U.S. Securities Law for International Financial Transactions and Capital Markets

This book review assesses Guy P. Lander\u27s two-volume work on U.S. Securities Law for International Financial Transactions and Capital Markets. The review finds Landers’ volumes reliable and complete, believing that they will be utilized in much the same manner and with the degree of regularity with which such established treatises as the Lipton and Steinberger work, Takeovers & Freeze-Outs, are consulted. The present state of U.S. securities laws and their application to international transactions are presented in a logical and instructive fashion. The material is presented with clarity, but without oversimplification

Simplifying the OpenFlexure microscope software with the web of things.

We present the OpenFlexure Microscope software stack which provides computer control of our open source motorised microscope. Our diverse community of users needs both graphical and script-based interfaces. We split the control code into client and server applications interfaced via a web API conforming to the W3C Web of Things standard. A graphical interface is viewed either in a web browser or in our cross-platform Electron application, and gives basic interactive control including common operations such as Z stack acquisition and tiled scanning. Automated control is possible from Python and Matlab, or any language that supports HTTP requests. Network control makes the software stack more robust, allows multiple microscopes to be controlled by one computer, and facilitates sharing of equipment. Graphical and script-based clients can run simultaneously, making it easier to monitor ongoing experiments. We have included an extension mechanism to add functionality, for example controlling additional hardware components or adding automation routines. Using a Web of Things approach has resulted in a user-friendly and extremely versatile software control solution for the OpenFlexure Microscope, and we believe this approach could be generalized in the future to make automated experiments involving several instruments much easier to implement

The OpenFlexure Project. The technical challenges of Co-Developing a microscope in the UK and Tanzania

The OpenFlexure Microscope is a 3D-printed laboratory-grade motorised microscope. Over the past 3 years, the microscope has primarily been co-developed between the University of Bath and the Tanzanian engineering company STICLab. We are beginning the process of preparing the microscope for medical certification, as an in-vitro diagnostic device. In this paper we detail the technical challenges of remote design of a complex scientific instrument. We believe that identifying and solving these issues is essential if we are to encourage research organisations in the Global North to design instrumentation with Africans, rather than "for Africa". </p

Fast, high-precision autofocus on a motorised microscope: Automating blood sample imaging on the OpenFlexure Microscope.

The OpenFlexure Microscope is a 3D-printed, low-cost microscope capable of automated image acquisition through the use of a motorised translation stage and a Raspberry Pi imaging system. This automation has applications in research and healthcare, including in supporting the diagnosis of malaria in low-resource settings. The plasmodium parasites that cause malaria require high magnification imaging, which has a shallow depth of field, necessitating the development of an accurate and precise autofocus procedure. We present methods of identifying the focal plane of the microscope, and procedures for reliably acquiring a stack of focused images on a system affected by backlash and drift. We also present and assess a method to verify the success of autofocus during the scan. The speed, reliability and precision of each method are evaluated, and the limitations discussed in terms of the end users' requirements

Agricultural Land Use Planning and Groundwater Quality

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75123/1/j.1468-2257.1983.tb00394.x.pd

The impact of the demographic transition on dengue in Thailand: Insights from a statistical analysis and mathematical modeling

Background: An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings: Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions: Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they have weakness, gait impairments and fatigue. Our primary study objective was to examine longitudinal changes in the six-minute walk test (6MWT) and to evaluate whether age and SMA type 3 subtype are associated with decline in ambulatory function. Data from three prospective natural history studies were used. Seventy-three participants who performed the 6MWT more than once, at least 6 months apart, were included; follow-up ranged from 0.5–9 years. Only data from patients who completed the 6MWT were included. The mean age of the participants was 13.5 years (range 2.6–49.1), with 52 having disease onset before age 3 years (type 3A). At baseline, type 3A participants walked a shorter distance on average (257.1 m) than type 3B participants (390.2 m) (difference = 133.1 m, 95% confidence interval [CI] 71.8–194.3, p < 0.001). Distance walked was weakly associated with age (r = 0.25, p = 0.04). Linear mixed effects models were used to estimate the mean annual rate of change. The overall mean rate of change was -7.8 m/year (95% CI -13.6 –-2.0, p = 0.009) and this did not differ by subtype (type 3A: -8.5 m/year, type 3B: -6.6 m/year, p = 0.78), but it did differ by age group (< 6: 9.8 m/year; 6–10: -7.9 m/year; 11–19: -20.8 m/year; ≥ 20: -9.7 m/year; p = 0.005). Our results showed an overall decline on the 6MWT over time, but different trajectories were observed depending on age. Young ambulant SMA patients gain function but in adolescence, patients lose function. Future clinical trials in ambulant SMA patients should consider in their design the different trajectories of ambulatory function over time, based on age

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors