The Caries Phenomenon: A Timeline from Witchcraft and Superstition to Opinions of the 1500s to Today's Science

This historical treatise follows the documented timeline of tooth decay into today's understanding, treatment, and teaching of caries biology. Caries has been attributed to many different causes for several millennia, however, only since the late 1900s has research revealed its complex multifactorial nature. European writers of the 1600s to 1700s held views that general health, mechanical injuries, trauma, and sudden temperature changes all caused caries—holding a common belief that decay was due to chemical agents, faulty saliva, and food particles. Until the early 1800s most writers believed that caries was due to inflammation from surrounding diseased alveolar bone. Today's science has demonstrated that caries is caused by indigenous oral microorganisms becoming a dynamic biofilm, that in the presence of fermentable sugars produce organic acids capable of dissolving inorganic enamel and dentin followed by the proteolytic destruction of collagen leaving soft infected dentin. As bacteria enter the pulp, infection follows

An Association Between Perceived Social Support and Posttraumatic Stress Symptom Severity Among Women With Lifetime Sexual Victimization: The Serial Mediating Role of Resilience and Coping

This study examined the association between perceived social support and severity of posttraumatic stress symptoms, serially mediated by resilience and coping among women exposed to different patterns of sexual victimization experiences: childhood sexual abuse (CSA) only, adult sexual assault (ASA) only, and sexual revictimization (SR). A total of 255 sexually victimized women recruited from four U.S. universities completed self-report measures online; 112 participants reported provisionally diagnosable levels of symptoms of posttraumatic stress disorder (PTSD). The proposed model was largely supported in the CSA only group and the SR group. Different patterns of mediational effects were found across the three groups. Clinical and theoretical implications are discussed

Comparing Chemistry to Outcome: The Development of a Chemical Distance Metric, Coupled with Clustering and Hierarchal Visualization Applied to Macromolecular Crystallography

Many bioscience fields employ high-throughput methods to screen multiple biochemical conditions. The analysis of these becomes tedious without a degree of automation. Crystallization, a rate limiting step in biological X-ray crystallography, is one of these fields. Screening of multiple potential crystallization conditions (cocktails) is the most effective method of probing a proteins phase diagram and guiding crystallization but the interpretation of results can be time-consuming. To aid this empirical approach a cocktail distance coefficient was developed to quantitatively compare macromolecule crystallization conditions and outcome. These coefficients were evaluated against an existing similarity metric developed for crystallization, the C6 metric, using both virtual crystallization screens and by comparison of two related 1,536-cocktail high-throughput crystallization screens. Hierarchical clustering was employed to visualize one of these screens and the crystallization results from an exopolyphosphatase-related protein from Bacteroides fragilis, (BfR192) overlaid on this clustering. This demonstrated a strong correlation between certain chemically related clusters and crystal lead conditions. While this analysis was not used to guide the initial crystallization optimization, it led to the re-evaluation of unexplained peaks in the electron density map of the protein and to the insertion and correct placement of sodium, potassium and phosphate atoms in the structure. With these in place, the resulting structure of the putative active site demonstrated features consistent with active sites of other phosphatases which are involved in binding the phosphoryl moieties of nucleotide triphosphates. The new distance coefficient, CDcoeff, appears to be robust in this application, and coupled with hierarchical clustering and the overlay of crystallization outcome, reveals information of biological relevance. While tested with a single example the potential applications related to crystallography appear promising and the distance coefficient, clustering, and hierarchal visualization of results undoubtedly have applications in wider fields

SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus

<p>Abstract</p> <p>Background</p> <p>Chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy.</p> <p>The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival.</p> <p>Methods/Design</p> <p>SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio.</p> <p>During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further 120 patients into each arm and compare the overall survival of both groups.</p> <p>All patients randomised into Phase II will contribute to the Phase III comparison of overall survival. In addition to overall survival, Phase III of the study will also assess toxicity, health related quality of life and cost effectiveness. A detailed radiotherapy protocol and quality assurance procedure has been incorporated into this trial.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN47718479">ISRCTN47718479</a></p

A Film Bulk Acoustic Resonator (FBAR) L Band Low Noise Oscillator for Digital Communications

Abstract — This paper describes the design and measured performance of a low-noise L band oscillator based on Agilent’s Film Bulk Acoustic Resonator (FBAR) for applications in digital communication systems. This experimental oscillator demonstrated at 1951 MHz with a phase noise of –115 dBc/Hz at 10KHz from the carrier represents the first example of a low noise Si-Bipolar FBAR oscillator

Integration of Leprosy Elimination into Primary Health Care in Orissa, India

BACKGROUND: Leprosy was eliminated as a public health problem (<1 case per 10,000) in India by December 2005. With this target in sight the need for a separate vertical programme was diminished. The second phase of the National Leprosy Eradication Programme was therefore initiated: decentralisation of the vertical programme, integration of leprosy services into the primary health care (PHC) system and development of a surveillance system to monitor programme performance. METHODOLOGY/PRINCIPAL FINDINGS: To study the process of integration a qualitative analysis of issues and perceptions of patients and providers, and a review of leprosy records and registers to evaluate programme performance was carried out in the state of Orissa, India. Program performance indicators such as a low mean defaulter rate of 3.83% and a low-misdiagnosis rate of 4.45% demonstrated no detrimental effect of integration on program success. PHC staff were generally found to be highly knowledgeable of diagnosis and management of leprosy cases due to frequent training and a support network of leprosy experts. However in urban hospitals district-level leprosy experts had assumed leprosy activities. The aim was to aid busy PHC staff but it also compromised their leprosy knowledge and management capacity. Inadequate monitoring of a policy of 'new case validation,' in which MDT was not initiated until primary diagnosis had been verified by a leprosy expert, may have led to approximately 26% of suspect cases awaiting confirmation of diagnosis 1-8 months after their initial PHC visit. CONCLUSIONS/SIGNIFICANCE: This study highlights the need for effective monitoring and evaluation of the integration process. Inadequate monitoring could lead to a reduction in early diagnosis, a delay in initiation of MDT and an increase in disability rates. This in turn could reverse some of the programme's achievements. These findings may help Andhra Pradesh and other states in India to improve their integration process and may also have implications for other disease elimination programmes such as polio and guinea worm (dracunculiasis) as they move closer to their elimination goals

Formin is associated with left-right asymmetry in the pond snail and the frog

While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signalling of Nodal, downstream of symmetry-breaking, may be an ancestral feature of the Bilateria. Here we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry-breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or over-expression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models, we discovered asymmetric gene expression in 2 and 4 cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro, together these results are consistent with the view that animals with diverse bodyplans may derive their asymmetries from the same intracellular chiral elements

Formin is associated with left-right asymmetry in the pond snail and the frog

While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signalling of Nodal, downstream of symmetry-breaking, may be an ancestral feature of the Bilateria. Here we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry-breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or over-expression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models, we discovered asymmetric gene expression in 2 and 4 cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro, together these results are consistent with the view that animals with diverse bodyplans may derive their asymmetries from the same intracellular chiral elements

Footprints- In the Footprints of Squier and Davis: Archeological Fieldwork in Ross County, Ohio

TABLE OF CONTENTS Acknowledgements....................................................................iList of Tables...................................................................vii List of Figures...................................................................ix Contributors .........................................................................xiii Chapter 1 In the Footprints of Squier and Davis : Archeological Fieldwork in Ross County, Ohio Mark J. Lynott................................................................................1 Previous Studies in Ohio ...................................................1 Hopewell Studies Today ................................................................4 Recent Field Research ..........................................................................6 Goal of this Volume ................................................................................12 Chapter 2 In Non-mound Space at the Hopewell Mound Group Jennifer Pederson Weinberger .........................................13 Geophysical Survey .......................................................15Western Village Area.....................................................................16 Near the East Village .....................................................................18 Central Area ............................................................................19 Discussion .......................................................................................19 Chapter 3 Field Studies of the Octagon and Great Circle, High Bank Earthworks Ross County, Ohio N’omi B. Greber and Orrin C. Shane III ..............................................23 Excavations at the Octagon ............................................................25 Geophysics at the Great Circle ............................................................30 Excavations at the Great Circle ..........................................................33 Radiocarbon Assays ...........................................................................41 Comments ....................................................................................44 Addendum ..........................................................................................46 Chapter 4 Spruce Hill Earthworks: The 1995-1996 National Park Service Investigations Bret J. Ruby .............................................................................................49 Background .......................................................................................49 The Spruce Hill Earthworks .......................................................................49 Spruce Hill Revisited ......................................................................53 The 1995-1996 National Park Service Investigations ............................53 Discussion and Conclusions ..............................................................61 Chapter 5 Falling Through a Crack in the Core: The Surprise and Demise of Anderson Earthwork William H. Pickard and Jeffrey W. Weinberger ........................................ 67 History and Setting ..................................................................................68 1993 Excavations ..................................................................................70 Discussion ..............................................................................................72 Conclusion ............................................................................................74 Chapter 6 Middle Woodland and Other Settlement Remains in the Overly Tract Near The Hopeton Earthwork, Ross County, Ohio William S. Dancey .....................................................................................................77 Research Design.............................................................................77 Artifact Categories and their Distributions..............................................80 Discussion............................................................................................92 Chapter 7 Hopewell Occupation at the Hopeton Earthworks: Large Scale Surface Survey Using GPS Technology Jarrod Burks and Dawn Walter Gagliano................................................97 The Survey Area ................................................................................98 Survey Methodology .............................................................................99 Survey Results ...................................................................................99 The Surface Data: A Siteless Approach .................................................103 Discussion and Conclusion .........................................................................106 Notes ...................................................................................................107 Chapter 8 Hopewellian Centers in Context: Investigations In and Around the Hopeton Earthworks Bret J. Ruby And Mark J. Lynott .................................................................109 Surface Survey ......................................................................................110 Redwing Site ...........................................................................................111 Comparisons .........................................................................................118 Conclusions ......................................................................................122 Chapter 9 Searching for Hopewell Settlements: The Triangle Site at the Hopeton Earthworks Mark Lynott ...................................................................................... 125 Field Investigations ............................................................................127 Geophysical Survey ............................................................................128 1998 Season ....................................................................................128 Features, Artifacts and Radiocarbon Dating ........................................130 Animal Remains ...............................................................................137 Plant Remains ................................................................................138 Interpretations ..............................................................................139 Chapter 10 Geophysical Investigations at the Hopeton Earthworks John Weymouth, Bruce Bevan, and Rinita Dalan ...............................145 The Cesium Gradiometer Survey ...........................................................146 Cesium Gradiometer Results ...................................................................146 Geoscan Instrument Surveys ..............................................................148 Comparison of Cesium Magnetic and Resistance Data ........................148 Small Circles...........................................................................................149 Trench Excavations ...................................................................................149 Discussion ................................................................................................152 Conclusions ......................................................................................157 Chapter 11 Archeological and Geoarcheological Study of the Rectangular Enclosure at the Hopeton Works Mark J. Lynott and Rolfe D. Mandel ......................................................159 The Study of the Rectangular Earthwork ................................................161 Geophysical Survey ..............................................................................163 Trench Excavations .............................................................................164 Chronology ........................................................................................170 Geoarcheological Analysis of Trench 1 .................................................172 Interpretations ................................................................................174 Chapter 12 Ohio Hopewell Ritual Craft Production Katherine A. Spielmann ............................................................ 179Raw Material Procurement ....................................................................180 Hopewell Crafting ................................................................................181 Deposition ...........................................................................................186 Conclusions ....................................................................................188 References Cited .....................................................................................................18

Inter-laboratory automation of the in vitro micronucleus assay using imaging flow cytometry and deep learning.

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25-5.0 μg/mL) and/or carbendazim (0.8-1.6 μg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the "DeepFlow" neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for 'mononucleates', 'binucleates', 'mononucleates with MN' and 'binucleates with MN', respectively. Successful classifications of 'trinucleates' (90%) and 'tetranucleates' (88%) in addition to 'other or unscorable' phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks