cssi/SciSciGPT-SciSciNet huggingface dataset:
The life cycle stages of Pneumocystis murina have opposing effects on the immune response to this opportunistic, fungal pathogen

ABSTRACT The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina. The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4+ T cells that produce IFN-γ. In vitro, bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4+ T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro, suggesting that the trophic forms dampen cyst-induced inflammation in vivo.
Computing competing cascades on signed networks

Often in marketing, political campaigns and social media, two competing products or opinions propagate over a social network. Studying social influence in such competing cascade scenarios enables building effective strategies for maximizing the propagation of one process by targeting the most “influential” nodes in the network. The majority of prior work, however, focuses on unsigned networks where individuals adopt the opinion of their neighbors with certain probability. In real life, relationships between individuals can be positive (e.g., friend of relationship) or negative (e.g., connection between “foes”). According to social theory, people tend to have similar opinions to their friends but opposite of their foes. We study the problem of competing cascades on signed networks, which has been relatively unexplored. Particularly, we study the progressive propagation of two competing cascades in a signed network under the Independent Cascade Model and Generalized Linear Threshold Model and provide an approximate analytical solution to compute the probability of infection of a node at any given time. We validate the quality of our approximation on several synthetic graphs. We leverage our analytical solution to the problem of competing cascades in signed networks to develop a heuristic for the influence maximization problem. We allow the seed-set to be initialized with populations of both cascades with the end goal of maximizing the spread of one cascade. We validate our approach on several large-scale real-world and synthetic networks. Our experiments demonstrate that our influence maximization heuristic significantly outperforms state-of-the-art methods, particularly when the network is dominated by distrust relationships.
Pilot Study of 99mTc-labeled Ethylene Dicysteine Deoxyglucose SPECT-CT Imaging in Treatment Response Evaluation in Patients with Locally Advanced Head and Neck Cancer.

Background The purpose of this study is to describe the preliminary findings of 99mTc-labeled ethylene dicysteine deoxyglucose (99mTc-EC-DG) performed four weeks after chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma. Methods Review of nine patients with locally advanced head and neck squamous cell carcinomas imaged with 99mTc-EC-DG single photon emission computed tomography-computed tomography (SPECT-CT) at baseline before treatment and at four weeks after treatment completion was performed. Results At four weeks post-treatment, five patients had either decreased activity or no significant activity on 99mTc-EC-DG SPECT-CT and were considered to have responded to treatment, whereas four patients did not have significantly decreased uptake on 99mTc-EC-DG SPECT-CT and were considered to have not adequately responded to treatment. Among the five patients considered to have treatment response at four weeks, all were free of disease (true-negative). Among the four patients considered to have stable activity on 99mTc-EC-DG SPECT-CT at four weeks, two were designated as having no response or incomplete response (true-positive), and two were designated as having complete response (false-positive) on subsequent composite assessment. Conclusions The pilot data is promising but warrants further investigation of 99mTc-EC-DG SPECT-CT for the assessment of locoregional treatment response at four weeks in patients with locally advanced head and neck squamous cell carcinomas.
In the Age of Breast Augmentation, Breast Reconstruction Provides an Opportunity to Augment the Breast.

Background:Augmentation mammoplasty remains the most common cosmetic surgery procedure performed. The objective of this article is to evaluate the impact of augmented volume of the reconstructed br...
Evaluating Special Educators’ Classroom Performance: Does Rater “Type” Matter?:

Classroom observations remain the predominant data source used in teacher evaluations, but little is known about how rater characteristics may affect teachers’ scores. For special educators, whose ...
Regime Type and FDI: A Transaction Cost Economics Approach to the Debate

A debate exists in international political economy on the relationship between regime type and foreign direct investment (FDI). The central point of contention focuses on whether multinational firms generally prefer to pursue business ventures in more democratic or autocratic countries. A considerable amount of theory has been developed on this topic; however, the arguments in previous studies lack consistency, and researchers have produced mixed empirical findings. A fundamental weakness in this literature is that while FDI has largely been treated conceptually as a homogeneous aggregate, in reality, it features divergent characteristics on multiple dimensions. Three possible dimensions that FDI can be decomposed on are: greenfield vs. brownfield, ownership type (wholly owned vs. joint venture), and horizontal vs. vertical. The most relevant dimensions to the problem at hand are: greenfield vs. brownfield, and horizontal vs. vertical. Five propositions, based on the notion of asset specificity, other investment attributes, and host nation domestic factors, are derived to predict how regime type might affect four types of FDI: vertical-greenfield; vertical-brownfield; horizontal-greenfield; and horizontal-brownfield. Depending on the type of FDI, multinational corporations may have no regime preference, an autocratic preference, or a democratic preference. This research contributes to empirical international relations theory by providing a useful example on how to resolve a scholarly debate, theoretically, and by laying out testable propositions for future empirical research.
Guided Wave Mode Propagation Influence for a Shear Horizontal Wave Source in An Anisotropic Viscoelastic Layer

Sensors are used in a variety of different manufacturing systems in order to improve product quality and process control. In a recent development by Menon et al. [1], guided waves are used to monitor part quality. The purpose of this paper is to explore the possibility of using shear horizontal (SH) waves for an anisotropic viscoelastic layer.
Radiation-Induced Cerebral Microbleeds in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy

Purpose Proton beam radiation therapy (PBT) has been increasingly used to treat pediatric brain tumors; however, limited information exists regarding radiation-induced cerebral microbleeds (CMBs) among these patients. The purpose of this study was to evaluate the incidence, risk factors, and imaging appearance of CMBs in pediatric patients with brain tumors treated with PBT. Materials and Methods A retrospective study was performed of 100 pediatric patients with primary brain tumors treated with PBT. CMBs were diagnosed by examination of serial magnetic resonance imaging scans, including susceptibility-weighted imaging. Radiation therapy plans were analyzed to determine doses to individual CMBs. Clinical records were used to determine risk factors associated with the development of CMBs in these patients. Results The mean age at time of PBT was 8.1 years. The median follow-up duration was 57 months. The median time to development of CMBs was 8 months (mean, 11 months; range, 3-28 months). The percentage of patients with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1 year, 2 years, 3 years, 4 years, 5 years, and >5 years from completion of proton radiation therapy. Most of the CMBs (87%) were found in areas of brain exposed to ≥30 Gy. Risk factors included maximum radiation therapy dose (P = .001), percentage and volume of brain exposed to ≥30 Gy (P = .0004, P = .0005), and patient age at time of PBT (P = .0004). Chemotherapy was not a significant risk factor (P = .35). No CMBs required surgical intervention. Conclusions CMBs develop in a high percentage of pediatric patients with brain tumors treated with proton radiation therapy within the first few years after treatment. Significant risk factors for development of CMBs include younger age at time of PBT, higher maximum radiation therapy dose, and higher percentage and volume of brain exposed to ≥30 Gy. These findings demonstrate similarities with CMBs that develop in pediatric patients with brain tumor treated with photon radiation therapy.
Abstract 2820: Synergistic antileukemic activity of the antibody-drug conjugate (IMGN779) combined with PARP inhibition in preclinical human acute myeloid leukemia models

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy of immature myeloid cells. Antibody-drug conjugates (ADC) comprising humanized anti-CD33 monoclonal antibodies linked to cytotoxic payloads are known to exert clinical activity in AML patients. However, dose-dependent effects of ADC therapy, specifically hepatotoxicity, myelosuppression and veno-occlusive disease, have limited their clinical utility in patients. Inhibitors of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP), so-called PARP inhibitors (PARPi), enhance tumor death by preventing repair of single-stranded DNA breaks. We have previously shown (Portwood S et al., ASH 2016) that the PARPi olaparib improves the activity of the anti-CD33 ADC (IMGN779) in preclinical AML models. Here we assessed the efficacy of multiple PARPi (olaparib, niraparib, rucaparib, veliparib, and talazoparib) alone and in combination with IMGN779 for AML therapy. Materials and Methods: Human AML cell lines (HEL, HL60) were characterized for CD33 expression using flow cytometry after staining with antibody-linked fluorescent QuantiBrite Beads. Cells were treated with varying doses of IMGN779 (100pM-1nM) and PARPi (10nM-100uM) alone and in combination for 96h. Viability was measured after treatment utilizing a WST-1 colorimetric assay. Induction of apoptosis, cell cycle effects, and DNA damage were characterized by flow cytometry following 72h of treatment. Synergy reports were generated using Compusyn software. Results: All PARPi demonstrated dose-dependent inhibition of AML (HEL, HL60) growth with the following IC50 ranges: talazoparib 200-400nM, niraparib 2.5-7.3 μM, olaparib 7.4-8.9 μM, rucaparib 39-75 μM, and veliparib 88-100 μM. Combination therapy with IMGN779 and four PARPi (veliparib, niraparib, olaparib, talazoparib) resulted in synergistic in vitro antileukemic effects with CI values Conclusions: Our results demonstrate that PARP inhibitors as a class exert dose-dependent antitumor activity against human CD33+ AML cells. Moreover, PARPi consistently induce in vitro synergistic antileukemic effects against human AML cells when combined with the anti-CD33 ADC (IMGN779). Studies evaluating the mechanisms of action and the efficacy of combinatorial therapy in primary AML cells are under way. These findings support further clinical studies of PARP inhibition as a potential means of enhancing the activity of ADCs for acute myeloid leukemia therapy. Citation Format: Claire Fritz, Scott M. Portwood, Julie Adams, Eunice S. Wang. Synergistic antileukemic activity of the antibody-drug conjugate (IMGN779) combined with PARP inhibition in preclinical human acute myeloid leukemia models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2820.
Branched-Tail Lipid Nanoparticles Potently Deliver mRNA In Vivo due to Enhanced Ionization at Endosomal pH

