cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim's efficacy and safety in other primary and secondary thrombocytopenic states.
Napping and Nighttime Sleep: Findings From an Occupation-Based Intervention

Objective To describe sleeping behaviors and trends over time among an ethnically diverse group of community-living older adults. Method A descriptive secondary data analysis of a subsample (n = 217) from the Lifestyle Redesign randomized controlled trial was done to explore baseline napping and sleeping patterns as well as 6-mo changes in these outcomes. Results At baseline, the average time sleeping was 8.2 hr daily (standard deviation = 1.7). Among all participants, 29% reported daytime napping at baseline, of which 36% no longer napped at follow-up. Among participants who stopped napping, those who received an occupation-based intervention (n = 98) replaced napping time with nighttime sleep, and those not receiving an intervention (n = 119) experienced a net loss of total sleep (p Conclusion Among participants who stopped napping, the occupation-based intervention may be related to enhanced sleep. More research examining the role of occupation-based interventions in improving sleep is warranted.
Inhibition of vascular endothelial cells by 1,4-phenylenebis (methylene)selenocyanate--a novel chemopreventive organoselenium compound.

Organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) was investigated for its effects on endothelial cell proliferation in vitro and angiogenesis in vivo. The organoselenium compound, p-XSC, has been shown to prevent carcinogen-induced tumorigenesis in murine model systems with low toxicity. Since tumor growth and metastasis are dependent on angiogenesis, we investigated the effects of the organoselenium compound on this process. Human umbilical vein endothelial cells treated with p-XSC showed concentration dependent inhibition of protein synthesis and cell viability in vitro with a TCID50 value of 6 microM. Subsequently, we studied the effects of p-XSC on experimental angiogenesis. Addition of p-XSC to three-dimensional cultures inhibited endothelial cell tube formation. Furthermore, p-XSC treatment inhibited growth factor induced angiogenesis in chick chorioallantoic membrane assays and i.p. administration of p-XSC inhibited neovascularization induced by tumor cells implanted subcutaneously into athymic mice. These studies suggest that vascular endothelium is an additional target for the chemopreventive organoselenium compound p-XSC.
International Policy Coordination and Emerging-Market Economies

This paper considers the debate over international economic policy coordination from an emerging-market standpoint. Since the global financial crisis, officials in emerging markets have been critical of the conventional and unconventional policies of advanced countries for failing to take into account their global spillover effects. I evaluate these criticisms through the dual lenses of theory and policy. Two important distinctions for evaluating these claims are the distinction between international policy coordination (the mutual adjustment of policies) and international cooperation (including information sharing) and between cooperation on monetary issues and financial issues. I conclude that the cases are strongest for international cooperation and for focusing on financial questions, respectively.
An experimental and theoretical study of the optical, electronic, and magnetic properties of novel inverted α-Cr2O3@α-Mn0.35Cr1.65O2.94 core shell nanoparticles

Magnetic core–shell nanoparticles (CSNs) have potential applications in spintronic devices, drug delivery systems, and magnetic random access memory. By use of our hydrothermal nano-phase epitaxy method, we have accomplished synthesis of novel, well-ordered α-Cr2O3@α-Mn0.35Cr1.65O2.94 inverted CSNs. XRD and TEM analyses show a core–shell structure with corundum phase throughout the core and shell with a minimal amount of interface defects. TEM-EDX and XPS data show Mn having the +2 oxidation state in the shell of the CSNs. Magnetization measurements at 5 K show a weak coercivity (HC) value of 8 Oe and an exchange bias field (HE) of 293 Oe. Ab initio calculations show that Mn incorporation in α-Cr2O3 results in narrowing of the energy band gap, substantiated by UV–Vis measurements, and half metallic behavior in case of Mn(III) substitution. Our calculations substantiate that Mn substitution in α-Cr2O3 results in a combination of antiferromagnetic and weak ferrimagnetic character of our CSNs.
Endogenous steroid hormone concentrations and risk of breast cancer: Does the association vary by a woman’s predicted breast cancer risk?

