cssi/SciSciGPT-SciSciNet huggingface dataset:
An RNA thermometer

The expression of a conserved set of heat shock proteins is induced when cells grown at low temperatures are shifted to higher temperatures. Heat shock proteins are molecular chaperones or proteases that act to fold, translocate, or degrade proteins that appear to be misfolded or denatured upon heat shock. The heat shock response has been the focus of much research, and how the temperature signal is sensed and transduced to the biosynthetic machinery has been studied extensively. The s (RpoH) alternative s-factor, which is encoded by the rpoH gene, is a key regulator of the Escherichia coli heat shock response (for review, see Gross 1996; Missiakas et al. 1996). Upon a temperature shift from 30°C to 42°C, s accumulates and directs RNA polymerase to the promoters of the heat shock genes (Fig. 1). Earlier studies showed that both increased synthesis and stability lead to the increased levels of s. The activity of s and its association with RNA polymerase are also modulated by heat shock. A great deal has been learned about the increased stability of s in response to increased temperature. During normal growth the half-life of s is ∼1 min; upon upshift the half-life is increased to ∼5 min. Interestingly, the heat shock proteins DnaK, DnaJ, GrpE and HflB, whose expression is regulated by s, function to destabilize s. These proteins interact with s, sequestering it away from RNA polymerase and targeting it for degradation. Misfolded proteins that accumulate after heat shock appear to titrate the DnaK, DnaJ, and GrpE chaperones and the HflB protease away from s. Therefore, the pool of misfolded proteins is thought to be one measure of elevated temperature in the cell. Increased s synthesis was known to occur at the level of translation. However, although the E. coli heat shock response has been under investigation for many years, the thermometer signaling the need for increased translation was not known. In this issue Morita et al. (1999) show that the secondary structure of the rpoH mRNA itself is a thermosensor. These investigators present strong correlations between the expression of rpoH–lacZ fusions and the predicted and actual thermostability of the rpoH mRNA secondary structure. In addition, rpoH–lacZ expression levels correlate with the formation of rpoH mRNA–30S ribosome– tRNAf Met complexes. Thus, the melting of the rpoH mRNA secondary structure at high temperature leads to ribosome binding and increased s synthesis. Here, I summarize the findings that led to this conclusion. I also contrast the rpoH mRNA with other proposed RNA and protein thermometers.
Antisocial behavior, academic failure, and school climate: A critical review.

Researchers have demonstrated a strong correlation between antisocial behavior and academic failure among students.Yet current educational programs designed to modify one or both of these patterns of conduct tend to be limited in at least two fundamental ways. First, they tend to treat conditions associated with academic achievement as separate from those associated with violent or other antisocial behavior. Second, they often focus narrowly on modifying selected cognitions or personality characteristics of the individual (e.g., changing attitudes and beliefs).Yet both antisocial behavior and academic failure are context specific; each occurs within a climate in which conditions can be identified that reasonably predict problematic behavior and can be modified to reduce such behavior.The success of prevention and intervention programs, therefore, hinges on their ability to identify and modify climates in which academic failure and antisocial behavior emerge. In this article we examine the role of school c...
A Meta-Analysis of Pornography Consumption and Actual Acts of Sexual Aggression in General Population Studies

Whether pornography consumption is a reliable correlate of sexually aggressive behavior continues to be debated. Meta-analyses of experimental studies have found effects on aggressive behavior and attitudes. That pornography consumption correlates with aggressive attitudes in naturalistic studies has also been found. Yet, no meta-analysis has addressed the question motivating this body of work: Is pornography consumption correlated with committing actual acts of sexual aggression? 22 studies from 7 different countries were analyzed. Consumption was associated with sexual aggression in the United States and internationally, among males and females, and in cross-sectional and longitudinal studies. Associations were stronger for verbal than physical sexual aggression, although both were significant. The general pattern of results suggested that violent content may be an exacerbating factor.
Christopher D. Lloyd, Ian G. Shuttleworth, and David W. S. Wong (Eds.), Social‐Spatial Segregation: Concepts, Processes, and Outcomes (Bristol, UK: Policy Press, 2014).

This book brings together multiple perspectives and methodological innovations in the study of segregation. Traditional measures of segregation have some serious limitations and this collection is ...
Defying the odds on gun regulation: The passage of bipartisan mental health laws across the states.