The potential of mRNA therapeutics will be realized only once safe and effective delivery systems are established. Unfortunately, delivery vehicle development is stymied by an inadequate understanding of how the molecular properties of a vehicle confer efficacy. Here, a small library of lipidoid materials is used to elucidate structure-function relationships and identify a previously unappreciated parameter-lipid nanoparticle surface ionization-that correlates with mRNA delivery efficacy. The two most potent materials of the library, 306O10 and 306Oi10 , induce substantial luciferase expression in mice following a single 0.75 mg kg-1 mRNA dose. These lipidoids, which have ten-carbon tails and identical molecular weights, vary only in that the 306O10 tail is straight and the 306Oi10 tail has a one-carbon branch. Remarkably, this small difference in structure conferred a tenfold improvement in 306Oi10 efficacy. The enhanced potency of this branched-tail lipidoid is attributed to its strong surface ionization at the late endosomal pH of 5.0. A secondary lipidoid library confirms that Oi10 materials ionize more strongly and deliver mRNA more potently than lipidoids containing linear tails. Together, these data highlight the exquisite control that lipid chemistry exerts on the mRNA delivery process and show that branched-tail lipids facilitate protein expression in animals.
TRADING SECRETS: CONSTRUCTIONS AND CONTEXTS OF TWO MIDDLE EASTERN JEWISH GUARDS IN THE EARLY PETAH TIKVA AGRICULTURAL COLONY

Two Arabic-speaking Jewish guards worked in the European Jewish agricultural colony of Petah Tikva soon after its founding, northeast of Jaffa, in 1878: Daud abu Yusuf from Baghdad and Yaʿqub bin Maymun Zirmati, a Maghribi Jew from Jaffa. The two men, who worked as traders among Bedouin but were recruited for a short time by the colony, offer a rare glimpse of contacts between Ashkenazi and Middle Eastern Jews in rural Jewish colonies established in the last quarter of the 19th century, colonies that are often regarded as detached from their local and Ottoman landscape. The article first argues that Zionist sources constructed these two men as bridges to the East in their roles as teachers of Arabic and perceived sources of legitimization for the European Jewish settlement project. It then reads beyond the sparse details offered in Ashkenazi Zionist sources to resituate these men in their broad imperial and regional context and argue that, contrary to the local Zionist accounts, the colony was in fact likely to have been marginal to these men's commercial and personal lives.
Grapevine Red Blotch Virus May Reduce Carbon Translocation Leading to Impaired Grape Berry Ripening.

Grapevine red blotch virus (GRBV) is suspected to alter berry ripening and chemistry. This study performed a physiological characterization of GRBV infected grapevines with attention to the factors...
A fast and stable Li metal anode incorporating an Mo6S8 artificial interphase with super Li-ion conductivity

The poor interfacial stability of Li metal leads to formation of unstable solid-electrolyte interphases (SEIs) and severely limits its practical applications. Protecting Li metal with an artificial SEI that has balanced stability, conductivity and mechanical strength is critical. Here we demonstrate a design strategy for stabilizing Li using Mo6S8/carbon artificial SEI films. These films are directly coated on Li foil and the Mo6S8 particles provide ordered conduction channels for fast but regulated Li-ion flux, and provide hybrid anodes that have nearly four times higher exchange current densities. They also have seamless contact with Li metal and protect it from parasitic reactions, and hence significantly improve its stability. Consequently, Li metal batteries in which the hybrid anodes were paired with LiNi0.8Mn0.1Co0.1O2 cathodes (3.0 mA h per cell) exhibited significantly improved cycling stability (63% vs. 25% retention) and a stabilized Li interphase compared with pristine Li anodes.
Angiocentric Glioma, Pilomyxoid Astrocytoma, and Pituicytoma: New Entities in the World Health Organization Classification

