Glioblastoma multiforme (GBM) is the most common malignant glioma. Despite innovative research efforts in tumor therapy, the outcome for most diagnosed patients remains poor; therefore, early diagnosis of GBM is the most effective method for achieving better patient outcomes. In recent years, combined research efforts including cellular, molecular, genetic, and bioinformatics methods have been used to investigate GBM, and the results show that variations in miRNA expression occur in GBM tissues and biological fluids. Some highly stable miRNAs circulate in the blood and cerebrospinal fluid (CSF) of both healthy individuals and diagnosed patients, thus raising the possibility that miRNAs may serve as novel diagnostic markers. In addition, increased understanding of the miRNA and mRNA interactions involved in GBM progression may lead to discovering predictive biomarkers, some of which are clinically relevant for targeted therapy and predicting prognosis. However, as this field is relatively new, some studies have yielded conflicting results. To progress in the field, different advanced techniques must be combined, including bioinformatics methods and molecular and cellular techniques. In addition, we must overcome the various challenges in non-invasive GBM biomarker detection. Here, we discuss the progress and potential of miRNAs as biomarkers for GBM and related signaling pathways. Studying the clinical relevance and applicability of these biomarkers may alter GBM patient diagnosis and treatment.

Objectives

Twenty-eight states in the U.S have legalized medical marijuana, yet its impacts on severe health consequences such as hospitalizations remain unknown. Meanwhile, the prevalence of opioid pain reliever (OPR) use and outcomes has increased dramatically. Recent studies suggested unintended impacts of legalizing medical marijuana on OPR, but the evidence is still limited. This study examined the associations between state medical marijuana policies and hospitalizations related to marijuana and OPR.

Methods

State-level annual administrative records of hospital discharges during 1997-2014 were obtained from the State Inpatient Databases (SID). The outcome variables were rates of hospitalizations involving marijuana dependence or abuse, opioid dependence or abuse, and OPR overdose in 1000 discharges. Linear time-series regressions were used to assess the associations of implementing medical marijuana policies to hospitalizations, controlling for other marijuana- and OPR-related policies, socioeconomic factors, and state and year fixed effects.

Results

Hospitalizations related to marijuana and OPR increased sharply by 300% on average in all states. Medical marijuana legalization was associated with 23% (p=0.008) and 13% (p=0.025) reductions in hospitalizations related to opioid dependence or abuse and OPR overdose, respectively; lagged effects were observed after policy implementation. The operation of medical marijuana dispensaries had no independent impacts on OPR-related hospitalizations. Medical marijuana polices had no associations with marijuana-related hospitalizations.

Conclusion

Medical marijuana policies were significantly associated with reduced OPR-related hospitalizations but had no associations with marijuana-related hospitalizations. Given the epidemic of problematic use of OPR, future investigation is needed to explore the causal pathways of these findings.

For the precise treatment of patients with glioblastoma multiforme (GBM), we classified and detected bevacizumab (BVZ)-responsive subtypes of GBM and found their differential expression (DE) of miRNAs and mRNAs, clinical characteristics, and related functional pathways. Based on miR-21 and miR-10b expression z-scores, approximately 30% of GBM patients were classified as having the GBM BVZ-responsive subtype. For this subtype, GBM patients had a significantly shorter survival time than other GBM patients (p = 0.014), and vascular endothelial growth factor A (VEGF) methylation was significantly lower than that in other GBM patients (p = 0.005). It also revealed 14 DE miRNAs and 7 DE mRNAs and revealed functional characteristics between GBM BVZ subgroups. After comparing several machine learning algorithms, the construction and cross-validation of the SVM classifier were performed. For clinical use, miR-197 was optimized and added to the miRNA panel for better classification. Afterwards, we validated the classifier with several GBM datasets and discovered some key related issues. According to this study, GBM BVZ subtypes can be classified and detected by a combination of SVM classifiers and miRNA panels in existing tissue GBM datasets. With certain modifications, the classifier may be used for the classification and detection of GBM BVZ subtypes for future clinical use.

Background and aims

Different cannabis administration methods have differential impacts on health. This study aimed to describe administration methods among cannabis users in the United States categorized by (1) use purpose and (2) state legalization status.

Design

Cross-sectional, probability-based online survey in 2020.

Setting

All 50 states and Washington DC in the United States.

Participants

A total of 21 903 adults (18+) were recruited from a probability-based online panel to provide nationally representative estimates.

Methods

Eleven administration methods were grouped into combustion, vaporization, ingestion and topicals. Weighted prevalence was reported among (1) medical-only, recreational-only and dual-purpose users based on self-reported purposes and (2) users in states that legalized both recreational and medical cannabis (RCL states), legalized medical cannabis only and did not legalize cannabis.

Findings

Among past-year users, the proportions of medical-only, recreational-only and dual-purpose users were 25.55, 43.81 and 30.64%, respectively. The most common primary methods were combustion (42.08%) and topicals (28.65%) for medical purposes and combustion (72.07%) and ingestion (15.05%) for recreational purposes. Dual-purpose users were more likely to report combustion and vaporization but less likely to report ingestion and topicals as primary methods for medical use than medical-only users (P < 0.001) and more likely to report combustion and topicals but less likely to report ingestion as primary methods for recreational use than recreational-only users (P < 0.041). A higher proportion of dual-purpose users (82.82%) used more than one method than medical-only (40.52%) and recreational-only users (63.91%) (P < 0.001). For both medical and recreational purposes, RCL states had the lowest rate of combustion and the highest rates of ingestion and topicals reported as primary methods (P < 0.033). The rate of using more than one administration method did not differ across states (P > 0.05).

