Craniometaphyseal dysplasia: the need for a natural history of disease study

Craniometaphyseal dysplasia (CMD) is a rare genetic skeletal disorder, whose biological understanding is not very well known. The disease manifests itself through bony hypertrophy of the skull base, craniofacial bones, and abnormal morphology of the long bones, present in the carrier of the disease. CMD has been previously determined through genetic analysis to be a result of one of 15 (to date) discovered mutations. Fourteen of those mutations are inherited in an autosomal dominant fashion, via mutations in the ANKH gene. One mutation has been discovered to result in CMD through autosomal recessive inheritance, via a locus found in the connexin 43 gene, coding for gap junction protein alpha-1. As the genetic foundation of CMD has become more clearly understood over time, there has been a lack of similar progress in understanding the clinical manifestations of CMD. To improve our understanding of the clinical characteristics of CMD, we propose a natural history of disease study to be conducted. This study serves as a pilot for this larger scale study, by using a smaller patient population comprised of CMD patient database at the Reichenberger Lab at University of Connecticut Health (UCH), and CMD patients reported in the literature, to understand what is currently known about the clinical manifestations of CMD, and what should be evaluated for further research. In this study, the existing literature on CMD has been compiled and sorted into distinct groups – created to guide those unfamiliar to the disease through the available information. Secondly, a set of 76 patient cases compiled at the Reichenberger lab at UCH were analyzed to determine what clinical information on CMD has already been collected. Lastly, from an in depth analysis of two specific case files from the Reichenberger Lab CMD patient database it was discovered that blood chemistry levels are an important parameter for analysis in future studies. From abnormalities in blood chemistry within both cases were found. . In both patients it was found that elevations in serum alkaline phosphatase were present congenitally, and persisted throughout the early childhood years. Specific attention to changing serum alkaline phosphatase concentrations over early childhood development is recommended. Additionally, from data present in patient case 2, blood urea nitrogen (BUN/creatinine) was found to be highly elevated through early childhood, though eventually slowly decreasing to the upwards bounds of the normal physiological reference range, by the time the patient grew from ages 1 to 12. No BUN/Creatinine data was provided by the first case. Lastly, from an analysis of the literature, the patient case files at the Reichenberger lab at UCH and an in depth study of two specific patient cases a list of clinical parameters useful for investigation in a full-scale natural history of disease study of CMD is presented

Diet Management for Adult Onset Diabetes Mellitus Type 2

In Southbury, Connecticut, diabetic diet management is an issue that perturbs both primary care providers and their patients. This project seeks to ameliorate the lack of readily available resources for diabetic dietary considerations. A brochure was made including helpful dietary information for patients that are unable or unwilling to see a Certified Diabetic Educator. As the incidence of diabetes continues to rise, patient education will be a powerful tool to help patients manage their diabetic care.https://scholarworks.uvm.edu/fmclerk/1424/thumbnail.jp

Enhancing the Strategic Management Process Through the Use of Professional Evaluation Methods and the Logic of Evaluation

Background: The evaluation discipline has the potential to enhance other disciplines by integrating evaluation specific methodologies and logic into processes within other disciplines and improving/strengthening the manner in which evaluation of processes, programs and policies are carried out. Purpose: This paper will highlight the evaluative nature of one of the most popular strategic management models (SMM) in corporate America, namely, Fred David’s (2013) SMM, and examine how professional evaluation logic and methodology can be used to improve David's SMM. Setting: NA Intervention: NA Research Design: The paper will make a comparative analysis between Michael Scriven's Key Evaluation Checklist (KEC) and David's SMM and highlight similarities and differences between the two models. Data Collection and Analysis: NA Findings: The paper will conclude by providing several suggestions to enhance and strengthen David's SMM to make it more robust, valuable, and useful in the business environment

Development of a Compact Neutron Source based on Field Ionization Processes

The authors report on the use of carbon nanofiber nanoemitters to ionize deuterium atoms for the generation of neutrons in a deuterium-deuterium reaction in a preloaded target. Acceleration voltages in the range of 50-80 kV are used. Field emission of electrons is investigated to characterize the emitters. The experimental setup and sample preparation are described and first data of neutron production are presented. Ongoing experiments to increase neutron production yields by optimizing the field emitter geometry and surface conditions are discussed.Comment: 4 pages, 5 figures; IVNC 201

Transportation Barriers to Healthcare in Adults 65+ in the Greater Burlington Area

Introduction. Missed appointments often lead to poorer health care outcomes for patients and pose a major economic burden on medical centers. Transportation is an obstacle to accessing medical care for elderly patients in Vermont and results in delayed medical appointments. Methods. We surveyed senior citizens in Chittenden county to determine both the type of transportation barriers and medical care missed due to the lack of transpor- tation. An original survey assessing the impact of transportation to health care was distributed in person and through an online platform. Participants were asked to identify the following in the past year: how often transportation was an issue for healthcare, specific barriers to transportation, and which specific health care appointments were missed due to lack of transportation. Ninety-six surveys out of a total of 251 collected were included in the analysis. Respondents were grouped into either having high transportation barriers, n=43, (always, often, sometimes had issues in the past year), or low transportation barriers, n=53, (rarely had issues). Results. The high barriers group reported more missed appointments, with eye appointments being the most frequent, and depended more on other modes of trans- portation. The low barriers group was able to drive themselves to their appointments more often. Conclusion. The results suggest a trend between barriers to transportation and a lack of access to healthcare appointments. Although more than half of the survey respondents indicated that they do not currently experience transportation barriers, many expressed concern about the transportation difficulties they could encounter in the future.https://scholarworks.uvm.edu/comphp_gallery/1263/thumbnail.jp

