextual implementation barriers (e.g., high student-teacher ratio) are remedied with attention to feasibility, acceptability, and cultural compatibility. This collaborative pilot study with Chinese school stakeholders examined the efficacy, feasibility, acceptability, and cultural compatibility of SIMS to match behavioral EBIs to students with externalizing behaviors. A concurrent multiple-baseline across-participant design was used with six students (three dyads). Visual and quantitative analyses evidenced the superior efficacy of SIMS in improving externalizing behaviors compared to the OSFA approach. Social validity data endorsed the feasibility, acceptability, and cultural compatibility of SIMS and the matched EBIs perceived by school stakeholders (educators, students, and parents). Implications, limitations, and future directions for adapting precision-based approaches in low-resource and populous countries were discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for A Precision-Based Approach to Implement Evidence-Based Interventions for Students With Externalizing Behaviors in Developing Countries: A Single Case Experimental Study in China

Supplemental Material for A Precision-Based Approach to Implement Evidence-Based Interventions for Students With Externalizing Behaviors in Developing Countries: A Single Case Experimental Study in China

From Early Life Adversities to adverse health outcomes: A translational precision-based approach

From Early Life Adversities to adverse health outcomes: A translational precision-based approach

Future landscape for the management of membranous nephropathy.

Among all glomerular diseases, membranous nephropathy (MN) is perhaps the one in which major progress has been made in recent decades, in both the understanding of the pathogenesis and treatment. Despite the overall significant response rates to these therapies-particularly rituximab and cyclical regimen based on corticosteroids and cyclophosphamide-cumulative experience over the years has shown, however, that 20%-30% of cases may confront resistant disease. Thus, these unmet challenges in the treatment of resistant forms of MN require newer approaches. Several emerging new agents-developed primarily for the treatment of hematological malignancies or rheumatoid diseases-are currently being evaluated in MN. Herein we conducted a narrative review on future therapeutic strategies in the disease. Among the different novel therapies, newer anti-CD20 agents (e.g. obinutuzumab), anti-CD38 (e.g. daratumumab, felzartamab), immunoadsorption or anti-complement therapies (e.g. iptacopan) have gained special attention. In addition, several technologies and innovations developed primarily for cancer (e.g. chimeric antigen receptor T-cell therapy, sweeping antibodies) seem particularly promising. In summary, the future therapeutic landscape in MN seems encouraging and will definitely move the management of this disease towards a more precision-based approach.

Choosing the right treatment for the right lesion, Part II: a narrative review of drug-coated balloon angioplasty and its evolving role in dialysis access maintenance.

Drug-coated balloons (DCBs) seek to inhibit restenosis in treated hemodialysis access lesions by delivering an anti-proliferative agent (paclitaxel) into the vessel wall. While DCBs have proven effective in the coronary and peripheral arterial vasculature, the evidence for their use in arteriovenous (AV) access has been less robust. In part two of this review, a comprehensive overview of DCB mechanisms, implementation, and design is provided, followed by an examination of the evidence basis for their use in AV access stenosis. An electronic search was performed on PubMed and EMBASE to identify relevant randomized controlled trials (RCTs) comparing DCBs and plain balloon angioplasty from January 1, 2010 to June 30, 2022 published in English. As part of this narrative review, a review of DCB mechanisms of action, implementation, and design is provided, followed by a review of available RCTs and other studies. Numerous DCBs have been developed, each with unique properties, although the degree to which these differences impact clinical outcomes is unclear. Target lesion preparation, achieved by pre-dilation, and balloon inflation time have proven important factors in achieving optimal DCB treatment. Numerous RCTs have been performed, but have suffered from significant heterogeneity, and have often reported contrasting clinical results, making it difficult to draw conclusions on how to implement DCBs in daily practice. On the whole, it is likely there is a population of patients who benefit from DCB use, but it is unclear which patients benefit most and what device, technical, and procedural factors lead to optimal outcomes. Importantly, DCBs use appears safe in the end-stage renal disease (ESRD) population. DCB implementation has been tempered by the lack of clear signal regarding the benefits of DCB use. As further evidence is obtained, it is possible that a precision-based approach to DCBs may shed light onto which patients will truly benefit from DCBs. Until that time, the evidence reviewed herein may serve to guide interventionalists in their decision making, knowing that DCBs appear safe when used in AV access and may provide some benefit in certain patients.

