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Combining granular daily data on temperatures across the continental United States with detailed establishment data from 1990 to 2015, we study the causal impact of temperature shocks on establishment sales and productivity. Using a large sample yielding precise estimates, we do not find evidence that temperature exposures significantly affect establishment-level sales or productivity, including among industries traditionally classified as “heat sensitive.” At the firm level, we find that temperature exposures aggregated across firm establishments are generally unrelated to sales, productivity, and profitability. Our results support existing findings of a tenuous relation between temperature and aggregate economic growth in rich countries.

PurposeA multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres.MethodsA steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%).ResultsForty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement).ConclusionPractitioners are encouraged to work towards adoption of these recommendations.

Supramolecular assemblies are essential components of living organisms. Cellular scaffolds, such as the cytoskeleton or the cell membrane, are formed via secondary interactions between proteins or lipids and direct biological processes such as metabolism, proliferation and transport. Inspired by nature’s evolution of function through structure formation, a range of synthetic nanomaterials has been developed in the past decade, with the goal of creating non-natural supramolecular assemblies inside living mammalian cells. Given the intricacy of biological pathways and the compartmentalization of the cell, different strategies can be employed to control the assembly formation within the highly crowded, dynamic cellular environment. In this Review, we highlight emerging molecular design concepts aimed at creating precursors that respond to endogenous stimuli to build nanostructures within the cell. We describe the underlying reaction mechanisms that can provide spatial and temporal control over the subcellular formation of synthetic nanostructures. Showcasing recent advances in the development of bioresponsive nanomaterials for intracellular self-assembly, we also discuss their impact on cellular function and the challenges associated with establishing structure–bioactivity relationships, as well as their relevance for the discovery of novel drugs and imaging agents, to address the shortfall of current solutions to pressing health issues. Creating artificial nanostructures inside living cells requires the careful design of molecules that can transform into active monomers within a complex cellular environment. This Review explores the recent development of bioresponsive precursors for the controlled formation of intracellular supramolecular assemblies.

The creation of synthetic polymer nanoobjects with well-defined hierarchical structures is important for a wide range of applications such as nanomaterial synthesis, catalysis, and therapeutics. Inspired by the programmability and precise three-dimensional architectures of biomolecules, here we demonstrate the strategy of fabricating controlled hierarchical structures through self-assembly of folded synthetic polymers. Linear poly(2-hydroxyethyl methacrylate) of different lengths are folded into cyclic polymers and their self-assembly into hierarchical structures is elucidated by various experimental techniques and molecular dynamics simulations. Based on their structural similarity, macrocyclic brush polymers with amphiphilic block side chains are synthesized, which can self-assemble into wormlike and higher-ordered structures. Our work points out the vital role of polymer folding in macromolecular self-assembly and establishes a versatile approach for constructing biomimetic hierarchical assemblies. Synthetic polymer nano-objects with well-defined hierarchical structures are important for a wide range of applications such as nanomaterial synthesis, catalysis, and therapeutics. Here the authors demonstrate the strategy of fabricating controlled hierarchical structures through self-assembly of folded synthetic polymers.

Fulfilling the demand of clean potable water to the general public has long been a challenging task in most developing countries due to various reasons. Large-scale membrane water treatment systems have proven to be successful in many advanced countries in the past two decades. This paves the way for developing countries to study the feasibility and adopt the utilization of membrane technology in water treatment. There are still many challenges to overcome, particularly on the much higher capital and operational cost of membrane technology compared to the conventional water treatment system. This review aims to delve into the progress of membrane technology for water treatment systems, particularly in developing countries. It first concentrates on membrane classification and its application in water treatment, including membrane technology progress for large-scale water treatment systems. Then, the fouling issue and ways to mitigate the fouling will be discussed. The feasibility of membrane technologies in developing countries was then evaluated, followed by a discussion on the challenges and opportunities of the membrane technology implementation. Finally, the current trend of membrane research was highlighted to address future perspectives of the membrane technologies for clean water production.