On the redundancy in large material datasets: efficient and robust learning with less data

Extensive efforts to gather materials data have largely overlooked potential data redundancy. In this study, we present evidence of a significant degree of redundancy across multiple large datasets for various material properties, by revealing that up to 95 % of data can be safely removed from machine learning training with little impact on in-distribution prediction performance. The redundant data is related to over-represented material types and does not mitigate the severe performance degradation on out-of-distribution samples. In addition, we show that uncertainty-based active learning algorithms can construct much smaller but equally informative datasets. We discuss the effectiveness of informative data in improving prediction performance and robustness and provide insights into efficient data acquisition and machine learning training. This work challenges the "bigger is better" mentality and calls for attention to the information richness of materials data rather than a narrow emphasis on data volume.Comment: Main text: 10 pages, 2 tables, 5 figures. Supplemental information: 29 pages, 1 table, 23 figure

PARN deadenylase is involved in miRNA-dependent degradation of TP53 mRNA in mammalian cells

mRNA deadenylation is under the control of cis-acting regulatory elements, which include AU-rich elements (AREs) and microRNA (miRNA) targeting sites, within the 3′ untranslated region (3′ UTRs) of eukaryotic mRNAs. Deadenylases promote miRNA-induced mRNA decay through their interaction with miRNA-induced silencing complex (miRISC). However, the role of poly(A) specific ribonuclease (PARN) deadenylase in miRNA-dependent mRNA degradation has not been elucidated. Here, we present evidence that not only ARE- but also miRNA-mediated pathways are involved in PARN-mediated regulation of the steady state levels of TP53 mRNA, which encodes the tumor suppressor p53. Supporting this, Argonaute-2 (Ago-2), the core component of miRISC, can coexist in complexes with PARN resulting in the activation of its deadenylase activity. PARN regulates TP53 mRNA stability through not only an ARE but also an adjacent miR-504/miR-125b-targeting site in the 3′ UTR. More importantly, we found that miR-125b-loaded miRISC contributes to the specific recruitment of PARN to TP53 mRNA, and that can be reverted by the ARE-binding protein HuR. Together, our studies provide new insights into the role of PARN in miRNA-dependent control of mRNA decay and into the mechanisms behind the regulation of p53 expression

World Health Organization Generic Protocol to Assess Drug-Resistant HIV Among Children <18 Months of Age and Newly Diagnosed With HIV in Resource-Limited Countries

Increased use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) in pregnant and breastfeeding women will result in fewer children infected with human immunodeficiency virus (HIV). However, among children infected despite prevention of mother-to-child transmission (PMTCT), a substantial proportion will acquire NNRTI-resistant HIV, potentially compromising response to NNRTI-based antiretroviral therapy (ART). In countries scaling up PMTCT and pediatric ART programs, it is crucial to assess the proportion of young children with drug-resistant HIV to improve health outcomes and support national and global decision making on optimal selection of pediatric first-line ART. This article summarizes a new World Health Organization surveillance protocol to assess resistance using remnant dried blood spot specimens from a representative sample of children aged <18 months being tested for early infant diagnosi

Active deformation and shallow structure of the Wagner, Consag, and Delfín Basins, northern Gulf of California, Mexico

Oblique rifting began synchronously along the length of the Gulf of California at 6 Ma, yet there is no evidence for the existence of oceanic crust or a spreading transform fault system in the northern Gulf. Instead, multichannel seismic data show a broad shallow depression, ∼70 × 200 km, marked by active distributed deformation and six ∼10-km-wide segmented basins lacking well-defined transform faults. We present detailed images of faulting and magmatism based on the high resolution and quality of these data. The northern Gulf crust contains a dense (up to 18 faults in 5 km) complex network of mainly oblique-normal faults, with small offsets, dips of 60–80° and strikes of N-N30°E. Faults with seafloor offsets of tens of meters bound the Lower and two Upper Delfín Basins. These subparallel basins developed along splays from a transtensional zone at the NW end of the Ballenas Transform Fault. Twelve volcanic knolls were identified and are associated with the strands or horsetails from this zone. A structural connection between the two Upper Delfín Basins is evident in the switching of the center of extension along axis. Sonobuoy refraction data suggest that the basement consists of mixed igneous sedimentary material, atypical of mid-ocean ridges. On the basis of the near-surface manifestations of active faulting and magmatism, seafloor spreading will likely first occur in the Lower Delfín Basin. We suggest the transition to seafloor spreading is delayed by the lack of strain-partitioned and focused deformation as a consequence of shear in a broad zone beneath a thick sediment cover

Absence of detectable HIV-1 viremia after treatment cessation in an infant

An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection