571 research outputs found
Italian Fertility, 1864 to 1951: An Analysis of Regional Trends
Below replacement level fertility rates in Italy have received much attention, with varying explanations offered for the protracted decline in fertility rates since the early 1970s. For a more complete understanding of Italian fertility, an analysis of historical fertility trends is useful. This paper employs Italian regional fertility data generated by the Princeton European Fertility Project to evaluate regional patterns of Italian fertility from 1864 to 1951. Regional fertility trends, both temporal and spatial, are described and basic regional convergence methods are applied. The results show that the regional fertility variation seen in Italy since World War II was well established in the 19th century and that a lack of convergence of regional fertility rates during the years of the demographic transition in Italy (late 1800s) helped emphasize regional differences. The impacts of experiences such as political unification, industrialization, the completion of the demographic transition, and mass emigration are cited as important clues to the change and persistence of regional fertility identities during this time period. This use of a rich historical data set placed in a geographic context not only helps illuminate the past, but also assists in the explanation of patterns of regional fertility seen in today?s Italy.
Italian Fertility, 1864 to 1951: An Analysis of Regional Trends
Below replacement level fertility rates in Italy have received much attention, with varying explanations offered for the protracted decline in fertility rates since the early 1970s. For a more complete understanding of Italian fertility, an analysis of historical fertility trends is useful. This paper employs Italian regional fertility data generated by the Princeton European Fertility Project to evaluate regional patterns of Italian fertility from 1864 to 1951. Regional fertility trends, both temporal and spatial, are described and basic regional convergence methods are applied. The results show that the regional fertility variation seen in Italy since World War II was well established in the 19th century and that a lack of convergence of regional fertility rates during the years of the demographic transition in Italy (late 1800s) helped emphasize regional differences. The impacts of experiences such as political unification, industrialization, the completion of the demographic transition, and mass emigration are cited as important clues to the change and persistence of regional fertility identities during this time period. This use of a rich historical data set placed in a geographic context not only helps illuminate the past, but also assists in the explanation of patterns of regional fertility seen in today's Italy
Bridging the Gap between Local Public Health and the Healthcare Community: The Public Health Talk
Background: District epidemiologists often rely on healthcare providers for medical information regarding reportable diseases in order to properly investigate cases. It becomes difficult when providers do not share patient information due to apprehension and/or lack of knowledge of HIPAA exemption laws. It is also challenging when the provider staff is not knowledgeable regarding disease specific information. When information is withheld, there is a delay in completing investigations, and high priority cases and outbreaks such as emerging infectious diseases can be missed or lost to follow up.
Methods: The Public Health Talk (The Talk) initiative was established at Cobb and Douglas Public Health in 2014 by the Epidemiology Department. The Talk includes a comprehensive binder that consists of information about the reportable diseases, emerging infectious diseases, sexually transmitted infections and provides guidelines and protocols as recommended by the Georgia Department of Public Health. It provides a forum for local epidemiologists to informally meet and educate staff of healthcare facilities (physicians, nurses, office managers, administrative assistants, etc). Pre-talk and post-talk surveys were developed to assess knowledge gained of the staff to which The Talk was presented.
Results: The initiative is ongoing, however, 31 Talks were completed by March 2016, but only 8 facilities were evaluated due to the delayed development of the surveys. It was found that 38% of staff members were not aware of the reportable diseases prior to the Talk. There was a noted increase in knowledge of local public health and the resources that are offered to healthcare facilities.
Conclusions: Healthcare providers have begun to utilize public health to aid in assessing and diagnosing diseases. The initiative is evolving and continuously improving, including the development of newsletters to improve communication and the resource binder will be reorganized to have specific information that is needed by the specialty of the provider
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Revealing sequences and modifications of intact proteins using electron fragmentation
People turn to mass spectrometry to answer some of life’s most important questions. From carbon dating of archeological finds to newborn blood screening tests, mass spectrometry allows us to measure molecules which helps advance our knowledge of life and the world we live in. One area of mass spectrometry that has seen particularly rapid development is the study of protein sequence and structure. While initial efforts focused on analyzing small peptide mixtures, advancements in instrumentation have now extended the size limit for protein research with mass spectrometry, allowing for the measurement of whole proteins and even entire viruses. This thesis explores the use of electron capture dissociation (ECD) to fragment intact proteins, revealing their sequence and modifications. The findings of this research push the boundaries of ECD for whole protein fragmentation, demonstrate the potential of ECD in elucidating disease mechanisms, and advance the characterization of protein therapeutics.
Throughout my PhD program, the majority of my research was conducted at e-MSion, Inc., an OSU-derived start up that is responsible for developing a technology for electron-based fragmentation, called the ExD cell. The new capabilities enabled by the ExD cell played a pivotal role in the success of my experiments.
Cu, Zn superoxide dismutase (SOD1) is an antioxidant enzyme that relies on copper and zinc atoms for its normal redox activity. Mutations in SOD1 lead to structural changes that cause the protein to lose one of its metals, resulting in toxicity to motor neurons and the development of amyotrophic lateral sclerosis (ALS). At the intact protein level, distinguishing between Cu-deficient and Zn-deficient SOD1 is challenging due to the overlapping isotopes of copper and zinc. However, ECD offers an opportunity to retain metal cofactors during fragmentation, allowing for the identification of metal-deficient SOD1 based on the detection of metal-containing fragments. Chapter 2 presents a published methods paper describing the analysis of SOD1 metalation using ECD fragmentation. These methods represent a significant step toward directly analyzing SOD1 metalation status in ALS-associated tissues.
