cssi/SciSciGPT-SciSciNet huggingface dataset:
Strategies To Identify Effective Treatments For Proteasome Inhibitor Resistant Multiple Myeloma

Despite the introduction of effective new agents in the treatment of myeloma, the disease is still mostly incurable. Among the most significant issues is the heterogeneity of the disease, with accumulation of multiple genetic abnormalities among patients, resulting in disease refractory to some highly active agents, or the emergence of resistance leading to aggressive relapse. We have focused efforts on modeling drug sensitivity, and generating both genetic and biomarker signatures of response and resistance to the proteasome inhibitors (PIs): bortezomib (Btz), MLN2238 (Takeda) and carfilzomob (Onyx). Using mouse and human myeloma cell lines we dose escalated with bortezomib and selected bortezomib-resistant (Btz-R) lines (that showed cross resistance to MLN2238 and carfilzomib). We previously reported the identification of gene expression signatures that distinguish sensitivity or resistance to bortezomib (Stessman, et al., Mol Cancer Ther 12:1140, 2013). We then took three approaches to identify effective strategies to treat bortezomib resistance: 1) The connectivity map (CMAP) data base contains treatment induced transcriptional signatures from over 1300 bioactive compounds in human cancer cell lines. We queried our Btz-R expression profiles against the CMAP data base and developed a correlation analysis to identify potential drugs that would be predicted to show toxicity to Btz-R lines. We identified HDAC-inhibitor and topoisomerase-inhibitor sensitivity profiles that were able to predict Btz-R tumor responsiveness to these drugs in vitro . 2) We found that Btz-R was associated with loss of PC maturation markers (CD69, CD93, BLIMP, CXCR4, spliced XBP-1), and were able to re-sensitize Btz-R cells to Btz sensitivity by inducing PC maturation. The correlation of expression markers we identified stratified survival outcomes in bortezomib containing clinical trials; thus demonstrating the markers we identified in the in vitro modeling are relevant to patient outcomes. 3) Finally, we designed a cell-based high throughput drug screening approach that led to the identification of several chemical structures with selective activity against Btz-R cells. Topoisomerase-inhibitors were among the top hits, a finding that independently supported our CMAP screening results. We also identified a more novel chemical lead (Velcade Re-sensitizing Compound 2; VRC-2) that showed modest but significant selectivity for Btz-R cells as a single agent, and most notably, exhibited potent Btz re-sensitizing activity when the 2 drugs were combined. The Btz re-sensitizing activity of VRC-2 was confirmed using multiple human and mouse Btz-R cell lines. The initial successes of the in vitro approaches that will be presented demonstrate the value of profiling resistant tumors as a means to identify secondary therapies, and demonstrate there are powerful screening approaches that can be used to effectively treat or reverse drug resistance. Disclosures: Van Ness: Millenium Pharnaceutical: Honoraria, Research Funding; Onyx Pharmaceutical: Research Funding.
United States food and drug administration product label changes

Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.
Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors.

Purpose The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)–induced angioedema is reviewed. Summary Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial ([NCT01919801][1]) will better define the role of icatibant in the management of ACEI-induced angioedema. Conclusion FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01919801&atom=%2Fajhp%2F73%2F12%2F873.atom
Isotretinoin: controversies, facts, and recommendations

Since it was introduced to the market by Hoffman-La Roche (Roche) in 1982, isotretinoin has remained the most effective treatment for severe and recalcitrant acne. However, it has also been surrounded by controversy due to its teratogenicity and inconsistent associations with depression, suicidality, inflammatory bowel disease, increases in lipid levels, and elevated transaminases. Areas covered: In this article, we reviewed data regarding safety of isotretinoin and its association with these conditions. A thorough and comprehensive search on the topics was performed using pubmed and google scholar. Expert commentary: Despite common misperceptions, there is weak evidence for increased incidence of depression, suicidality, or inflammatory bowel disease with isotretinoin use. Furthermore, data indicates that transient increases in transaminases and lipid levels do not typically necessitate discontinuation of therapy. We hope to provide clinicians with information necessary to have meaningful discussions with patients regarding the safety and efficacy of isotretinoin.
What is Transnational Education

Many universities in industrialized countries maintain branch campuses overseas, and have students who are learning (face-to-face, blended, e-learning) in countries that are different from the country of the academic institution. This approach of internationalization in postsecondary education is referred to as transnational education (Allport, 2002; Goodfellow, Lea, Gonzalez, & Mason, 2001).
TAK1 Regulates the Nrf2 Antioxidant System Through Modulating p62/SQSTM1.

