cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinician perceived barriers to the use of regional anaesthesia and analgesia

Summary Background Clinician preference may be an important aspect of anaesthesia and pain management therapy. Preferences for, and barriers to, the use of regional anaesthetic and analgesic techniques may play an important part in the choice of anaesthetic and acute postoperative pain management techniques offered to patients. Methods The existence of perceived barriers to the use of regional techniques for anaesthesia and pain management was assessed using a survey tool in a multidisciplinary group of perioperative care providers at an urban Level-I trauma centre. Results The preferences identified include utilizing regional techniques whenever appropriate and/or in patients with co-morbid conditions where regional techniques would be beneficial in decreasing anaesthetic risks. The barriers identified in the survey: procedural risk, lack of nursing education regarding postoperative care, time constraints, and patient anxiety. Conclusions Although the origins of these preferences and perceived barriers have supported validity when examined in the literature, no previous work has focused solely on the subject of the existence and nature of clinician preferences and perceived barriers to the use of regional anaesthesia techniques. Further research in this area may focus on preference and barrier identification on a broader scale as well as weighted analysis of individual responses.
Regulation of MBK-2/DYRK by CDK-1 and the Pseudophosphatases EGG-4 and EGG-5 during the Oocyte-to-Embryo Transition

Summary DYRKs are kinases that self-activate in vitro by autophosphorylation of a YTY motif in the kinase domain, but their regulation in vivo is not well understood. In C. elegans zygotes, MBK-2/DYRK phosphorylates oocyte proteins at the end of the meiotic divisions to promote the oocyte-to-embryo transition. Here we demonstrate that MBK-2 is under both positive and negative regulation during the transition. MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68, a residue outside of the kinase domain required for full activity in vivo. The pseudotyrosine phosphatases EGG-4 and EGG-5 sequester activated MBK-2 until the meiotic divisions by binding to the YTY motif and inhibiting MBK-2′s kinase activity directly, using a mixed-inhibition mechanism that does not involve tyrosine dephosphorylation. Our findings link cell-cycle progression to MBK-2/DYRK activation and the oocyte-to-embryo transition.
Comparison of gene order of GIGANTEA loci in yellow-poplar, monocots, and eudicots.

GIGANTEA plays an important role in the control of circadian rhythms and photoperiodic flowering. The GIGANTEA gene has been studied in various species, but not in basal angiosperms. Moreover, to t...
Non-equilibrium nanoscale nanosecond plasma discharge in liquid for biomedic al applications

Generation of plasma in liquid phase and at liquid interfaces has been previously restricted to thermal plasma for a variety of applications. The new and emerging field of plasma medicine provides a clear demand for development of non-thermal plasma for generation in liquid phase and at liquid interfaces. Primary application of such plasma includes sterilization applications for prosthetic implants related both to generation of reactive oxygen species as well as activation of antibiotics contained within the polymerized surfaces of the implants.
The physiological effects of hyperosmolar resuscitation: 5% vs 3% hypertonic saline

Abstract Background Use of 5% normal saline (NS) is gaining renewed interest. The primary aim of our study was to compare the physiological effects after the administration of different concentrations of hypertonic saline (3% vs 5%NS) in the initial resuscitation of trauma. Methods We performed a retrospective analysis of a prospectively collected database of all trauma patients who received hypertonic saline during initial resuscitation. Medical records were reviewed for serum electrolytes and serum osmolarity, coagulation parameters, complications, and mortality. Results A total of 212 patients were included in the study, of which 170 patients received 5%NS and 42 patients received 3%NS. Both groups were similar in age (41.16 ± 19 vs 44.17 + 23.6; P = .45) and ISS score (26 [17 to 29] vs 25 [16 to 27]; P = .6). Mean serum osmolarity (316 ± 20.3 vs 294 ± 22.5; P = .02) and serum sodium levels (143 ± 8.6 vs 137 ± 10.9; P P = .01); however, at 48 and 72 hours (7.40 ± .07 vs 7.41 ± .07; P = .7), no difference was found. There was no difference in blood products requirement (1,734 vs 2,253 mL; P = .11) between the 2 groups. Conclusions The 5%NS has sustained higher serum osmolarity and serum sodium concentration within the first 72 hours without any increase in adverse effects in comparison with 3%NS.
Whole-body lift and ground effect during pectoral fin locomotion in the northern spearnose poacher (Agonopsis vulsa).

Abstract The northern spearnose poacher, Agonopsis vulsa , is a benthic, heavily armored fish that swims primarily using pectoral fins. High-speed kinematics, whole-body lift measurements, and flow visualization were used to study how A. vulsa overcomes substantial negative buoyancy while generating forward thrust. Kinematics for five freely swimming poachers indicate that individuals tend to swim near the bottom (within 1 cm) with a consistently small (less than 1°) pitch angle of the body. When the poachers swam more than 1 cm above the bottom, however, body pitch angles were higher and varied inversely with speed, suggesting that lift may help overcome negative buoyancy. To determine the contribution of the body to total lift, fins were removed from euthanized fish ( n =3) and the lift and drag from the body were measured in a flume. Lift and drag were found to increase with increasing flow velocity and angle of attack (ANCOVA, p
Altered calcium sequestration by subcellular fractions of vascular smooth muscle from spontaneously hypertensive rats.

Abstract The calcium sequestration characteristics of microsomal and mitochondrial fractions prepared from aortae of spontaneously hypertensive (SHR), Kyoto Wistar normotensive (NWR), and normotensive Sprague-Dawley (NSDR) rats were studied. Calcium uptake by the microsomal vesicles of SHR was significantly lower as compared to NWR and NSDR. However, mitochondria isolated from SHR aortae did not differ from NWR in their calcium uptake characteristics. Microsomal vesicles of NSDR aortae accumulated consistently more calcium than NWR. These findings illustrate the significance of relevant controls for SHR. Calcium-dependent ATPase activity in the microsomal fraction was significantly increased in SHR as compared to NWR. This may indicate a compensatory phenomenon on the part of the smooth muscle cell to increase Ca 2+ uptake by the microsomal vesicles. These results suggest that a decreased ability to sequester calcium by the microsomal fraction of vascular smooth muscle of SHR may result in altered calcium distribution in the muscle cell.
The G Protein–Coupled Receptor GALR2 Promotes Angiogenesis in Head and Neck Cancer

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor patient survival. Galanin receptor 2 (GALR2) is a G protein-coupled receptor that induces aggressive tumor growth in SCCHN. The objective of this study was to investigate the mechanism by which GALR2 promotes angiogenesis, a critical oncogenic phenotype required for tumor growth. The impact of GALR2 expression on secretion of proangiogenic cytokines in multiple SCCHN cell lines was investigated by ELISA and in vitro angiogenesis assays. Chemical inhibitor and genetic knockdown strategies were used to understand the key regulators. The in vivo impact of GALR2 on angiogenesis was investigated in mouse xenograft, chick chorioallantoic membrane, and the clinically relevant mouse orthotopic floor-of-mouth models. GALR2 induced angiogenesis via p38-MAPK-mediated secretion of proangiogenic cytokines, VEGF, and interleukin-6 (IL-6). Moreover, GALR2 activated small-GTP-protein, RAP1B, thereby inducing p38-mediated inactivation of tristetraprolin (TTP), which functions to destabilize cytokine transcripts. This resulted in enhanced secretion of proangiogenic cytokines and angiogenesis in vitro and in vivo. In SCCHN cells overexpressing GALR2, inactivation of TTP increased secretion of IL-6 and VEGF, whereas inhibition of p38 activated TTP and decreased cytokine secretion. Here, we report that GALR2 stimulates tumor angiogenesis in SCCHN via p38-mediated inhibition of TTP with resultant enhanced cytokine secretion. Given that p38 inhibitors are in clinical use for inflammatory disorders, GALR2/p38-mediated cytokine secretion may be an excellent target for new adjuvant therapy in SCCHN.
Cortical Shift Tracking Using a Laser Range Scanner and Deformable Registration Methods.

A novel brain shift tracking protocol is introduced in this paper which utilizes laser range scan (LRS) data and 2D deformable image registration. This protocol builds on previous efforts to incorporate intra-operative LRS data into a model-updated image guided surgery paradigm for brain shift compensation. The shift tracking method employs the use of a LRS system capable of capturing textures of the intra-operative scene during range data acquisition. Textures from serial range images are then registered using a 2D deformable registration approach that uses local support radial basis functions and mutual information. Given the deformation field provided by the registration, 3D points in serial LRS datasets can then be tracked. Results from this paper indicate that the error associated with tracking brain movement is 1.1mm on average given brain shifts of approximately 20.5mm. Equally important, a strategy is presented to rapidly acquire intra-operative measurements of shift which are compatible with model-based strategies for brain deformation compensation.
Brain stem extracellular fluid pH and respiratory drive during hypoxia in newborn pigs

In response to moderate hypoxia many newborn animals are capable of increasing ventilation only transiently. To examine the hypothesis that changes in brain stem extracellular fluid (ECF) pH explain this transient ventilatory response, we measured brain stem ECF pH and respiratory drive during hypoxia in newborn pigs. The animals were anesthetized with alpha-chloralose-urethan, paralyzed, vagotomized, and mechanically ventilated with a servo-controlled ventilator to regulate end-tidal CO2. Hypoxic ventilation for 6 min was achieved by changing inspired gas from 100% to 10-15% O2. Respiration, measured as integrated phrenic nerve activity, showed a range of responses. In 13 trials increased phrenic activity early in the hypoxic period was sustained or further augmented for the duration of the period. In contrast, in eight other trials phrenic activity increased and then declined. Regardless of the respiratory response, ECF pH (measured with a flat-surface electrode) increased slightly (0.009 +/- 0.002 U) during the first 2.5 min of hypoxia and then declined 0.061 +/- 0.017 U by the 6th min. This acidotic shift in ECF pH is inconsistent with the hypothesis that an alkalotic shift causes the nonsustained respiratory response of newborn pigs.
Marconi’s Representations of the Wireless

