Landscape Transformation During Ceramic Age and Colonial Occupations of Barbuda, West Indies

This research documented the history of landscape transformation on the island of Barbuda in the Lesser Antilles, Caribbean through cross-disciplinary research approaches. Excavations confirmed a human presence for the seasonal exploitation of conch meat and other mollusks during the Archaic Age (c.3000–500 BC), but more substantial impacts to terrestrial ecosystems likely began during the Ceramic Age (c.500 BC–AD 1500). Our combined sedimentary and charcoal records revealed that human-induced environmental transformations began with Ceramic Age peoples as they cleared vegetation for settlements and gardens with intentional burning. Sedimentary charcoal indicated a dramatic decline in fire during post-Ceramic Age abandonment, continuing through the Colonial Period, as the dominant human activities shifted to herding, farming, and selective wood harvesting. Historical sources showed that during the Colonial Period (post-1492), the island was intermittently settled until the mid-seventeenth century, while the Codrington family of Antigua held the lease to the island from 1681 to 1870. They used the island for farming and stock-rearing, exporting meat and draught animals along with lime, timber, and subsistence crops. Macrocharcoal recovered from Colonial Period archaeological sites reflect the use of a variety of local species and wood imported to the island or harvested from shipwrecks

Issues in design and interpretation of MDR-TB clinical trials: report of the first Global MDR-TB Clinical Trials Landscape Meeting

Recognizing that the current MDR-TB regimen is suboptimal and based on low-quality evidence, the Global MDR-TB Clinical Trials Landscape Meeting was held in December, 2014 to strategize about coordination of research and development of new treatment regimens for this disease that affects millions of people worldwide every year. Sixty international experts on multidrug-resistant tuberculosis (MDR-TB) met in Washington D.C. and Cape Town, South Africa to consider key MDR-TB trial-related issues, including: standardization of definitions; clinical trial capacity building and; regimens optimized to foster compliance, avoid the emergence of resistance and have clinical relevance for special populations, including children and those co-infected with HIV. Underpinning all of this is the generation of a sufficient evidence base to facilitate regulatory approval and improved normative guidance. Participants discussed treatment combinations currently being studied in Phase 2B and Phase 3 trials as well as other promising new regimens and combinations that may be evaluated in the near future. These include regimens designed specifically to enable shorter duration and all-oral treatment as a means of maximizing treatment completion. It is hoped that clear definition of these challenges will facilitate the process of identifying solutions that accelerate progress towards effective, non-toxic treatments that can be programmatically implemented

A theoretical study of the structural phases of Group 5B - 6B metals and their transport properties

In order to predict the stable and metastable phases of the bcc metals in the block of the Periodic Table defined by groups 5B to 6B and periods 4 to 6, as well as the structure dependence of their transport properties, we have performed full potential computations of the total energies per unit cell as a function of the c/a ratio at constant experimental volume. In all cases, a metastable body centered tetragonal (bct) phase was predicted from the calculations. The total energy differences between the calculated stable and metastable phases ranged from 0.09 eV/cell (vanadium) to 0.39 eV/cell (tungsten). The trends in resistivity as a function of structure and atomic number are discussed in terms of a model of electron transport in metals. Theoretical calculations of the electrical resistivity and other transport properties show that bct phases derived from group 5B elements are more conductive than the corresponding bcc phases, while bct phases formed from group 6B elements are less conductive than the corresponding bcc phases. Special attention is paid to the phases of tantalum where we show that the frequently observed beta phase is not a simple tetragonal distortion of bcc tantalum

Revolutionizing Alzheimer\u27s disease and clinical trials through biomarkers

AbstractThe Alzheimer's Association's Research Roundtable met in May 2014 to explore recent progress in developing biomarkers to improve understanding of disease pathogenesis and expedite drug development. Although existing biomarkers have proved extremely useful for enrichment of subjects in clinical trials, there is a clear need to develop novel biomarkers that are minimally invasive and that more broadly characterize underlying pathogenic mechanisms, including neurodegeneration, neuroinflammation, and synaptic dysfunction. These may include blood-based assays and new neuropsychological testing protocols, as well as novel ligands for positron emission tomography imaging, and advanced magnetic resonance imaging methodologies. In addition, there is a need for biomarkers that can serve as theragnostic markers of response to treatment. Standardization remains a challenge, although international consortia have made substantial progress in this area and provide lessons for future standardization efforts