Abstract Aims: Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is the master transcriptional regulator of antioxidant gene expression. On increased oxidative stress, an adaptor for Nrf2 degradation, Kelch-like ECH-associated protein 1 (Keap1), is directly modulated by oxidants in the cytoplasm, which results in stabilization and activation of Nrf2. Nrf2 is also constitutively active, to some extent, in the absence of exogenous oxidative stress. We have previously demonstrated that intestinal epithelium-specific TGF-β-activated kinase 1 (TAK1) deletion downregulates the level of Nrf2 protein, resulting in an increase of reactive oxygen species (ROS) in a mouse model. We aim at determining the mechanism by which TAK1 modulates the level of Nrf2. Results: We found that TAK1 upregulated serine 351 phosphorylation of an autophagic adaptor protein, p62/Sequestosome-1 (SQSTM1), which facilitates interaction between p62/SQSTM1 and Keap1 and subsequent Keap1 degradation. This, ultimately, causes increas...
Effects of grip span in one-handed thumb interaction with a smartphone: Beyond the thumb’s length limitation

The purpose of this study was to investigate whether different grip spans affected the touch performance of one-handed thumb interaction with a smartphone. Tapping time, hit count, and thumb-tip displacement were measured while using three mock-ups of an iPhone 5S, 6, and 6 Plus, respectively. In the tapping task, four positions were tested: top-left, top-right, bottom-left, and bottom-right. The results showed that the hit count (F2,14=8.596, p=.004) and thumb-tip displacement (F2,14=11.348, p=.001) significantly decreased as the grip span increased. Thus, we concluded that there existed another problem beyond the limit of thumb length that caused a reachability issue when using a large smartphone. Thus, this should be considered in the user interface design of a large smartphone.
Distributed Network Reconfiguration in Response to Jamming at HF

The use of relays is known to increase the resistance of communication links to interference. In a multi-user network it is necessary to establish robust management techniques that allow the users to take advantage of the relaying power a network inherently possesses. In this paper we consider an Intra Task Force (ITF) Network that operates at HF. We employ a network architecture that provides for the automated selection of relay nodes without the need for a central controller. Under this architecture the network reorganizes itself in response to topology changes such as those that result from jamming. Communication range models suitable for a jammed HF channel are presented. We demonstrate that the combination of spread spectrum signaling, error correcting coding, path redundancy through frequency diversity, and adaptive relaying using automated network restructuring provide this network with a strong defense against jamming.
An optimization-based operability framework for process design and intensification of modular natural gas utilization systems

Abstract This paper introduces a novel operability-based framework for process design and intensification of modular systems. This framework is based on nonlinear programming concepts, including bilevel optimization, and extends the application domain of classical operability approaches to process simulator runs (Aspen Plus) for obtaining the relationship between input and output spaces, in addition to first-principles models. As potential modular applications of the proposed approach, a catalytic membrane reactor (MR) for the direct methane aromatization (DMA) conversion to fuels and chemicals, and a natural gas combined cycle (NGCC) system for power generation, are addressed. These applications are especially motivated by the advent of the shale gas revolution that allowed the recent discovery of stranded shale/natural gas deposits at different shale formations in the U.S. The utilization of such deposits could be capitalized by employing modular technologies for the production of power, value-added chemicals and fuels at the site. However, the design and intensification of modular energy systems is a challenging task as these processes are represented by complex and nonlinear models. The obtained results indicate that the proposed framework has the potential to accelerate the realization of the concept of modular manufacturing with reduced footprint and maximized efficiency, resulting in future cost savings. In particular for the NGCC process, the results provide the gas and steam turbine cycle conditions that could enable modular plants that are about three orders of magnitude smaller in terms of power generation than typical operating processes.
Bilateral movements increase sustained extensor force in the paretic arm.

AbstractPurpose: Muscle weakness in the extensors poststroke is a common motor impairment. Unfortunately, research is unclear on whether bilateral movements increase extensor force production in the paretic arm. This study investigated sustained force production while stroke individuals maximally extended their wrist and fingers on their paretic arm. Specifically, we determined isometric force production in three conditions: (a) unilateral paretic arm, (b) unilateral nonparetic arm, and (c) bilateral (both arms executing the same movement simultaneously).Methods: Seventeen chronic stroke patients produced isometric sustained force by executing wrist and fingers extension in unilateral and bilateral contraction conditions. Mean force, force variability (coefficient of variation), and signal-to-noise ratio were calculated for each contraction condition.Results: Analysis of two-way (Arm × Type of Condition: 2 × 2; Paretic or Nonparetic Arm × Unilateral or Bilateral Conditions) within-subjects ANOVAs revealed...
Effective interventions to improve young adults’ linkage to HIV care in Sub-Saharan Africa: a systematic review

