Optimal screening with securities

Confined aquifer dewatering optimization with a modified simulation–optimization method capable of determining the optimal well screen length and depth

Prevalence of and optimal screening tool for postpartum depression in a community-based population in China

Cancer screening and early detection efforts have been partially successful in reducing incidence and mortality, but many improvements are needed. Although current medical practice is informed by epidemiologic studies and experts, the decisions for guidelines are ultimately ad hoc. We propose here that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain "window of opportunity" for intervention when early cancer development may be observable. Alternative to a strictly empirical approach or microsimulations of a multitude of possible scenarios, biologically based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett's esophagus, these methods were applied for a model of esophageal adenocarcinoma that was previously calibrated to U.S. cancer registry data. Optimal screening ages for patients with symptomatic gastroesophageal reflux disease were older (58 for men and 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Collectively, our framework captures critical aspects of cancer evolution within patients with Barrett's esophagus for a more personalized screening design. SIGNIFICANCE: This study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes, with the added potential to improve surveillance regimes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/4/1123/F1.large.jpg.

A CHANGE OF HEART: A CASE OF CARDIAC AMYLOIDOSIS

Gene dosage amplification is an effective strategy to improve the performance of heterologous genes and pathways. Pichia pastoris is an excellent recombinant protein expression host with high efficiency in protein folding and glycosylation. However, the traditional iterative multicopy integration method typically faces challenges such as being time-consuming and having high cost and potential gene mutations. Accordingly, we established CRISPR-mediated rDNA integration and fluorescence screening for pathway optimization (CRISPO) for multicopy pathway integration in a single-step and antibiotic-free manner. With geraniol biosynthesis as a case study, we designed CRISPO based on the use of glycerol-induced and glucose-repressed promoters (CRISPOi) or strong constitutive promoters (CRISPOc) to drive the expression of the red fluorescent protein mCherry as the screening marker. We employed CRISPOi for stable strain construction by multicopy integration of the geraniol synthase encoding gene, achieving a 19.5-fold increase in geraniol production. We demonstrated CRISPOc for visualizing and determining the rate-limiting steps of the mevalonate pathway, with HMG1 and ERG12 identified as the major rate-limiting enzymes through two rounds of exploration. Ultimately, CRISPO enabled us to construct an engineered P.pastoris strain producing 1.66 g/L geraniol (with a total of 2.12 g/L monoterpenoids) and 6.27 g/L geraniol (with a total of 6.48 g/L monoterpenoids) in 24-well plates and 5 L fermenters, respectively, representing the highest titer and productivity of geraniol ever reported. CRISPO is an important addition to the synthetic biology toolbox for the construction and optimization of P.pastoris cell factories.

OC-014: Molecular screening for cancer treatment optimization in head and neck cancer (MOSCATO 01)

Background: Several studies suggest that test characteristics for the fecal immunochemical test (FIT) differ by gender, triggering a debate on whether men and women should be screened differently. We used the microsimulation model MISCAN-Colon to evaluate whether screening stratified by gender is cost-effective.Methods: We estimated gender-specific FIT characteristics based on first-round positivity and detection rates observed in a FIT screening pilot (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and costs of 480 gender-specific FIT screening strategies and compared them with uniform screening.Results: Biennial FIT screening from ages 50 to 75 was less effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY) gained, respectively] at higher costs (€42,161 vs. -€5,471, respectively). However, the incremental QALYs gained and costs of annual screening compared with biennial screening were more similar for both genders (8.7 QALYs gained and €26,394 for women vs. 6.7 QALYs gained and €20,863 for men). Considering all evaluated screening strategies, optimal gender-based screening yielded at most 7% more QALYs gained than optimal uniform screening and even resulted in equal costs and QALYs gained from a willingness-to-pay threshold of €1,300.Conclusions: FIT screening is less effective in women, but the incremental cost-effectiveness is similar in men and women. Consequently, screening stratified by gender is not more cost-effective than uniform FIT screening.Impact: Our conclusions support the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev; 26(8); 1328-36. ©2017 AACR.

The determination of optimum process mean and screening limits based on quality loss function

Gestational diabetes mellitus (GDM) is one of the most common metabolic complications of pregnancy. Ever since the first systematic evaluation of the oral glucose tolerance test by O’Sullivan and colleagues was carried out in 1964, there has been controversy with respect to the optimal screening and diagnostic criteria to detect GDM. The recently proposed International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for GDM has found fairly widespread acceptance, but it is still debated by several societies. This review intends to provide an overview of the evolution of the screening and diagnostic criteria for GDM. Debatable issues regarding optimal screening strategies, especially in the low resource settings of low and middle income countries are highlighted. The recent Women in India with GDM Strategy (WINGS) project carried out in Chennai, India tried to develop a Model of Care for GDM suitable for resource constrained settings. The findings related to screening and diagnosis of GDM based on WINGS are also highlighted in this review. Based on the WINGS experience we believe that despite the constraints in low and middle income countries at the present time, the IADPSG criteria appears to be the best. This will also help to bring out a uniform criteria for screening and diagnosis of GDM worldwide.

Chapter 19 - Approaches for fabrication of point-of-care biosensors for viral infection

Background. The insulin tolerance test (ITT) is the “gold standard” of the secondary adrenal insufficiency (SAI) diagnosis but it is rather difficult to carry out, has some contraindications and requires patient’s hospitalization. The availability of a reliable screening method could reduce the necessity of using ITT.Aim: to compare different methods of screening with ITT and to work out an optimal diagnostic algorithm of SAI.Methods. 40 patients (20 women) after craniospinal (CSI) irradiation in a doze 35 Gy were examined. The average age at the time of the observation was 19,5±3 years, at the time of treatment 12,5±3,5 years. Patient’s blood samples were collected for basal cortisol (BC), DHEA-S. ITT was performed for all patients, glucagon stimulation test (GST) was for 27 persons. Patients were divided into groups: SAI and without SAI (W-SAI) after ITT. ROC- analysis was conducted to identify the thresholds for BC, DHEA-S and GST. Cut-off points for BC and DHEA-S levels corresponding to 100% sensitivity (Se) for SAI group and 100% specificity (Sp) for W-SAI patients were estimated to select a group of patients which do not require stimulative tests. Linear regression was used to construct a predictive model (PM) of SAI occurrence after CSI.Results. 22/40 subjects failed ITT, 13/27 passed GST. 3 patients failed ITT but passed GST. Their level of neutrophils and monocytes was higher than the other patients'. SAI-patients had BC and DHEA-S lower than W-SAI (321±102 vs 516± 183; p=0,003 and 2,6±1,4 vs 5,1±2,1, p=0,003). ROC-analysis showed area under curve (AUC) for GST=0,91 with optimal cut-off for cortisol=489 which corresponds to 100% Sp and 62% Se. AUC was 0,83 for BC and 0,84 for DHEA-S.In 70% patients' BC was in a “grey zone” (32% of them passed ITT), 8% had BC lower than 200 (which corresponds to 100% Se) and 22% more than 499 (100% Sp). 50% of patients were in a “grey zone” for DHEA-S (50% of them had SAI), 18% had DHEA-S level below 2,0 and 32% above 4,7. A combination of BC and DHEA-S in the PM of SAI (0,592+0,001*BC+0,11*DHEA-S) had AUC 94%. This PM didn’t give the prognosis of SAI for 32% (CI: 18-49%) of patients. The addition of maximal cortisol (MC) level during GST (0,53+0,01*BC+0,066*DHEA-S+0,001*MC) increased AUC to 99% and didn’t allow to predict SAI in 8% (3,2% - 24,9%) of patients only.Conclusions. When the screening methods were used separately, they showed comparable accuracy and it was not high. The PM may be used as optimal screening method for SAI and may allow to use ITT more rarely. But further studies are required to validate the PM proposed in this study.

It has long been appreciated that the measurement of biochemical parameters for prenatal screening for neural tube defects, and later aneuploidy, is not as simple as measuring hemoglobin or hematocrit. Early in the game, it was recognized that there are gestational age curves, and that since α-fetoprotein (AFP), for example, is a fetal product, its distribution varies as a function of maternal plasma volume, and therefore the weight of the mother. A number of different adjustment factors have been used for AFP and other parameters for years, with varying degrees of consistency and reliability. Here we review a number of adjustments that have been used, and try to give priority to those that have been most effective. Furthermore, laboratories and programs need to be cognizant that with newer parameters being added, the specifics of requirements will vary on a case-by-case parameter basis, and optimal screening can only be achieved with the appropriate adjustments.

Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies. The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients. Answers were obtained from 121/241 transplant centres (50%) across 15 European countries. Screening practices for diabetes mellitus during the transplant work-up varied, with only 13% of centres using the recommended oral glucose tolerance test (OGTT) and 14% not screening at all. At transplantation, 19% of centres tailored the immunosuppressive regimen based on perceived PTDM risk, using strategies such as cyclosporin use or early steroid withdrawal. Fifty-two percent adopted strict glycaemic control with basal insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days-6 months), primarily based on fasting glycaemia and/or HbA1c, while only a minority (7%) incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycaemia (<45 days) and by 58% in established PTDM (>45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycaemia (<45 days) and PTDM (>45 days). The use of SGLT2 inhibitors and GLP-analogues increased >45 days post-transplantation. This European survey underscores the significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for more explicit guidance in approaching this complication.

Simple SummaryIn advanced pancreatic cancer, the majority of patients experience pancreatic exocrine insufficiency (PEI), which can negatively impact nutritional status, quality of life and survival rates. Unfortunately, PEI is often diagnosed too late. The aim of our prospective observational study was to identify a screening panel that was simple to use in the outpatient setting, to identify patients that required more timely intervention with pancreatic enzyme replacement therapy. The screening panel proposed is a simple tool that can be used in a clinical setting to identify patients at higher risk of PEI and needing prompt dietetic input.Introduction: Pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC) is well documented, but there is no consensus regarding optimal screening. Methods and analysis: Patients diagnosed with aPC referred for palliative therapy were prospectively recruited. A full dietetic assessment (including Mid-Upper Arm Circumference (MUAC), handgrip and stair-climb test), nutritional blood panel, faecal elastase (FE-1) and 13C-mixed triglyceride breath tests were performed. Primary objective: prevalence of dietitian-assessed PEI (demographic cohort (De-ch)); design (diagnostic cohort (Di-ch)) and validation (follow-up cohort (Fol-ch)) of a PEI screening tool. Logistic and Cox regressions were used for statistical analysis. Results: Between 1 July 2018 and 30 October 2020, 112 patients were recruited (50 (De-ch), 25 (Di-ch) and 37 (Fol-ch)). Prevalence of PEI (De-ch) was 64.0% (flatus (84.0%), weight loss (84.0%), abdominal discomfort (50.0%) and steatorrhea (48.0%)). The derived PEI screening panel (Di-ch) included FE-1 (normal/missing (0 points); low (1 point)) and MUAC (normal/missing (>percentile 25) (0 points); low (2 points)) and identified patients at high-risk (2–3 total points) of PEI [vs. low-medium risk (0–1 total points)]. When patients from the De-ch and Di-ch were analysed together, those classified by the screening panel as “high-risk” had shorter overall survival (multivariable Hazard Ratio (mHR) 1.86 (95% CI 1.03–3.36); p-value 0.040). The screening panel was tested in the Fol-ch; 78.4% patients classified as “high-risk”, of whom 89.6% had dietitian-confirmed PEI. The panel was feasible for use in clinical practice (64.8% patients completed all assessments), with high acceptability (87.5% would repeat it). Most patients (91.3%) recommended dietetic input for all patients with aPC. Conclusions: PEI is present in most patients with aPC; early dietetic input provides a holistic nutritional overview, including, but not limited to, PEI. This proposed screening panel may help to prioritise those at higher risk of PEI, requiring urgent dietitian input. Its prognostic role needs further validation.

Background: Cervical cancer is the fourth most common cancer among women worldwide. Cervical cancer usually develops from human papillomavirus (HPV) infection, which leads to cervical intraepithelial neoplasia (CIN1/2/3) and eventually invasive cervical cancer. Therefore, early-screening and detection of cervical lesions are crucial for preventing and treating cervical cancer. However, different regions have different levels of medical resources and availability of diagnostic methods. There is a need to compare the efficiency of different methods and combinations for detecting cervical lesions and provide recommendations for the optimal screening and detection strategies. Methods: The current clinical methods for screening and detection of cervical lesions mainly include TruScreen (TS), Thinprep cytologic test (TCT), HPV testing, and colposcopy, but their sensitivity and specificity vary and there is no standard protocol recommended. In this study, we retrospectively reviewed 2286 female samples that underwent cervical biopsy and compared the efficiency of different methods and combinations for detecting cervical lesions. Results: HPV screening showed the highest sensitivity for identifying women with CIN2+ cervical lesions compared with other single methods. Our results also showed the importance and necessary of the secondary diagnostic test like TCT and TS as a triage method before colposcopy examination and guided biopsy. Conclusions: Our study provides recommendations for the optimal screening and detection strategies for cervical lesions in different regions with different levels of development. As a non-invasive, easily operated, and portable device, TS is a promising tool to replace TCT for detecting cervical lesions in the health care center with insufficient medical resources.