This article documents an important exception to the conventional wisdom that politicians just will not tighten gun laws. Over the past decade, and mostly under the radar, both state and federal legislators have enacted more than 80 laws designed to regulate access to guns by people with mental illness and to support programs to reduce gun violence within that population. This study begins with a brief overview and evaluation of the barriers to enacting firearms regulations (of all sorts) in America. The author next reviews lawmaking at the nexus of mental health and firearms over the past decade. The author provides an overview of the types of laws that have been enacted and the political circumstances that have facilitated their passage. The author concludes with some thoughts about whether these cases provide any generalizable lessons for consensus-based policymaking on guns. (PsycINFO Database Record Language: en
How should surgical pathology evolve

This lecture will attempt to address the nebulous and perhaps philosophical issue of the manner in which surgical pathology should evolve in the next 10–20 years. Currently, surgical pathology reports provide more detailed and more clinically valuable (in fact currently irreplaceable!) information than ever before – at a time when fashion seeks to dictate that molecular genetic and genomic testing has the power to supersede conventional pathology almost entirely. ‘Personalised (or ‘precision’) medicine’, at whatever cost, is believed by many physicians (and patients) to be the way forward. Yet surgical pathologists continue to be of critical importance to optimal patient care through incorporation of novel tests that are properly validated (and cost-effective), integration of data from different testing modalities and also through guiding clinical decision-making and serving as a patient advocate.
Occupational respiratory diseases.

Materials inhaled in the workplace can lead to all the major chronic lung diseases except those due to vascular disease. The physician should consider the possibility of occupational exposure when a working or retired adult presents with unexplained respiratory illness. Even exposure in office buildings1 and hospitals2 occasionally causes illness. Identifying a workplace-related cause of disease is important because it can lead to cure and to prevention for others. Because of differences in the metabolism and susceptibility of hosts, one occupational agent may cause many diseases, just as cigarette smoke causes several distinct disorders. Conversely, one respiratory disease may have . . .
Bending the Elastica with Mathematics

A classroom illustration is presented which uses Mathematica™ to solve the classical problem of bending the elastica.
The “Corporate Contract” Today

This chapter of the Oxford Handbook of Corporate Law and Governance examines the theoretical and empirical validity of the “contractarian” theory of corporate governance. Beginning with an overview of the contractarian theory and its conceptualization of the relationship between public company managers and shareholders, it explains how the theoretical assumptions of the contractarian theory have turned out to be invalid, and how the empirical predictions of the theory have not been borne out. The process by which “corporate contracts” develop do not fit the neoclassical model of atomistic competition. For this reason and others, the customization and innovation that the contractarian theory predicts do not occur — either at the IPO stage or at the “midstream” stage when companies are publicly traded.
Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans

ABSTRACT Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which in C. neoformans is predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA) genes have to be deleted to generate a chitosan-deficient C. neoformans strain. This cda1Δ2Δ3Δ strain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of the cda1Δ2Δ3Δ strain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in the cda1Δ2Δ3Δ strain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-type C. neoformans strain. Moreover, protective immunity was also induced in mice vaccinated with heat-killed cda1Δ2Δ3Δ cells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop the cda1Δ2Δ3Δ strain as a potential vaccine candidate for C. neoformans infection. IMPORTANCE The most commonly used anticryptococcal therapies include amphotericin B, 5-fluorocytosine, and fluconazole alone or in combination. Major drawbacks of these treatment options are their limited efficacy, poor availability in limited resource areas, and potential toxicity. The development of antifungal vaccines and immune-based therapeutic interventions is promising and an attractive alternative to chemotherapeutics. Currently, there are no fungal vaccines in clinical use. This is the first report of a C. neoformans deletion strain with an avirulent phenotype in mice exhibiting protective immunity when used as a vaccine after heat inactivation, although other strains that overexpress fungal or murine proteins have recently been shown to induce a protective response. The data presented here demonstrate the potential for developing the avirulent cda1Δ2Δ3Δ strain into a vaccine-based therapy to treat C. neoformans infection.
STD update: screening and therapeutic options.

Sexually transmitted diseases (STDs) are some of the most common causes of illness worldwide. Prevention and educational programs have helped to curb the rise of syphilis, gonorrhea, non-gonococcal urethritis, chancroid, granuloma inguinale and lymphogranuloma venereum within most of the United States. However, there are still "hot spots" in the southern U.S. and in non-Caucasian and urban populations, and these diseases continue to be prevalent in underdeveloped countries. Molluscum contagiosum and condyloma acuminata are increasing throughout the world. Herpes simplex is in the midst of an epidemic, having increased in the United States by 30% in the last 15 years. The failure of preventive programs to halt or reverse these epidemics stems from a combination of factors involving both patients and the medical profession. Patient and sexual partner ignorance, denial and deliberate deception play an important role. However, healthcare professional ignorance and failure to keep a high index of suspicion are also crucial. These issues are compounded by the quick-visit concept propagated by managed care, which dilutes most educational efforts. Teens particularly suffer from the lack of an unhurried discussion of sexual practices, and the sharp rise in STDs in this population reflects failure in the medical system. This paper will review the classical presentations of the various STDs, and will detail in what ways the coexistence of HIV disease alters clinical appearance and disease progress. Subtle variations in presentations that often lead to misdiagnosis are discussed. Diagnosis and treatment of STDs change rapidly as new developments occur, and the latest recommendations are examined. The ways in which these therapies differ in special need groups such as HIV and pregnancy are specifically detailed. The goal of this review is to arm the clinician with all of the necessary ingredients for timely and accurate diagnosis and treatment, as well as ways to assist the patient in dealing with these difficult topics. Patient education is highlighted, as it, along with practitioner expertise, is the key to disease eradication. We are the missing link in STD eradication.
A Novel Membrane Process for Autotrophic Denitrification

Biological denitrification by heterotrophic bacteria is common in the wastewater industry in the U.S. and in drinking water processing in Europe.To facilitate heterotrophic denitrification, organic compounds such as methanol, ethanol and acetic acid are added to provide a carbon source for the bacteria. The resulting organic carbon residual may create problems with chlorination. The addition of these carbon compounds is expensive and results in added sludge production. This study focused on the use of autotrophic hydrogen oxidizing bacteria for denitrification. The method transfers hydrogen gas to solution via microporous hollow fiber membranes. Typically, gases are supplied to a system using conventional bubble diffusers. The conventional bubble aeration system has a low gas transfer efficiency, and, as a result, the cost of dissolving the required amount of gas is very high. In this study, microporous hollow fiber membranes were employed to supply hydrogen gas to hydrogen oxidizing autotrophic bacteria. Laboratory scale membrane modules were constructed and mass transfer studies were carried out to develop the design correlations for hydrogen gas transfer. A mixed culture was obtained and acclimated for batch denitrification studies. Both Sodium carbonate and carbon dioxide were used to deliver inorganic carbon. Bench scale continuous flow biofilm reactors containing plastic media were operated to remove nitrate from water. The required hydrogen gas was supplied at a constant rate via gas transfer modules, containing sealed end microporous hollow fiber membranes. The reactors were optimized for removal of nitrate and nitrite by varying the recycle ratios and hydraulic detention time. Experimental results indicated the presence of hydrogen oxidizing denitrifiers in wastewater sludge. Adequate pH control was possible and the pH averaged around 6.95. Gas transfer studies indicated that hydrogen transfer was primarily controlled by liquid film diffusion. Hydrogen gas was successfully delivered to the reactor via the hollow fiber membrane gas transfer module. Nitrate and hydrogen concentration measurements indicated that the system did not experience hydrogen limitations at detention times of 3.25 hours or greater. The use of hollow fiber membrane module appears to be a viable technology for transferring hydrogen gas to water. The research results in this report provide valuable information for pilot and full-scale studies for the water/wastewater community focusing on membrane processes for autotrophic denitrification. This title belongs to WERF Research Report Series ISBN: 9781843396437 (Print) ISBN: 9781780403229 (eBook)
Athena Unbound: Policy for women in science

‘For women there are undoubtedly great difficulties in the path, but so much the more to overcome,’ exulted Maria Mitchell (1818–1889), the first female professor of astronomy in the U.S., at the then newly founded Vassar College. More than a century later, on the 175th anniversary of her birth, women's scientific aspirations are still restricted by ‘tradition and authority’ (Enna, 1993). Few female scientists are as happy as the nineteenth century astronomer Mitchell to have put up a brave front in the face of a host of gender-related problems. Despite significant improvement, especially in the numbers of women who wish to enter scientific careers, many of the organizational structures of science, and some scientists, continue to resist women's full participation. Additional steps are necessary, beyond encouraging women to take up science, to insure that science is open to them (Lovitts, 1996). In this final chapter, we discuss the policy implications of our findings in terms of motivators and inhibitors that shape the experiences of women and conditions of inequality in academic science. First, the arguments behind each thesis are described and its accomplishments and shortfalls reviewed. Second, we argue for new policy recommendations related to department reform, the factor that is most relevant to the organizational issues explored in the preceding chapters and that we have identified as a means by which programs for change can be implemented. Five strategies have been suggested during the past thirty years to promote improvement of the condition of women in academic science.
‘Wee cannot … returne to our selves’: Volpone

Apart from being so close in date,1 Volpone and The Revenger’s Tragedy have a surprising number of features in common. As each play opens the main character is playing the satirist, Vindice denouncing the corrupt ducal court while Volpone gleefully uncovers the avarice of the Venetian upper class. The emphasis then quickly shifts from moral analysis to dazzling theatrical performance: Vindice’s inventive black comedy in using the skull of Gloriana to poison the Duke, or Volpone’s creation of convincing new personae when he plays Scoto de Mantua and the commenda- tore. Yet neither dramatist allows such energetic histrionics to triumph completely. The protagonists overreach themselves, betrayed by their obsessive sense of theatre. As the playwright— director and actor who wants the credit for a job ‘wittily’ done, Vindice admits to his crime and is punished accordingly. Volpone, not content with one ‘masterpiece’, turns his servant Mosca into his rival when he shams dead, and thus is able to restore dramatic control only by unmasking and thereby throwing himself on the mercy of the Venetian judges.
Modulation identification for cognitive aeronautical air-ground communications

The main objectives for deploying Cognitive Radio (CR) technology in aeronautical communications are to achieve reliable communications and to avoid the expected congestion that is bound to occur in the near future. CR allows a very flexible and dynamic radio management system leading to improved radio spectrum utilization. Realizing CR features in aeronautical communications requires the ability to identify the modulation type of the received signal. In this paper, we introduce a modulation identification algorithm to distinguish the aeronautical signals from other modulated signals based on wavelet transform (WT) analysis. The proposed identification algorithm is able to recognize multicarrier and single-carrier modulated signals and is also able to discriminate linear and non-linear modulations. Simulation results are provided to demonstrate the performance of the identification algorithm for an aeronautical channel modeled as a Ricean fading channel in presence of Gaussian noise.
Sensors for Biological Thiols

The most common low molecular weight aminothiols are glutathione (GSH), cysteine (Cys), and homocysteine (Hcy). They each play major roles in biology and biomedicine in both enzymatic and nonenzymatic processes. In the latter regard, the distinctive redox and nucleophilic properties imparted by their sulfhydryl groups enable them to modulate a variety of physiological states. The traditional probes and abiotic sensors for the biothiols are mainly dye molecules functionalized with universal electrophile moieties to enable conjugation to all thiol-containing compounds. More recently, the field has focused on optical reagents that can selectivity differentiate GSH, Cys, and Hcy from each other, in addition to many other components in natural media, since each of the biothiol analytes is involved in distinct biological processes. Herein, examples are presented of how the covalent reactivity of electrophilic dyes toward biothiols can be modulated via supramolecular chemistry to attain highly selective probes and sensors for each of the biothiols. In addition, significant opportunities and needs in the field of biothiol sensing are presented, highlighting relatively under-investigated biomedical issues.
Scalable learning and knowledge discovery via adaptive sampling

Scalability is an important issue in data mining and knowledge discovery in real-world applications where hugedata sets often render ordinary learning algorithms infeasible. As an important technique for parameter estimation and hypothesis testing widely used in statistical analysis, random sampling can be exploited to address the issue of scalable learning and knowledge discovery. Adaptive sampling is typically more efficient than traditional batch sampling methods because it can determine the sample size based on the samples seen so far. Recently a new adaptive sampling method for estimating the mean of a Bernoulli random variable was proposed in [2], which was empirically shown to require significantly lower sample size (i.e., the number of sampled instances) while maintaining competitive accuracy and confidence when compared with existing approaches. This paper presents theoretical analysis of properties of the proposed sampling method, as well as a brief outline on how to utilize the proposed sampling method to develop an efficient ensemble learning method with Boosting.
The Suicide Probability Scale: A Means to Assess Substance Abusing Clients' Suicide Risk