This chapter analyzes the topoi Marconi used when presenting the wireless to a technical audience. Marconi’s rhetoric promotes the wireless’s viability and necessity for members of the Royal Institution and the Royal Society of Arts, London. Before the wireless became the radio, Marconi prophesized its usefulness, linking it to cultural values. The wireless embodies certain industrial traits—speed, efficiency, profitability, evolution/advancement—and these technical presentations employ such values. At the time of Marconi’s presentations, the wireless was not yet a major commercial product. In order to have a successful product, the wireless had to be portrayed as possible and progressive. The wireless did not replace extant technologies, but it did expand the reach of communication and, therefore, mass communication. As an important mouthpiece for the wireless, Marconi offered his audiences not the physical product but the idea of a potential product to mark human advancement and bolster economic progress.
Dispelling five myths about hypothesis testing in biological systematics

The emphasis on testing phylogenetic hypotheses has been prominent since the English language introductions of Willi Hennig’s Phylogenetic Systematics (1966) and Karl Popper’s (1959) Logic of Scientific Discovery. While the mechanics of hypothesis and theory testing are well established in other fields of science, adherence to those prescriptions in biological systematics has rarely been formally recognized. The consequence has been the development of potentially contradictory approaches to empirically evaluating phylogenetic hypotheses under the guise of testing. In his brief review of the topic, Assis (Cladistics, 30:240–242, 2014) identified five different views on phylogenetic hypothesis testing: (1) total evidence, (2) taxonomic congruence, (3) reciprocal illumination, (4) homology assessment, and (5) taxa sampling. The present paper examines the validity of these views against the actual inferential steps required to infer hypotheses and subsequently engage in testing, i.e., abduction, deduction, and induction (sensu stricto), respectively. It is shown that none of the tests discussed by Assis are valid, and while it is straightforward to outline what is required to properly test phylogenetic hypotheses, the feasibility of accomplishing such tests is operationally impractical in most instances.
Embryology of Phaenicia Sericata (Meigen)1 Diptera: Calliphoridae Part III. the Gastrular Tube

The author has previously described the embryonic development of Phaenicia sericata (Meigen) from the process of fertilization to the formation of the blastoderm (primary epithelium). The purpose of this paper is the presentation of the phases of development involved in the formation of the gastrular or mesodermal tube.
Effect of tocopherol feeding on the composition of turkey tissues.

SummaryMixed tocopherols, about one-half α and the rest chiefly γ, fed to 28 female turkeys for 2.5 to 35 days before slaughter at levels 0.01, 0.1, 1 or 2% of the feed produced measurable increases in the tocopherol content of liver, heart, gizzard and muscle. The 0.1% level fed for 35 days produced the most efficient transfer of tocopherol, but the total amount of the supplement retained in this and the other groups was extremely small. The liver usually contained more tocopherol than any other tissue, 23 to 225 mg per kg fresh tissue, the heart contained 28 to 145, the gizzard 15 to 45, the leg muscle 11 to 50, and the breast muscle 8 to 25. Bioassay of liver and leg muscle indicated the presence of a-tocopherol in amounts within 10% of those obtained by the chemical procedure. No relationship was found between the tocopherol and the vit. A and carotene contents of the 15 livers examined. The peroxide numbers of the fat under the skin and the abdominal fat before and after frozen storage for 3: 5, 6, o...
Experimental Study of Swirling Jets and Axial Forcing on Round Jets

In jets, swirl can significantly enhance growth and mixing. This can lead to better chemical process efficiencies, increased combustion completeness, lower exhaust plume temperatures, and reduction in pollutant by-products. Exciting natural instabilities can enhance mixing further. Past research on forcing of swirling jets resulted in limited change in flow behavior. This could be attributed to either low Reynolds numbers or imposed modes that were solely axial or azimuthal. In our experiment, both round and free swirling jets are created by independently controlling the axial and azimuthal momentum injection rates; the resulting water stream discharges into a large tank. Axial forcing on a round jet is varied for Strouhal number ranging from 0 to 0.45 and Reynolds number, Re, of 5,700 for small amplitudes. An unforced swirling jet is also presented for Re of 1,100 and 5,800 with a Swirl of 0.05. While the highest Reynolds number studied here is relevant to industrial applications, there is a dearth of experimental data in this range. Flow structures in the shear layer are identified with PLIF. Fluorescent dye is injected uniformly in the circumference of the boundary layer; this allows visualizing the effect of forcing and swirl on the shear layer in the near and far field. The results offer insight into controlling the spacing of the vortex rings formed by axial forcing.Copyright © 2013 by ASME
A Thermodynamically Consistent Cohesive Zone Model for Mixed-Mode Fracture