ABSTRACTHIV/AIDS remains a major public health problem despite the efforts to prevent and decrease its spread. Sub-Saharan Africa (SSA) represents 70% of the global number of people living with HIV and 73% of all HIV/AIDS-related deaths. Young adults age 15–24 years are disproportionately impacted by HIV/AIDS in SSA with 34% of people living with HIV (PLWHIV) and 37% of newly diagnosed individuals being in this age group. It is important that PLWHIV be linked to care to facilitate antiretroviral therapy (ART) initiation and limit the spread of infection. We conducted a systematic literature review to identify effective interventions designed to improve linkage to care among HIV-infected young adults in SSA. One hundred and forty-six titles and abstracts were screened, 28 full-texts were reviewed, and 6 articles met the inclusion and exclusion criteria. Home-based HIV counseling and testing, home-based HIV self-testing, and mobile HIV counseling and testing followed by proper referral of HIV-positive patie...
Bring New Advances of Basic Medical Research Closer to Patient Care

C l i n M e d International Library Citation: Yang X (2015) Bring New Advances of Basic Medical Research Closer to Patient Care. Int Arch Transl Med 1:001e Received: February 23, 2015: Accepted: February 24, 2015: Published: February 25, 2015 Copyright: © 2015 Yang X. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Yang. Int Arch Transl Med 2015, 1:1
An estrogen replacement therapy containing nine synthetic plant-based conjugated estrogens promotes neuronal survival.

Epidemiological data from retrospective and case–control studies have indicated that estrogen replacement therapy can decrease the risk of developing Alzheimer’s disease. In addition, estrogen repl...
Adaptive Computation with Splines on Triangulations with Hanging Vertices

It is shown how computational methods based on Bernstein–Bezier methods for polynomial splines on triangulations can be carried over to compute with splines on triangulations with hanging vertices. Allowing triangulations with hanging vertices provides much more flexibility than using ordinary triangulations and allows for simple adaptive algorithms based on local refinements. The use of these techniques is illustrated for two application areas of splines—namely, function fitting and the solution of boundary value problems.
Gay and Lesbian Experiences of Discrimination, Health, and Well-Being: Surrounding the Presidential Election

Sexual minorities have poorer mental and physical health than heterosexuals; these health disparities are consistently attributed to discrimination. However, the mechanisms linking discrimination w...
A Subcubic Millimeter Wireless Implantable Intraocular Pressure Monitor Microsystem

We present a sub-mm3, fully wireless, implantable intraocular pressure monitor microsystem (IMM) that comprises a powering coil, an antenna, a piezoresistive micro-electro-mechanical system pressure sensor, and a pressure sensing IC. The system provides a 24-h intraocular pressure monitoring, which is not possible with currently used tonometric measurements. The IMM volume is limited to 0.38 mm3 (4 × smaller than previous state-of-the-art) for the studies on laboratory rodents prior to human use. A cavity resonator magnetic coupling delivers the wireless power to the chip with 4.89% efficiency. The chip senses a change in a differential sensor resistance by providing a low-power differential resistance to frequency conversion with the measured standard deviation in differential resistance sensing of $\text{133}\ {\rm{m}}\Omega $ . The data packets are wirelessly transmitted by an ultralow power 2.4-GHz ISM band OOK transmitter. The IMM is integrated on a 5- μ m-thick biocompatible Parylene C substrate. Implemented in a 0.18-μm CMOS process, the system achieves 0.67-mmHg pressure sensitivity with differential resistance sensing and dissipates only 6.3 nW with 30 min of measurement intervals. We verify the IMM functionality in the in vivo biological experiment.
Strategies and mechanisms to enable dialogue agents to respond appropriately to indirect speech acts

Humans often use indirect speech acts (ISAs) when issuing directives. Much of the work in handling ISAs in computational dialogue architectures has focused on correctly identifying and handling the underlying non-literal meaning. There has been less attention devoted to how linguistic responses to ISAs might differ from those given to literal directives and how to enable different response forms in these computational dialogue systems. In this paper, we present ongoing work toward developing dialogue mechanisms within a cognitive, robotic architecture that enables a richer set of response strategies to non-literal directives.
Case-Mix Adjustment of the Bereaved Family Survey.

Surveys of bereaved family members are increasingly being used to evaluate end-of-life (EOL) care and to measure organizational performance in EOL care quality. The Bereaved Family Survey (BFS) is ...
War, Law and Diplomacy

This chapter explores the central role played by mining in the circumscription of neutral rights at sea over the first year of the conflict. German minelaying was seen in Britain as a breach of basic norms of warfare, and was the justification for retaliatory British measures to restrict neutral use of the seas. This escalatory spiral soon resulted in the German use of submarines against merchant vessels, with its resultant impact on diplomatic relations. Mine warfare lay at the centre of this debate throughout the first year of the conflict, until the U-boat campaign signified a further escalation in belligerence.
Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models.

Parkinson’s disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respectively. Additionally, eat-3, an inner mitochondrial membrane fusion component, an OPA1 homolog, is also down regulated. These changes are associated with a metabolite-induced decline in mitochondrial membrane potential and enhanced DA neurodegeneration that is dependent on PINK-1 function. Genetic analysis also indicates an association between the cell death pathway and drp-1 following S. ven exposure. Metabolite-induced neurotoxicity can be suppressed by DA-neuron-specific RNAi knockdown of eat-3. AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) ameliorated metabolite- or PINK-1-induced neurotoxicity; however, it enhanced neurotoxicity under normal conditions. These studies underscore the critical role of mitochondrial dynamics in DA neurodegeneration. Moreover, given the largely undefined environmental components of PD etiology, these results highlight a response to an environmental factor that defines distinct mechanisms underlying a potential contributor to the progressive DA neurodegeneration observed in PD.
GLOBAL CHANGE | Sea Level Change

Sea level rise is expected to become a serious problem in the future as the Earth warms. Changes in global average sea level are an excellent indicator of how the Earth is responding to climate change because it responds to the melting of land ice and increases in ocean heat content. Satellite altimeter and gravity measurements have revolutionized how we monitor and understand sea level change. Currently, sea level is rising at a rate of ∼3 mm year −1 with roughly equal contributions from thermal expansion, the melting of ice in Greenland and Antarctica, and the melting of mountain glaciers.
On the Law of the Iterated Logarithm for Local Times of Recurrent Random Walks

We consider the law of the iterated logarithm (LIL) for the local time of one-dimensional recurrent random walks. First we show that the constants in the LIL for the local time and for its supremum (with respect to the space variable) are equal under a very general condition given in Jain and Pruitt (1984). Second we evaluate the common value of the constants, as the random walk is in the domain of attraction of a not necessarily symmetric stable law. The first problem relies on a special maximal inequality established in this paper and the second on the LIL for Markovian additive functionals given in the author’s recent work.
Ahoofe Kasa!: Skin Bleaching and the Function of Beauty Among Ghanaian Women

Globally, the practice of skin bleaching has reached pandemic proportions, and in Ghana, the focus of the current research, upwards of 30% of the female population currently actively bleaches. Medical professionals and public commentators all agree that the desire to be seen as beautiful motivates the practice. Advancing the popular Ghanaian aphorism “ahoofe kasa,” which means literally “beauty talks,” this article explores the politics of beauty among women in Ghana, particularly those who currently use or at one time have used skin lightening agents. More specifically, the study relies primarily upon qualitative data to investigate the relationship between gender, skin bleaching, light skin, and beauty. Although the participants interviewed indeed express that their use of skin lightening agents is fueled by their desire to be perceived as more noticeably beautiful, critical analysis of the data reveals that what they are seeking is not an arbitrary beauty, but one that is functional and materializes via light skin. In this way, beauty via light skin as gained through skin bleaching allows participants access to social capital, and for many, their newfound light skin color becomes a bartering tool negotiable for economic capital.
Commentary on the Multimodal Treatment Study of Children with ADHD

The multimodal treatment study of attention deficit hyperactivity disorder (MTA Study) constitutes a landmark in the history of treatment research in child psychopathology, being the largest single study of its kind ever undertaken. Important findings have emerged from this project, as the papers in the present volume will attest. This commentary focuses on several concerns about the assumptions that appear to have guided the design of the MTA study, particularly its psychosocial treatment component, as well as the manner in which treatment results have been presented to date. In particular, no explicit theory of ADHD appears to have guided the construction of the treatment components, relying instead on implicit theories associated with those treatments, such as the notion that the symptoms of ADHD arise through faulty learning and defective contingencies of reinforcement. Future articles from this study will need to address these and other concerns if the results of the study are to be properly interpreted and the scientific and clinical yield is to be maximized.
Influence of dimethylaminoazobenzene on leukocyte production in the rat.

1. Supplementation with p -dimethylaminoazobenzene plus vitamin B12 prevented leukopemia in rats fed a methionine-deficient basal diet. p -Dimethylaminoazobenzene was ineffective in this regard in the absence of supplementary vitamins B12. 2. Possible relationships of this observation to the theory of p -dimethylaminoazobenzene carcinogenesis are discussed.
The Influence of the Fiber/Matrix Interface on Local Glass Transition Temperature

Determining the local structure and properties of the interphase is crucial to understanding how the interphase influences overall thermo-mechanical behavior of a composite. Several theoretical investigations have presented evidence for the existence of an interphase region with a glass transition temperature that is significantly lower than that of the neat resin. In the current study both interferometric measurements and single fiber critical length tests are performed on samples with tailored interphases to further investigate variations in local glass transition temperature and its influence on micro-mechanical behavior. Two different interphase conditions are considered: fibers coated with a low Tg resin and untreated fibers (no coating). Micro-interferometry was utilized to study differences in thermally induced axial displacements for the two different interphase conditions. Additionally, single fiber critical length tests were performed over a range of temperatures to determine the effects of the interphase glass transition on the value of interfacial shear strength. Experimental results support the existence of a reduced glass transition temperature near the fiber surface.
Recognition and killing of Brugia malayi microfilariae by human immune cells is dependent on the parasite sample and is not altered by ivermectin treatment

Mass administration of macrocyclic lactones targets the transmission of the causative agents of lymphatic filariasis to their insect vectors by rapidly clearing microfilariae (Mf) from the circulation. It has been proposed that the anti-filarial action of these drugs may be mediated through the host immune system. We recently developed an in vitro assay for monitoring the attachment to and killing of B. malayi Mf by human neutrophils (PMNs) and monocytes (PBMCs), however, the levels of both cell to worm attachment and leukocyte mediated Mf killing varied greatly between individual experiments. To determine whether differences in an individual's immune cells or the Mf themselves might account for the variability in survival, PMNs and PBMCs were isolated from 12 donors every week for 4 weeks and the cells used for survival assays with a different batch of Mf, thereby keeping donors constant but varying the Mf sample. Results from these experiments indicate that, overall, killing is Mf-rather than donor-dependent. To assess whether ivermectin (IVM) or diethylcarbamazine (DEC) increase killing, Mf were incubated either alone or with immune cells in the presence of IVM or DEC. Neither drug induced a significant difference in the survival of Mf whether cultured with or without cells, with the exception of DEC at 2 h post incubation. In addition, human PBMCs and PMNs were incubated with IVM or DEC for 1 h or 16 h prior to RNA extraction and Illumina sequencing. Although donor-to-donor variation may mask subtle differences in gene expression, principle component analysis of the RNASeq data indicates that there is no significant change in the expression of any genes from the treated cells versus controls. Together these data suggest that IVM and DEC have little direct effect on immune cells involved in the rapid clearance of Mf from the circulation.
The safety of atovaquone-proguanil for the prevention and treatment of malaria in pregnancy: A systematic review.

Abstract Background Malaria infection poses a significant risk in pregnancy, yet chemoprophylaxis for pregnant women is limited. A systematic review was conducted to evaluate the incidence of adverse outcomes after atovaquone-proguanil (AP) exposure during pregnancy. Methods Following PRISMA guidelines, the authors searched PubMed, MEDLINE, and the Malaria in Pregnancy Consortium Library to identify relevant literature including infant outcomes after exposure to atovaquone, proguanil, or AP in pregnancy. Two authors independently screened the titles, abstracts, and full texts, and extracted data into an EpiInfo database. Overall proportions and 95% confidence intervals of adverse outcomes were determined by pooling data across studies. Results Of 455 records identified, 16 studies were included: ten AP studies and six proguanil studies. The overall proportions and 95% confidence intervals (CI) of adverse outcomes reported for the 446 women exposed to AP include miscarriage (8.08% CI: 5.07, 12.08%), stillbirth (1.05% CI: 0.03, 5.73%), early neonatal death (0% CI: 0, 7.4%), and congenital anomalies (2.56% CI: 1.28, 4.53%). Conclusions The limited available data suggest that outcomes following AP exposure during pregnancy are similar to expected rates in similar populations. AP may be a promising option for pregnant women, but further data are needed on its safety in pregnancy.
Extraction and Purification of Wall-Bound Polymers of Gram-Positive Bacteria

The envelope of gram-positive bacteria encompasses the cell wall, a rigid exoskeleton comprised of peptidoglycan that provides protection against lysis and governs bacterial cell shapes. Peptidoglycan also serves as the site of attachment for proteins and nonproteinaceous polymers that interact with the bacterial environment. Nonproteinaceous molecules include teichoic acids, capsular polysaccharides, and secondary cell wall polysaccharides (SCWP). Treatment of gram-positive bacterial cells with proteases, nucleases, and detergents results in the isolation of "murein sacculi" (i.e., peptidoglycan with bound carbohydrate polymers). Incubation of sacculi with acid or base releases carbohydrate polymers that can be purified for further biochemical characterization. This protocol describes the hydrofluoric acid extraction and purification of the secondary cell wall polymer of Bacillus anthracis that is also found in the envelope of the other members of the Bacillus cereus sensu lato group of bacteria.
Letter--Community Pharmacy Versus Mail Order: An Uneven Comparison

DISCLOSURES: No outside funding supported the writing of this letter. Farley has received funding from the National Community Pharmacy Association for previous research. Schondelmeyer advises the U...
Thermal conductivity of YBa2Cu3O7- below 1 K: Evidence for normal-carrier transport well below Tc

We report measurements of thermal conductivity at temperatures below 1 K on superconducting and insulating (oxygen-deficient) ceramic YBa/sub 2/Cu/sub 3/O/sub 7-//sub delta/. For the superconductor the temperature dependence of the thermal conductivity, kappa, begins to weaken below approx.0.5 K, approaching a T-linear behavior. Below 1 K the insulating material, produced by vacuum-annealing the superconductor, exhibits a kappa proportionalT/sup 3/ dependence characteristic of phonon boundary scattering. Reannealing samples in flowing oxygen restores superconductivity at 90 K and the T-linear behavior of the thermal conductivity at the lowest temperatures. Scanning electron micrographs reveal an identical grain structure before and after successive heat treatments, indicating that the anomaly in kappa for the superconductor is not associated with the specific geometry of the microstructure. The data are consistent with the presence of a small number of normal carriers in the high-T/sub c/ material.
Theory vs. practice: Teaching undergraduate econometrics

Econometrics is a standard component of the undergraduate curriculum (Kassens, “Taking a Path Less Travelled—Teaching Econometrics without a Textbook,” forthcoming), although newly-minted graduates...
The impact of age on in-hospital outcomes after transcarotid artery revascularization, transfemoral carotid artery stenting, and carotid endarterectomy.

Abstract Objective Previous data showed superior outcomes of carotid endarterectomy (CEA) compared with transfemoral carotid artery stenting (TFCAS) in elderly patients because of an increased stroke risk in TFCAS-treated patients. Transcarotid artery revascularization (TCAR) with flow reversal was developed to mitigate the maneuvers at highest risk for causing stroke during TFCAS, such as manipulation of a diseased aortic arch and crossing of the carotid lesion before deployment of an embolic protection device. This study aimed to compare the association between age and outcomes after TCAR, TFCAS, and CEA. Methods All patients undergoing carotid procedures in the Society for Vascular Surgery Vascular Quality Initiative database between 2015 and November 2018 were included. Patients were divided into three different age groups (≤70 years, 71-79 years, and ≥80 years). In-hospital outcomes after TCAR vs TFCAS and after TCAR vs CEA were compared in each age group by introducing an interaction term between treatment type and age in the logistic regression analysis after adjustment for patients' preoperative characteristics. Results The study cohort included 3152 TCAR, 10,381 TFCAS, and 61,650 CEA cases. The absolute and adjusted in-hospital outcomes after TCAR did not change across the different age groups. The rates of in-hospital stroke/death after TCAR were 1.4% in patients ≤70 years vs 1.9% in patients 71 to 79 years and 1.5% in patients ≥80 years (P = .55). Comparison of TCAR to CEA across different age groups showed no significant differences in outcomes, and no interaction was noted between treatment and age in predicting in-hospital stroke/death (P = .80). In contrast, TCAR was associated with a 72% reduction in stroke risk (4.7% vs 1%; odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12-0.65; P Conclusions TCAR is a relatively safe procedure regardless of the patient's age. The advantages of TCAR become more pronounced in elderly patients, with significant reductions in in-hospital stroke compared with TFCAS in patients ≥77 years old, independent of symptomatic status and other medical comorbidities. These findings suggest that TCAR should be preferred to TFCAS in elderly patients who are at high surgical risk.
Protein and lymphatic loss conditions

Abstract Protein loss is a recognized cause of hypogammaglobulinemia and lymphatic loss appears in nearly every differential diagnosis of low T cells, yet, the practical approach to identification and management of these conditions is poorly studied. This chapter approaches the topic from the setting of an immunologist called to dissect the mechanism and management.
Exploiting the Syntax-Model Consistency for Neural Relation Extraction

This paper studies the task of Relation Extraction (RE) that aims to identify the semantic relations between two entity mentions in text. In the deep learning models for RE, it has been beneficial to incorporate the syntactic structures from the dependency trees of the input sentences. In such models, the dependency trees are often used to directly structure the network architectures or to obtain the dependency relations between the word pairs to inject the syntactic information into the models via multi-task learning. The major problem with these approaches is the lack of generalization beyond the syntactic structures in the training data or the failure to capture the syntactic importance of the words for RE. In order to overcome these issues, we propose a novel deep learning model for RE that uses the dependency trees to extract the syntax-based importance scores for the words, serving as a tree representation to introduce syntactic information into the models with greater generalization. In particular, we leverage Ordered-Neuron Long-Short Term Memory Networks (ON-LSTM) to infer the model-based importance scores for RE for every word in the sentences that are then regulated to be consistent with the syntax-based scores to enable syntactic information injection. We perform extensive experiments to demonstrate the effectiveness of the proposed method, leading to the state-of-the-art performance on three RE benchmark datasets.
Balancing the Epistemic and Social Realms of Science to Promote Nature of Science for Social Justice

Driven by a strong focus on narrowly conceived epistemic aspects of science, the majority of studies with a nature of science (NOS) agenda have contributed scarce insights to those concerned with issues of equity and social justice. On the other hand, orientations to science education with STSE, multicultural, place-based, and informal science offer, mostly implicitly, alternative paradigms for thinking about the nature of science. In this chapter, I propose that holistic NOS frameworks that balance the epistemic and social realms of science lend themselves to supporting rigorous science learning within a social justice agenda. I then illustrate how one such framework, the Family Resemblance Approach to nature of science (Erduran S, Dagher ZR: Reconceptualizing nature of science for science education: scientific knowledge, practices, and other family categories. Springer, Dordrecht, 2014) can serve as a bridge for connecting “cold” or discipline-based to “warm” or community-based notions of nature of science. The chapter concludes with a discussion of NOS features that allow the restoration of its rightful place within a social justice agenda.
Sediment of the Tigris and Euphrates rivers: an early modern perspective

Sediment deposition by the Tigris and Euphrates rivers created the physical landscape on which the civilizations of ancient Iraq evolved. Scholars in the past century have combined material with textual evidence to capture the complexity of this sedimentary context and assess its role in human history over the long term. This essay uses untapped archival sources generated by the Ottoman Empire to shine a new light on the subject, emphasizing the impact of sedimentation on irrigation agriculture and channel movement during the early modern period. Ottoman documents, moreover, improve our understanding of how states and societies adapted to the opportunities and challenges provided by sediment transport. In their capacity as giant conduits for sedimentary movement, the Tigris and Euphrates formed selective pressures on the Ottoman state in Iraq that shaped and was reshaped by it. For the study of river systems worldwide, the early modern history of the Tigris and Euphrates reveals the utility of taking fluvial sediment into account when analyzing other hydrological processes such as avulsion.
Parental intervention in school, academic pressure, and childhood diagnoses of ADHD.

Abstract Childhood diagnoses of attention-deficit/hyperactivity disorder (ADHD) have increased dramatically in the U.S. in recent decades. Prior research has alluded to the possibility that high levels of parental intervention in school are associated with increased diagnoses of ADHD, but this relationship remains understudied. This study investigates: 1) whether the children of intervening parents are more likely to be diagnosed with ADHD, and; 2) whether parental intervention moderates the extent to which children's pre-diagnosis behavioral problems and exposure to strict educational accountability policies predict ADHD diagnosis. Analyses of longitudinal, population-level data from the Early Childhood Longitudinal Study-Kindergarten Cohort of 1998–99 (n = 9,750) reveal that a standard deviation increase above the mean on parental intervention in school is associated with a 20% increase in the odds of ADHD diagnosis among elementary school children. This relationship is robust to differences in children's pre-diagnosis behavioral problems, academic achievement, parental knowledge of/exposure to ADHD, and school selection, and can arise because parents who intervene in school on average exhibit heightened sensitivity to behavioral problems and academic pressure from accountability-based educational policies. In light of prior work establishing both social class and racial/ethnic differences in parental intervention in school, this positive relationship between parental intervention in school and children's diagnoses of ADHD may carry important implications for the production of inequality in children's mental health and educational opportunities.
Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.

The modulation and selectivity mechanisms of seven mixed-action kappa opioid receptor (KOR)/mu opioid receptor (MOR) bitopic modulators were explored. Molecular modeling results indicated that the ...
Isavuconazole Treatment of Invasive Fungal Sinusitis: A Post Hoc Analysis of the SECURE and VITAL Trials.

This post-hoc analysis of international phase III isavuconazole trials identified 50 patients (90% immunocompromised or diabetic) with invasive fungal sinusitis (88% mucormycetes, Aspergillus) who received isavuconazole as primary (33) or salvage (17) therapy for median 82 days (range 2-882). Overall survival was 82% at day 42, 70% at day 84.
Modeling individual noise-induced hearing loss risk with proxy measurements of external-ear amplification.