To highlight the importance of the ExD cell technology for protein research, Chapter 3 presents a review of the development of the ExD cell from its conception to its current state, highlighting notable applications enabled by ExD technology. The remaining chapters all utilized the ExD cell for the characterization of whole proteins to uncover the sequences and modifications that drive their biological functions.
Chapter 4 provides insights into the hyper-phosphorylation of the SARS-CoV nucleocapsid protein, which is an essential step in viral replication. Hyper-phosphorylation of the nucleocapsid occurs in a flexible serine/arginine rich region that has challenged measurement with traditional peptide-centric techniques. However, efficient measurement was achieved by employing electron-based fragmentation of the entire serine/arginine-rich region enabling the identification of up to 9 phosphorylation sites. Furthermore, these results provide proteoform-specific information, confirming expected and revealing unexpected details about nucleocapsid phosphorylation by GSK-3β.
The production of therapeutic antibodies often leads to undesired modifications that significantly affect their efficacy, immunogenicity, and stability. Therefore, accurate characterization of antibodies is crucial for pharmaceutical development. While mass spectrometry-based techniques are considered the gold standard for antibody characterization, current methods require extensive sample digestion with multiple proteases and increases the risk of introducing artifacts. Therefore, Chapter 5 describes a fast method for fragmenting an entire antibody at once, enabling sequencing of both chains without the need for complex sample preparation. Importantly, pre-activation of antibodies before ECD facilitated the sequencing of disulfide-bonded regions. This method greatly simplifies and speeds the analysis of antibodies in minutes, which are the major focus of Biopharma
Dyslexic Adults Can Learn from Repeated Stimulus Presentation but Have Difficulties in Excluding External Noise
We examined whether the characteristic impairments of dyslexia are due to a deficit in excluding external noise or a deficit in taking advantage of repeated stimulus presentation. We compared non-impaired adults and adults with poor reading performance on a visual letter detection task that varied two aspects: the presence or absence of background visual noise, and a small or large stimulus set. There was no interaction between group and stimulus set size, indicating that the poor readers took advantage of repeated stimulus presentation as well as the non-impaired readers. The poor readers had higher thresholds than non-impaired readers in the presence of high external noise, but not in the absence of external noise. The results support the hypothesis that an external noise exclusion deficit, not a perceptual anchoring deficit, impairs reading for adults
Single Synonymous Mutations in KRAS Cause Transformed Phenotypes in NIH3T3 Cells
Synonymous mutations in the KRAS gene are clustered at G12, G13, and G60 in human cancers. We constructed 9 stable NIH3T3 cell lines expressing KRAS, each with one of these synonymous mutations. Compared to the negative control cell line expressing the wild type human KRAS gene, all the synonymous mutant lines expressed more KRAS protein, grew more rapidly and to higher densities, and were more invasive in multiple assays. Three of the cell lines showed dramatic loss of contact inhibition, were more refractile under phase contrast, and their refractility was greatly reduced by treatment with trametinib. Codon usage at these glycines is highly conserved in KRAS compared to HRAS, indicating selective pressure. These transformed phenotypes suggest that synonymous mutations found in driver genes such as KRAS may play a role in human cancers
Lurasidone for the treatment of bipolar depression: an evidence-based review
Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients’ lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D[subscript 2], 5-HT[subscript 2A], and 5-HT[subscript 7] receptors; moderate-affinity antagonism at α[subscript 2C]-adrenergic receptors; low- to very low-affinity antagonism at α[subscript 1A]-adrenergic, α[subscript 2A]-adrenergic, H[subscript 1], M[subscript 1], and 5-HT[subscript 2C] receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2–3 weeks of treatment (as measured by the Montgomery–Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine–fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed
Method Illustration
This article outlines a form of practice formed on BA Illustration at Camberwell College of Arts, called method illustration. It alludes to an embodiment of experience and understanding before or during the production of illustration in relation to a topic or theme, challenging the expectation of illustration always ending on an image. It plays on the term method acting, which is built on techniques from the Stanislavski System and contemporized. The article includes examples of students work and how this practice can be applied
Relational Contracting In A Digital Age; Panel Discussion
If, as it has sometimes been argued, changes in contract rules and theory are strongly affected by changes in economic conditions, we should note that the world has changed a good deal since the early 1960s when relational contract theory began to bloom. The economic world of 2004 is very different from the world of 1964. Modern relational contract theory was born about the same time as its great theoretical competitor, the rational choice approach of the legal economists. It came before the vast changes wrought by the information revolution and the increased globalization of the economy. What has relational theory taught us over the past forty years? How has it changed and adapted in light of those great economic changes? Where is it going in the future? Those were the general topics at a panel discussion which took place June 8, 2004, at the Oxstalls campus of the University of Gloucestershire in Gloucester, England. It was part of a conference entitled, The Common Law of Contracts as a World Force in Two Ages of Revolution, which marked the 150th anniversary of one of the most famous contracts cases of all time, Hadley v. Baxendale, and is the theme of the present Symposium. The Conference\u27s object was to explore how the common law adapts to and influences the kind of revolutionary changes that have swept over our society in the past forty years, and which swept over England in the forty years before Hadley v. Baxendale
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