Practical approaches to Bayesian sample size determination in non-inferiority trials with binary outcomes.

Bayesian analysis of a non-inferiority trial is advantageous in allowing direct probability statements to be made about the relative treatment difference rather than relying on an arbitrary and often poorly justified non-inferiority margin. When the primary analysis will be Bayesian, a Bayesian approach to sample size determination will often be appropriate for consistency with the analysis. We demonstrate three Bayesian approaches to choosing sample size for non-inferiority trials with binary outcomes and review their advantages and disadvantages. First, we present a predictive power approach for determining sample size using the probability that the trial will produce a convincing result in the final analysis. Next, we determine sample size by considering the expected posterior probability of non-inferiority in the trial. Finally, we demonstrate a precision-based approach. We apply these methods to a non-inferiority trial in antiretroviral therapy for treatment of HIV-infected children. A predictive power approach would be most accessible in practical settings, because it is analogous to the standard frequentist approach. Sample sizes are larger than with frequentist calculations unless an informative analysis prior is specified, because appropriate allowance is made for uncertainty in the assumed design parameters, ignored in frequentist calculations. An expected posterior probability approach will lead to a smaller sample size and is appropriate when the focus is on estimating posterior probability rather than on testing. A precision-based approach would be useful when sample size is restricted by limits on recruitment or costs, but it would be difficult to decide on sample size using this approach alone.

Treatment Strategies for Multiple Myeloma Treatment and the Role of High-Throughput Screening for Precision Cancer Therapy.

In the past few years, development of approved drug candidates has improved the disease management of multiple myeloma (MM). However, due to drug resistance, some of the patients do not respond positively, while some of the patients acquire drug resistance, thereby these patients eventually relapse. Hence, there are no other therapeutic options for multiple myeloma patients. Therefore, this necessitates a precision-based approach to multiple myeloma therapy. The use of patient's samples to test drug sensitivity to increase efficacy and reduce treatment-related toxicities is the goal of functional precision medicine. Platforms such as high-throughput-based drug repurposing technology can be used to select effective single drug and drug combinations based on the efficacy and toxicity studies within a time frame of couple of weeks. In this article, we describe the clinical and cytogenetic features of MM. We highlight the various treatment strategies and elaborate on the role of high-throughput screening platforms in a precision-based approach towards clinical treatment.

INSP-11. Patient-centered monitoring and care of cognitive late effects in pediatric brain tumor survivors with and without Cerebellar Mutism Syndrome (CMS).

Abstract Risks of cognitive late effects in children with brain tumors is well-established. However, group heterogeneity may limit generalizability and result in inadequate neurocognitive monitoring and care. Children with CMS have unique long-term cognitive risks and current knowledge may not adequately describe their experience or needs. The establishment and implementation of patient-centered, empirically-derived assessment of cognitive change following tumor diagnosis and treatment is a novel, precision-based approach to patient care. METHODS: 30 patients diagnosed with posterior fossa tumor who had at least 2 neuropsychological evaluations were included. Primary outcomes were processing speed (Wechsler PSI) and working memory (WMI). Secondary outcomes were verbal and nonverbal intellect. Reliable change indices (RCIs) were computed (Chelune et al., 1993). Using an 80% CI, 10% would be expected to decline, while 90% would stay stable or improve. RESULTS: Mean age in the full sample was 9.2 (3.32) years at T1 and 13.0 (4.11) years at T2, with an average of 2.7 (2.58) years between assessments. Males made up 56.7% of the sample. Five of the 30 (17%) were CMS+. The CMS+ patients were similar in age to CMS- patients, were predominantly male (80%), and mostly received photon radiation (60%). The full sample showed greater prevalence of declining verbal (21%), spatial (58%) and working memory (29%) functions than the expected (10%). The CMS+ group had higher rates of processing speed (50% v. 7%) and working memory (50% v. 27%) declines than the CMS- group. In contrast, the CMS- group appeared to show more prevalent declines in spatial reasoning than the CMS+ group (67% v. 33%). CONCLUSIONS: There appear to be unique domains impacted in the CMS+ group, which can convey specific long-term outcomes specific to this subgroup of patients. These results highlight the utility of individualized, empirically-driven analysis of change in cognitive functioning in this patient population.

Adherence Index: sleep depth and nocturnal hypoventilation predict long-term adherence with positive airway pressure therapy in severe obstructive sleep apnea.

Treatment of obstructive sleep apnea with positive airway pressure (PAP) devices is limited by poor long-term adherence. Early identification of individual patients' probability of long-term PAP adherence would help in their management. We determined whether conventional polysomnogram (PSG) scoring and measures of sleep depth based on the odds ratio product would predict adherence with PAP therapy 12 months after it was started. Patients with obstructive sleep apnea referred to an academic sleep center had split-night PSG, arterial blood gases, and a sleep questionnaire. Multiple linear regression analysis of conventional PSG scoring and the odds ratio product both during diagnostic PSG and PAP titration provided an "Adherence Index," which was correlated with PAP use 12 months later. Patients with obstructive sleep apnea (n = 236, apnea-hypopnea index 72.2 ± 34.1 events/h) were prescribed PAP therapy (82% received continuous PAP, 18% received bilevel PAP). Each patient's adherence with PAP therapy 12 months later was categorized as "never used," "quit using," "poor adherence," and "good adherence." PSG measures that were most strongly correlated with PAP adherence were apnea-hypopnea index and odds ratio product during nonrapid eye movement sleep; the additional contribution of nocturnal hypoxemia to this correlation was confined to those with chronic hypoventilation treated with bilevel PAP. The Adherence Index derived from these measures, during both diagnostic PSG and PAP titration, was strongly correlated with PAP adherence 12 months later. Long-term adherence with PAP therapy can be predicted from diagnostic PSG in patients with severe obstructive sleep apnea, which may facilitate a precision-based approach to PAP management. Younes MK, Beaudin AE, Raneri JK, Gerardy BJ, Hanly PJ. Adherence Index: sleep depth and nocturnal hypoventilation predict long-term adherence with positive airway pressure therapy in severe obstructive sleep apnea. J Clin Sleep Med. 2022:18(8):1933-1944.

Pediatric sepsis screening in US hospitals.

Sepsis is a major cause of morbidity and mortality in children. While adverse outcomes can be reduced through prompt initiation of sepsis protocols including fluid resuscitation and antibiotics, provision of these therapies relies on clinician recognition of sepsis. Recognition is challenging in children because early signs of shock such as tachycardia and tachypnea have low specificity while hypotension often does not occur until late in the clinical course. This narrative review highlights the important context that has led to the rapid growth of pediatric sepsis screening in the United States. In this review, we (1) describe different screening tools used in US emergency department, inpatient, and intensive care unit settings; (2) highlight details of the design, implementation, and evaluation of specific tools; (3) review the available data on the process of integrating sepsis screening into an overall sepsis quality improvement program and on the effect of these screening tools on patient outcomes; (4) discuss potential harms of sepsis screening including alarm fatigue; and (5) highlight several future directions in sepsis screening, such as novel tools that incorporate artificial intelligence and machine learning methods to augment sepsis identification with the ultimate goal of precision-based approaches to sepsis recognition and treatment.Impact This narrative review highlights the context that has led to the rapid growth of pediatric sepsis screening nationally.Screening tools used in US emergency department, inpatient, and intensive care unit settings are described in terms of their design, implementation, and clinical performance.Limitations and potential harms of these tools are highlighted, as well as future directions that may lead to a more precision-based approach to sepsis recognition and treatment.