Significant variability in noise-induced hearing loss (NIHL) susceptibility suggests there are factors beyond sound level and duration of exposure that contribute to individual susceptibility. External-ear amplification (EEA) from external-ear structures varies significantly due to ear size and shape, potentially influencing NIHL susceptibility. This study tested the hypothesis that EEA can be predicted using non-technical proxy measurements including pinna height (cm), body height (m), and earcanal volume (cm3). 158 participants (4–78 years) completed otoscopy, tympanometry, pinna measurements, body height measurements, and two EEA measurements: (1) total real-ear unaided gain (REUG) of the open ear and (2) real-ear to coupler difference (RECD), representing unaided gain from the earcanal. Participants' individual noise doses were compared in hypothetical exposures. REUG ranged from 5 to 19 dBA and was correlated with pinna height. High-REUG participants were estimated to accrue noise doses at least 5 times higher than low-REUG participants. RECD ranged from 7 to 24 dBA and was correlated with earcanal volume and body height. The results support the hypothesis that EEA measurement could significantly improve estimation of an individual's position along the NIHL risk spectrum. Non-technical proxy measurements of EEA (pinna height, body height, earcanal volume) were statistically significant but yielded high variability in individual EEA prediction.
Predator reduction results in compensatory shifts in losses of avian ground nests

Summary 1. Nesting birds can be vulnerable to predation. Wildlife managers sometimes manipulate predator communities to enhance avian productivity and abundance. Managers need to know the predation risk from different predator species responsible for nest failures to maximize success. This issue is especially important when considering reductions in only a part of the predator community in complex ecosystems. 2. We conducted a 7-year crossover experiment at four study sites to examine the effect of mesomammalian predator control on nest success of northern bobwhite Colinus virginianus in the southeastern USA. Nests were monitored using 24-h near-infrared video. We hypothesized that nest failures caused by different predator guilds may not be independent and may lead to compensation by other predators as one predator guild was reduced. 3. We compared levels of bobwhite nest predation by mesomammals, snakes and other predators in years with and without mesomammal control. 4. Control of mesomammal predators reduced the levels of mesomammal nest predation, but predation levels by snakes and other predators increased such that total nest mortality was not reduced. Nest mortality among predator groups was best described as compensatory, and total nest mortality differed among sites. 5. Synthesis and applications. Our findings suggest that reductions in predation risk from one predator guild can be compensated by an increased risk from other predators in complex ecosystems. Predator removal within one group may not translate to additive increases in overall nest success, but rather results in shifts in the identity of predators responsible for nest failures. Management efforts focused on manipulating predator communities to enhance avian reproduction are encouraged to examine cause-specific nest fates to determine the effectiveness of predator reduction programmes.
Learning from the Dead

Taphonomy A Process Approach. Ronald E. Martin. Cambridge University Press, New York, 1999. 524 pp. $100. ISBN 0-521-59171-6. Paper, $44.95. ISBN 0-521-59833-8. Martin9s review of the study of incompleteness and bias in the fossil record pulls together case studies from marine microfossils, marine invertebrates, vertebrates, plants, and pollen.
Constraints on the Parent Bodies of Collected Interplanetary Dust Particles

Samples of interplanetary dust particles (IDPs) have now been collected from the stratosphere, from the Earth’s ocean beds, and from the ice caps of Greenland and Antarctica. The most likely candidates for the sources of these particles are comets and asteroids. Comparison of the infrared spectra, elemental compositions, and mineralogy of the collected dust with atmospheric entry models and data obtained from cometary probes and telescopic observations has provided important constraints on the possible sources of the various types of collected dust. These constraints lead to the following conclusions. First, most of the deep sea, Greenland, and Antarctic spherules larger than 100 μm are derived from asteroids. Second, the stratospheric IDPs dominated by hydrated layer-lattice silicate minerals are also most likely derived from asteroids. Finally, the stratospheric IDPs dominated by the anhydrous minerals olivine and pyroxene are most likely from comets. The consequences of these parent body assignments are discussed.
Turbocharging a bi-fuel engine for performance equivalent to gasoline

A bi-fuel engine capable of operating either on compressed natural gas (CNG) or gasoline is being developed for the transition to alternate fuel usage. A Saturn 1.9 liter 4-cylinder engine was selected as a base powerplant. A turbocharger was installed to increase the density of the intake charge and thereby regain the volumetric efficiency lost with CNG. Reductions from baseline in hydrocarbon and carbon dioxide emissions were achieved at power levels equivalent to and slightly higher than the baseline. Brake thermal efficiency values were not significantly different in any case. 8 refs., 12 figs.