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The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging. Macromolecular drugs display low stability and poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that can efficiently penetrate the GI mucosa and deliver insulin systemically. In addition, we performed in vitro studies to characterize insulin release and the penetration capacity of microinjectors and measure in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin trans-mucosally to the systemic circulation at similar levels to intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these novel microinjectors could significantly advance drug delivery across the GI tract mucosa to the systemic circulation.

HighlightsThe Surface Renewal (SR), Eddy Covariance (EC), and FAO56 methods were used to estimate crop evapotranspiration.An independently calibrated SR approach was used with a low-cost cup anemometer and assumed energy balance closure.All three approaches (SR, EC, and FAO56) resulted in similar crop ET values during later stages of growth (R2 = 0.87).SR has the potential to lower field-scale ET measurement costs and equipment requirements.Abstract. Evapotranspiration (ET) is important for many agricultural and hydrological applications, but its measurement normally requires expensive instrumentation. The Surface Renewal method (SR) has been proposed as a relatively low-cost alternative to measure ET, but the need for local calibration has been cited as a shortcoming. Castellví (2004)(2004) proposed a similarity-based SR approach to address this shortcoming, but field comparisons evaluating the accuracy of the approach using low-cost anemometry are currently lacking. The objective of this study was to evaluate the reliability of the similarity-based SR approach using low-cost anemometry (cup anemometer) for estimating cotton ET in comparison to the Eddy Covariance (EC) and FAO56 methods (Allen et al., 1998). Concurrent estimates of cotton ET were taken in 2019 at two adjacent cotton fields in South Carolina using the SR, EC, and FAO56 methods. SR and EC measurements of sensible heat flux were replicated using two in-field tower locations in the north field and ET was derived using the energy balance closure approach. An analysis was made to ensure =90% of the EC and SR seasonal data came from the field area (Kljun et al., 2015), with additional filtering to ensure that the higher-mounted EC had >90% footprint from the field area for each half-hour of analysis. In general, the results showed very good agreement between the daily crop ET values measured by SR and EC (R2north = 0.93, R2south = 0.97) for all of the season, and good agreement between SR and FAO56 measurements when crop height was more developed (R2north = 0.92, R2south = 0.87), near or above a canopy height of 0.75 m. There was disagreement between the non-continuous north tower SR measurements and FAO56 measurements in earlier stages of growth (June and July R2 = 0.09), which may have been due to uncertainty with the FAO56 local single crop coefficients or with a lack of energy balance closure. The results suggest that the use of low-cost anemometry with the independently calibrated SR approach is a useful alternative to measure crop ET under the conditions of this study, but further research may be necessary to evaluate the use of low-cost anemometry for direct SR ET measurements. Keywords: Cotton irrigation, Crop coefficients, Eddy covariance, Evapotranspiration, ET, Surface renewal.

BackgroundGastrointestinal tumors are a leading cause of mortality worldwide. Our previous research demonstrated that miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. We therefore aimed to explore the potential of circulating miR-1290 as a biomarker for gastrointestinal cancer.MethodsSerum miRNA sequence analysis was performed. Then, circulating miRNA detection technologies were established. miR-1290 expression levels in gastrointestinal tumor cell lines and cellular supernatants were analyzed. Expression levels of circulating miR-1290 in clinical samples were examined. Associations between miR-1290 expression and clinicopathologic characteristics were analyzed. Xenograft models were conducted to assess the fluctuation of serum miR-1290 during disease progression.ResultsThrough miRNA sequencing, we identified that miR-1290 was overexpressed in CRC serum. We confirmed that human gastrointestinal tumor cells express and secret miR-1290. Circulating miR-1290 was up-regulated in pancreatic cancer (PC) (p < 0.01), CRC (p < 0.05), and gastric cancer (GC) (p < 0.01). High expression levels of miR-1290 were associated with tumor size, lymphatic invasion, vascular invasion, distant metastasis, tumor differentiation and AJCC stage in PC and CRC. The area under the curve (AUC) was 0.8857 in PC, with 60.9% sensitivity and 90.0% specificity. The AUC was 0.7852 in CRC, with 42.0% sensitivity and 90.0% specificity. In GC, the AUC was 0.6576, with 26.0% sensitivity and 90.0% specificity. The in vivo model verified that circulating miR-1290 levels significantly increased after tumor formation and decreased after drug treatment.ConclusionsOur findings demonstrate that circulating miR-1290 is a potential diagnostic and disease monitoring biomarker in gastrointestinal cancer.

BACKGROUND The increasing incidence of inflammatory bowel disease (IBD) has imposed heavy financial burdens for Chinese patients; however, data about their financial status and access to health care are still lacking. This information is important for informing patients with IBD about disease treatment budgets and health care strategies. OBJECTIVE The aim of this study was to evaluate the economic status and medical care access of patients with IBD through the China Crohn’s & Colitis Foundation web-based platform in China. METHODS Our study was performed in 14 IBD centers in mainland China between 2018 and 2019 through WeChat. Participants were asked to complete a 64-item web-based questionnaire. Data were collected by the Wenjuanxing survey program. We mainly focused on income and insurance status, medical costs, and access to health care providers. Respondents were stratified by income and the associations of income with medical costs and emergency visit times were analyzed. RESULTS In this study, 3000 patients with IBD, that is, 1922 patients with Crohn disease, 973 patients with ulcerative colitis, and 105 patients with undetermined colitis were included. During the last 12 months, the mean (SD) direct and indirect costs for per patient with IBD were approximately US $11,668.68 ($7944.44) and US $74.90 ($253.60) in China. The average reimbursement ratios for most outpatient and inpatient costs were less than 50%. However, the income of 85.5% (2565/3000) of the patients was less than ¥10,000 (US $1445) per month. Approximately 96.5% (2894/3000) of the patients were covered by health insurance, but only 24.7% (741/3000) of the patients had private commercial insurance, which has higher imbursement ratios. Nearly 98.0% (2954/3000) of the patients worried about their financial situation. Thus, 79.7% (2392/3000) of the patients with IBD tried to save money for health care and even delayed their medical treatments. About half of the respondents (1282/3000, 42.7%) had no primary care provider, and 52.2% (1567/3000) of the patients had to visit the emergency room 1-4 times per year for the treatment of their IBD. Multivariate analysis revealed that lower income (P=.001) and higher transportation (P=.004) and accommodation costs (P=.001) were significantly associated with the increased number of emergency visits of the patients. CONCLUSIONS Chinese patients with IBD have enormous financial burdens and difficulties in accessing health care, which have increased their financial anxiety and inevitably influenced their disease outcomes. Early purchase of private insurance, thereby increasing the reimbursement ratio for medical expenses, and developing the use of telemedicine would be effective strategies for saving on health care costs.

We thank the principal investigators of the AmeriFlux network, and the U.S. Department of Energy’s Office of Science for funding the AmeriFlux data resources. We thank the U.S. Department of Energy Lawrence Berkeley Lab Ameriflux Network Management Project for core site support. This research was supported through the National Science Foundation award EF1137306/MIT subaward 5710003122 to the University of California Davis; and other government, industry and foundation sponsors of the MIT Joint Program on the Science and Policy of Global Change. For a complete list of sponsors and U.S. government funding sources, please visit http://globalchange.mit.edu/sponsors/all.

Background Currently, WeChat is widely used in disease education for patients with Crohn’s disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. Methods In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. Results Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn’s and Colitis Foundation (CCCF) (73%), “IBD Academic Officer” (21%) and “IBD in love” (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients’ expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p

Background:Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.Objective:To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.Methods:Clinical isolates ofStaphylococcus aureus,Enterococcus faecium,Pseudomonas aeruginosa, andKlebsiella pneumoniaewere obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.Results:Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.Conclusions:Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.

Interest in highly parallelized analysis of single molecules and single cells is growing rapidly. Here we develop hydrogel-based virtual microfluidics as a simple alternative to complex engineered microfluidic systems for the compartmentalization of nucleic acid amplification reactions. We applied digital multiple displacement amplification (dMDA) to purified DNA templates, cultured bacterial cells, and human microbiome samples in the virtual microfluidics system and demonstrated recovery and whole-genome sequencing of single-cell MDA products. Our results from control samples showed excellent coverage uniformity and markedly reduced chimerism compared with single-cell data obtained from conventional liquid MDA reactions. We also demonstrate the applicability of the hydrogel method for genomic studies of naturally occurring microbes in human microbiome samples. The virtual microfluidics approach is a simple and robust method that will enable many laboratories to perform single-cell genomic analyses.

Background Nowadays internet and social media community have provided a great amount of information for patients with inflammatory bowel disease (IBD). We aimed to assess the sources and needs of Chinese IBD patients through the internet and their impact on disease management. Methods Between November 24, 2017 and March 1, 2018. Totally 414 questionnaires were recruited online from seven different large urban hospitals in China. Internet usage, IBD knowledge and medication adherence were examined. One-way ANOVA, student t-tests and multivariate regression were used for statistical analysis. Results In all, 382 surveys were used for analysis, in which 291 (76.2%) had Crohn’s disease (CD), 74 (19.4%) ulcerative colitis (UC) and 17 (4.5%) undetermined colitis. The most common IBD-specific information sources were gastroenterologists (81.7%), Internet (58.6%), and WeChat or other social media (48.7%). Patients most frequently visited Baidu (65.2%), WeChat (58.9%) and Haodaifu network platform (33.2%) for personal information searching of IBD. Among ten WeChat public accounts of IBD, the China Crohn’s and Colitis Foundation (CCCF) (69.1%) and Changzaixin (20.2%) were most popular. A significant association was found between education (PP=0.003), frequent internet use in IBD-related information (PPP=0.003) and also had better medication adherence than undetermined patients (p=0.009). The majority of patients preferred obtaining information mainly through communication with (77.7%) or reference in the paper from IBD specialists (73%), only 18.6% patients preferred mainly from internet searching by themselves. They were interested in information about diet and daily life health care of IBD (81.2%), disease aetiology and course (80.1%), and medication advances and side effects (78.5%) from the Internet. Conclusions Internet and social media like WeChat have become the major information source for IBD education in China. This is beneficial to gain disease-related knowledge and improve future self-management for patients. Future initiatives should focus on providing more high-quality IBD information and increase interaction in patient education and disease organisation.

