Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Wind Forced Variability in Eddy Formation, Eddy Shedding, and the Separation of the East Australian Current

The East Australian Current (EAC), like many other subtropical western boundary currents, is believed to be penetrating further poleward in recent decades. Previous observational and model studies have used steady state dynamics to relate changes in the westerly winds to changes in the separation behavior of the EAC. As yet, little work has been undertaken on the impact of forcing variability on the EAC and Tasman Sea circulation. Here using an eddy‐permitting regional ocean model, we present a suite of simulations forced by the same time‐mean fields, but with different atmospheric and remote ocean variability. These eddy‐permitting results demonstrate the nonlinear response of the EAC to variable, nonstationary inhomogeneous forcing. These simulations show an EAC with high intrinsic variability and stochastic eddy shedding. We show that wind stress variability on time scales shorter than 56 days leads to increases in eddy shedding rates and southward eddy propagation, producing an increased transport and southward reach of the mean EAC extension. We adopt an energetics framework that shows the EAC extension changes to be coincident with an increase in offshore, upstream eddy variance (via increased barotropic instability) and increase in subsurface mean kinetic energy along the length of the EAC. The response of EAC separation to regional variable wind stress has important implications for both past and future climate change studies

The separation of the East Australian Current: A Lagrangian approach to potential vorticity and upstream control

The East Australian Current (EAC) is the western boundary current flowing along the east coast of Australia separating from the coast at approximately 34°S. After the separation two main pathways can be distinguished, the eastward flowing Tasman Front and the extension of the EAC flowing southward. The area south of the separation latitude is eddy-rich and the separation latitude of the EAC is variable. Little is known of the properties of the water masses that separate at the bifurcation of the EAC. This paper presents new insights from the Lagrangian perspective, where the water masses that veer east and those that continue south are tracked in an eddy-permitting numerical model. The transport along the two pathways is computed, and a 1:3 ratio between transport in the EAC extension and transport in the Tasman Front is found. The results show that the "fate" of the particles is to first order already determined by the particle distribution within the EAC current upstream of the separation latitude, where 85% of the particles following the EAC extension originate from below 460 m and 90% of the particles following the Tasman Front originate from the top 460 m depth at 28°S. The separation and pathways are controlled by the structure of the isopycnals in this region. Analysis of anomalies in potential vorticity show that in the region where the two water masses overlap, the fate of the water depends on the presence of anticyclonic eddies that push isopycnals down and therefore enable particles to travel further south

Legislative Alert: Election Support Consolidation and Efficiency Act (H.R. 672)

[Excerpt] I am writing on behalf of the AFL-CIO to urge you to oppose the Election Support Consolidation and Efficiency Act (HR 672), legislation to dismantle the Election Administration Commission (EAC) sixty days after enactment. The work of the EAC aims to ensure the reliability and trustworthiness of our nation\u27s complex and diversified election administration system, and this agency should not be abolished

Is the East African Community an Optimum Currency Area?

This paper investigates whether the East African Community (EAC) constitutes an optimum currency area (OCA) by estimating the degree and evolution of business cycle synchronization between the EAC countries. We also investigate whether the degree of business cycle synchronization has improved after signing of the EAC treaty in 1999. The degree of business cycle synchronization is estimated using an unobserved components model of structural shocks obtained from a structural VAR model. We then use a time-varying parameter model to estimate the evolution of business cycle synchronization. Our results indicate that the proportion of shocks that is common across different countries is small, implying weak synchronization. However, we also find that the degree of synchronization has improved after signing of the EAC treaty in 1999.East African Community, Optimum Currency Area, Business Cycle Synchronization, Structural VAR, State-Space Model

RNA-based liquid biopsies for better clinical management of Barrett’s esophagus and esophageal adenocarcinoma

In the past decades the incidence of esophageal adenocarcinoma (EAC) has increased dramatically in most Western populations. Due to the lack of symptoms EAC is often detected in a late stage, contributing to a poor 5-year survival rate. The potential of RNA (coding and miRNA) as circulating biomarker in blood has already been shown for many cancer entities but requires further investigation for EAC. In this study we will explore several RNA types in blood, including microRNA, messenger RNA, long non-coding RNA and circular RNA as a potential liquid biomarker to facilitate early diagnosis, prognosis and monitoring of esophageal adenocarcinoma We have been collecting blood and tissue samples from patients with non-dysplastic Barrett’s esophagus (NDBE), high-grade dysplasia (HGD) and EAC. Currently, our biobank includes >5000 samples from 120 patients. A proof-of-concept study was conducted including 17 patients from three groups (EAC, HGD and NDBE). For each patient, biopsies from diseased tissue and healthy tissue as well as blood were collected and analyzed using small RNA and total RNA sequencing. Gene expression analysis was performed to identify differentially expressed genes across the three groups. The highest number of significantly differentially expressed m(i)RNAs were present in the tissues of EAC versus NDBE patients, while these differences were much lower or even absent in the plasma samples. Moreover, we have identified between 1500 and 7500 unique circular RNAs in individual EAC cancer patients’ plasma, indicating promising opportunities for a blood-based liquid biomarker for BE and EAC. Currently, we are collecting additional samples to significantly increase the power of the differential expression study as well as to verify the results of our proof-of-concept study

The electron donating capacity of biochar is dramatically underestimated

Biochars have gathered considerable interest for agronomic and engineering applications. In addition to their high sorption ability, biochars have been shown to accept or donate considerable amounts of electrons to/from their environment via abiotic or microbial processes. Here, we measured the electron accepting (EAC) and electron donating (EDC) capacities of wood-based biochars pyrolyzed at three different highest treatment temperatures (HTTs: 400, 500, 600 °C) via hydrodynamic electrochemical techniques using a rotating disc electrode. EACs and EDCs varied with HTT in accordance with a previous report with a maximal EAC at 500 °C (0.4 mmol(e−).gchar−1) and a large decrease of EDC with HTT. However, while we monitored similar EAC values than in the preceding study, we show that the EDCs have been underestimated by at least 1 order of magnitude, up to 7 mmol(e−).gchar−1 for a HTT of 400 °C. We attribute this existing underestimation to unnoticed slow kinetics of electron transfer from biochars to the dissolved redox mediators used in the monitoring. The EDC of other soil organic constituents such as humic substances may also have been underestimated. These results imply that the redox properties of biochars may have a much bigger impact on soil biogeochemical processes than previously conjectured

EAC: A program for the error analysis of STAGS results for plates

A computer code is now available for estimating the error in results from the STAGS finite element code for a shell unit consisting of a rectangular orthotropic plate. This memorandum contains basic information about the computer code EAC (Error Analysis and Correction) and describes the connection between the input data for the STAGS shell units and the input data necessary to run the error analysis code. The STAGS code returns a set of nodal displacements and a discrete set of stress resultants; the EAC code returns a continuous solution for displacements and stress resultants. The continuous solution is defined by a set of generalized coordinates computed in EAC. The theory and the assumptions that determine the continuous solution are also outlined in this memorandum. An example of application of the code is presented and instructions on its usage on the Cyber and the VAX machines have been provided

Non-tariff barriers in EAC customs union: implications for trade between Uganda and other EAC countries

A key objective for the adoption of East African Community (EAC) Customs Union was to enhance economic gains through elimination of tariffs and non-tariff barriers (NTBs) within the member states. This study has established that several NTBs continue to exist, and some have persisted. The NTBs that have persisted for more than three years include a long list of customs documentation requirements, cumbersome formalities, and limited testing and certification arrangements. Other NTBs that still exist include: un-standardized weighbridges; several road blocks; lack of recognition of individual country’s standards; and the existence of several un-harmonised standards. The simulation results of spatial equilibrium model of maize trade with and without NTBs show that at the EAC level there are positive production, trade and welfare implications attributable to elimination of NTBs in intra-regional maize trade. The gains are greatest in trade and production in Uganda compared to Kenya and Tanzania. To eliminate the existing NTBs and to reduce the possibility of new ones being created, first and foremost, the EAC countries need to design effective mechanisms for identifying and verifying information about NTBs and ensuring their elimination. This will require giving the EAC Secretariat the mandate to compel individual countries to eliminate any identified NTB and to ensure that no new ones are created. Second, policy and legislative decisions made by, for example, Council of Ministers should be communicated in time for effective implementation...Non-tariff barriers, East African Community, EPRC, Uganda, Agribusiness, Agricultural Finance, Community/Rural/Urban Development, Consumer/Household Economics, Financial Economics, Industrial Organization, Labor and Human Capital, Productivity Analysis, Public Economics,

Regional Initiatives in Support of Surveillance in East Africa: The East Africa Integrated Disease Surveillance Network (EAIDSNet) Experience.

The East African Integrated Disease Surveillance Network (EAIDSNet) was formed in response to a growing frequency of cross-border malaria outbreaks in the 1990s and a growing recognition that fragmented disease interventions, coupled with weak laboratory capacity, were making it difficult to respond in a timely manner to the outbreaks of malaria and other infectious diseases. The East Africa Community (EAC) partner states, with financial support from the Rockefeller Foundation, established EAIDSNet in 2000 to develop and strengthen the communication channels necessary for integrated cross-border disease surveillance and control efforts. The objective of this paper is to review the regional EAIDSNet initiative and highlight achievements and challenges in its implementation. Major accomplishments of EAIDSNet include influencing the establishment of a Department of Health within the EAC Secretariat to support a regional health agenda; successfully completing a regional field simulation exercise in pandemic influenza preparedness; and piloting a web-based portal for linking animal and human health disease surveillance. The strategic direction of EAIDSNet was shaped, in part, by lessons learned following a visit to the more established Mekong Basin Disease Surveillance (MBDS) regional network. Looking to the future, EAIDSNet is collaborating with the East, Central and Southern Africa Health Community (ECSA-HC), EAC partner states, and the World Health Organization to implement the World Bank-funded East Africa Public Health Laboratory Networking Project (EAPHLNP). The network has also begun lobbying East African countries for funding to support EAIDSNet activities