3212 Endogenous hormones are associated with an increased risk of breast cancer in postmenopausal women, but whether the association varies by a woman’s predicted risk of breast cancer has not been investigated in detail. To assess this question, we evaluated the associations of plasma levels of estradiol and testosterone with subsequent risk of breast cancer in a prospective, nested case-control study within the Nurses’ Health Study. Blood samples were collected in 1989-90; among 11,169 postmenopausal women not using postmenopausal hormones, 417 cases of breast cancer were reported through June 2000. Two controls were matched per case on age, fasting status, and month and time of day of blood draw (n=816). Women were classified both by first-degree family history of breast cancer and predicted risk of breast cancer. We used a modified Gail model to calculate predicted risk of invasive breast cancer in the 5 years following blood collection, based on age, ages at menarche and first live birth, number of affected first-degree relatives, and here, history of benign breast disease. We also stratified by risk scores from the Rosner risk prediction model. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for matching factors and breast cancer risk factors. Among women with a family history (104 cases, 143 controls), estradiol was associated with an increased risk of breast cancer (top vs. bottom fourth, RR=3.5, 95% CI (1.5-7.9), p-trend=0.002), while testosterone was not associated with risk, (comparable RR=1.0, 95% CI (0.4-2.3), p-trend=0.87). Among women with a modified Gail predicted risk of breast cancer ≥1.66% (252 cases, 460 controls), both hormones were associated with an increased risk of breast cancer (top vs. bottom fourth, RR=2.2, 95% CI (1.4-3.4), p-trend
Ultrasensitive laser isotope analysis of krypton in an ion storage ring

In our proposed instrument, sample ions are continuously injected into a small racetrack-shaped ring where they are stored for several orbits as the undesired species are removed.1 This multistaged separation technique has three elements (see Fig. 1). First, the ions are mass separated by two 180° bending magnets. After this first stage of enrichment the ions are neutralized in a charge exchange cell. The beam is then reionized by a laser before it passes back into the magnets for the second time to be further concentrated. After the desired degree of enrichment is attained, the ions are directed to a particle multiplier.
Making Do With What We Have.

Authors from the FDA described data submitted to the FDA Adverse Event Reporting System on 29 patients receiving HCV treatment with DAA–based regimens who had reactivation of hepatitis B virus. The...
Abstract LB-105: Characterization of total mutational burden in the GENIE cohort: Small and large panels can provide TMB information but to varying degrees

Introduction: Total mutation burden (TMB) correlates with response to immune checkpoint inhibition. AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) recently released clinical sequencing data for ~19000 cases from 8 institutions. We determined the ability of diverse sequencing panels to assess TMB. Methods: De-identified sequencing data from eight international academic cancer centers were used to investigate the per sample non-silent total somatic mutational burden (TMB) per 1Mb sequenced for all submitted samples. Summary: We first limited TMB characterization to three sites with sequencing data from large gene panels (sampling greater than approximately 1Mb) comprising 14472 samples. The distribution of the TMB normalized per Mb sequenced demonstrated a wide range of mutational rates both within and between tumor types (Table 1). The other five sites utilized smaller targeted sequencing panels. We then restricted the large panel data to the footprint of the smaller targeted panels and compared the number of mutations in the footprint of the small panels to the TMB of each sample from the larger panel data. We found that samples with >5 mutations in the footprint of the smaller targeted panels almost always had a high TMB (94%). In contrast, samples with no mutations in the footprint of the small panels almost never had a high TMB (2%). However, in samples with 1-5 mutations (which represented 2/3 of the samples) the footprint of the smaller targeted panels was not predictive of TMB. Conclusions: While whole exome analyses remain the gold standard for determination of total mutational burden, large sequencing panels (covering greater than approximately 1Mb) can be used to estimate TMB in diverse tumor types. Smaller targeted panels can also predict TMB for a subset of samples, with either 0 or >5 mutations, but this approach appropriately characterizes only just under a third of cases. The majority of cases need the increased genomic sampling of the larger gene panels (or whole exome analyses) to accurately quantify TMB. In summary, while the detection of high mutational burden cases by smaller targeted panel data is quite specific it lacks sensitivity. [A. S. B. and T. S. contributed equally to this work.] Citation Format: Alexander S. Baras, Thomas Stricker, on behalf of the AACR Project GENIE Consortium. Characterization of total mutational burden in the GENIE cohort: Small and large panels can provide TMB information but to varying degrees [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-105. doi:10.1158/1538-7445.AM2017-LB-105
A highly enantioselective [4+2] cycloaddition involving aldehydes and β,γ-unsaturated-α-keto esters

Abstract A stereoselective inverse electron demand oxo-Diels-Alder reaction involving electron poor dienes (γ-aryl-β,γ-unsaturated-α-keto ester) and electron rich dienophiles has been studied. These cycloaddition reactions are extremely useful for the construction of O-, N-, S-centered heterocyclic compounds, which are routinely used in both synthetic organic and medicinal chemistry. The [4+2] hetero cycloaddition reactions involving various aldehydes and β,γ-unsaturated-α-keto esters were carried out in which three different types of substituted proline catalysts were examined. For these reactions, high selectivities (enantiomeric excess 93–98%) were obtained using catalyst 3. Due to the bulkiness of catalyst 3, compared to the other catalysts tested, it is more efficient at catalyzing these type reactions.
Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study

Purpose: We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma.Materials and Methods: A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event.Results: This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preo...
The Hard Lefschetz Theorem

The pioneering study of the topology of algebraic varieties was carried out by Lefschetz in his monograph [79] published in 1924. He suggested working inductively, by comparing the homology of a smooth projective variety with its intersection with a single hyperplane and eventually a suitable family of them. There were two basic results, nowadays called the weak and hard Lefschetz theorems. In this chapter, we discuss both of these but focus on the latter. In one of its incarnations, it gives the structure of cohomology under cup product with a hyperplane class. The first correct proof of this was due to Hodge using harmonic forms, and we present a version of this. The hard Lefschetz theorem has a number of important consequences for the topology of projective, and more generally Kahler, manifolds, and we will discuss a number of these. We also want to interpret this using Lefschetz’s original more geometric point of view, which, remarkably, played a role in Deligne’s proof of the Weil conjectures [25] and in his subsequent arithmetic proof of hard Lefschetz [27].
Sensitivity of NRZ and PAM4 signaling schemes to channel insertion loss deviation

Paper discusses channel Insertion Loss Deviation (ILD) effects on binary and multi-level signaling in high-speed link design. Overview of ILD phenomenon is given and its sources in a multi-stage transmission line are discussed. Comparison tests are provided for channels with different amount of ILD. The test channels were simulated to mimic backplane channels with daughter cards. In order to cause significant ILD, impedance mismatches and interconnect parasitic effects were introduced into the model. Results are analyzed in terms of eye diagram degradations due to ILD induced ISI noise.
Conventional Mechanical Ventilation

This chapter explores the basic tenets of mechanical ventilation. We explore normal and abnormal lung physiology and physiologic changes that occur with mechanical ventilation. Next, we explore the advantages and disadvantages of various modes of ventilation. The clinical applications of mechanical ventilation are addressed, covering the basics of how to care for a patient who is mechanically ventilated, how to trouble shoot the ventilator, and how to wean from ventilation.
Are peripheral blood eosinophil counts a guideline for omalizumab treatment? STELLAIR says no!

Response to omalizumab is not dependent on peripheral blood eosinophil values http://ow.ly/J7KT30jOlYC
Gis Model Applications for Sustainable Development and Environmental Planning at the Regional Level

A 5-year cooperation between the Universities of Munich (Germany) and Redlands (USA) has resulted in the development of GIS processing tools and models to support regional environmental planning and management. Large spatial databases were structured and modern geoprocessing technologies such as ESRI's ModelBuilder were used to develop frameworks of GIS models and decision support tools. The results include a Decision Support System in the form of a complete database and models that can be easily adjusted to different planning goals or regions and allow identification of land use conflicts, sensitivity analysis, assessment of development scenarios and their impacts, besides graphical representation of the processing workflows and high quality output maps. Actual planning projects were the bases for application examples in the Munich Region: the Landscape Development Concept, and the urban growth model framework.
Effects of Grid Resolution On the Simulation of Internal Tides

We simulate two cases to examine the effect of horizontal grid resolution on simulation of the semidiurnal internal tide in Monterey Bay: a coarse grid (~2 900 m resolution) and a fine grid (~290 m resolution). All other inputs--barotropic M2 tidal velocity boundary conditions, initial conditions, and other physical and numerical parameters--remain constant between the two runs. The results show that the choice of grid resolution and the associated interpolated bathymetry are crucial to properly simulate the internal tides. The coarse grid acts like a filter to remove critical locations where internal tides are generated, and this grid loses the ability to capture energetic small-scale motions. The fine grid yields results consistent with field measurements. Instantaneous velocity results show multiple internal tidal beams emanating from numerous locations. These beams are composed of coherent high velocity rays that travel along the seafloor bottom and intersect with other beams in the middle of the water column forming hotspots of velocity. Furthermore, accurate results from the fine grid may be used to calculate energetics within Monterey Bay, thereby giving credibility to the idea that internal tides may be partly responsible for increased mixing and dissipation within the coastal ocean.
Reconstruction of Abdominal Wall in Trauma Patients After Damage Control

Reconstruction of the abdominal wall in trauma patients after damage control requires a well-thought-out management plan. In addition, there is a need for early recognition and initiation of damage control principles, optimizing resuscitation while being mindful of fluid overload, selective ventilation strategies, aggressive nutritional support, and infection management. The abdomen is initially managed with one of several temporary abdominal wall closure options. Each has advantages and disadvantages as the ideal closure method has yet to be defined. Regardless of which method is chosen, preventing loss of abdominal wall domain remains the key objective. Timing and patient selection are key factors in successful early abdominal wall closure. Aggressive diuresis after hemodynamic stabilization assists in reducing abdominal wall edema and facilitating early closure. When early closure is not possible, assessing the health of skin and fascia serves as a key step in determining management. In patients with sufficient skin, the fascia is assessed and management planned accordingly. For those with insufficient skin, we recommend considering the use of tissue expanders or complex tissue rearrangement techniques. A few select patients may require panniculectomy at time of operation to facilitate optimal closure. For patients with sufficient fascia, we recommend primary fascial closure with mesh onlay. For patients who have significant loss of abdominal domain and whose fascia is insufficient for primary closure, we recommend either component separation with subsequent primary fascial closure and mesh onlay or interpositional mesh with mesh onlay.
Fished species uniformly reduced escape behaviors in response to protection

Abstract Predation is a critical ecological process that alters the structure and functioning of ecosystems through density-mediated and trait-mediated effects on lower trophic levels. Although studies have focused on harvest-driven reductions in abundances and sizes of targeted species, human harvest also alters species morphologies, life histories, and behaviors by selection, plasticity, and shifts in species interactions. Restricting harvest can recover the biomass of targeted species, but it is less clear how behavioral phenotypes recover, particularly relative to the impacts of potentially opposing pathways of human influence. We investigated the effects of protection on the behavioral traits of a marine fish assemblage, recording behavior of 1377 individual fishes of nine targeted kelp forest species across 16 California marine protected areas (MPAs) varying in age, protection level, and diver visitation. With long-term, full protection from harvest, all fish species exhibited shorter flight initiation distance (FID, or the distance at which an animal flees from an approaching threat) and longer time delays before fleeing, despite differences in trophic position, microhabitat use, and other ecological characteristics. These escape behaviors were amplified across new MPAs regardless of protection level, suggesting that recovery is slow and likely the result of differences in genetic or early-life experience among individuals in these long-lived species. Although the effects of full protection from harvest were partially offset by recovering populations of large piscivorous predators, the net effect of long-term, full protection on fish behavior was shorter FID. Additionally, all species had shorter FID at sites more frequently visited by divers, and this effect was greater in sites with long-term, full protection from fishing. To the extent that escape behavior is correlated with foraging behavior and predation rates, these results suggest that human-induced behavioral changes may affect ecosystem processes, even after abundances have recovered. If recovery of ecosystem functioning and services are the management goal, assessments should be broadened to include the recovery of functional traits (including behavior).
Stable isotopes in the eye lenses of Doryteuthis plei (Blainville 1823): Exploring natal origins and migratory patterns in the eastern Gulf of Mexico

Abstract Eye lenses of Doryteuthis plei (Blainville 1823), the slender inshore squid or arrow squid, were used to re-create lifetime δ13C and δ15N histories for 42 individuals (21 males, 21 females) collected by trawl from the West Florida Shelf (WFS). These histories were compared against isoscapes for the Gulf of Mexico to infer geographic movements over the squid’s life. Most individuals (62%) had significant lifetime increases in δ13C, indicating landward movement, while only 12% of individuals indicated seaward movement. Males appeared to have a reduced tendency to move landward (38 vs 86% in females). Lifetime increases in δ15N indicated males and females had similar tendencies toward northward movement (71 vs 62%). The above patterns were interpreted as being geographic because the slopes of coupled changes in δ15N and δ13C were largely inconsistent with numeric expectations of increasing trophic level during life. Lifetime habitat shifts appeared to be continuous rather than saltatory (stepped). When plotted together, δ13C and δ15N did not occur in discrete clusters and often varied together in a linear manner. Isotopes from the central core of the lens, which represents the earliest period of post-embryonic life, were variable, with no apparent clustering when plotted, suggesting widely dispersed spawning grounds. Core isotope values were consistent with spawning on the outer WFS, possibly in association with the deep chlorophyll maximum.
A comparison of crude oil hydrocarbon mobilization by vaporization gas drive into methane, ethane, and carbon dioxide at 15.6 MPa and 42 °C

Abstract An innovative sampling method was developed that allowed crude oil hydrocarbons dissolved in the upper gas-rich phase to be collected and quantitatively measured while maintaining constant reservoir conditions of 15.6 MPa and 42 °C. Crude oil was allowed to come to equilibrium with the injected gas phase (ca. 1/1 vol ratio) prior to collecting the dissolved hydrocarbons via a heated flow restrictor and analyzing them using high-resolution gas chromatography. As solvents, the three fluids’ efficacy parallel their minimum miscibility pressures (MMPs) for the test crude oil. Methane (MMP = 28.1 MPa) was a very poor hydrocarbon solvent, and was only able to dissolve ca. 18 mg oil/g methane. In contrast, CO2 (MMP = 9.68 MPa) dissolved up to 133 mg oil/g CO2 and ethane (MMP = 5.27 MPa) dissolved 722 mg oil/g ethane. Sequential collections of the dissolved oil hydrocarbons in the gas-dominated phase showed progressively lower concentrations for ethane and CO2, which demonstrated that liquid/liquid partitioning (and not saturation solubility) between the gas-dominated and oil-dominated phases controls the amounts of dissolved hydrocarbons. Thus, the lower the ratio of injected ethane or CO2 to the bulk crude oil, the higher the dissolved hydrocarbon concentrations. Both methane and CO2 showed a bias against dissolving heavier hydrocarbons. Methane was only capable of dissolving the lightest hydrocarbons (up to about C12), while CO2 preferentially dissolved light and middle hydrocarbons (up to about C16), leaving a residual oil rich in higher molecular weight hydrocarbons with significantly higher viscosity and density (lower API gravity) than the original unexposed crude oil. In contrast, ethane was capable of efficiently dissolving the entire range of hydrocarbons, with only a small bias against the heavier hydrocarbons. These lab studies show that, at the constant reservoir pressure and temperature used, ethane is a far superior hydrocarbon solvent for crude oil hydrocarbons than CO2, while CO2 is far superior to methane. Thus, ethane may ultimately yield higher oil recovery efficiencies (used either instead of CO2 or after a CO2 flood), while reducing the deposition of paraffinic and other higher molecular weight hydrocarbons in the reservoir.
Edges of Exposure: Toxicology and the Problem of Capacity in Postcolonial Senegal: by Noémi Tousignant, Durham, NC, Duke University Press, 2018, 224 pp.

In this succinct and well-written book, Noemi Tousignant tackles the problem of toxic waste in Africa from the perspective of Senegalese toxicologists. Environmental and food contamination from tox...
Improving Ambulation and Minimizing Disability with Therapeutic Plasma Exchange in a Stiff-person Syndrome Patient with Recurrent Falls.

Stiff-person syndrome (SPS) is a rare, autoimmune, neuromuscular disorder that manifests with axial and proximal muscle stiffness, rigidity, and painful muscle spasms, often causing progressive disability due to limited movement. First-line therapies comprise symptomatic management with γ-aminobutyric acid-modulating drugs such as benzodiazepines and baclofen. Patients resistant to these treatments are often given intravenous immunoglobulin (IVIg). Severe disease refractory to first-line therapy and IVIg may be treated with therapeutic plasma exchange (TPE) or immunomodulatory agents such as rituximab. Current evidence derived from case reports and case series has shown that roughly half of SPS patients treated with TPE report benefits. Here, we report the case of a 68-year-old man with a 20-year history of severe SPS and recurrent falls who was admitted to the emergency department for a traumatic hip fracture. He had significant rigidity in the axial and extremity muscles with persistent spasms of the quadriceps femoris muscle. Postoperatively, he was unable to participate in physical therapy (PT) due to these symptoms. He previously failed treatment with diazepam, baclofen, and monthly IVIg. Under our care, he underwent seven TPE treatments. By the end of treatment, he reported significant improvement in mobility with a resolution of muscle spasms and was able to be discharged to inpatient rehabilitation. This suggests that TPE may offer an effective, safe treatment modality for patients with severe refractory SPS that may significantly improve mobility and disability associated with the disease.
Neuronal vulnerability to fetal hypoxia-reoxygenation injury and motor deficit development relies on regional brain tetrahydrobiopterin levels

Abstract Hypertonia is pathognomonic of cerebral palsy (CP), often caused by brain injury before birth. To understand the early driving events of hypertonia, we utilized magnetic resonance imaging (MRI) assessment of early critical brain injury in rabbit fetuses (79% term) that will predict hypertonia after birth following antenatal hypoxia-ischemia. We examined if individual variations in the tetrahydrobiopterin cofactor in the parts of the brain controlling motor function could indicate a role in specific damage to motor regions and disruption of circuit integration as an underlying mechanism for acquiring motor disorders, which has not been considered before. The rabbit model mimicked acute placental insufficiency and used uterine ischemia at a premature gestation. MRI during the time of hypoxia-ischemia was used to differentiate which individual fetal brains would become hypertonic. Four brain regions collected immediately after hypoxia-ischemia or 48 h later were analyzed in a blinded fashion. Age-matched sham-operated animals were used as controls. Changes in the reactive nitrogen species and gene expression of the tetrahydrobiopterin biosynthetic enzymes in brain regions were also studied. We found that a combination of low tetrahydrobiopterin content in the cortex, basal ganglia, cerebellum, and thalamus brain regions, but not a unique low threshold of tetrahydrobiopterin, contributed etiologically to hypertonia. The biggest contribution was from the thalamus. Evidence for increased reactive nitrogen species was found in the cortex. By 48 h, tetrahydrobiopterin and gene expression levels in the different parts of the brain were not different between MRI stratified hypertonia and non-hypertonia groups. Sepiapterin treatment given to pregnant dams immediately after hypoxia-ischemia ameliorated hypertonia and death. We conclude that a developmental tetrahydrobiopterin variation is necessary with fetal hypoxia-ischemia and is critical for disrupting normal motor circuits that develop into hypertonia. The possible mechanistic pathway involves reactive nitrogen species.
Misplaced from the start: Israel’s state identity and the search for regional acceptance

This paper considers the elements that constitute Israel’s state identity, from its deepest layers of corporate identity through the middle layer of identification processes between self and other,...
OssDsign cranioplasty in children: a single-centre experience.

OssDsign have developed a new type of cranioplasty plate, consisting of calcium phosphate reinforced with titanium. Currently, there is little known about the cosmetic outcomes and infection rate when OssDsign cranioplasty plates are implanted into paediatric patients. A retrospective case series was performed to include all paediatric patients who received an OssDsign cranioplasty at a single centre, Sheffield Children’s Hospital. The cosmetic outcomes were subjectively reported by the parents of the children. We identified seven paediatric patients where OssDsign cranioplasty was performed. This included two bifrontal and five hemicranioplasties. However, there was failure to implant an OssDsign hemicranioplasty in one patient where a titanium plate was subsequently used. The median duration of follow-up was 15 months. The infection rate was zero. The parents of the patients who successfully received OssDsign cranioplasties were pleased with the cosmetic outcomes. There were cosmetic complaints from the parents of the one patient who received a titanium plate. Our early experience with OssDsign cranioplasty in paediatric patients indicates that it may potentially be associated with a low rate of infection and good cosmetic outcomes.
Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.
DNA metabarcoding effectively quantifies diatom responses to nutrients in streams.

Nutrient pollution from human activities remains a common problem facing stream ecosystems. Identifying ecological responses to phosphorus and nitrogen can inform decisions affecting the protection and management of streams and their watersheds. Diatoms are particularly useful because they are a highly diverse group of unicellular algae found in nearly all aquatic environments and are sensitive responders to increased nutrient concentrations. Here, we used DNA metabarcoding of stream diatoms as an approach to quantifying effects of total phosphorus (TP) and total nitrogen (TN). Threshold indicator taxa analysis (TITAN) identified operational taxonomic units (OTUs) that increased or decreased along TP and TN gradients along with nutrient concentrations at which assemblages had substantial changes in the occurrences and relative abundances of OTUs. Boosted regression trees showed that relative abundances of gene sequence reads for OTUs identified by TITAN as low P, high P, low N, or high N diatoms had strong relationships with nutrient concentrations, which provided support for potentially using these groups of diatoms as metrics in monitoring programs. Gradient forest analysis provided complementary information by characterizing multi-taxa assemblage change using multiple predictors and results from random forest models for each OTU. Collectively, these analyses showed that notable changes in diatom assemblage structure and OTUs began around 20 µg TP/L, low P diatoms decreased substantially and community change points occurred from 75 to 150 µg/L, and high P diatoms became increasingly dominant from 150 to 300 µg/L. Diatoms also responded to TN with large decreases in low N diatoms occurring from 280 to 525 µg TN/L and a transition to dominance by high N diatoms from 525-850 µg/L. These diatom responses to TP and TN could be used to inform protection efforts (i.e., anti-degradation) and management goals (i.e., nutrient reduction) in streams and watersheds. Our results add to the growing support for using diatom metabarcoding in monitoring programs.
Direct Evidence of Photoinduced Charge Transport Mechanism in 2D Conductive Metal Organic Frameworks

Conductive metal organic frameworks (MOFs) represent a promising class of porous crystalline materials that have demonstrated potential in photo-electronics and photocatalytic applications. However, the lack of fundamental understanding on charge transport (CT) mechanism as well as the correlation of CT mechanism with their structure hampered their further development. Herein, we report the direct evidence of CT mechanism in 2D Cu-THQ MOFs and the correlation of temporal and spatial behaviors of charge carriers with their photoconductivity by combining three advanced spectroscopic methods, including time resolved optical and X-ray absorption spectroscopy and terahertz spectroscopy. In addition to Cu-THQ, the CT in Cu/Zn-THQ after incorporating Zn2+ guest metal was also examined to uncover the contribution of through space pathway, as the presence of the redox inactive 3d10 Zn2+ is expected to perturb the long range in-plane CT. We show that the hot carriers in Cu-THQ generated after photoexcitation are highly mobile and undergo fast localization to a lower energy state (cool carriers) with electrons occupying Cu center and holes in ligands. The cool carriers, which have super long lifetime (>17 ns), are responsible for the long-term photoconductivity in Cu-THQ and transport through the O-Cu-O motif with negligible contribution from interlayer ligand π-π stacking, as incorporation of Zn2+ in Cu-THQ significantly reduced photoconductivity. These unprecedented results not only demonstrate the capability to experimentally probe CT mechanism but also provide important insight in the rational design of 2D MOFs for photoelectronic and photocatalytic applications.
A real-time multiplex PCR assay for detection of the causative agents of rat bite fever, Streptobacillus moniliformis and zoonoticStreptobacillus species

Rat bite fever (RBF) caused by Streptobacillus moniliformis has been described as a diagnostic challenge. While it has a favorable prognosis with treatment, timely diagnosis is hindered by the lack of culture-free identification methods. Here we present a multiplex real-time PCR assay that detects the zoonotic Streptobacillus spp. as well as differentiate the primary causative agent of RBF, Streptobacillus moniliformis. The performance of this assay was evaluated using mock clinical specimens for blood, serum, and urine. Analytical sensitivity was determined to be 3-4 genome equivalents (GE)/µl for the zoonotic Streptobacillus spp. target, and 1-2 GE/µl for the S. moniliformis specific target. The assay correctly detected only the intended targets with no cross-reactivity identified. The pathogen was detected in all spiked matrices and not detected in the negative non-spiked specimens. This rapid diagnostic assay may permit quicker diagnosis of RBF patients.
RAPID DISSOLUTION OF ALLOPHANE AND KAOLINITE-HALLOYSITE AFTER DEHYDRATION

Differential dissolution in NaOH solution was investigated as a means of purification of clay. It was discovered that a large quantity of allophane and free alumina and silica were dissolved from clay preparations in 0.5 N NaOH solution by boiling for as little as 2.5 min, provided the ratio of clay weight to solution volume was kept less than 100 mg to 100 ml. Reprecipitation of dissolved silica occurred if a more prolonged digestion or higher sample to solution ratio was employed. Also, prolonged digestion in the NaOH solution (for 80 min) dissolved as much as 50 percent of kaolinite (Merck) and 25 percent of Wyoming montmorillonite, but only a small quantity of these crystalline minerals was dissolved during the 2.5 min digestion period. Subsequent dithionitecitrate-bicarbonate treatment removed the released iron. Marked improvement of x-ray diffraction patterns of the clays resulted. This rapid and selective dissolution of allophane and free oxides greatly improves the quantitative analysis of crystalline minerals by conventional methods. After dehydroxylation at 500°C, kaolinite and halloysite became amorphous and also dissolved by the same differential dissolution procedure. Heat-stable (aluminous) montmorillonite and chlorite were only slightly dissolved by this treatment. The selective removal of the 1: 1 layer aluminosilicates greatly improves the quantitative analysis of the remaining crystalline components of clays by conventional methods.
Abstract 16451: The Temporal Trend in the Utilization of Noninvasive Cardiac Test for Chest Pain Evaluation and Its Impact on Cardiac Catheterization Trends

Introduction: Noninvasive diagnostic testing serves as gatekeepers to invasive cardiac catheterization. Computed tomography coronary angiogram (CTCA) has been shown to have high sensitivity and neg...
Requirements of CAD Databases

There are generally three approaches to the task of giving a systematic presentation of the requirements of CAD databases. First, we may survey as wide a range as possible of individual implementations and uses of database control software, collect the features and functions that are proper to CAD, extract from them application independent elements and state them in more abstract terms. This is the inductive approach. Second, we may take the deductive approach in which the database requirements derive from a still more abstract and comprehensive conception of the world of design objects and processes. Such a premise must be given by a general theory of design. Since both approaches raise obvious difficulties, we will have to rely on the third one which may imprecisely but conveniently be called abductive. That is, we assume a firm though not quite comprehensive position concerning our universe of discourse, examine the requirements contained in a selection of concrete examples and proposals, and refine and extrapolate them in accordance with this position. To use a popular metaphor, it is like looking closely at sampled specimens through a magnifying glass and portraying a complete picture constituted of those directly observed as well as unobserved portions.
Natural Environment Training

Naturalistic behavioral approaches to intervention are designed for children with ASD and have a solid evidence base in the literature, earning an “established” evidence level from the National Research Council (2001), the National Autism Center (2009), and the National Professional Development Center on Autism Spectrum Disorders (2011). These treatments are effective for teaching language, play, and social skills in children, adolescents, and adults with ASD (Goldstein 2002; Matson et al. 1996; Schreibman and Anderson 2001). This chapter will provide an overview of the naturalistic behavioral approaches available for the treatment of children with ASD and will identify current and future directions in behavioral intervention research.
Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis delta-endotoxin.

Abstract Receptor binding studies were performed with 125I-labeled trypsin-activated insecticidal toxins, CryIA(a) and CryIA(c), from Bacillus thuringiensis on brush-border membrane vesicles (BBMV) prepared from Bombyx mori larval midgut. Bioassays were performed by gently force feeding B. mori with diluted toxins. CryIA(a) toxin (LD50; 0.002 micrograms) was 200 times more active against B. mori larvae than CryIA(c) toxin (LD50; 0.421 micrograms) and showed high-affinity saturable binding. The Kd and the binding site concentration for CryIA(a) toxin were 3.5 nM and 7.95 pmol/mg, respectively. CryIA(c) toxin (Kd, 50.35 nM; Bmax, 2.85 pmol/mg) did not demonstrate high-affinity binding to B. mori BBMV. Control experiments with CryIA(a) and CryIA(c) toxins revealed no binding to mouse small intestine BBMV and nonspecific binding to pig kidney BBMV. These data provide evidence that binding to a specific receptor on the membrane of midgut epithelial cells is an important determinant with respect to differences in insecticidal spectrum of insecticidal crystal proteins. To locate a B. mori receptor binding region on the CryIA(a) toxin, homologous and heterologous competition binding studies were performed with a set of mutant proteins which had previously been used to define the B. mori "specificity domain" on this toxin (Ge, A. Z., Shivarova, N. I., and Dean, D. H. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4037-4041). These mutant proteins have had regions of their genes reciprocally exchanged with the cryIA(c) gene. A B. mori receptor binding region on CryIA(a) toxin includes the amino-terminal portion of the hypervariable region, amino acids 332-450, which is identical to the previously described B. mori specificity determining region. These data provide direct evidence that delta-endotoxins contain a tract of amino acids that comprise a binding region and as a results determines the specificity of a toxin.
Cisplatin inhibits the activation of MMP2 in ovarian carcinoma cell lines by altering the relative extracellular levels of TIMP1 and TIMP2

3343 Objectives: Cancer cell invasion is one of the crucial events in local spreading, growth and metastasis of tumors and is mediated by Matrix Metallo-Proteinases such as MMP2. The present study investigates one of the mechanism underlying the anti-invasive action of cisplatin and its effect on the activation of MMP2 in ovarian carcinoma cells. Methods: SKOV-3 cells, ovarian cancer cell lines, were cultured in Dulbecco’s Modified Eagle’s Medium. Cells were treated in vitro with different concentrations of Cisplatin. The ability of SKOV3 chemotherapy-treated ovarian carcinoma cells to invade through Matrigel was assessed by plating SKOV3 cells atop culture inserts with PET membranes coated with Matrigel. After a 48-hour period of incubation at 37 o C, the number of cells invading through the membrane was counted. Migration of chemotherapy-treated SOKV3 cells was determined using a modified invasion assay where the ovarian carcinoma cells were applied atop uncoated cell culture inserts. To investigate the regulation of MMPs, TIMPs, MT1-MMP proteins, the SKOV3 cells were treated with Cisplatin. Following treatment, conditioned medium and cells were collected for immunoblotting and zymography. 30 μg of cell lysate total protein was run on 10% SDS-polyacrylamide gels. For analysis of conditioned media, conditioned media was concentrated and 10 μg of protein were electrophoresed on 12% SDS-polyacrylamide gels. After electrotransferring the proteins to PVDF membranes, the membranes were immunoblotted using specific primary antibodies against TIMP-1, TIMP-2 and MT1-MMP. The signals were then detected, visualized and quantified. For gel zymography, conditioned media was concentrated and 10 μg of protein were electrophoresed on 10% SDS-polyacrylamide gels containing 1 mg/ml of gelatin Type A. The gels were washed, incubated overnight at 37 o C, stained and finally destained. The obtained gels were analyzed and the signals quantified. The results were then compared using two-tailed paired t-tests. Results: SKOV3 cells showed a 10.6-fold reduction in cell invasion using 20 μg/mL of Cisplatin when compared to untreated controls (p=0.0006). Treatment with cisplatin resulted in a 6-fold reduction in the total amount of activated MMP2 present in the supernatant (p=0.0138). In vivo the activity and activation of MMP2 are principally regulated by TIMP2, TIMP1 in the supernatant as well as the membrane bound MT1-MMP. Treatment with cisplatin resulted in a 5.7-fold and 3.3-fold reduction in the amount of TIMP1 and TIMP2 present in the supernatant respectively (p=0.0372 and p=0.0172 respectively), the amount of MT1-MMP was however unaffected. Conclusions: This study provides evidence that treatment of SKOV3 ovarian cancer cells with cisplatin decreases the amount of activated MMP2 by profoundly affecting the levels of TIMP1 and TIMP2 thereby reducing their invasive potential.