cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5358: Comprehensive evaluation of Illumina’s TruSight® Tumor 170 Panel to estimate tumor mutational burden

Tumor mutational burden (TMB), or the density of variants in a tumor, is typically assessed by whole exome sequencing (WES) and has been shown to correlate with efficacy of immunotherapy treatment. Targeted cancer gene panels are broadly used to assess mutational status in cancer related genes but have not historically been used to estimate TMB. Recently, two studies have demonstrated that TMB can be accurately estimated using these cancer gene panelsi,ii. Illumina’s TruSight® Tumor 170 (TST170, research use only, RUO) panel is a comprehensive next-generation sequencing (NGS) assay that covers the coding regions of 170 genes associated with solid tumors. TST170 targets DNA and RNA variants from the same FFPE tumor sample in a single sequencing run. Here we evaluate the performance of TMB estimation with TST170. TST170 is an enrichment-based targeted panel designed to capture mutational changes, including single nucleotide variant, indels, amplifications, splice variants and fusions. The TST170 analysis pipeline is able to call variants with frequencies down to 5%. In the current study, TMB was calculated as the number of reported variants per megabase after germline polymorphism filtering. First, we evaluated the performance of TST170 for TMB estimation using 6,000 TCGA samples that had been analyzed by WES. TMB estimated from the TST170 targeted regions showed a high correlation to TMB estimated from WES (R2=0.91). Next, we evaluated the prognostic value of TMB estimated from TST170 by overlapping the TST170 targeted regions with WES data for 202 subjects treated with CTLA-4 or PD-1 from three clinical studies. Higher TMB estimated from the TST170 targeted regions was observed in subjects who responded to checkpoint inhibitors. Finally, we assessed the correlation of TMB estimation using matched samples profiled with both WES and TST170 and again saw high correlation between the two methods. In summary, our analysis indicates that the panel content of TST170 can be used to accurately estimate TMB from tumor samples. i Garofalo A, Sholl L, Reardon B, et al. The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine. Genome Med. 2016;8(1):79. doi:10.1186/s13073-016-0333-9. ii Campesato, L., Barroso-Sousa, R., Jimenez, L., et al. Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget, 2015;6(33), 34221-34227. Citation Format: Shile Zhang, Alex S. So, Shannon Kaplan, Kristina M. Kruglyak. Comprehensive evaluation of Illumina’s TruSight® Tumor 170 Panel to estimate tumor mutational burden [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 5358. doi:10.1158/1538-7445.AM2017-5358
Factors Associated With Medical School Graduates' Intention to Work With Underserved Populations: Policy Implications for Advancing Workforce Diversity.

PurposeGiven projected U.S. physician shortages across all specialties that will likely impact underserved areas disproportionately, the authors sought to explore factors most correlated with medical school graduates’ intention to work with underserved populations (IWUP).MethodData from the 2010–201
Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase

Influenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages - A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). These vectors were evaluated for immunogenicity and protective efficacy against H7N3 virus in a murine model of intranasal challenge. High levels of H7-, N3-, and N9-specific antibodies, including neutralizing antibodies, were induced by the MVA-HA and MVA-NA vectors. Mice vaccinated with MVA vectors expressing any of the H7 antigens were protected, suggesting cross-protection among H7 viruses. In addition, MVA vectors expressing N3 but not N9 elicited protection against H7N3 virus challenge. Similar outcomes were obtained when immune sera from MVA vector-immunized mice were passively transferred to naive mice prior to challenge with the H7N3 virus. The results support the further development of an MVA vector platform as a candidate vaccine for influenza strains with pandemic potential.
An efficient simulation-based approach to ambulance fleet allocation and dynamic redeployment

We present an efficient approach to ambulance fleet allocation and dynamic redeployment, where the goal is to position an entire fleet of ambulances to base locations to maximize the service level (or utility) of the Emergency Medical Services (EMS) system. We take a simulation-based approach, where the utility of an allocation is measured by directly simulating emergency requests. In both the static and dynamic settings, this modeling approach leads to an exponentially large action space (with respect to the number of ambulances). Futhermore, the utility of any particular allocation can only be measured via a seemingly "black box" simulator. Despite this complexity, we show that embedding our simulator within a simple and efficient greedy allocation algorithm produces good solutions. We derive data-driven performance guarantees which yield small optimality gap. Given its efficiency, we can repeatedly employ this approach in real-time for dynamic repositioning. We conduct simulation experiments based on real usage data of an EMS system from a large Asian city, and demonstrate significant improvement in the system's service levels using static allocations and redeployment policies discovered by our approach.
Ozone: an effective and scalable saturable absorber for KrF lasers

We report the first documentation of an effective scalable saturable absorber for KrF lasers. Our measurements show that a 4-cm path length of ozone (O3) at a partial pressure of 0.4 Torr will attenuate energy densities under 50 mJ/cm2 by a factor of ~50 while allowing transmission of 90% of fluences above 1 J/cm2.
A DSC Study of the Heat Capacity of Vicinal Water in Porous Materials

Vicinal water is belived to possess structures which differ notably from the bulk structure. if this is indeed true, then measureable differnces must be expected in the thermodynamic properties. Ling and Drost-Hansen (6) attempted a DTA study of water. in porous glass, and thd data obtainted were suggestive of diffrences in the properties of bulk water and water in narrow pores (range 20 nm to 200 nm). We have continued the study of thormodynamic propoties employing a DSC metgod utlizing different types of porous materials. The result to data have not provided firm additional evidence for the occurrences of thermal anomalies. However, the data do suggest that the heat capacity of water in porous glass, activated charcoal, a zeolite, and diamond powder is significantly larger than the value obtained for bulk water (measurd by the same technique). Assuming all the water present process a modified structure, the apparent heat capacity is at least 20% larger than that for bulk water; and, to a first approximation, Independent of the specific chemical nature of the solid material. This observation rules out the possibility that the anomalous values obtained in porous glass are due to some type of silicic acid formation. fourthermore, the substrate-independence agress qualitatively with the “para-doxial effect” observed for the temperature of vicinal water transitions [Drost-hansen, 3).
Protective ethnicity: how Armenian immigrants’ extracurricular youth organisations redistribute cultural capital to the second-generation in Los Angeles

ABSTRACTResearch shows the children of educationally-select immigrant groups benefit from a cultural advantage that allows them to realise higher educational outcomes than scholars would predict ba...
Further Results by the Weisner Method

We will now use the Weisner method to obtain generating functions for the modified Laguerre polynomials \( \left\{ {{{( - 1)}^{{n}}}\,L_n^{{ - \beta - n}}(x)} \right\}, \), the simple Bessel polynomials, and the Gegenbauer polynomials. Since the details of this method were given in Chapter II, we will discuss only briefly the procedure followed in obtaining generating functions for the sets of this chapter.
Variable, two-color acquisition beam for free-space laser communication terminals

This paper reports on a two-color acquisition beam with continuously variable divergence for free-space laser communication links. This approach is useful for terminals using wavelength-separated beacon and communi- cation signals amplified by a common high-power optical amplifier (HPOA). The acquisition beam features a controllable power-split ratio between the two waveforms that varies during the acquisition sequence. With this scheme, the area of the acquisition beam can be expanded by a factor of 100, while maintaining power levels of the two colors within a specified range on an acquisition sensor in a partner terminal. An optical transmitter produces beacon and communication waveforms from distinct master oscillators, and balances these signal levels during a multi-step transition sequence to achieve the desired relative power levels at each wavelength. An HPOA then boosts this transmitter signal to power levels necessary to overcome link losses. The HPOA and transmitter adjust power levels during the sequence to maintain beacon and communication irradiances within specified ranges. A divergence setting assembly (DSA) simultaneously adjusts the beam width from a 10x broadened beacon to a narrow, diffraction-limited beam. We demonstrate control of the on-axis beacon power to within a 10-dB dynamic range while the beacon area varies by a factor of approximately 20 dB. This paper describes the hardware and software control of the various units used to perform acquisition.
Investigation of tribological behavior of Styrene-Butadiene Rubber compound on asphalt-like surfaces

Abstract Tribological behavior of Styrene-Butadiene Rubber (SBR) compound reinforced by silica and carbon-black fillers on two different asphalt-like surfaces is studied using theoretical and experimental approaches. Linear sliding friction and wear tests were performed on two different roofing asphalt papers. The surface roughness power spectra of asphalts and the master curves of the large-strain viscoelastic modulus of SBR compound were used to model the contact area and friction coefficient theoretically. The theoretical results are in good agreement with experiment providing the tribochemical degradation is not the dominant wear mechanism. When the formation of a tribo-modified layer prevails the mechanical abrasion, the wear rate, in terms of mass loss, does not necessarily increase with the increase of frictional work as expected theoretically.
Optimization of Sonic Hedgehog Delivery to the Penis from Self-Assembling Nanofiber Hydrogels to Preserve Penile Morphology after Cavernous Nerve Injury.