Background Typical Infection Prevention to detect pathogen transmission in hospitals has relied on observation of (1) uncommon pathogen phenotypes or (2) greater than expected number of pathogen phenotypes in a given timeframe and/or location. Genome sequencing of targeted organisms in conjunction with routine patient geo-temporal information and antibiotic susceptibility data holds promise in identifying transmissions with greater sensitivity and specificity, saving time and effort in reviewing for transmission events. Methods In an on-going genomic sequencing surveillance effort in a tertiary care hospital, drug-resistant clinical isolates from the “ESKAPE” pathogens were routinely sequenced in 2017. In parallel, potential clusters were identified for 2017 through conventional Infection Prevention approaches. Groups identified by their genetic distances along with visualizations on antimicrobial susceptibilities, and patient location histories and dates were displayed in an interactive interface, Philips IntelliSpace Epidemiology (PIE), and reviewed by Infection Prevention. Results Among 656 patients, 1,239 drug-resistant ESKAPE samples were sequenced. Thirty-eight genetically related groups involving 196 patients were identified. Groups ranged in size from two to 44 patients, primarily consisting of VRE and MRSA. Notably, a review of the 38 groups identified 20 groups where the information at hand suggested a concern for transmission. 16 of the 20 were not previously identified by Infection Prevention. Using PIE to review all 38 groups identified from 1 year’s worth of data required 3 hours of time by an Infection Prevention professional, averaging less than 5 minutes per cluster, less than 1 minute per patient, and 11 minutes of review time per actionable opportunity. By conventional means, approximately 23 hours would have been required to review the genomic groups without the aid of the PIE tool. Conclusion The use of PIE’s genomic-defined groups, along with the integrated clinical data platform, allows for a greater ability, certainty, and speed to detect clusters of organisms representing transmission in the hospital setting. Applied prospectively, PIE can detect transmissions sooner than by conventional means for potential patient safety gains and cost savings. Disclosures D. Chen, Philips: Scientific Advisor, Consulting fee. M. Fortunato-Habib, Philips Healthcare: Collaborator and Employee, Salary. A. Hoss, Philips: Employee, Salary. R. Kolde, Philips: Employee, Salary. A. Dhand, Merck: Speaker’s Bureau, Speaker honorarium. Astellas: Scientific Advisor, Consulting fee. R. Sussner, Philips: Scientific Advisor, Consulting fee. J. Carmona, Philips Healthcare: Employee, Salary. B. Gross, Philips Healthcare: Employee, Investigator, Research Contractor, Scientific Advisor and Shareholder, Salary. J. Fallon, Philips Healthcare: Investigator, Research support.

A quantitative understanding of the rate at which land ecosystems are sequestering or losing carbon at national-, regional-, and state-level scales is needed to develop policies to mitigate climate change. In this study, a new improved historical land use and land cover change data set is developed and combined with a process-based ecosystem model to estimate carbon sources and sinks in land ecosystems of the conterminous United States for the contemporary period of 2001–2005 and over the last three centuries. We estimate that land ecosystems in the conterminous United States sequestered 323 Tg C yr−1 at the beginning of the 21st century with forests accounting for 97% of this sink. This land carbon sink varied substantially across the conterminous United States, with the largest sinks occurring in the Southeast. Land sinks are large enough to completely compensate fossil fuel emissions in Maine and Mississippi, but nationally, carbon sinks compensate for only 20% of U.S. fossil fuel emissions. We find that regions that are currently large carbon sinks (e.g., Southeast) tend to have been large carbon sources over the longer historical period. Both the land use history and fate of harvested products can be important in determining a region's overall impact on the atmospheric carbon budget. While there are numerous options for reducing fossil fuels (e.g., increase efficiency and displacement by renewable resources), new land management opportunities for sequestering carbon need to be explored. Opportunities include reforestation and managing forest age structure. These opportunities will vary from state to state and over time across the United States.

We are leveraging recent advances in rapid nucleic acid amplification chemistries, self-powered microfluidics, and low-cost optoelectronics to develop instrumentation for pathogen genotyping in the developing world. A growing number of correlations are emerging between genetic mutations in pathogens and their infectivity, origin, and drug resistance. Particularly for diseases like tuberculosis, where multi-drug resistance is a growing concern, a rapid diagnostic which could inform prescription decisions for newly diagnosed patients would not only save lives and reduce prolonged sickness but would help slow the emergence of more virulent strains. Additionally, for pathogens such as HIV, there is a need for new assay formats which can inexpensively and quantitativly monitor pathogen load. We have developed a portable instrument which uses disposable microfluidic assay cartridges pre-loaded with lyophilized reagents for genetic amplification of multiple markers. The cartridges can be adapted for a variety of sample types (blood, sputum, saliva). The instrument controls assay temperature and quantitatively monitors real-time fluorescence signals from 96 individual reaction chambers. The platform can be tailored for different economic situations — from a quantitative electronic readout to a simple binary readout with the naked eye.