The objective of this paper is to propose a thermodynamically consistent cohesive zone model for mixed-mode fracture, which enables a cohesive element to exhibit designated behaviors when subject to mixed-mode loading. Some fundamentals of the cohesive zone model, continuum damage mechanics, and thermodynamics are briefed, and the concept of the irreversible deformation is introduced. The cohesive law in the undamaged configuration, the damage evolution law, and the cohesive law in the damaged configuration are subsequently derived, and a novel delamination criterion is proposed. The applicability and power of the proposed cohesive zone model are demonstrated using examples such as predicting the traction-relative displacement and damage factor-relative displacement curves of cohesive elements of various cohesive properties. More sophisticated cohesive properties can be incorporated into the proposed model.
Ectopic growth of endometrium depends on its structural integrity and proteolytic activity in the cynomolgus monkey (Macaca fascicularis) model of endometriosis

Objective To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis. Design Prospective, comparative study. Setting Animal research unit. Subjects Thirty regularly cycling cynomolgus monkeys in three groups of 10 each. Interventions Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor. Main Outcome Measures Staging laparotomies after 3weeks and 3months. Results In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3weeks and in eight, three, and two monkeys, respectively, at 3months. Conclusion An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.
Depressive Symptoms in Mothers and Daughters: Attachment Style Moderates Reporter Agreement

Parents and adolescents show only modest agreement when reporting on depressive symptoms. Drawing from attachment theory and previous research on informant discrepancies, we tested hypotheses about how adolescent attachment style may impact reporting agreement in a sample of 184 low-income mother-adolescent daughter dyads (adolescent mean age = 15.4 (SD = 1.05), maternal mean age = 41.4 (SD = 7.60); 58 % Latina, 26 % African-American/Black, 16 % as non-Hispanic, White). Mothers and adolescents reported on their own and each others’ depressive symptoms and adolescents reported on attachment style. Using a moderated Actor Partner Interdependence Model (APIM) to calculate reporter bias and accuracy estimates, we tested whether attachment style moderated maternal and adolescent accuracy in theoretically consistent ways. Mothers and adolescents showed similar levels of accuracy and bias when reporting on each other. Consistent with hypotheses, we found that adolescents who reported high levels of preoccupation were less accurate when reporting on their mothers because they tended to observe symptoms that their mothers did not endorse. Conversely, mothers were the most accurate in these dyads, potentially because preoccupied adolescents tend to elevate displays of emotional distress. Reporting accuracy was not affected by a dismissive style. These results add to literature indicating that parent-child reporting discrepancies often reflect meaningful information about relationships, and highlight the need to consider different sources of reporting bias and accuracy in assessment and treatment.
Dynamic Analysis on Dental Caries Status among Primary and Middle School Students in Futian District of Shenzhen City during 2005-2009

[Objective]To understand the epidemic status of dental caries among primary and middle school students in Futian district of Shenzhen,provide the scientific basis for implementation of control measures.[Methods]The dental caries status among primary and middle school students in Futian district during 2005-2009 were analyzed.[Results]From 2005-2009,the caries incidence rate of primary and middle school students in Futian district was 18.31%,16.03%,23.81%,27.37% and 32.65%,respectively.The total caries incidence rate of primary and middle school students was 23.71%,that of primary school students was 31.09%,that of junior middle school students was 15.96%,that of senior middle school students was 17.01%,and there was significant difference among these three groups(χ2 = 905.85,P 0.01).The caries incidence rate of girls was significantly higher than that of boys(χ2 = 3.88,P 0.05).[Conclusion]The caries incidence rate of primary and middle school students in Futian district showed an increasing trend,and the prevention and control of dental caries among students should be strengthened.
Low Incidence of Bone Flap Resorption After Native Bone Cranioplasty in Adults.

Objective Cranioplasty via use of the patient's autologous bone is performed often after craniectomy procedures. Bone resorption remains a matter of concern in patients with native bone cranioplasty. The objective of this study was to evaluate the rate of native bone resorption in adults and review associated factors that may increase the risk of resorption. Methods This is a single-center retrospective cohort study that assessed consecutive patients who had cranioplasty via use of the patient's native bone flap. A total of 114 patients were identified. Electronic medical records were reviewed for demographic and operative data. Results The mean age was 51.2 years. The main indications for initial craniectomy included subarachnoid hemorrhage (SAH) in 50.9%, intracerebral hemorrhage in 17.5%, ischemic stroke in 14.9%, and trauma in 13.2% of patients. Mean interval between craniectomy and cranioplasty was 6 months. Mean follow-up after cranioplasty was 25 months. Bone resorption occurred in 3 patients (2.7%): at 6 months in a 30-year-old woman who presented with SAH followed by decompressive craniectomy and cranioplasty 3.5 months later; at 19 months in a 67-year-old female patient who presented with intracerebral hemorrhage followed by decompressive craniectomy and cranioplasty 6 months later; and at 9 months in a 50-year-old man who presented with SAH followed by craniectomy for clip ligation and cranioplasty 3 months later. Two of these patients underwent replacement of the native flap with synthetic material. Conclusions The rate of autologous bone flap resorption in adult patients undergoing cranioplasty is low even after a mean interval for cranioplasty of 6 months.
Clinical validation of NGS technology for HLA: An early adopter’s perspective

Clinical validation of NGS for HLA typing has been a topic of interest with many laboratories investigating the merits. NGS has proven effective at reducing ambiguities and costs while providing more detailed information on HLA genes not previously sequenced. The ability of NGS to multiplex many patients within a single run presents unique challenges and sequencing new regions of HLA genes requires application of our knowledge of genetics to accurately determine HLA typing. This review represents my laboratory's experience in validation of NGS for HLA typing. It describes the obstacles faced with validation of NGS and is broken down into pre-analytic, analytic, and post-analytic challenges. Each section includes solutions to address them.
Leukemia-Specific Ligands Against Childhood Acute Lymphoblastic leukemia

Abstract Abstract 3269 The one-bead-one-compound (OBOC) combinatorial library method was invented by Kit Lam to identify cancer cell surface targeting ligands (Peng L et al. Nat. Chem. Biol. 2006, Aina OH et al., Mol. Pharm. 2007). Using this method, LLP2A, a ligand against activated a4b1 integrin, was discovered that targets malignant lymphoma with high affinity and specificity (Peng L et al., Mol Cancer Ther. 2008). We tested whether childhood acute lymphoblastic leukemia (ALL) cells expressed activated a4b1 integrin and bound to LLP2A using primary leukemia cells and leukemia cells engrafted in NOD/SCID/IL2Rg null (NSG) mice. Expression of activated a4b1 integrin was observed in three primary leukemia samples (1 T-ALL, 1 precursor B (preB) ALL, and 1 relapsed preB ALL) by the rainbow beads (color-coded polystyrene bead mixture displaying unique ligands against known receptors such as a4b1, a3b1, avb3, a5b1 integrins (Luo J et al., J. Comb. Chem. 2008). To quantify activated a4b1 integrin expression, primary leukemia cells were analyzed by flow cytometry using biotinylated LLP2A/streptavidin-PE. Nine samples (7 preB ALL and 2 relapsed preB ALL) were analyzed. All samples, except for one relapsed preB ALL sample, showed expression of activated a4b1 integrin at different levels. In order to determine the specificity of activated a4b1 integrin expression, hematopoietic stem cells from three normal bone marrow (BM) samples were analyzed and showed very low levels of activated a4b1 integrin expression. Furthermore, we have identified 32 analogues of LLP2A using three fresh preB ALL samples to screen two LLP2A-focused libraries. Peptide microarrays using a polystyrene slide coated with neutravidin and biotinylated ligands will be prepared with these analogues. We will determine the binding affinity and specificity of these analogues to a series of primary ALL cells. Binding specificity to leukemia cells will be determined by excluding ligands which bind to normal hematopoietic progenitor (CD34) cells. The property of the selected ligands will be tested in vivo using NSG mice engrafted with primary ALL cells. Updated results with these new ligands will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.
The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2015 ☆

Abstract This is a review of papers published in the year 2015 that focus on the synthesis, reactivity, or properties of compounds containing a carbon-transition metal double or triple bond. Highlights for the year 2015 include: (1) significant advances in the design of new precursors to carbene complex intermediates that serve as safer alternatives to potentially hazardous diazo compounds, (2) continued vast employment of olefin metathesis for the synthesis of complex small molecules and polymers, including many examples of Z-selective reactions, (3) design of novel transformations employing metallacumulene intermediates, (4) preparation of novel aromatic ring systems incorporating transition elements, and (5) uses of alkyne metathesis for preparation of highly functionalized macrocyclic compounds and novel polymeric materials.
Epidemiology and Genetics (Including High Risk Patients, Polyomavirus, Prognostic Factors)

Merkel cell carcinoma (MCC) is a rare, highly aggressive form of skin cancer that has a strong propensity toward local recurrence, regional nodal metastasis, distant metastasis, and high mortality rates. MCC usually affects elderly white persons and has been described with many different names, given the uncertainty of the cell of origin. The most commonly used names include trabecular carcinoma of the skin, cutaneous neuroendocrine carcinoma, and Merkel cell carcinoma. The name Merkel cell carcinoma was suggested in 1980 and is the most common name used today. The incidence of MCC in the United States is estimated at 0.6 per 100,000 person-years. Because of the rarity of this form of skin cancer, studies have been limited in the past regarding MCC etiologic characteristics, risk factors, prevention strategies, and therapeutic approach. However, population-based data have been accessed recently, mainly from cancer registries, allowing for more detailed information to come to light on the demographic characteristics of primary MCC in the general population. Recently, discoveries of factors that could contribute to the development of MCC have been made, including the identification of the Merkel cell polyomavirus and genetic mutations.
P3.138 Macrolide- and fluoroquinolone-resistant mycoplasma genitalium in african americans in alabama

Introduction: Mycoplasma genitalium (MG) is a sexually transmitted microbe associated with urethritis in men and several inflammatory syndromes in women. Macrolides and fluoroquinolones have been recommended treatments for MG infections. However, resistance of both drug classes is increasing worldwide and treatment failures have been described. There are very little data available on antimicrobial resistance in MG from the USA. Methods We investigated the prevalence of macrolide- and fluoroquinolone-resistant MG in African American men and women who presented to a Sexually Transmitted Diseases Clinic in Birmingham, Alabama during 2015–2016; most were couples. A real-time PCR assay was validated for detecting MG 23S rRNA mutations known to confer macrolide resistance directly from clinical specimens. Two nested PCRs were used to detect mutations in the quinolone resistant determination regions (QRDRs) in gyrA and parC genes. Results Oral, rectal, urine, and/or vaginal specimens from 90 men and 81 women have been tested thus far. A total of 23 MG-positive patients have been identified (4 couples and 15 singles), giving a prevalence rate for MG of 13.5% in this cohort; 11 (12.2%) of men and 12 (14.8%) of women were MG positive. Eleven (47.8%) patients (6 men and 5 women) carried macrolide-resistant MG. Sequencing of the PCR products indicated that A2071G and A2072G transitions in the 23S rRNA gene was the major mutations. No mutation was found in gyrA QRDR. Three patients (13.6%), including 1 couple, carried G248T (S83I) mutation in parC QRDR. The female of the couple also carried a parC G259C (D87H) mutant group. Two individuals (a couple) carried organisms that had markers for both macrolide and fluoroquinolone resistance. Conclusion This is the first study based in the USA to document both fluoroquinolone and macrolide resistance in MG using a molecular-based assay. We plan to genotype MG directly from the clinical specimens to investigate the genetic relatedness of antimicrobial-susceptible and resistant-MG, as well as the concordance of MG in couples.
TerraWatchers, Crowdsourcing, and At-Risk World Heritage in the Middle East

Cultural resources, like natural resources, are finite. Every country has cultural resources that reflect local history and prehistory and are vital both economically for tourism and socially as a foundation of cultural identity. This material cultural record is part of world heritage, something recognized by UNESCO since 1972 (http://whc.unesco.org). As archaeological and historical sites occur in relatively restricted areas, they are a limited resource that should be cared for, curated, and preserved for local, national, and international communities. Like natural resources, cultural resources are sensitive to human and natural intervention. Unfortunately, over the past 4 years, more than any other region on the planet, archaeological heritage sites in the Eastern Mediterranean and Middle East have suffered destruction at an alarming rate. Political instability, war, extreme ideologies, economic downturns, and other factors have led to the wanton destruction of heritage sites. As part of the University of California Office of the President Catalyst Grant project “At-Risk Cultural Heritage and the Digital Humanities,” the TerraWatchers Crowdsourcing platform is being used to involve citizen scientists in monitoring archaeological site destruction in war-torn Syria and Iraq using satellite imagery. This chapter presents an overview of TerraWatchers, how it relies on the expertise of the American Schools of Oriental Research (ASOR) Cultural Heritage Initiatives to identify at-risk sites in the region, and how university students in a classroom setting were trained to participate in this digital cultural heritage experiment.
Adaptive SVRG Methods under Error Bound Conditions with Unknown Growth Parameter

Error bound, an inherent property of an optimization problem, has recently revived in the development of algorithms with improved global convergence without strong convexity. The most studied error bound is the quadratic error bound, which generalizes strong convexity and is satisfied by a large family of machine learning problems. Quadratic error bound have been leveraged to achieve linear convergence in many first-order methods including the stochastic variance reduced gradient (SVRG) method, which is one of the most important stochastic optimization methods in machine learning. However, the studies along this direction face the critical issue that the algorithms must depend on an unknown growth parameter (a generalization of strong convexity modulus) in the error bound. This parameter is difficult to estimate exactly and the algorithms choosing this parameter heuristically do not have theoretical convergence guarantee. To address this issue, we propose novel SVRG methods that automatically search for this unknown parameter on the fly of optimization while still obtain almost the same convergence rate as when this parameter is known. We also analyze the convergence property of SVRG methods under H\"{o}lderian error bound, which generalizes the quadratic error bound.
A computational framework for converting high-throughput DNA sequencing data into neural circuit connectivity