Conclusion

Cannabis users whose purposes are medical, recreational or both tend to differ in their selected administration methods.

Background: While an elevated white blood cell count (WBC) is a widely utilized measure for evidence of infection and an important criterion for evaluation of systemic inflammatory response syndrome (SIRS), its component band count occupies a more contested position within clinical emergency medicine. Recent studies indicate that bandemia is highly predictive of a serious infection, suggesting that clinicians who do not appreciate the value of band counts may delay diagnosis or overlook severe infections. Objectives: Whereas previous studies focused on determining the quantitative value of the band count (i.e. determining sensitivity, threshold for bandemia, etc.), this study directs attention to patient-centered outcomes, hypothesizing that the degree of bandemia predisposes patients to subsequent negative clinical outcomes associated with underappreciated severe infections. Methods: This retrospective study of electronic medical records includes patients who initially presented to the Emergency Department (ED) with bandemia and were subsequently discharged from the ED. These patients were screened for repeat ED visits within 7 days and death within 30 days. Results: In patients with severe bandemia who were discharged from the ED, there was a 20.9% revisit rate at 7 days and a 4.9% mortality rate at 30 days, placing severely bandemic patients at 5 times significantly greater mortality compared to non-bandemic patients (p=0.032). Conclusion: Our review of patient outcomes suggests that the degree of bandemia, especially in the setting of concurrent tachycardia or fever, is associated with greater likelihood of negative clinical outcomes.

This dissertation elucidates the domestic politics of China's outward direct investments and its international implications. A current puzzle in CPE/IPE research is whether international investors from autocracies, particularly state-owned enterprises (SOEs), are profit- maximizing firms or agents of the state. Using formal analysis and two sets of original firm-level data on Chinese investments, I demonstrate that the behaviors of China's SOEs reflect both state preferences and firms' profit incentives and that the interaction of the two can lead to perverse outcomes unintended by the state : China's political elites depend on SOEs to carry out certain state objectives (e.g. energy security) and devise preferential policies (e.g. subsidies, insurance, bailouts) that enable firms to accomplish these objectives. SOEs, however, take advantage of these policy perquisites to seek rents. Knowing that the state will bail them out when investments fail, they take excessive risks when choosing host countries to earn high returns, ultimately passing on the cost of failed investments to the disenfranchised public. I apply this core insight to evaluate three aspects of China's approach to outbound investments: investment decisions by Chinese firms; the effect of Chinese investment on host country development and governance; and China's foreign policy toward economies that are the sites of its foreign investment

With the steady progress of high performance electronic systems, the complexity of the electronic systems grows continuously and new features like high-speed, low power and low cost, become the key issues. The interconnection in the electronic systems distributes the power, clock and transfers the electrical signals among numerous components. As the feature size of microelectronic technology becomes smaller, the design and analysis of the interconnection are more important for the performance and cost of the system. The escape routing design is a new important problem in the interconnection design because the number of chip/package input/output (I/O) pins has continuously been growing for high-speed high-performance system. The traditional escape routing strategy and several improvements, pins/pads special placement and routing resource exploration, could not handle large number of I/Os efficiently and usually require increased cost. We introduce a novel concept, escape sequence, develop efficient escape routing strategies based on the new concept and model the escaping wires using 3D extraction. For square grid array, we formulate and solve a maximum flow problem to analyze the escape bottleneck in area array. The layer count can be decreased dramatically by optimizing the I/O escape sequence. Two new escape routing strategies, central triangular escape routing and two-sided escape routing, are proposed and the number of escape routing layers could be reduced dramatically. We implement an automatic escape routing program to verify our analysis and to compare different escape sequence strategies. The escaping wires could be modeled as frequency dependent RLGC circuit for signal performance analysis. For hexagonal area array, we analyze its preponderant properties that the hexagonal array could increase the density of I/Os in the array remarkably. We propose three escape routing strategies for the hexagonal array: column-by-column horizontal escape routing, two- sided horizontal/vertical escape routing, and multi- direction hybrid channel escape routing. We can escape I/ Os in the hexagonal array in the same or less number of routing layers compared with square grid array. Therefore, we could reduce the number of escape routing layers as well as increase the density of I/Os. The eye diagram prediction is an important problem in the interconnection analysis because an eye diagram provides the most fundamental and intuitive view to evaluate the signal quality of high-speed communication. The traditional method to obtain the eye diagram involves performing a time domain simulation. It requires a very long simulation time and usually could not accurately characterize the communication systems because the limited length pseudorandom bit sequence (PRBS) as the input stimulus. Several eye diagram prediction methods, analytical techniques, analysis based on unit pulse response and analysis based on step response, have their application constraints because of their assumptions and usually could not handle general systems. We introduce an efficient and accurate method, the accumulative prediction method, to predict the eye diagram for high-speed signaling systems. We use the step response of the signaling system to extract the worst-case eye diagram, including the eye opening and timing jitter. Furthermore, this method generates the input data patterns which produce the worst- case inter-symbol interference. The main advantage is that this general-purpose method can handle signals with asymmetric as well as symmetric rise/fall time. Furthermore, the complexity of the proposed method is linear O(n), where n is the number of time points of step response. This method can be applied to analyze the signal performance in escape routing. It is very useful to analyze various high speed signaling systems