The 2007 World Health Organization (WHO) Classification of CNS Tumors added three new entities to its compendium of primary CNS neoplasms which are similar in that they consist of relatively monomorphous spindle cells: angiocentric glioma (AG), pilomyxoid astrocytoma (PMA), and pituicytoma. This chapter describes the clinical features, histopathology, diagnosis, treatment, and prognosis of these three newly codified entities. Angiocentric glioma, a cortically-based neoplasm that causes intractable epilepsy in young people, shares many similarities with ependymoma. However, these similarities were not enough to classify it as an ependymoma subtype, and AG is under “Other Neuroepithelial Tumors” in the new classification. A WHO Grade I tumor, it is an indolent, slow-growing neoplasm characterized by bipolar cells with spindled nuclei that tend to cluster around intratumoral vessels (giving this tumor its name). The primary differential diagnosis is cortical ependymoma but also includes pilomyxoid astrocytoma. Angiocentric glioma is usually cured with surgical excision, even in subtotally resected tumors. Pilomyxoid astrocytoma is categorized as an aggressive variant of pilocytic astrocytoma encountered mainly in very young children but may present in older children or adults. PMA is usually located in the optic chiasm/hypothalamic region. Histologically, PMA is a strikingly monomorphous tumor composed of bipolar cells in a richly myxoid background which lacks the biphasic pattern of pilocytic astrocytoma and in which the tumor cells form ependymoma-like perivascular pseudorosettes. Considerations in the differential of PMA include pilocytic astrocytoma with a myxoid component, angiocentric glioma, and infiltrating glioma. Because PMA behaves more aggressively, following a biopsy diagnosis, it is treated with chemotherapy for low-grade gliomas with or without gross total resection, depending on tumor burden. Last, pituicytoma is listed as a separate entity under “Tumors of the Sellar Region” and is a solid tumor of the posterior pituitary and stalk. Thought to be derived from pituicytes, the glial cells of the pituitary stalk and neurohypophysis, this tumor presents in adults as an intrasellar or suprasellar mass causing visual or hormonal disturbances. Histopathologically, pituicytomas are composed of spindled, bipolar cells which arrange themselves in a characteristic storiform pattern. The differential diagnosis of pituicytoma includes pituitary adenoma, spindle cell oncocytoma, and granular cell tumor. Pituicytoma is cured by surgical excision and is WHO Grade I.
Intestinal Transplantation for Total Intestinal Aganglionosis

Intestinal transplantation is a successful treatment for children with irreversible intestinal failure who experience life-threatening complications of parenteral nutrition. Total or near-total intestinal aganglionosis is a rare form of Hirschprung’s disease (HD) with high morbidity and mortality and near-certain dependence on parenteral nutrition. Advances in surgical techniques, immunosuppressive regimens, and posttransplant surveillance and management have led to improvements in patient and graft survival following intestinal transplantation. Intestinal transplantation may provide a life-saving treatment option for children with total or near-total intestinal aganglionosis.
Abstract 4860: Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients

Background: Oral mucositis is a very painful and debilitating complication of radiotherapy, occurring in nearly all head and neck cancer patients. It can severely affect quality of life and lead to treatment interruptions that subsequently impact clinical outcomes. With limited treatment options, there is an urgent need to develop new strategies for mucositis prevention. Animal studies have shown that sensitivity to genotoxic stress strongly depends on the time of a day therapy is administered. Therefore, radiotherapy could be conducted at optimal times of a day associated with best tolerability, to reduce mucosal damage. This hypothesis is partially supported by two clinical trials that reported less severe oral mucositis in head and neck cancer patients treated in the morning vs. late afternoon; but results were not significant and times of a day not fully covered. Methods: This study examined the associations between timing of radiotherapy and development of oral mucositis in 219 head neck cancer patients treated at Roswell Park Comprehensive Cancer Center, using data from Electronic Medical Records. Patients’ treatment time was consistent throughout a 6/7-week course, and mucositis survey was self-reported weekly during treatment, providing a unique resource for this study. The primary endpoint is “soreness quality score” (SQS), a five-level score “0-no, 1-a little, 2-moderate, 3-quite a lot, and 4-extreme” in assessing patients’ soreness severity for mouth and throat in the past 24 hours. We used a generalized linear model approach to assess the association between radiotherapy time and the maximum SQS (MSQS) reported during treatment, adjusting for age, smoking, treatment type, survey week and cancer site. Results: Multivariate analyses revealed treatment time to be significantly associated with MSQS (p-value=0.025), with lowest MSQS (lsmean=2.26, ste=0.18) seen for patients treated in the early morning (8:30- Conclusion: To our knowledge, this is the first study to find a significant variation of oral mucositis severity by treatment hour of radiotherapy; the variation shows an arc shape with the peak in the early afternoon. Our results suggest that identifying an optimal time of a day for radiotherapy may substantially prevent severe oral mucositis in head and neck cancer patients. Further studies are worthwhile to confirm our findings, and to find optimal treatment times for individual patients. Citation Format: Fangyi Gu, William D. Duncan, YingDong Feng, Austin Miller, Nicolas Schlecht, Alan Hutson, Anurag K. Singh. Association between timing of radiotherapy and severity of oral mucositis in head-neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4860.
Outcomes of Allogeneic Stem Cell Transplant for Elderly Patients with Hematologic Malignancies