There is growing interest in determining the connectivity of neural circuits-the "connectome"-at single neuron resolution. Most approaches to circuit mapping rely on either microscopy or physiology, but these approaches have very limited throughput. We have recently proposed BOINC (Barcoding of Individual Neuronal Connectivity), a radically different approach to connectivity mapping based on high-throughput DNA sequencing. Here we describe the set of computational algorithms that serve to convert sequencing data into neural connectivity. We apply our computational pipeline to the results of proof-of-principle experiments illustrating an implementation of BOINC based on pseudorabies virus (PRV). PRV is capable of traversing individual synapses and carry DNA barcodes from one cell to another. Using this high-throughput sequencing data, we obtain 456-by-486 connectivity matrix between putative neurons. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution would represent a major advance in neuroscience.
Thermal diffusivity determination using heterodyne phase insensitive transient grating spectroscopy

The elastic and thermal transport properties of opaque materials may be measured using transient grating spectroscopy (TGS) by inducing and monitoring periodic excitations in both reflectivity and surface displacement. The “phase grating” response encodes both properties of interest, but complicates quantitative analysis by convolving temperature dynamics with surface displacement dynamics. Thus, thermal transport characteristics are typically determined using the “amplitude grating” response to isolate the surface temperature dynamics. However, this signal character requires absolute heterodyne phase calibration and contains no elastic property information. Here, a method is developed by which phase grating TGS measurements may be consistently analyzed to determine thermal diffusivity with no prior knowledge of the expected properties. To demonstrate this ability, the wavelength-dependent 1D effective thermal diffusivity of pure germanium is measured using this type of response and found to be consistent with theoretical predictions made by solving the Boltzmann transport equation. This ability to determine the elastic and thermal properties from a single set of TGS measurements will be particularly advantageous for new in situ implementations of the technique being used to study dynamic materials systems.
A threshold model for receptor tyrosine kinase signaling specificity and cell fate determination

Upon ligand engagement, the single-pass transmembrane receptor tyrosine kinases (RTKs) dimerize to transmit qualitatively and quantitatively different intracellular signals that alter the transcriptional landscape and thereby determine the cellular response. The molecular mechanisms underlying these fundamental events are not well understood. Considering recent insights into the structural biology of fibroblast growth factor signaling, we propose a threshold model for RTK signaling specificity in which quantitative differences in the strength/longevity of ligand-induced receptor dimers on the cell surface lead to quantitative differences in the phosphorylation of activation loop (A-loop) tyrosines as well as qualitative differences in the phosphorylation of tyrosines mediating substrate recruitment. In this model, quantitative differences on A-loop tyrosine phosphorylation result in gradations in kinase activation, leading to the generation of intracellular signals of varying amplitude/duration. In contrast, qualitative differences in the pattern of tyrosine phosphorylation on the receptor result in the recruitment/activation of distinct substrates/intracellular pathways. Commensurate with both the dynamics of the intracellular signal and the types of intracellular pathways activated, unique transcriptional signatures are established. Our model provides a framework for engineering clinically useful ligands that can tune receptor dimerization stability so as to bias the cellular transcriptome to achieve a desired cellular output.
Embryonic Stem Cells: A Biological Tool to Translate the Mechanisms of Heart Development

Heart organogenesis is sensitive to both genetic and environmental factors and heart malformations account for the majority of birth defects. The development of the mammalian heart is a complex morphogenetic process that ultimately results in a contractile, four-chambered organ that is formed from progenitor cells of mesodermal and neural crest origins. Studies in animal models with primitive hearts such as drosophila, zebrafish, and xenopus have provided important insights into the way the heart begins to form and the molecular cues that guide the early stages of cardiac morphogenesis. Much of what we know about the development of the heart in higher vertebrates comes mostly from embryological investigations in chick and mouse. In addition, genetic studies in zebrafish and mouse, including loss- and gain-of-function approaches, have been especially valuable for gaining information about the role of individual genes in heart development. However, the various animal models also have a number of limitations regarding lack of genetic tools (chick, xenopus), inaccessibility to observation and embryological manipulation (mouse), or unsuitability for high-throughput screens to identify pharmacologic compounds to treat cardiac defects. Mouse embryonic stem (ES) cells give rise to a wide variety of organ-specific cell types, offering an accessible and relevant system to investigate how cell lineages emerge and grow. The ES cell model is particularly pertinent for studying the molecular mechanisms regulating the specification and differentiation of cardiovascular progenitor cells, because these cells appear relatively early during embryonic development and ES cell differentiation. This chapter reviews a selective number of studies that have applied the in vitro differentiation of embryonic stem cells toward understanding the regulatory steps of cardiac development.
Monitoring and Quality Assurance for Hazardous Waste Site Assessment

Abstract In response to the chemical and legal requirements of the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (Superfund), the Office of Research and Development, U.S. Environmental Protection Agency, has established a monitoring and quality assurance program for the sampling and analysis of chemicals and complex mixtures obtained from hazardous waste sites. This includes the production of documents that will provide information on the special equipment and unique protocols necessary to sample and analyze the complex mixtures obtained by site monitoring. It also provides for laboratory evaluations, contractor capability evaluations, reference samples, inter-comparison studies and data audit. The objective being, the production of data of a known quality. In parallel programs, a high hazard materials laboratory has been established to provide quick response analyses to complex samples and to act as a referee laboratory in the intercomparison of State, Federal and industry protocols. Procedures from private industry, State and other Federal Agencies were adapted to design a comprehensive remote sensing program to provide data on abandoned waste sites prior to entry. The use of geophysical monitoring, and remote sensing are being investigated for application to ensure that the population, surface and groundwater are not contaminated by a closed hazardous releases site. The long term program includes establishing quality assurance procedures to be used in enforcement settlement agreements between EPA and. private industry, and the continued monitoring of sites covered by enforcement actions.
Engineering Microfluidics Based Technologies for Rapid Sorting of White Blood Cells

Blood is a valuable resource rich in cellular populations reflective of the immediate immune and inflammatory status of the body. Much of this information is contained in the nucleated White Blood Cells (WBCs). Current WBC isolation techniques are time consuming and result in artifactual changes in WBC gene expression. Using engineering approaches and basic fluid flow phenomenon in the microscale we have developed a microfluidic sorting device that can isolate WBC sub-populations rapidly based on size. This technique relies on osmosis to amplify size differences between different cell populations to ensure clear separation of different sub-populations based on size. The dynamics of cell size increase is determined in a microfluidic cell docking device which can be used to study instantaneous and time-dependent increase of cells to changing extra-cellular tonicity. Sorting is then accomplished in a microfluidic spiral sorter that exploits the balance between inertial lift forces and Dean’s forces that developed in the microchannels. This paper demonstrates proof-of-concept of the ability to measure osmosis dependent cell size increase using MOLT-3 cells and sorting using 15 and 25 μm beads and confirms that this method holds promise for WBC sorting.
FRI0254 COMBINED PANEL OF NINE TESTS HAS THE GREATEST SENSITIVITY BUT THE LOWEST SPECIFICITY TO DETECT ANTIPHOSPHOLIPID ANTIBODY SYNDROME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background Antiphospholipid antibody syndrome (APS) is an autoimmune hypercoagulable state caused by antiphospholipid antibodies (aPL) which represent a diagnostic criterion and underlie significant comorbidities in patients with and without systemic lupus erythematosus (SLE). Although several tests exist for APS diagnosis, their utilization has been highly variable among laboratories and physicians. Objectives We have evaluated a panel of nine tests and conducted a retrospective study to determine their sensitivity and specificity for supporting the diagnosis of APS in SLE at our Institution between 2010 and 2018. Methods 1633 SLE patients, who satisfied the ACR criteria for a definitive diagnosis [1 2], were evaluated for the presence of APS as earlier described [3]. Lupus anticoagulants were assessed by Staclot LA hexagonal phase phospholipid neutralization assay (HPPNA; delta Results 222/1633 SLE patients had APS when using a combination of nine tests. Table 1 shows the frequency of positive and negative test results and p value for each assay. The greatest sensitivity was seen when all nine tests were performed together for detecting APS in SLE patients (74%; χ2p=0.0003). In contrast, combining all tests had the lowest specificity (52%; p Conclusion This study demonstrates that utilizing a combined 9-test panel has the greatest sensitivity but lowest specificity for detecting APS in SLE subjects. Thus, a failure to employ the complete panel may lead to exclusion of patients who may meet criteria for identifying patients with APS who need long-term anticoagulation for preventing life-threatening thrombotic events. References [1] Tan, E.M., et al., The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1982. 25(11): p.1271-7. [2] Hochberg, M.C., Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1997.40(9): p. 1725. [3] Miyakis, S., et al., International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost, 2006. 4(2): p.295-306. [4] Triplett, D.A., et al., Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol, 1983. 79(6): p.678-82. [5] Genzen, J.R. andJ.L. Miller, Presence of direct thrombin inhibitors can affect the results and interpretation of lupus anticoagulant testing. Am J Clin Pathol, 2005. 124(4): p.586-93. Disclosure of Interests None declared
Workplace Organization and Asset Pricing

Flexible workplace organization (WO) increases the efficiency of a firm’s future capital investment. Hence, investment in WO positively predicts future capital investment and exposure to future aggregate investment-specific technology (IST) shocks. As a result, firms that invest in WO become riskier and systematically experience higher equity returns. This paper documents a robust positive correlation between firms’ WO investments and future equity returns. Firms with higher industry-adjusted WO investments have average returns that are 3.7% higher than those of firms with lower WO investments. In addition, firms with high WO investments experience a high conditional IST beta in the future. I tie all my empirical findings together in a production-based equilibrium model with closed-form solutions.
Effect of trichloroethylene exposure on autoimmune-mediated cholangitis in NOD.c3c4 mice

Primary biliary cirrhosis (PBC) is characterized by autoimmune-mediated destruction of bile ducts and has both genetic and environmental components. Specific chemicals that cause PBC have not been ...