The promise of precision medicine in autism

Autism spectrum disorder (ASD) is a clinically and etiologically diverse developmental condition characterized by diminished social interactions, impaired communication, and repetitive and/or restrictive behaviors. Recent advances in ASD genetics pave the way for implementation of precision medicine in clinical management of autism.

Policy Management System: Overview

For any insurance contract to see the light of day, a particular process flow is usually followed. This process flow begins with the customer calling an agent to obtain insurance, and ends with the customer receiving a quote for the coverage. Precision methods focus on improving precision and quality and on planning measures that absolutely address issues and meet the necessary requirements. Unlike automation where the focus is on speeding up tasks and processes, a precision-based approach is centered around improving the quality of the process. More current practices call for ceaselessly examining and retooling tasks/operations to achieve ever more noteworthy business esteem. In this paper, the Insurance Policy Administration System is covered in detail. The format, layout, and key details that the insurance policy entails are thoroughly covered. Some key functionalities like The Policy Submission, Risk Analysis, Policy changes and renewals, Policy cancellation in a typical Policy Administration System are reviewed. Since the Policy Administration System cannot be a standalone service and has to be used along with external systems, the integration of this typical policy administration system with an external system like a user management system is also discussed.

Luminescent Phage-Based Detection of Klebsiella pneumoniae: From Engineering to Diagnostics.

Bacteriophages (“phages”) infect and multiply within specific bacterial strains, causing lysis of their target. Due to the specific nature of these interactions, phages allow a high-precision approach for therapy which can also be exploited for the detection of phage-sensitive pathogens associated with chronic diseases due to gut microbiome imbalance. As rapid phage-mediated detection assays becoming standard-of-care diagnostic tools, they will advance the more widespread application of phage therapy in a precision approach. Using a conventional method and a new cloning approach to develop luminescent phages, we engineered two phages that specifically detect a disease-associated microbial strain. We performed phage sensitivity assays in liquid culture and in fecal matrices and tested the stability of spiked fecal samples stored under different conditions. Different reporter gene structures and genome insertion sites were required to successfully develop the two nluc-reporter phages. The reporter phages detected spiked bacteria in five fecal samples with high specificity. Fecal samples stored under different conditions for up to 30 days did not display major losses in reporter-phage-based detection. Luminescent phage-based diagnostics can provide a rapid co-diagnostic tool to guide the growing field of phage therapy, particularly for a precision-based approach to chronic diseases treatment.

A comparative study between ILS and GBAS approaches: The case of Viseu airfield

Purpose: The article aims to show the viability of installing a precision-based approach system in Viseu airfield, in Portugal. This work looks to evidence to what extent the implementation of ILS (Instrument Landing System) or GBAS (Ground Based Augmentation System) in the airfield is viable, and which of the two would be the better option for this case, from a technical and economic view and as a way to increase safety levels.Design/methodology/approach: The article analyses the airfield’s evolution over time and forecasts its movements for the future, over a 10-year period, by utilising two different models: multiple linear regression and IATA traffic forecasts. The different types of airfield taxes were also reviewed and their values were estimated for the following years. The equipment’s technical aspects and individual prices were analysed to accurately determine the time needed for the airfield to recover the investment done, allied with an 80% funding European project.Findings: Approach systems are being modernized, and throughout the years more airports and airfields are starting to replace old approach systems for satellite-based new ones. When compared to ILS, GBAS offers more advantages at a technical and economic level, and even for smaller airfields with a low traffic volume, sometimes it can be technically and economically possible to have such systems implemented.Originality/value: Studies about the implementation of new radio aids are usually prepared for big airports by airport operators or ANSPs before major investment projects. However, for most small regional airports in the country, where traffic is not near as big, such studies don’t exist, and for that reason, investigating the possibility of installing such kind of equipment is very important, especially taking into consideration the safety they provide and other benefits that naturally come up with it.

Is It Time for Precision Dialysis?

In 2015, President Obama announced funding for precision medicine to augment personalized medicine, which has been described as “the right treatment for the right patient in the right place at the right time.” Patients with ESKD experience high symptom burden and mortality, necessitating more