Abstract Erectile dysfunction (ED) is a significant medical condition, with high impact on patient quality of life. Current treatments are minimally effective in prostatectomy, diabetic and aging patients due to injury to the cavernous nerve (CN); loss of innervation causes extensive smooth muscle (SM) apoptosis, increased collagen and ED. Sonic hedgehog (SHH) is a critical regulator of penile SM. We developed a self-assembling peptide amphiphile (PA) nanofiber hydrogel for extended release of SHH protein to the penis after CN injury, to suppress SM apoptosis. In this study we optimize the animal model, SHH concentration, duration of suppression, and location of delivery, to maximize SM preservation. SHH treatment suppressed apoptosis and preserved SM 48%. Increased SHH duration preserved SM 100%. Simultaneous penis/CN delivery increased SM 127%. Optimization of SHH PA delivery is essential for clinical translation to ED patients, and the PA vehicle has wide applicability as an in vivo delivery tool.
Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21days post-fracture, and examined bone quality and callus outcomes at 21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.
Federating the Raj: Hyderabad, sovereign kingship, and partition

This article explores the idea of federation in late-colonial India. Projects of federation sought to codify the uncodified and fragmented sovereign landscape of the British Raj. They were ambitious projects that raised crucial questions about sovereignty, kingship, territoriality, the potential of constitutional law in transforming the colonial state into a democratic one, and India's political future more broadly. In the years after 1919, federation became a capacious model for imagining a wide array of political futures. An all-India Indian federation was seen as the most plausible means of maintaining India's unity, introducing representative government, and overcoming the Hindu–Muslim majority–minority problem. By bringing together ‘princely’ India and British India, federation made the Indian states central players in late-colonial contestations over sovereignty. This article explores the role of the states in constitutional debates, their place in Indian political imaginaries, and articulations of kingship in late-colonial India. It does so through the example of Hyderabad, the premier princely state, whose ruler made an unsuccessful bid for independence between 1947 and 1948. Hyderabad occupied a curious position in competing visions of India's future. Ultimately, the princely states were a decisive factor in the failure of federation and the turn to partition as a means of overcoming India's constitutional impasse.
Correction to: Using Optogenetics to Dissect the Neural Circuits Underlying OCD and Related Disorders

The article Using Optogenetics to Dissect the Neural Circuits Underlying OCD and Related Disorders, written by Sean C. Piantadosi and Susanne E. Ahmari, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 15 July 2015 without open access.
Thermodynamic consistency of a pseudopotential lattice Boltzmann fluid with interface curvature

Thermodynamic consistency of pseudopotential lattice Boltzmann models is a major topic that needs comprehensive evaluations. When interface is flat, pseudopotential models can give density-pressure isotherms in excellent agreement with those from equation of state. When interface is curved, thermodynamic equilibriums are affected by interface curvature, and consistency of pseudopotential models has not been systematically evaluated. In this study, we show that the effect of Laplace pressure on phase equilibrium is quantitatively consistent with Kelvin equation at high reduced temperatures (≥0.7). At low temperatures, inconsistency that can be attributed to the effect of orientation of the interface was noted, and it can be improved by tuning of the pseudopotential. By relating interfacial tension of a simulated fluid to that of a real fluid, the lattice spacing of pseudopotential model is found to be on the order of several molecular diameters, the typical range of intermolecular interactions. Interfacial thickness at different temperatures in pseudopotential model compared well with experiments and molecular dynamics simulations, which confirms that the calculated length scale is reasonable. Evaluation of a free energy lattice Boltzmann model indicate that it is consistent with Kelvin equation at high temperatures. The free energy model, however, is not as accurate as the tested pseudopotential model, and discrepancies may come from the relative inaccuracies in the predictions of vapor densities and the thinner interfaces.
New coronavirus outbreak: Framing questions for pandemic prevention.

We need to understand and quantify the dominant variables that govern the SARS–CoV-2 outbreak, rather than relying exclusively on confirmed cases and their geospatial spread.
Conclusion: The Search for Stability

In this chapter, Ilunga argues that the search for stability and peace remains central to the political environment within the DRC. Despite some positive economic progress observed in the region and in the country, the future of the region is still characterized by its fragility and the potential for a relapse into violent conflict due to many unaddressed situations, including the multidimensional manifestations of humanitarian crises. Moreover, the DRC’s humanitarian crises have yet to be effectively addressed as consequences and promoters of insecurity and violence. To the question of what to do with this crisis in the DRC and the broader Central African region, the author contends that stability and recovery are contingent on the use of innovative approaches to humanitarian and security issues, based on the use of the humanitarian-security-development paradigm as an inclusive operational framework.
A Phenomenological Study: The Experience of Live Supervision during a Pre-practicum Counseling Techniques Course

The experiences of live supervision for three, master’s level, prepracticum counseling students were explored using a phenomenological methodology. Using semi-structured interviews, this study resulted in a thick description of the experience of live supervision capturing participants’ thoughts, emotions, and behaviors. Data revealed that live supervision during pre-practicum is a multifaceted experience comprised of numerous roles that not only contribute to counselor skill development, but counselor identity development. Participants’ stories reflected the benefit and impact that live supervision provides in the educational context. Keywords: Phenomenological Research, Live Supervision, Prepracticum, Counseling Students A primary task when obtaining a master’s degree in counselor education is learning the basic skills of counseling; yet, research is lacking that could potentially
Ultralow-Noise Room-Temperature Quantum Memory for Polarization Qubits

Implementing noise-free quantum devices at room temperature is the key to bring quantum technology from the laboratory to the public. So far this has been impossible, due to the inherent noise in thermal systems. The authors superpose spin waves by mapping photonic polarization qubits onto collective excitations of rubidium atoms. By manipulating the resultant quantum coherence, they obtain a room-temperature high-fidelity quantum memory. Such devices could have great impact as quantum repeaters, the cornerstones of elementary quantum networks.
Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect. Patients and Methods Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area. Results Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8+ T cells and CD163+ macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, p < 0.001) and in LN (slope = 0.62, p < 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE. Conclusion Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
Predictors of Mental Health Diagnoses Among Youth in Psychiatric Residential Care: A Retrospective Case Record Analysis

In this study the relation between familial risk factors and maltreatment types and mental health diagnoses among youth in residential care were examined. Using data from a larger study, six separate hierarchical logistic regression models were specified using family risk factors and maltreatment type to predict risk for attention deficit hyperactivity disorder (ADHD), conduct disorder, generalized anxiety disorder, post-traumatic stress disorder (PTSD), reactive attachment disorder, and major depressive disorder. The results show that, for this population, demographic characteristics are more predictive of diagnoses compared to family risk factors and maltreatment. Specifically, age and gender significantly predicted four out of the six diagnoses. Maltreatment types were associated with two diagnoses, ADHD and PTSD. Findings from this study suggest residential treatment programs should include person-centered treatment plans considering demographics and maltreatment experiences.
Phantom Phenomena—An Introduction to “Phantom Penis: Extrapolating Neuroscience and Employing Imagination for Trans Male Sexual Embodiment”

This paper provides an introduction to the phenomena of phantom sensations. We recall the events that first led us to survey transsexual men about phantom penises and review some of our recent work...
In 2 O 3 -Ga 2 O 3 Alloys as Potential Buffer Layers in Cd Te Thin-Film Solar Cells

The efficiency of state-of-the-art $\mathrm{Cd}\mathrm{Te}$ solar cells remains limited by the relatively low open-circuit voltage (${V}_{OC}$). Improving the front interface is key towards realizing a higher ${V}_{OC}$ after achieving the necessary bulk carrier density and lifetime. Recent efforts in identifying buffer layers beyond $\mathrm{Cd}\mathrm{S}$ have focused on ${\mathrm{Mg}}_{x}{\mathrm{Zn}}_{1\ensuremath{-}x}\mathrm{O}$, which offers tunability of the band offsets, but often suffers from high interfacial defect densities. ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$-based buffer layers demonstrate tremendous improvements in interfacial defect passivation in crystalline silicon and dye-sensitized solar cells, leading to record high ${V}_{OC}$, yet remain largely unexplored in $\mathrm{Cd}\mathrm{Te}$-based devices. Here, we perform hybrid density-functional-theory calculations to investigate pure ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ and ${\mathrm{In}\mathrm{Ga}\mathrm{O}}_{3}$ alloys as a window layer in $\mathrm{Cd}\mathrm{Te}$ photovoltaics. We report calculated band offsets for several pairs of solid-solid interfaces comprising transparent conducting oxide (TCO) and $\mathrm{Cd}\mathrm{Te}$ heterojunctions. The results support a large conduction band offset spike of 0.67 eV for the $\mathrm{Cd}\mathrm{Te}/{\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ (100) interface, while the offset is reduced to 0.18 eV for the ${\mathrm{In}\mathrm{Ga}\mathrm{O}}_{3}$ alloy and matches closely with the preferred optimum value of 0.2 eV. Device-level modeling tests of $\mathrm{Cd}\mathrm{Te}$ solar cells integrating our results indicate that the highest efficiency is achieved with ${\mathrm{In}\mathrm{Ga}\mathrm{O}}_{3}$ acting both as a buffer layer and TCO. Our results suggest that alloys of ${\mathrm{In}}_{2}{\mathrm{O}}_{3}$ and ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ may be attractive alternatives to ${\mathrm{Mg}}_{x}{\mathrm{Zn}}_{1\ensuremath{-}x}\mathrm{O}$ for tailoring optimal conduction-band offsets of the buffer and TCO layers in high-efficiency $\mathrm{Cd}\mathrm{Te}$ thin-film solar cells.
Closing the Wearable Gap–Part IX: Validation of an Improved Ankle Motion Capture Wearable

Soft robotic sensors, a class of pliable, embeddable sensors, are well-suited for applications in wearable technology because of their ease of integration with common clothing articles. The suitability of soft robotic sensors for estimation of human joint angles has been proven; this research represents another step towards development of a reliable laboratory data collection platform for the human ankle joint complex. In this research, the accuracy and repeatability of a newly-developed wearable prototype are evaluated as a potential replacement for camera-based motion capture by measuring differences between simultaneously collected motion capture and stretch sensor data. The accuracy of these measurements is compared to measurements collected using a previous prototype for validation. Results show that the newly-developed prototype is capable of joint angle estimation within 1.86° mean-absolute-error during complex, dynamic movements and that wearing shoes over the sock prototype does not significantly degrade performance.
A Retrospective Analysis of Rituximab Treatment for B Cell Depletion in Different Pediatric Indications

Background: Rituximab (RTX) is used in cancer therapy as well as in the treatment of autoimmune diseases and alloimmune responses after transplantation. It depletes the disease-causing B cells by binding to the CD (cluster of differentiation) 20 antigen. We evaluate different pediatric treatment protocols (via fixed treatment schedule, B cell- or symptom-controlled) and their therapeutic effects. Methods: Demographic information, clinical and laboratory characteristics, and special laboratory values such as immunoglobulin G (IgG), CD19 positive B cells and Epstein-Barr viral load were retrospectively analysed in children treated with RTX between 2008 and 2016. Results: Seventy-six patients aged 1 to 19 (median 13) years were treated with 259 RTX infusions. The spectrum of diseases was very heterogeneous. RTX led to a complete depletion of the B cells. The reconstitution time varied between patients and was dependent on the application schedule (median 11.8 months). Fourteen out of 27 (52%) patients developed hypogamma¬globulinaemia. The risk of IgG deficiency was 2.6 times higher in children under 4 years of age than in olderones. In the last group IgG deficiency developed in only 38% of the cases (n=8). Recurrent and severe infections were observed each in 11/72 (15%) patients. Treatment-related reactions occurred in 24/76 (32%) cases; however, treatment had to be discontinued in only 1 case. In 16/25 (76%), the Epstein-Barr viral load dropped below the detection limit after the first RTX infusion. Conclusion: RTX is an effective and well-tolerated drug for the treatment of oncological diseases as well as autoimmune and alloimmune conditions in children. B cell depletion and reconstitution varies both intra- und interindividually, suggesting that symptom-oriented and B cell-controlled therapy may be favorable. Treatment-related reactions, IgG deficiency and infections must be taken into account.
USE OF HYDRODYNAMIC SHEAR STRESS TO ANALYZE CELL ADHESION

Cell adhesion is central to understanding how cells interact and coordinate their behavior in multicellular organisms. It needs to be carefully regulated in development, homeostasis, and response to wounding and invasion. It is mediated by the specific binding of adhesion receptors to ligands expressed on the surface of adjacent cells or in the surrounding extracellular matrix. Because of the technical barriers to the analysis of adhesion receptor binding in the cell substrate contact zone, most of our data on the binding reaction and its control are based on the use of soluble systems. The objective of this chapter is to describe the progress made in bridging this technical gap using hydrodynamic shear stress methods. Methods are described in which the force developed by hydrodynamic shear is directly proportional to the number of adhesion receptor–ligand bonds that mediate the adhesion. The relationship can be used to provide a measure of the relative number of adhesive bonds and, if driven toward saturation, can be used to measure the effective KD of adhesion receptor–ligand binding in the cell contact zone. This is the parameter that determines the proportion of receptors that are bound. The number of bound receptors determines both the adhesion strength and the strength of adhesion-mediated signals. Issues of bond strength, mechanisms of adhesion control, mechanisms of cell detachment under fluid shear stress, and cytoskeletal mechanics are considered in the adhesion context. This provides a model system in which to expand analysis of adhesion receptor binding in cell adhesion.
Juxtaductal aortic coarctation. Analysis of 84 patients studied hemodynamically, angiographically, and morphologically after age 1 year.

Although many studies of juxtaductal coarctation of the aorta have been reported, none has correlated clinical, hemodynamic, angiographic, anatomic, and operative findings. Of 84 patients (62 male and 22 female; age range, 1 to 49 years [mean 17]), all had murmurs; 76 had absent, diminished, or delayed femoral pulsations; 50 had cuff systolic blood pressures in the arm >140 mm Hg, and 30 had diastolic pressures >90 mm Hg. The average pressure gradients (mm Hg) by direct measurements above and below the coarctation in 35 patients were peak systolic, 45; mean, 17; and diastolic, 5. Rib notching, visible in chest roentgenograms in 43 patients, correlated directly with age and inversely with the diameter of the coarctation. Moderate or marked cardiomegaly by radiograph was present in only 1 of 48 patients with isolated coarctation and in 17 of 36 with associated cardiovascular malformations. Electrocardiograms were abnormal in more than two thirds of patients with associated anomalies, but were normal in more than three fourths of those with isolated coarctation. In 70 excised, serially sectioned coarctations the aortic lumens were completely occluded in 4 patients, up to 0.5 mm in internal diameter in 22 patients, from 0.6 to 2 mm in 26 patients, from 2.1 to 5 mm in 14, and >5 mm in 4, and correlated directly with lumens measured angiographically. The most significant anatomic factor causing the coarctation was invagination of the media from the posterior aortic wall, but intimal proliferation (jet lesion) at and immediately distal to the invagination contributed to the narrowing. Three (each with associated anomalies) of 70 patients died early after coarctation repair. Systolic or diastolic blood pressures decreased early postoperatively in 58 (87%) of 67 surviving patients, and both pressures decreased in 42 (63%). Late postoperatively (mean follow-up, 4.7 years), the systolic blood pressure remained elevated in 25% of patients.
Interaction of bacterial luciferase with aldehyde substrates and inhibitors.

Bacterial luciferase catalyzes the reaction of FMNH2, O2, and an aliphatic aldehyde to yield the carboxylic acid, FMN, water and blue-green light. The kinetics of the bacterial luciferase reaction were measured by stopped-flow spectrophotometry at pH 7 and 25 degrees C for the series of aldehydes from n-heptanal to n-undecanal. The rate of formation of the 4a-hydroperoxyflavin intermediate was dependent on the aldehyde concentration when mixtures of enzyme, FMNH2, and aldehyde were rapidly mixed with O2. At saturating aldehyde, the rate of formation of this intermediate was 100-fold slower than in the absence of aldehyde, demonstrating that an enzyme. FMNH2.aldehyde complex can be formed. Numerical simulation of the time courses for these experiments supported the formation of this intermediate and its direct reaction with O2. The kinetics of the light emitting reaction were dependent upon the chain length of the aldehyde substrate. Although the initial light intensity and the light emission decay rate were different for each aldehyde, the quantum yield for the reaction was independent of the aldehyde used. Luciferase was inhibited by high levels of the aldehyde substrate when the enzyme was assayed by mixing FMNH2 with an aerobic mixture of enzyme and aldehyde. The extent of inhibition was dependent on the particular aldehyde used, and the binding affinity of the aldehyde for the free enzyme increased in parallel with the aldehyde chain length. The kinetics of the formation and decay of the various intermediates were also studied in the presence of n-alkyladehyde analogs. These compounds decreased the rate of formation of the 4a-hydroperoxyflavin intermediate in much the same way as the aldehyde substrate, presumably by the formation of the enzyme. FMNH2.analog ternary complex.
Muscle Stem Cells: Their Discovery, Properties, and In‐Vitro Manipulation

Skeletal muscle is a sophisticated, hierarchically bundled tissue that is responsible for contracting to produce force within the body. Such muscle possesses a remarkable capacity to regenerate throughout adult life – an ability that is attributable to the contribution of muscle stem cells. Although satellite cells represent the primary, physiological muscle stem cell, other cell types exist that can contribute to myogenesis under varying circumstances. The cell fate decisions of satellite cells are influenced by multiple levels of regulation in vivo, and in-vitro culture systems have only just begun to scratch the surface of employing various soluble, physical, and substrate factors to mimic the physiological microenvironment and augment muscle stem cell proliferation in culture. Keywords: Stem cell; Myogenesis; Quiescence; Satellite cell; Myoblast; Myotube; Myofiber; Myonuclei; Microenvironment
A Causal Modeling Framework for Generating Clinical Practice Guidelines from Data

The practice of medicine is becoming increasingly evidence-based and clinical practice guidelines (CPGs) are necessary for advancing evidence-based medicine (EBM). We hypothesize that machine learning methods can play an important role in learning CPGs automatically from data . Automatically induced CPGs can then be used for further manual refinement and deployment, for automated guideline compliance checking, for better understanding of disease processes, and for improved physician education. We discuss why learning CPGs is a special form of computational causal discovery and why simply predictive (i.e., non-causal) methods may not be appropriate for this task.
Experimental and theoretical study of K2SeO4 at low temperature and high pressure

Abstract Raman scattering measurements have been performed on K2SeO4 crystals at 103 K up to pressures of 2.2 GPa, covering the Pnam and incommensurate phases. A recent first principles theory based on quantum chemistry calculations and the Gordon-Kim model has been used to calculate the effects of pressure on the K2SeO4 in the Pnam phase. Lattice dynamical calculations have been performed to determine the zone-center vibrational frequencies. The agreement between experiment and theory is very good.
Synthesis, Crystal Structures, and DFT Calculations of Three New Cyano(phenylsulfonyl)indoles and a Key Synthetic Precursor Compound

Three cyano-1-(phenylsulfonyl)indole derivatives, 3-cyano-1-(phenylsulfonyl) indole, (I), 2-cyano-1-(phenylsulfonyl)indole, (II), and 2,3-dicyano-1-(phenylsulfonyl) indole, (III), and a key synthetic precursor 1-(phenylsulfonyl)-1-(1,1-dimethylethyl) indole-3-carboxamide, (IV), have been synthesized and their structures determined by single crystal X-ray crystallography. (I), C15H10N2O2S, is orthorhombic with space group P 212121 and cell constants: a = 4.9459(3) A, b = 10.5401(7) A, c = 25.0813(14) A, V = 1307.50(14) A3 and Z = 4. (II), C15H10N2O2S, is monoclinic with space group C 2/c and cell constants: a = 18.062(2) A, b = 11.293(2) A, c = 15.922(3) A, α = 90°, β = 124.49(2)°, g = 90°, V = 2676.7 A3 and Z = 8. (III), C16H9N3O2S, is triclinic with space group P-1 and cell constants: a = 8.1986(8) A, b = 9.6381(11) A, c = 9.8113(5) A, α = 95.053(6)°, β = 101.441(6)°, g = 108.071(9)°, V = 713.02(11) A3 and Z = 2. (IV), C19H20N2O3S, is orthorhombic with space group P ccn and cell constants: a = 13.7605(8) A, b = 27.3177(14) A, c = 9.7584(6) A, α = 90°, β = 90°, g =90°, V = 3668.2(4) A3 and Z = 8. All four compounds have the same indole nitrogen phenylsulfonyl substituent and (I), (II), and (III) are nitrile derivatives. (IV) is a tert-butylamide. In the crystals, the dihedral angle between the mean planes of the indole and phenylsulfonyl groups are 85.4(2)° (I), 87.2(7)° (II), 75.1(7)° (III), and 88.6(2)° (IV), respectively. Additionally, DFT geometry-optimized molecular orbital calculations were performed and frontier molecular orbitals of each compound are displayed. Correlation between the calculated molecular orbital energies (eV) for the surfaces of the frontier molecular orbitals to the electronic excitation transitions from the absorption spectra of each compound has been proposed.
Studies of pseudo-binary laves-phase systems containing lanthanides: I. Constitution and magnetic properties of the GdAl2-GdFe2, GdAl2-GdCo2 and ErCo2-ErAl2 systems☆

Abstract Crystallographic and magnetic characteristics (susceptibilities and saturation magnetization at 4.2°K) are presented for the pseudo-binary systems GdAl2-GdFe2, GdAl2-GdCo2 and ErAl2-ErCo2. A C14 structure is observed at compositions GdFeAl, GdCoAl and ErCoAl. The composition range over which this structure and the two C15 terminal phases exist was determined. The structure change produced when Co or Fe is replaced by Al is ascribed to Brillouin Zone filling effects such as have been observed with the prototype Laves phases. The phase boundary for the terminal phase based on GdFe2, GdCo2 or ErCo2 corresponds to near filling of the second Brillouin Zone for the C15 structure, i.e. contact of the Fermi Surface with the 220 faces. The evidence supports the concept of electron transfer from Gd, Er or Al to Fe or Co. The transfer occurs to the extent that Fe and Co are apparently non-magnetic in alloys containing more than 36 and 90 mole % GdAl2 in GdCo2 and GdFe2. respectively.
HIV/AIDS Caregiving

Abstract HIV/AIDS continues to be a serious public health issue. As HIV changes from an acute disease to a more chronic illness, it places increased responsibility on family caregivers to provide on-going assistance. Based on a conceptual model of caregiving resilience, this study found high variation in caregiving outcomes with many caregivers demonstrating high levels of well-being despite adverse life circumstances. Factors that contributed significantly to caregiver well-being included income, caregiver health, discrimination, multiple loss, dispositional optimism and self-empowerment. These findings suggest that HIV/AIDS and caregiving entail more than stress and distress and that future research needs to consider caregiving within the context of a historically disadvantaged community, resilience of informal caregivers, and risk and protective factors at the personal, cultural and community levels. Such information is necessary to design community-based interventions to support informal caregivers an...
Influence of growth medium on adsorption of Streptococcus mutans, Actinomyces viscosus, and Actinomyces naeslundii to saliva-treated hydroxyapatite surfaces.

The influence of the growth medium on the ability of strains of Streptococcus mutans, Actinomyces viscosus and A. naeslundii to attach to saliva-treated hydroxyapatite (S-HA) surfaces was studied. Preliminary experiments indicated that cells of each species harvested in lag, log, and early stationary phases of growth adsorbed comparably to S-HA; thus, early stationary phase cells were used in all subsequent assays. Strains were grown in chemically defined medium (CDM), in CDM supplemented with gastric mucin or with filter-sterilized or 60Co-irradiated saliva from human donors of blood types A, B, or O, and in Trypticase soy broth (BBL Microbiology Systems) and Todd-Hewitt broth. Adherence of S. mutans H12 to S-HA tended to vary when the streptococci were grown in saliva-supplemented CDM, but the number of cells which attached was generally within twofold of that of CDM-grown cells. Attachment of A. viscosus S2 and LY7 and of A. naeslundii S4 and L13 was generally similar when grown in CDM or in CDM supplemented with saliva, but it tended to increase for organisms grown in CDM supplemented with gastric mucin. None of the strains studied appeared to destroy the blood group reactivity of the added salivary components, and they attached equally well to HA treated with homologous or heterogous saliva from that present in the medium in which they were grown. The A. viscosus strains adsorbed in 25 to 40% higher numbers to HA treated with blood type B saliva than with type A saliva, irrespective of the medium used for growth. S. mutans H12 cells displayed α- and β-glucosidase and α-galactosidase activity; the Actinomyces strains exhibited these activities plus β-galactosidase when grown in all media. However, the levels of these glycoside hydrolases did not correlate with cell adsorption to S-HA. The apparent weak influence of the growth medium on attachment of S. mutans was studied further. Strains of S. mutans isolated from the saliva of five human donors were made resistant to streptomycin, grown in CDM, and then added to new saliva samples from the respective donors from which they were obtained. The in vitro-grown cells were found to attach to S-HA comparably to S. mutans cells present naturally in the saliva.
Attitude study of parents of mentally retarded children. II. Initial reactions and concerns of parents to a diagnosis of mental retardation.

Initial reactions and concerns of parents to a diagnosis of mental retardation in their child are recorded in 67 families. The cause of the retardation and rejection of the child were the two chief areas of subjective concern. Other reactions were rejection of the diagnosis and solicitude for other medical problems of the child. Even after complete diagnostic study, rejection of the diagnosis of retardation occurred in one third of these families. Our data suggest that initial counseling of parents of retarded children should be centered primarily on a discussion of diagnosis, etiology, and immediate problems. Subsequent counseling should be directed toward the problems of future care. The importance of sympathetic follow-up care by the physician is emphasized.
The Concept of Bundling: When the Package Contains More than Its Parts

In the marketing discipline, “bundling” has been defined as the sale of two or more separate products in one package. This article examines bundling from an in-depth perspective discussing various characteristics of the concept inclusive of bundle forms and content. Taking a promotional perspective, the most impactful way to motivate the purchase of a bundle is revealed with a theoretical basis in mental accounting and prospect theory. The article concludes with suggestions for areas that are ripe for further research in the area of bundling. Keywords: Bundle; prospect theory; mental accounting; attribution; mixed bundle; BOGO; disconfirmation
Lorentz invariance violation and the observed spectrum of ultrahigh energy cosmic rays

Abstract There has been much interest in possible violations of Lorentz invariance, particularly motivated by quantum gravity theories. It has been suggested that a small amount of Lorentz invariance violation (LIV) could turn off photomeson interactions of ultrahigh energy cosmic rays (UHECRs) with photons of the cosmic background radiation and thereby eliminate the resulting sharp steepening in the spectrum of the highest energy CRs predicted by Greisen Zatsepin and Kuzmin (GZK). Recent measurements of the UHECR spectrum reported by the HiRes and Auger collaborations, however, indicate the presence of the GZK effect. We present the results of a detailed calculation of the modification of the UHECR spectrum caused by LIV using the formalism of Coleman and Glashow. We then compare these results with the experimental UHECR data from Auger and HiRes. Based on these data, we find a best-fit amount of LIV of 4.5 - 4.5 + 1.5 × 10 - 23 , consistent with an upper limit of 6 × 10 - 23 . This possible amount of LIV can lead to a recovery of the cosmic ray spectrum at higher energies than presently observed. Such an LIV recovery effect can be tested observationally using future detectors.
A Conceptual Model for Nurses’ Decision-making with the Aggressive Psychiatric Patient

Violence in the acute care psychiatric setting is an ongoing serious problem. Maintenance of a safe therapeutic environment is a paramount responsibility of nurses practicing in this area. Ethical and legal standards demand that the nurse intervenes in aggressive situations in a manner that employs the least intrusive and restrictive measures necessary to provide safety. Therefore, accurate and effective decision-making in aggressive situations, which can escalate rapidly, is of great importance. This paper discusses a theoretical model for decision-making in selecting interventions with aggressive psychiatric patients. This model may provide a basis for the development of training and education programs for effective decision-making in this area.