Telehealth interventions are effective in hypertension management. However, the cost-effectiveness of using them for managing patients with hypertension remains inconclusive. Further research is required to understand the effectiveness and cost-effectiveness in the real-world setting. The Primary Technology-Enhanced Care for Hypertension (PTEC-HT) scaling program, a telehealth intervention for hypertension management, is currently being scaled nationwide in Singapore. The program comprises remote blood pressure (BP) monitoring at home, health care team support through teleconsultations, and in-app support with a digital chatbot. This study aimed to evaluate the program's effectiveness and cost-effectiveness. For patients under the PTEC-HT scaling program, BP readings over 6 months and 12 months, age, and gender were collected within the program. Health care use, health care cost, and patient ethnicity were extracted from the National Healthcare Group Polyclinics. For patients in the usual care group, demographic information, clinical data, health care use, and health care costs were extracted from the national claims records. Comparing the PTEC-HT scaling program with usual care, a trial-based economic evaluation using patient-level data was conducted to examine the effectiveness and cost-effectiveness over time horizons of 6 months and 12 months. The health care system's perspective was adopted. Regression analysis and exact matching were used to control for the differences between the PTEC-HT group and the usual care group. For the 6-month analysis, 427 patients were included in the PTEC-HT group, and 64,679 patients were included in the usual care group. For the 12-month analysis, 338 patients were included in the PTEC-HT group, and 7324 patients were included in the usual care group. Using exact matching plus regression, in the 6-month analysis, the probability of having controlled BP was 13.5% (95% CI 6.3%-20.7%) higher for the PTEC-HT group compared to the usual care group. In the 12-month analysis, the probability of having controlled BP was 16% (95% CI 10.7%-21.3%) higher for the PTEC-HT group. Without considering the cost of the BP machine and program maintenance cost, the direct medical cost was S $57.7 (95% CI 54.4-61.0; a currency exchange rate of S $1=US $0.74 was applicable;) lower per patient for the PTEC-HT group in the 6-month analysis and S $170.9 (95% CI 151.9-189.9) lower per patient for the PTEC-HT group in the 12-month analysis. With the cost of the BP machine and program maintenance considered, compared to usual care, the PTEC-HT program reached breakeven at around the sixth month and saved S $52.6 (95% CI 33.6-71.6) per patient at the 12th month. Implemented in a real-world setting in Singapore, our study showed that the PTEC-HT scaling program is more effective in controlling BP status with lower cost compared to the usual care over 12 months.

Abstract Objectives Clinical flow cytometry is laborious, time-consuming, and expensive given the need for data review by highly trained personnel such as technologists and pathologists as well as the significant number of normal cases. Given these issues, automation in analysis and diagnosis holds the key to major efficiency gains. The objective was to design an automated pipeline for the diagnosis of B-cell malignancies in flow cytometry and evaluate its performance against our standard clinical diagnostic flow cytometry process. Methods Using 3,417 cases of peripheral blood data over 6 months from our 10-color B-cell screening tube, we used a newly described method for feature extraction and dimensionality reduction called UMAP on the raw flow cytometry data followed by random forest classification to classify cases without gating on specific population. Results Our automated classifier was able to achieve greater than 95% accuracy in diagnosing all B-cell malignancies, and even better performance for specific malignancies for which the panel was designed, such as chronic lymphocytic leukemia. By adjusting classifier cutoffs, 100% sensitivity could be achieved with an albeit low 14% specificity. Hypothetically, this would allow 11% of the cases to be autoverified without human intervention. Conclusions These results suggest that a clinical implementation of this pipeline can greatly assist in quality control, improve turnaround time, and decrease staff workloads.

We derive a foreign ownership return as the weighted average return of foreign stocks that are connected to a stock through common ownership. The foreign ownership return is of similar economic significance as traditional country and industry factors in explaining international stock returns. It is not related to omitted fundamentals or wealth effects but shifts substantially around ADR and index listings when the investor habitat changes. A decomposition shows that the foreign ownership return is driven by active reallocations of global institutions as opposed to fund flows from end investors. Our findings have important implications for international portfolio diversification.

Delta checks are a powerful technique for monitoring clinical assays in many disciplines but have not been routinely used in molecular testing. To determine if the biologically determined kinetics of BCR-ABL1's rise and fall could allow the development of a delta check in BCR-ABL1 testing. Nine years of BCR-ABL1 p210 results were evaluated and patients with 3 or more results were selected for inclusion. The kinetics of these percentages of international standard values were plotted against time along with the median and the 90th and 95th percentile lines. A Monte Carlo simulation of a batch mix-up was performed for 6 months of data to determine the efficacy of the proposed cutoff. The median kinetics showed a 1-log drop of the percentage of international standard in 90 days, with less than 5% of cases showing faster than a 2-log drop in 90 days, and less than 2.5% showing a faster than 3-log drop in 90 days (extrapolated to 1 log in 30 days). The Monte Carlo simulation of a batch mix-up showed that an average batch mix-up of 23 samples could routinely be flagged by this cutoff, albeit with wide variance. These results suggest that using a drop in the percentage of international standard of greater than 1 log in 30 days can be a useful trigger in implementing a delta-check system for this molecular test.