Abstract Reduced-intensity conditioning (RIC) regimens, improved HLA matching, and better supportive care allow allogeneic stem cell transplant (alloSCT) to be offered to older patients. Only a small percentage of eligible patients between ages 65 and 74 years actually undergo alloSCT, and comprehensive outcome data from the aging population are still lacking. We examined the outcome of older patients who underwent alloSCT using melphalan-based RIC for hematologic malignancies at our institution. We identified 125 patients older than 65 years (median, 69; range, 66 to 77) who underwent matched related donor, matched unrelated donor, or combined haploidentical/umbilical cord alloSCT between 2012 through November, 2017. Among them, 52 (41.6%) and 70 (56%) had, respectively, intermediate and high/very high Center for International Blood and Marrow Transplant Research (CIBMTR) disease risk index (DRI). One hundred six patients (85%) received fludarabine/melphalan-based RIC regimen with either antithymocyte globulin (ATG) or alemtuzumab. The median time to neutrophil engraftment was 13 days (range, 8 to 37) and platelet engraftment 17 days (range, 9 to 169). The cumulative incidence of nonrelapse mortality was 11.5% at 100 days and 30.1% and 34.8% at 1 and 2 years, respectively. The cumulative incidence of relapse was 35% and 40% at 1 and 2 years. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) at day 100 and 6 months was 29.5% and 34.5%, and chronic GVHD at 6, 12, and 24 months was 2.5%, 5.2%, and 6.3%, respectively. With a median follow-up of 32 months, the 1-, 2-, and 3-year progression-free survival (PFS) was 34.6%, 24.4%, and 16.5%, respectively. The graft GVHD-free survival was 24.6%, 16.1%, and 9.3%, respectively. The 1-, 2-, and 3-year overall survival (OS) was 44.5%, 30.7%, and 26.5%, respectively. In multivariable analysis, low albumin was predictive of poor PFS and OS and high hematopoietic cell transplantation–specific comorbidity index, and CIBMTR DRI was predictive of worse graft GVHD-free survival. Among long-term survivors the median Karnofsky performance status was 80. Older patients, even when referred with advanced disease, can benefit from melphalan-based alloSCT with HLA-matched or alternative donor sources without discernible impact of donor source on outcome. Using alemtuzumab- or ATG-based in vivo T cell depletion, the incidence of chronic GVHD is extremely low. Performance status in survivors is excellent. Better predictors for outcome in this patient population need to be identified.
Frequency and severity of autonomic symptoms in idiopathic hypersomnia

Study Objectives:We aimed to quantify the symptoms of autonomic nervous system dysfunction in a large online cohort of patients with idiopathic hypersomnia, and to determine how the severity of the...
Developing Practical Knowledge and Skills of Online Instructional Design Students through Authentic Learning and Real-World Activities.

Integrating authentic learning opportunities into online courses can be particularly challenging. These challenges have contributed to a lack of examples (i.e., case studies) of how online instructors have successfully integrated authentic learning into their courses (Vo et al. 2018). This article fills this gap by describing the process of redesigning an online graduate-level instructional design course to incorporate authentic learning activities. This course integrated authentic learning principles and a real-world project situated in a real-life context, allowing students to develop instructional design skills, including project management, stakeholder negotiation, and product design, development, and testing.
A Technological Assessment of the North Pacific Seafaring Hypothesis: Informed by California Channel Island Research

The proposal of an initial human coastal migration into the New World during the late Pleistocene has gained considerable support in recent years. However, the methods of such a migration are not c...
Applications of Joint Polar Satellite System Data and Products for Severe Weather Events and Climate Monitoring

Radiances and Environmental Data Records (EDR) from the Joint Polar Satellite System (JPSS) are critical for weather prediction. A variety of EDRs such as fire detection, retrievals of aerosols and water vapor are used by forecasters to provide warnings and alerts during disasters. Several JPSS products also provide continuity of essential climate variables such as upper atmospheric temperature and ozone concentration for climate change monitoring.
Pharmacokinetics of Sublingual vs. Oral Estradiol in Transgender Women.