Plasmodium knowlesi in Human, Indonesian Borneo

Plasmodium knowlesi is now established as the fifth Plasmodium species to cause malaria in humans. We describe a case of P. knowlesi infection acquired in Indonesian Borneo that was imported into Australia. Clinicians need to consider this diagnosis in a patient who has acquired malaria in forest areas of Southeast Asia

Reconsidering frameworks of Alzheimer’s dementia when assessing psychosocial outcomes

The purpose of this introductory article to the special issue on psychosocial outcome measures in Alzheimer’s & Dementia: Translational Research & Clinical Interventions is to outline new frameworks to more effectively capture and measure the full range of how people living with Alzheimer’s dementia and their family caregivers experience the disease process. Specifically, we consider the strengths and weaknesses of alternative perspectives, including person‐centered, strength‐based, and resilience‐focused approaches that may complement and extend the dominant deficit paradigm to reflect the entirety of the dementia experience. Our aim is to encourage innovative methods to measure psychosocial aspects of Alzheimer’s dementia and caregiving that have not yet received sufficient attention, including resources (e.g., services and supports) and positive caregiver and care recipient outcomes (e.g., positive mood and adaptation).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152840/1/trc2jtrci201902008.pd

Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist

<p>Abstract</p> <p>Background</p> <p>Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports.</p> <p>Methods</p> <p>The purpose of this project is to develop the entire set of elements in the synoptic templates or "worksheets" for hematologic and lymphoid neoplasms using the World Health Organization (WHO) Classification and the College of American Pathologists (CAP) Cancer Checklists. The CAP checklists' content was supplemented with the most updated classification scheme (WHO classification), specimen details, staging as well as information on various ancillary techniques such as cytochemical studies, immunophenotyping, cytogenetics including Fluorescent In-situ Hybridization (FISH) studies and genotyping. We have used a digital synoptic reporting system as part of an existing laboratory information system (LIS), CoPathPlus, from Cerner DHT, Inc. The synoptic elements are presented as discrete data points, so that a data element such as tumor type is assigned from the synoptic value dictionary under the value of tumor type, allowing the user to search for just those cases that have that value point populated.</p> <p>Results</p> <p>These synoptic worksheets are implemented for use in our LIS. The data is stored as discrete data elements appear as an accession summary within the final pathology report. In addition, the synoptic data can be exported to research databases for linking pathological details on banked tissues.</p> <p>Conclusion</p> <p>Synoptic reporting provides a structured method for entering the diagnostic as well as prognostic information for a particular pathology specimen or sample, thereby reducing transcription services and reducing specimen turnaround time. Furthermore, it provides accurate and consistent diagnostic information dictated by pathologists as a basis for appropriate therapeutic modalities. Using synoptic reports, consistent data elements with minimized typographical and transcription errors can be generated and placed in the LIS relational database, enabling quicker access to desired information and improved communication for appropriate cancer management. The templates will also eventually serve as a conduit for capturing and storing data in the virtual biorepository for translational research. Such uniformity of data lends itself to subsequent ease of data viewing and extraction, as demonstrated by rapid production of standardized, high-quality data from the hemopoietic and lymphoid neoplasm specimens.</p

The roles of inflammation and immune mechanisms in Alzheimer's disease

AbstractThe Alzheimer's Association's Research roundtable met in April 2015 to explore the role of neuroinflammatory mechanisms in the progression of Alzheimer's disease (AD). The ability of innate immune cells, particularly microglia and astrocytes, to mediate neuroinflammation in AD has been implicated as a significant contributor to disease pathogenesis. Adaptive immunity, which plays an important role in responding to injury and some diseases of the central nervous system, may contribute to neuroinflammation in AD as well. Communication between the central and peripheral immune systems may also be important in AD. An increased understanding of the physiology of the innate immune system may aid the identification of new therapeutic targets or mechanisms. The development of predictive animal models and translatable neuroinflammation biomarkers for AD would also facilitate the advancement of novel treatments for innate immunity. Important challenges impeding the advancement of new therapeutic agents and strategies to overcome them were discussed

Precompetitive data sharing as a catalyst to address unmet needs in Parkinson's disease

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease

\u3ci\u3eFundulus\u3c/i\u3e as the premier teleost model in environmental biology: Opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms