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PubMed2026

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (ρ = 0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2 ≈ 12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2 ≈ 41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (≈1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

Humans↗

PubMed2005

Analgesia and sedation during mechanical ventilation in neonates.

BACKGROUND: Endotracheal intubation and mechanical ventilation are major components of routine intensive care for very low birth weight newborns and sick full-term newborns. These procedures are associated with physiologic, biochemical, and clinical responses indicating pain and stress in the newborn. Most neonates receive some form of analgesia and sedation during mechanical ventilation, although there are marked variations in clinical practice. Clinical guidelines for pharmacologic analgesia and sedation in newborns based on robust scientific data are lacking, as are measures of clinical efficacy. OBJECTIVE: This article represents a preliminary attempt to develop a scientific rationale for analgesia sedation in mechanically ventilated newborns based on a systematic analysis of published clinical trials. METHODS: The current literature was reviewed with regard to the use of opioids (fentanyl, morphine, diamorphine), sedative-hypnotics (midazolam), nonsteroidal anti-inflammatory drugs (ibuprofen, indomethacin), and acetaminophen in ventilated neonates. Original meta-analyses were conducted that collated the data from randomized clinical comparisons of morphine or fentanyl with placebo, or morphine with fentanyl. RESULTS: The results of randomized trials comparing fentanyl, morphine, or midazolam with placebo, and fentanyl with morphine were inconclusive because of small sample sizes. Meta-analyses of the randomized controlled trials indicated that morphine and fentanyl can reduce behavioral and physiologic measures of pain and stress in mechanically ventilated preterm neonates but may prolong the duration of ventilation or produce other adverse effects. Randomized trials of midazolam compared with placebo reported significant adverse effects (P < 0.05) and no apparent clinical benefit; the findings of a meta-analysis suggest that there are insufficient data to justify use of IV midazolam for sedation in ventilated neonates. CONCLUSIONS: Despite ongoing research in this area, huge gaps in our knowledge remain. Well-designed and adequately powered clinical trials are needed to establish the safety, efficacy, and short- and long-term outcomes of analgesia and sedation in the mechanically ventilated newborn.

Analgesia↗

PubMed2004

Reconstruction of microbial transcriptional regulatory networks.

Although metabolic networks can be readily reconstructed through comparative genomics, the reconstruction of regulatory networks has been hindered by the relatively low level of evolutionary conservation of their molecular components. Recent developments in experimental techniques have allowed the generation of vast amounts of data related to regulatory networks. This data together with literature-derived knowledge has opened the way for genome-scale reconstruction of transcriptional regulatory networks. Large-scale regulatory network reconstructions can be converted to in silico models that allow systematic analysis of network behavior in response to changes in environmental conditions. These models can further be combined with genome-scale metabolic models to build integrated models of cellular function including both metabolism and its regulation.

Bacteria↗

PubMed2006

Enhancement of soluble protein expression through the use of fusion tags.

The soluble expression of heterologous proteins in Escherichia coli remains a serious bottleneck in protein production. Although alteration of expression conditions can sometimes solve the problem, the best available tools to date have been fusion tags that enhance the solubility of expressed proteins. However, a systematic analysis of the utility of these solubility fusions has been difficult, and it appears that many proteins react differently to the presence of different solubility tags. The advent of high-throughput structural genomics programs and advances in cloning and expression technology afford us a new way to compare the effectiveness of solubility tags. This data should allow us to better predict the effectiveness of tags currently in use, and might also provide the information needed to identify new fusion tags.

Biotechnology↗

PubMed2026

Effects of exercise snacking on neuromuscular performance in insufficiently active adults: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of exercise snacking (ES) on neuromuscular performance in insufficiently active adults. METHODS: Six databases were searched from inception to July 17, 2026. Randomized controlled trials and non-randomized studies of interventions involving insufficiently active adults undertaking ES interventions were included. Outcomes were functional performance, muscular strength, and muscular power. A three-level random-effects meta-analysis was performed. Risk of bias was assessed with RoB 2 or ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Nine studies (13 reports) involving 313 participants were included. In the primary three-level model, ES showed a small positive overall effect on neuromuscular performance (g = 0.37, 95% CI 0.16-0.58, p = 0.001), which remained supported under trial-clustered robust inference with small-sample adjustment. Domain-specific estimates for muscular power/velocity, functional performance, and muscular strength were positive but imprecise and were not statistically supported after small-sample robust adjustment. Robust moderator tests provided no evidence of between-subgroup differences, and the certainty of evidence was low for all outcomes. CONCLUSION: Current low-certainty evidence suggests that ES may produce a small improvement in overall neuromuscular performance. However, domain-specific effects remain uncertain because of the limited number of independent trials, and the overall prediction interval crossed zero, indicating uncertainty across future populations and settings. Larger, preregistered randomized controlled trials are needed to confirm these preliminary findings.

Adult↗

PubMed2006

Effectiveness of stereotactic radiosurgery alone or in combination with whole brain radiotherapy compared to conventional surgery and/or whole brain radiotherapy for the treatment of one or more brain metastases: a systematic review and meta-analysis.

PURPOSE: To assess the effectiveness of SRS alone or in combination with WBRT compared to surgery and/or WBRT in prolonging survival and improving the quality-of-life and functional status of patients with brain metastases. METHODS AND MATERIALS: A meta-analysis of randomized controlled trials and concurrent cohort studies examining SRS versus SRS + WBRT, SRS versus WBRT +/- surgical resection, SRS versus surgical resection only, or SRS + WBRT versus WBRT was conducted. Trial registers, bibliographic databases, and reference lists from selected studies and recent issues of relevant journals were searched. Neuro-oncology specialists were also contacted. All studies were analyzed independently by two reviewers, applying validated critical appraisal techniques. RESULTS: The review identified three RCTs and one cohort study. Among patients with multiple metastases, no difference in survival between those treated with WBRT + SRS and those treated with WBRT was found. However, in patients with one metastasis, a statistically significant difference, favoring those treated with WBRT + SRS, was observed. Regarding local tumor control at 24 months, rates were significantly higher in the WBRT + SRS treatment arm, regardless of the number of metastases. CONCLUSIONS: Adding SRS to WBRT improves survival in patients with one brain metastasis. Combining SRS and WBRT improves local tumour control and functional independence in all patients.

Brain Neoplasms↗

PubMed2006

Effects of different chemotherapy regimens on survival for advanced cervical cancer: systematic review and meta-analysis.

BACKGROUND: A large number of trials have assessed various chemotherapy regimens for the treatment of advanced cervical cancer, but there is uncertainty about the magnitude of survival benefits. METHODS: We searched (last update January 2006) for trials in women with locally advanced or disseminated cervical cancer that compared neo-adjuvant or concurrent chemotherapy plus radiotherapy versus radiotherapy alone; or different chemotherapy regimens among themselves (with or without background radiotherapy in both arms). Sixty-five trials were identified with survival data on 11,180 women. Results for survival were combined with fixed and random effects models and between-study heterogeneity was estimated. Separate results were obtained for different regimens, cycle length, and type of chemotherapy (neo-adjuvant, concurrent, without radiotherapy). RESULTS: Twenty two comparisons had survival data on 3837 women randomized to receive chemotherapy plus radiotherapy versus radiotherapy alone; the summary relative hazard for mortality was 0.95, 95% CI, 0.83-1.08. Modest between-study heterogeneity (I2=38%) seemed to be due to contradictory results in early trials; trials published in the last decade had a summary relative hazard 0.89 (95% CI, 0.78-1.02) and no between-study heterogeneity (I2=0%). Results were similar for neo-adjuvant chemotherapy and for concurrent chemo-radiotherapy. Cisplatin or cisplatin-based combinations had no significant benefit overall, but a potential benefit was seen with short-length cycles (14 days) and a marginally significant harm with longer-length cycles (summary relative hazards 0.80, 95% CI, 0.66-0.99 and 1.18, 95% CI, 1.02-1.38, respectively). The summary relative hazard was 1.02, (95% CI, 0.84-1.24) for trials using neo-adjuvant chemotherapy and 0.85 (95% CI, 0.73-1.00) for trials using concurrent chemotherapy. CONCLUSIONS: Evidence on chemotherapy in women with advanced cervical cancer is not encouraging for major survival benefits. However, small benefits have been observed in some trials, especially with short-length cycles of cisplatin-based regimens and concurrent chemotherapy and radiotherapy.

Antineoplastic Agents↗

PubMed2005

PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis.

Phosphoinositides play important roles in regulating the cytoskeleton and vesicle trafficking, potentially important processes at the cleavage furrow. However, it remains unclear which, if any, of the phosphoinositides play a role during cytokinesis. A systematic analysis to determine if any of the phosphoinositides might be present or of functional importance at the cleavage furrow has not been published. Several studies hint at a possible role for one or more phosphoinositides at the cleavage furrow. The best of these are genetic data identifying mutations in phosphoinositide-modifying enzymes (a PtdIns(4)P-5-kinase in S. pombe and a PI-4-kinase in D. melanogaster) that interfere with cytokinesis. The genetic nature of these experiments leaves questions as to how direct may be their contribution to cytokinesis. Here we show that a single phosphoinositide, PtdIns(4,5)P2, specifically accumulates at the furrow. Interference with PtdIns(4,5)P2 interferes with adhesion of the plasma membrane to the contractile ring at the furrow. Finally, four distinct interventions to specifically interfere with PtdIns(4,5)P2 each impair cytokinesis. We conclude that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal cytokinesis at least in part because of a role in adhesion between the contractile ring and the plasma membrane.

Actins↗

PubMed2006

Circadian orchestration of the hepatic proteome.

Circadian rhythms are essential to health. Their disruption is associated with metabolic diseases in experimental animals and man. Local metabolic rhythms represent an output of tissue-based circadian clocks. Attempts to define how local metabolism is temporally coordinated have focused on gene expression by defining extensive and divergent "circadian transcriptomes" involving 5%-10% of genes assayed. These analyses are inevitably incomplete, not least because metabolic coordination depends ultimately upon temporal regulation of proteins. We therefore conducted a systematic analysis of a mammalian "circadian proteome." Our analysis revealed that up to 20% of soluble proteins assayed in mouse liver are subject to circadian control. Many of these circadian proteins are novel and cluster into discrete phase groups so that the liver's enzymatic profile contrasts dramatically between day and night. Unexpectedly, almost half of the cycling proteins lack a corresponding cycling transcript, as determined by quantitative PCR, microarray, or both and revealing for the first time the extent of posttranscriptional mechanisms as circadian control points. The circadian proteome includes rate-limiting factors in vital pathways, including urea formation and sugar metabolism. These findings provide a new perspective on the extensive contribution of circadian programming to hepatic physiology.

Animals↗

PubMed2005

Identification and characterization of factors required for microtubule growth and nucleation in the early C. elegans embryo.

Microtubules (MTs) are dynamic polymers that undergo cell cycle and position-sensitive regulation of polymerization and depolymerization. Although many different factors that regulate MT dynamics have been described, to date there has been no systematic analysis of genes required for MT dynamics in a single system. Here, we use a transgenic EB1::GFP strain, which labels the growing plus ends of MTs, to analyze the growth rate, nucleation rate, and distribution of growing MTs in the Caenorhabditis elegans embryo. We also present the results from an RNAi screen of 40 genes previously implicated in MT-based processes. Our findings suggest that fast microtubule growth is dependent on the amount of free tubulin and the ZYG-9-TAC-1 complex. Robust MT nucleation by centrosomes requires AIR-1, SPD-2, SPD-5, and gamma-tubulin. However, we found that centrosomes do not nucleate MTs to saturation; rather, the depolymerizing kinesin-13 subfamily member KLP-7 is required to limit microtubule outgrowth from centrosomes.

Animals↗

PubMed2005

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men.

Tumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we conducted a meta-analysis of aspirin, beta-carotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention.

Animals↗

PubMed2026

Effect of renin-angiotensin system inhibitors on survival in glioma patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of renin-angiotensin system inhibitors (RASIs) on the survival outcomes of glioma patients, determine whether using RASIs correlates with survival benefit, and provide evidence-based guidance for the clinical treatment. METHODS: Studies assessing the effects of using RASIs versus non-use in glioma patients were retrieved from the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to April 17, 2024. The included studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS), as well as the effect on brain edema and steroid dosing in patients. RESULTS: Seven articles involving 2660 patients were included in this study. Pooled results indicated there was no significant difference in OS (HR = 0.89, 95% CI 0.75-1.06, P = 0.204) or PFS (HR = 0.98, 95% CI 0.82-1.18, P = 0.847) between RASIs-treated patients and non-RASIs-treated patients. Sensitivity analysis identified the ACEIs-focused trial reported by Happold et al. as a major contributor to inter-study heterogeneity. Subgroup analyses revealed that in recurrent glioblastoma, pooled OS was significantly longer in RASIs-treated patients than non-RASIs-treated patients (HR = 0.70, 95% CI 0.54-0.92, P = 0.01). Similarly, compared with bevacizumab monotherapy, bevacizumab combined with RASIs significantly extended OS in glioblastoma patients (HR = 0.73, 95% CI 0.63-0.86, P < 0.001). CONCLUSION: The results revealed that treatment with RASIs may show a trend toward prolonged overall survival (OS) in patients with glioma. For patients with glioblastoma, RASI therapy could prolong OS in those with recurrent disease. Furthermore, compared with bevacizumab monotherapy, the combination of RASIs and bevacizumab was associated with improved OS in glioblastoma patients.

Humans↗

PubMed2005

The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the tolerability, safety and efficacy of antimuscarinic drugs used to treat overactive bladder and to identify any differences between individual antimuscarinics. METHODS: Medline, Embase, CCTR and Cinahl databases were searched for published RCTs including an antimuscarinic agent from 1966 to August 2004. Data from included trials were extracted and meta-analysed where possible. RESULTS: Fifty-six trials were included. The antimuscarinics were found to be safe and efficacious. All antimuscarinics apart from oxybutynin IR were found to be well tolerated. Dry mouth was the most commonly reported adverse event and no drug was associated with an increase in any serious adverse event. There were significant differences between the antimuscarinics in rates of withdrawal and rates and range of adverse events and efficacy outcomes. CONCLUSIONS: The antimuscarinics have different tolerability and safety profiles, which are clinically significant.

Clinical Trials as Topic↗

PubMed2004

Region-specific cell grafting into cervical and lumbar spinal cord in rat: a qualitative and quantitative stereological study.

In the present study, we have characterized an atraumatic grafting technique which permits multiple, segmental, and lamina-specific injections into cervical or lumbar spinal cord. Cell injections were performed in spinally mounted rats of different ages and spinal cord size, using a micromanipulator and glass microcapillary connected to a digital microinjector. For grafting, we used human neuroteratoma (hNT) cells, BrdU-labeled rat spinal precursors or primary embryonic spinal cord neurons isolated from E14 spinal cord of the eGFP+ rat. Systematic quantification of grafted cells was performed using stereological principles of systematic random sampling and semi-automated optical Disector software. Volume reconstruction was performed using serial sections from grafted areas and custom-developed software (Ellipse) which permits "two reference points" semi-automated alignment of images, as well as volume reconstruction and calculation. By coupling these techniques, it is possible to achieve a relatively precise and atraumatic cell delivery into multiple spinal cord segments and specific spinal laminae. Consistency of the multiple grafts position in the targeted laminar areas was verified by a systematic volume reconstruction. Good survival of implanted cells for the three different cell lines used indicate that this grafting technique coupled with a systematic analysis of the individual grafting sites can represent a valuable implantation-analytical system.

Animals↗

PubMed2026

Diversification of yeast proteins as an approach for the development of sustainable food systems.

Despite growing trend in sustainable protein sources, yeast proteins have mainly been explored as a source of bioactive peptides using a monospecies and general protein approach. The contribution of highly abundant protein fractions in the yeast proteome to peptide formation remains insufficiently investigated, limiting a comprehensive understanding of yeast proteins as optimized peptide sources. The current review presents a systematic analysis of yeast proteins as emerging protein sources and evaluates the suitability of high-abundance proteins as bioactive peptide precursors by in silico techniques. Moreover, brewery by-product and single-cell yeast protein approaches are compared in terms of composition and techno-functionality whereas peptide formation mechanisms (in situ and ex situ) and regulatory aspects for food applications are also addressed. Cytoplasmic metabolic proteins, particularly glycolytic enzymes (GAPDH), are identified as highly abundant fractions of the yeast proteome. Proteins associated with cell and organelle membranes also contribute substantially based on cellular localization. These findings imply that such proteins may act as key precursors of yeast-derived bioactive peptides. In silico hydrolysis with Alcalase suggests a tendency toward the generation of short-chain peptides (3-11/14 aa), which may support biological activity. Moreover, peptide profiles appear to vary across yeast species, highlighting the role of species diversity in peptide generation. While single-cell yeast protein allows more controlled production than brewery by-products, nucleic acid content in both may limit applications. Overall, yeast proteins appear to be metabolically adaptable and species-diverse sources for various biological peptides.

Saccharomyces cerevisiae↗

PubMed2004

Automatic screening in postmortem toxicology.

The systematic analysis of postmortem samples is one of the most challenging tasks in forensic toxicology. For determining cause of death, analysis of different tissues can be indispensable. Automation of these analyses would increase reproducibility and therefore lead to more reliable and comparable results. Recent developments in analytical toxicology and the availability of automation devices for various analytical stages, such as sampling, preliminary testing, sample extraction, chromatographic separation, identification, and data processing are examined and discussed. At present only parts of the analytical procedure have been automated-however, the goal should be the integration of these parts into a single, continuous process. Currently, only one "fully-automated" procedure for the comprehensive screening of blood and urine (excluding sample pretreatment, which remains separate) has been published. But it can be expected that automation of analytical procedures in forensic toxicology will indeed progress, even with regard to the very complex screening of postmortem samples.

Chromatography, Liquid↗

PubMed2025

Utility of genome sequencing and group-enrichment to support splice variant interpretation in Marfan syndrome.

PURPOSE: To quantify the impact of noncanonical FBN1 splice site variants in undiagnosed Marfan syndrome (MFS), a connective tissue disorder associated with skeletal abnormalities and familial thoracic aortic aneurysm disease (FTAAD). METHODS: A systematic analysis of ultrarare FBN1 variants was performed using genome sequencing data from the 100,000 Genomes Project. Variants were annotated with SpliceAI and the significance of enrichment among individuals with FTAAD was assessed using Fisher's exact test. Experimental validation used RNA sequencing, reverse transcriptase polymerase chain reaction, minigene constructs, and replication analysis was with data from UK Biobank. RESULTS: Using aggregate data for 78,195 individuals, we identified 13,864 singleton single-nucleotide variants in FBN1 of which 21 were predicted to affect splicing (SpliceAI > 0.5). Incidence of candidate splice variants in individuals recruited with FTAAD (9/703) was significantly elevated compared with that seen in non-FTAAD participants (12/77,492; odds ratio = 84, P = 9.7 × 10-14). Additional analysis uncovered a further 14 families harboring 11 different FBN1 splice variants. A total of 20 candidate splice variants in 23 families were identified, of which 70% lay beyond the ±8 splice regions. RNA testing confirmed the predicted splice aberration in 16 of 20 and for 9 of 20, pseudoexonization was the likely splicing anomaly. CONCLUSION: Our findings indicate that noncanonical splice variants may account for approximately 3% of families with undiagnosed FTAAD, highlighting the importance of incorporating analysis of introns and confirmatory RNA testing into genetic testing for Marfan syndrome.

Humans↗

PubMed2005

Informal payment for health care: evidence from Hungary.

While there is a growing body of evidence that informal payments for health care are widespread and enduring in the former communist countries of Central and Eastern Europe and Central Asia, evidence on the scale of the phenomenon is not only limited, but what is available is often conflicting. Hungary exemplifies this controversy, as the available literature provides conflicting figures, differing by an order of magnitude among various surveys, with a similarly large difference between survey findings and expert estimates. This study advances understanding of the methodological issues involved in researching informal payments by providing a systematic analysis of the methodology of available empirical research and official statistics on the scale of informal payments in Hungary. The paper explores the potential sources of differences, to assess the scope to reduce the differences between various estimates and to define the upper and lower boundaries within which the true magnitude of informal payments can be expected to lie. Our analysis suggests that in 2001 the overall magnitude of informal payments lay between 16.2 and 50.9 billion HUF (euro 64.8- euro 203.6 million, US dollars 77.1-242.4 million), which amounted to 1.5-4.6% of total health expenditures in Hungary. Looked at this way, informal payments do not seem to be an important source of health care financing. However, as informal payments are unequally distributed among health workers, with the bulk of the money going to physicians, with some not taking any informal payments, family doctors and some specialists may have earned between 60 and 236% of their net official income from this source in 2001. This suggests that it is not the overall amount of informal payment that makes it a policy concern, but the consequences of its unequal distribution among health workers. What is remarkable about informal payments in Hungary is that a relatively small amount of money can keep the system running, which gives rise to the hypothesis that, in certain cases, it is the hope of substantial informal payments in the future that motivates physicians to remain in the system. This is a difficult challenge for policy-makers as it would require a much larger amount of money to achieve equilibrium under any formal alternative.

Delivery of Health Care↗