Abstract: Objective To investigate the pharmacokinetics of 17s-estradiol administered orally versus sublingually in transgender women. Methods Single doses of 17s-estradiol were administered orally (1 mg) to ten transgender women, then sublingually (1 mg) after a one-week washout. Blood samples were taken at baseline and T = 1,2,3,4,6,8 hours after dosing. Samples were frozen and analyzed using LC-MS/MS (liquid chromatography mass spectrometry) and immunoassay. Results Results demonstrated that sublingual estradiol had a significantly higher peak serum estradiol (E2) concentration at 144 pg/mL by LC-MS/MS compared to oral estradiol at 35 pg/mL by LC-MS/MS (p= 0.003). Sublingual estradiol peaked at hour 1 and oral estradiol peaked at hour 8 when measured by LC-MS/MS. The area under the curve (AUC) 0-8h for sublingual estradiol measured by LC-MS/MS showed a 1.8-fold higher level compared to the AUC 0-8h for oral estradiol measured by LC-MS/MS. Additionally, sublingual E2 was found to have an increased E2 to estrone (E1) ratio at all timepoints (1.1 ± 1.0 v. 0.7 ± 0.4, p= Conclusion Oral estradiol administered sublingually has a different pharmacokinetic profile, with higher serum estradiol levels and AUC (0-8h) than traditionally administered oral E2. Multi-daily dosing may be necessary to suppress testosterone levels with sublingual estradiol. The appropriate dosing, efficacy and safety of sublingual estradiol compared to other estradiol preparations is unknown.
Brace Considerations for Posterior Cruciate Ligament Injuries of the Knee

Bracing can play a prominent role in the management of posterior cruciate ligament (PCL) injuries, for both operative and nonoperative management strategies. Understanding the nuances of bracing for PCL injuries is critical for proper management and for providing the best chance for a stable, functional, and pain-free knee in the long term. Braces used for PCL injuries come in a variety of designs, each with advantages and disadvantages that should be appropriately matched to the individual patient. Outcome studies of bracing PCL injuries are rare, and the variety of protocols applied in these studies makes it difficult to form a consensus on how to achieve the best functional results. Regardless of the bracing protocol used, patient compliance is crucial and dependent on ongoing communication between the patient and the treating physician.
Chapter 20 - Olympic values and the rights of the child: Chapter taken from Human Rights in Youth Sport: A Critical Review of Children's Rights in Competitive Sport ISBN: 978-0-415-30558-7

(2012). Chapter 20 - Olympic values and the rights of the child. Routledge Online Studies on the Olympic and Paralympic Games: Vol. 1, Human Rights in Youth Sport: A Critical Review of Children's Rights in Competitive Sport, pp. 250-255.
Treatment of extensive carcinoma of the cervix with the "transperineal parametrial butterfly": a prelimary report on the revival of Waterman's approach.

In advanced carcinoma of the cervix the associated obliteration of the fornices or contracture of the vagina may interfere with accurate placement of conventional intracavitary applicators. Poorly placed applicators fail to irradiate the pelvis homogeneously. Waterman (and others)10solved this dilemma by transvaginal radium implants many years ago; however, despite good survival figures, this technique has not gained popularity, presumably because of excessive exposure to personnel. In this paper, we describe a technique which largely eliminates the exposure problem and at the same time improves the homogeneity of pelvic endoradiotherapy. We locate what is in essence a pair of “paravaginal intterstitial colpostats” in both parametria in combination with the usual intrauterine randem. This helps to distribute the dose laterally, with relative sparing of bladder and rectum. The technique employs a template to guide the insertion into the parametria of a group of 18 gauge hollow steel needles transperineally. Afterloading with 192Ir is accomplished when the patient has returned to her room (after orthogonal radiography and computer dosimetry). Doses to point B compare very favorably to those at point A.
Selected Factors Associated with Wrestling Success

Abstract The purpose of this study was to investigate the relationships among total response times for two wrestling take down maneuvers, a strength test, and initial take down ability. Two response time measures of actual take down maneuvers used in wrestling and the 4-Item Total Proportional Strength Test were secured on 100 Illinois high school varsity wrestlers. These measures were compared to actual competitive initial take down performances based on 1029 individual matches and 815 initial take downs during the 1957–58 season. Wrestlers were divided into successful and unsuccessful groups on the criterion of having won a place in the sectional or state tournament. Significant differences beyond the 5 percent level of confidence in favor of successful wrestlers over unsuccessful wrestlers were found on right grip, left grip, and back lift strength measures. Both groups of wrestlers, however, when compared to three different scoring tables were rated average to below average on all strength measures. T...
Vaginal injury due to coitus.

Abstract L aceration or rupture of the vagina may occur during sexual intercourse. Although this accident is uncommon, it has been described before and several good reviews concerning this subject are available. 6,7,11,13,14,17,19 It is the purpose of this report to summarize 14 cases of vaginal injury due to coitus treated at Parkland Memorial Hospital since 1947, to tabulate recent cases reported in the medical literature, and to emphasize the importance of this injury as a gynecologic entity. To avoid needless repetition, the important points of each case report are summarized in Table I. There were no deaths in the series.
Insulin-Receptor Interaction in the Obese-Hyperglycemic Mouse: A MODEL OF INSULIN RESISTANCE

The interaction of insulin with its receptor was studied in purified liver plasma membranes and isolated hepatocytes of the obese hyperglycemic mouse (ob/ob) and its thin litter mate. The ob/ob mouse is a genetic mutant characterized by marked obesity, hyperinsulinism, and resistance to both endogenous and exogenous insulin. Under identical conditions of preparation and incubation, the membranes of the ob/ob mouse bind only 20 to 25% as much insulin per mg of protein as those of their thin litter mates. Scatchard analysis suggests that this decrease in binding is due to a decrease in the number of receptor sites in the membrane of the obese mouse, especially those of higher affinity. The result with isolated hepatocytes was qualitatively the same. In contrast to the marked decrease in insulin receptors, the membranes of the obese mouse were similar to those of their thin litter mates in activity of membrane marker enzymes, protein subunit structure, and binding of 125I-human growth hormone and isoproterenol. There was a decrease in 125I-glucagon binding but to a much smaller extent than that observed in insulin binding. The decrease in insulin receptors in the ob/ob mouse correlates well with the insulin resistance which they exhibit.
Is there a common SUV threshold in oncological FDG PET/CT, at least for some common indications? A retrospective study.

AbstractPurpose. We retrospectively compared the maximum standard uptake value (SUVmax) of FDG PET in four different sites to evaluate whether a common diagnostic SUVmax threshold may exist in these tumor locations. We further postulate that the SUVmax thresholds are higher in thoracic lesions than in extrathoracic lesions. Material and methods. N = 143 patients in four subgroups underwent a FDG PET/CT: a) 42 patients for solitary pulmonary nodules (SPNs) characterization with b) respective mediastinal lymph nodes (LNs), c) 65 patients for LN staging of head and neck cancer, and d) 36 cancer patients diagnosed with adrenal lesions. Receiver operating characteristics of SUVmax values were evaluated. Results. The SUVmax were statistically significantly greater in malignant than in benign lesions. For SPNs and mediastinal LNs, a SUVmax > 3.6 each resulted in a sensitivity of 81% and 87%, and a specificity of 94% and 89%. For cervical LNs and adrenal glands, a SUVmax > 2.2 each showed a sensitivity of 98% and...
The postnatal spatial and temporal development of corticospinal projections in cats.

Orthograde labeling and immunocytochemical techniques were used to study the postnatal spatial and temporal development of corticospinal projections in cats. Findings from the orthograde labeling studies indicate that there are three major phases in the spatial development of corticospinal projections: an early period (1–10 postnatal days) when cortical axons grow into the spinal gray from the white matter; an intermediate period (2–5 postnatal weeks) where corticospinal axons develop terminal arborizations in a rostral to caudal, medial to lateral and intermediate gray to dorsal and ventral horn sequence; and, a late period (6–7 postnatal weeks) during which some corticospinal projections are eliminated. The time period over which cortical axons grow into the spinal cord was determined immunocytochemically using a monoclonal antibody against a microtubule associated protein (MAP 1B) present in growing axons. The corticospinal tracts were strongly immunoreactive for MAP 1B during the first three postnatal weeks. MAP 1B immunostaining of these tracts started to decline in the fourth postnatal week and was completely absent by five weeks of age. These findings indicate that the postnatal development of corticospinal projections is spatially and temporally protracted in cats.
Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist and its relation to mastitis caused by intramammary challenge with Staphylococcus aureus

Staphylococcus aureus is a common cause of chronic mammary gland infections in dairy cattle. However, the inflammatory response and duration of infection following pathogen exposure is variable between individual animals. To investigate interanimal differences in immune response, dermal fibroblast cultures were established from skin biopsies collected from 50 early lactation Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to assign a response phenotype to the animals. Five high-responding and 5 low-responding animals were then selected for an intramammary challenge with S. aureus to evaluate differences in the inflammatory response, chronicity of infection, and development of antibodies to the pathogen. All animals exhibited clinical symptoms of mastitis at 24h postchallenge. Animals previously classified as high responders experienced a greater inflammatory response characterized by elevated levels of milk somatic cell count, IL-8, and BSA following the challenge compared with low responders. In addition, antibodies toward the challenge strain of S. aureus reached higher levels in whey from the challenged gland of high responders compared with low responders. Despite the antibody response, all 5 high responders were chronically infected for the 6-wk duration of the study, whereas 2 of the low responders cleared the infection, although 1 of these did become reinfected. The observed differences between animals classified as low and high responders based on their fibroblast responsiveness suggests that this cell type can be used to further examine the causes of interanimal variation in response to mammary infection.
Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability.

Parasympathetic Withdrawal and Blockade Effects on HRV. introduction: Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated. Methods and Results: To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete β-adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex-mediated parasympathetic withdrawal and (2) low-dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five-minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5-minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low-dose atropine: 869 ± 96 msec and nitroprusside 875 ± 99 msec). The root mean square of the successive RR interval differences was lower following low-dose atropine than following parasympathetic withdrawal with nitroprusside (16 ± 11 msec vs 22 ± 15 msec; P < 0.02). During parasympathetic withdrawal, the low-frequency (LF) power was 0.917 ± 0.602 bpm2 and the high-frequency (HF) power was 0.501 ± 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 ± 0.474 bpm2, P < 0.005; and 0.198 ± 0.207 bpm2, P < 0.02). Conclusion: These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.
Allosteric switching of agonist/antagonist activity by a single point mutation in the interluekin-1 receptor antagonist, IL-1Ra.

The pleiotropic pro-inflammatory cytokine interleukin (IL)-1β has co-evolved with a competitive inhibitor, IL-1 receptor antagonist (IL-1Ra). IL-1β initiates cell signaling by binding the IL-1 receptor (IL-1R) whereas IL-1Ra acts as an antagonist, blocking receptor signaling. The current paradigm for agonist/antagonist functions for these two proteins is based on the receptor–ligand interaction observed in the crystal structures of the receptor–ligand complexes. While IL-1Ra and IL-1β are structurally homologous, IL-1Ra engages only two of the three extracellular domains of the receptor, whereas IL-1β engages all three. We find that an allosteric functional switch exists within a highly conserved pocket of residues, residues 111–120. This region is maintained across all IL-1 family members and serves as a hydrophobic mini-core for IL-1β folding. A key difference across species is a conserved aromatic residue at position 117 in IL-1β, versus a conserved cysteine in IL-1Ra at the analogous position, 116. We find that the replacement of C116 with a phenylalanine switches the protein from an antagonist to an agonist despite the distant location of C116 relative to receptor interaction sites. These results suggest new ways to develop designer cytokine activity into the β-trefoil fold and may be of general use in regulation of this large family of signaling proteins.
Association of aortic atherosclerosis and renal dysfunction.

Background Both aortic atherosclerosis (AA) and renal dysfunction are associated with increased morbidity and mortality. We sought to assess the association between AA and renal dysfunction. Methods The study consisted of 200 consecutive patients (62% were male, mean age 69 ± 11 years) who underwent transesophageal echocardiography. Demographic and clinical data were recorded. On transesophageal echocardiography, descending and aortic arch atherosclerosis were recorded (in millimeters) using off-line planimetry. The patients were graded with normal AA (group 1, n=83), mild AA (≤4 mm in thickness, group 2, n=53), or severe AA (>4 mm in thickness or complex, group 3, n=64). Glomerular filtration rate (GFR) (expressed as milliliters/minute/1.73 meters squared) was calculated as 186 × (serum creatinine −1.154 ) × (age −0.203 ) × 1.212 (if black) × 0.742 (if female). Results The mean GFR decreased significantly with increasing severity of AA (89 ± 20 for group 1, 72 ± 20 for group 2, and 49 ± 23 for group 3, P P P P Conclusion There exists a strong association between AA and renal dysfunction.
Probing Methylene Blue Photocatalytic Degradation by Adsorbed Ethanol with In Situ IR

The dynamic behavior of infrared (IR)-observable species during the methylene blue [i.e., MB, (CH3)2N(C6H3)NS+(C6H3)N(CH3)2Cl-] photocatalytic degradation (PCD) on TiO2 has been investigated at 30 °C. Exposure of MB/TiO2 to UV illumination led to the scission of the N−CH3 bond followed by breaking of the C−H and CN bonds in the MB central aromatic ring and the side aromatic rings, indicating demethylation as the first step of the MB PCD. The bond breaking in the MB molecule and subsequent reactions produced charge-containing intermediates (i.e., carboxylate (RCOO-) and R−NH3+), slowing down the conversion of MB to CO2, H2O, NH4+, and SO42-. Probing the MB PCD by adsorbed ethanol revealed that the demethylation step was initiated by the OH/OD radical (·OH/·OD) and the breaking of CN and CS−C in the MB central aromatic ring by H+/electron transfer. In situ IR coupled with the use of ethanol as a probe molecule provides an excellent method for investigating the PCD mechanism.
A NUMERICAL STUDY OF THE FLOW OVER ELLIPSOIDAL OBJECTS INSIDE A CYLINDRICAL TUBE

A numerical scheme is developed to obtain the flow field around one, two and five ellipsoidal objects inside a cylindrical tube. The scheme uses the Galerkin finite element technique and the primitive variable (u-υ-p) formulation. The two-dimensional incompressible Navier-Stokes equations are solved numerically by using the direct mixed interpolation method. A Picard iteration scheme is used for the solution of the resulting system of non-linear algebraic equations. The computer code is verified by checking with known analytical solutions for the flow past a sphere. Results for the shear stress distributions along the ellipsoids, forces and drag coefficients are obtained for different geometric ratios and Reynolds numbers. Some of the intermediate computational results on the velocity fields developed are also reported.