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Objective To broaden the differential diagnosis thinking of diffuse cystic lung diseases and multiple nodular lung disease, and to deepen the understanding of clinical phenotypes of tuberous sclerosis complex (TSC). Methods A case of TSC with complaint of diffuse lung diseases detected during a routine check-up was presented and relevant literatures were reviewed. Results Further examination confirmed multisystem involvement in the patient including heart, kidney, liver and bone, mimicking metabolic malignant tumor. However, percutaneous renal mass biopsy showed angiomyolipoma, which suggested TSC combined with “Confetti” skin lesions found on physical examination. Peripheral blood whole exome sequencing confirmed the diagnosis of TSC. The pulmonary lesions were improved after treatment with sirolimus. Conclusions High clinical awareness of TSC is essential in the patients with diffuse cystic lung diseases and multiple nodular lung diseases, especially in women. In-depth knowledge of multisystem manifestation in TSC is critical for early diagnosis and treatment of this rare disease.

The Medicare Shared Savings Program (MSSP) was created under the Patient Protection and Affordable Care Act to control escalating Medicare spending by incentivizing providers to deliver healthcare more efficiently. Medicare providers that enroll in the MSSP earn bonus payments for reducing spending to below a risk-adjusted financial benchmark that depends on the provider's historical spending. To generate savings, a provider must invest to improve efficiency, which is a cost that is absorbed entirely by the provider under the current contract. This has proven to be challenging for the MSSP, with amajority of participating providers unable to generate savingsowing to the associated costs. In this paper, we propose a predictive analytics approach to redesigning the MSSP contract with the goal of better aligning incentives and improving financial outcomes from the MSSP. We formulate the MSSP as a principal-agent model and propose an alternate contract that includes a performance-based subsidy to partially reimburse the provider's investment. We prove the existence of a subsidy-based contract that dominates the current MSSP contract by producing a strictly higher expected payoff for both Medicare and the provider. We then propose an estimator based on inverse optimization for estimating the parameters of ourmodel. Weuse a data set containing the financial performance of providers enrolled in the MSSP,which together accounts for 7 million beneficiaries and more than $70 billion inMedicare spending.We estimate that introducing performance-based subsidies to the MSSP can boost Medicare savings by up to 40% without compromising provider participation in the MSSP. We also find that the subsidy-based contract performs well in comparison with a fully flexible nonparametric contract.

Due to the particularity of biomedical industry, it has become necessary for biomedical enterprises to seek innovative research and development (R&D) cooperation to maintain advanced technologies and products in multiple fields. Under such circumstance, the biomedical industry has gradually formed a certain cluster to promote the development of the industry. So far, the biomedical industry cluster has formed in China, mainly within the Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei three urban agglomerations. Within the industrial clusters, the frequency of innovation cooperation among enterprises, universities, research institutions, and other relevant organizations in the biomedical area is high, and the capacity for innovation cooperation is strong as well. This paper used the representative cross-section data of cooperative patents from the medical science and technology patent database of China National Knowledge Infrastructure (CNKI), researching the R&D cooperation within the three major urban agglomerations in China from 2008 to 2016 (Yangtze River Delta Urban Agglomeration, Pearl River Delta Urban Agglomeration, Beijing-Tianjin-Hebei Urban Agglomeration) on total 36 cities' spatial pattern characteristics of biomedical cooperation and the influencing factors. The spatial interaction model was used to study the spatial, economic, political, and R&D influencing factors of cross-city cooperation. The degree of aggregation showed that cross-city R&D cooperation mainly occurred in well-developed and central cities of urban agglomerations. Econometric results revealed that spatial, economic, political, and R&D bias factors did have a significant impact on the frequency of biomedical R&D cooperation across cities.

In flexible manufacturing lines with delayed differentiation, the production process may fluctuate sharply when a control action is performed. As a result, the steady-state analysis algorithm is inaccurate for these production lines, and transient behavior studies have become crucial. However, dynamic analysis remains unexplored compared with the well-established theoretical system of steady-state analysis. Therefore, in this study, we propose a fast algorithm for predicting the production process performance in the delayed differentiation-based flexible production line under operation control. We first formulate practical problems existing in the auto, food, and furniture industries into a mathematical formation. Then, we offer closed-form formulae for predicting the production process performance using the built stochastic model in the production line with three machines. We also propose an algorithm to predict the performance of a production line having more than three machines. The proposed methods were verified to be highly accurate through comparison experiments. In terms of theoretical contributions, this study offers a research foundation for other transient-based studies. From a practical perspective, the proposed algorithms can be employed to predict the production process performance of processing lines under production control in advance. [ABSTRACT FROM AUTHOR]

Purpose: The Centiloid project helps calibrate the quantitative amyloid-β (Aβ) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aβ deposition in CL using [18F]Flutemetamol and evaluate regional Aβ deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aβ deposition by measuring regional CL in equivocal cases showing negative global CL. Methods: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aβ positivity. Results: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aβ deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aβ positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. Conclusion: The expression of regional brain Aβ deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aβ deposition that can be detected by measuring regional CL. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the connective tissue growth factor inhibitor pamrevlumab decrease the rate of decline in lung function for patients with idiopathic pulmonary fibrosis compared with placebo? Findings: In this phase 3 randomized clinical trial including 356 adults with idiopathic pulmonary fibrosis, the decline in forced vital capacity at 48 weeks did not differ significantly between patients treated with pamrevlumab (–260 mL) vs placebo (–330 mL). Meaning: Use of pamrevlumab among patients with idiopathic pulmonary fibrosis did not result in a difference in decline in forced vital capacity from baseline to 48 weeks compared with placebo. Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, −260 mL [95% CI, −350 to −170 mL] in the pamrevlumab group vs −330 mL [95% CI, −430 to −230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, −60 to 190 mL], P =.29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146 This randomized clinical trial compares the efficacy and safety of pamrevlumab vs placebo for patients with idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Many invertebrates and vertebrates secrete mucus from their body surface, which plays a crucial role in protecting themselves from attacks by microorganism or predators. This study reports on the potential functions of mucus secreted from the body surface of larvae of the moth Phauda flammans (Walker) (Lepidoptera: Phaudidae). We tested whether the mucus could inhibit the growth of the fungus Beauveria bassiana PfBb (Bals.‐Criv.) Vuill. (Hypocreales) and attract and/or deter predators such as the crazy ant, Paratrechina longicornis (Latreille) (Hymenoptera: Formicidae), and the predatory bug Eocanthecona furcellata (Wolff) (Hemiptera: Pentatomidae). Our results showed that de‐ and rehydrated mucus concentrations of 0.5–1.0 mg mL−1 had an inhibitory effect on the conidial germination and colony growth of B. bassiana PfBb; however, P. flammans mucus did not significantly affect fungal sporulation. Raw mucus and mucus concentrations of 1.0–4.0 mg mL−1 attracted P. longicornis workers in a Y‐tube olfactometer, whereas the physical viscosity of raw mucus hindered their foraging for food in a laboratory test. The E. furcellata adults did not display a preference for the odour of P. flammans mucus. Therefore, P. flammans mucus may inhibit pathogenic microorganisms and attract or repel predators, but the mucus does not act as a complete deterrent. [ABSTRACT FROM AUTHOR]

To understand non-compliance behaviors in investment goods in pandemic preparedness and resilience, we resort to a form of bounded rationality that people suffer from a lack of self-control due to "present bias", and differ in their sophistication levels (the degree to which they are aware of such compliance barriers). We focus on (i) the manufacturer's pricing strategy under an advance selling framework, and (ii) the subsidy policy to mitigate under-adoption, to generate operational insights. We show that subsidizing the manufacturer is more cost-effective than subsidizing consumers, because the latter subsidy will not fully trickle down to consumers when the manufacturering manipulates prices in response. In particular, when the subsidy program is budget-constrained, the manufacturer subsidy should be provided only in the spot period. In contrast, when the budget constraint is relaxed, subsidies in both periods should be provided. Surprisingly, such a subsidy program has non-monotone impacts on consumers' adoption quantities. Intuitively, this is because the spot-period subsidy induces consumers' non-compliance behaviors in the advance period. In response, the manufacturer/seller will shift to a pricing strategy that may further reduce the advance-selling quantity. This result provides a natural explanation to reconcile the mixed effects of adoption subsidies. [ABSTRACT FROM AUTHOR]

Inverse optimization refers to the inference of unknown parameters of an optimization problem based on knowledge of its optimal solutions. This paper considers inverse optimization in the setting where measurements of the optimal solutions of a convex optimization problem are corrupted by noise. We first provide a formulation for inverse optimization and prove it to be NP-hard. In contrast to existing methods, we show that the parameter estimates produced by our formulation are statistically consistent. Our approach involves combining a new duality-based reformulation for bilevel programs with a regularization scheme that smooths discontinuities in the formulation. Using epiconvergence theory,we showthe regularization parameter can be adjusted to approximate the original inverse optimization problem to arbitrary accuracy, whichwe use to prove our consistency results. Next, we propose two solution algorithms based on our duality-based formulation. The first is an enumeration algorithm that is applicable to settings where the dimensionality of the parameter space is modest, and the second is a semiparametric approach that combines nonparametric statistics with a modified version of our formulation. These numerical algorithms are shown to maintain the statistical consistency of the underlying formulation. Finally, using both synthetic and real data, we demonstrate that our approach performs competitively when compared with existing heuristics.

Abstract Population screening played a substantial role in safely reopening the economy and avoiding new outbreaks of COVID-19. PCR-based pooled screening makes it possible to test the population with limited resources by pooling multiple individual samples. Our study compared different population-wide screening methods as transmission-mitigating interventions, including pooled PCR, individual PCR, and antigen screening. Incorporating testing-isolation process and individual-level viral load trajectories into an epidemic model, we further studied the impacts of testing-isolation on test sensitivities. Results show that the testing-isolation process could maintain a stable test sensitivity during the outbreak by removing most infected individuals, especially during the epidemic decline. Moreover, we compared the efficiency, accuracy, and cost of different screening methods during the pandemic. Our results show that PCR-based pooled screening is cost-effective in reversing the pandemic at low prevalence. When the prevalence is high, PCR-based pooled screening may not stop the outbreak. In contrast, antigen screening with sufficient frequency could reverse the epidemic, despite the high cost and the large numbers of false positives in the screening process.