Although substance abusing clients may not be the primary treatment population that most counselors serve, it is nearly inevitable that at one time or another, the vast majority of counselors will ...
Flexible Light-Emitting Nanocomposite Based on ZnO Nanotetrapods

Flexible, light-emitting materials have shown promise in a wide range of applications. Here, we develop an inverse soft-lithography process for embedding zinc oxide nanotetrapods (ZnO NTP) uniformly and nondestructively into a host matrix. The crystalline NTPs were synthesized using a catalyst-free, environmentally friendly chemical vapor transport method. The fluorescent emission of the ZnO NTPs was measured before and after the embedding process. Cyclical mechanical bend tests (N > 100) were performed. The emission of the nanomaterial remains throughout.
Efficient Strategies for Estimating the Spatial Coherence of Backscatter

The spatial coherence of ultrasound backscatter has been proposed to reduce clutter in medical imaging, to measure the anisotropy of the scattering source, and to improve the detection of blood flow. These techniques rely on correlation estimates that are obtained using computationally expensive strategies. In this paper, we assess the existing spatial coherence estimation methods and propose three computationally efficient modifications: a reduced kernel, a downsampled receive aperture, and the use of an ensemble correlation coefficient. The proposed methods are implemented in simulation and in vivo studies. Reducing the kernel to a single sample improved computational throughput and improved axial resolution. Downsampling the receive aperture was found to have negligible effect on estimator variance, and improved computational throughput by an order of magnitude for a downsample factor of 4. The ensemble correlation estimator demonstrated lower variance than the currently used average correlation. Combining the three methods, the throughput was improved 105-fold in simulation with a downsample factor of 4- and 20-fold in vivo with a downsample factor of 2.
Laser Direct Writing for VLSI

Publisher Summary This chapter discusses the work in the area of laser–chemical direct writing in which microscopic chemical reactions are used to modify surfaces. It describes specific methods for addition and deletion of structures by local deposition, etching, and doping of various thin-film and substrate materials. It also reviews some of the underlying laser-material interactions and presents some of the consequences of these considerations on process development. In general, laser direct-writing processes may be activated by photochemistry, for example, by free-radical processes under highly non-thermalized conditions or by thermalized chemistry that uses localized laser heating. Photochemical activation represents a more fundamental deviation from conventional planar processing conditions. It has been found from recent experiments that the spatial resolution possible for laser direct writing is, in many cases, from 0.2 to 0.5 μ m with currently available laser sources and focusing optics.
Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department.

OBJECTIVES Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED). METHODS A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate. RESULTS Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM. CONCLUSIONS The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.
Storing and generalizing multiple instances while maintaining knowledge-level parallelism

One of the primary problems in knowledge representation and learning is determining how multiple instances of concepts should be organized and represented. Symbolic approaches, such as semantic networks, have been successful at representing structured knowledge for parallel access. However, such approaches have had difficulty organizing multiple instances for automatic generalization and efficient retrieval. Parallel distributed processing systems (PDP) appear to offer a solution to these problems. Unfortunately, current PDP models have not yet been able to satisfactorily represent complex knowledge structures and they remain sequential at the knowledge level. This paper presents an approach which stores multiple instances in ensembles of PDP units and organizes the ensembles in a semantic network for parallelism and structure. Thus, the best features of both styles of representation are obtained.
An achievable dream

Jacobson talks about achieving a clean and renewable energy in the whole world. Despite the naysaying, he remains optimistic that a complete transition can happen globally. In the first issue of sustainable energy journal Joule, their team at Stanford University and the University of California Berkeley, set out road maps to achieve 100 per cent clean, renewable energy in 139 countries, responsible for more than 99 per cent of all emissions. These show how a transition of all forms of energy for all uses to electricity is possible, supplied by 80 per cent wind, water and solar power by 2030 and 100 per cent by 2050.
Traditional Science in a World of Change

The contrasting experiences of permanence and change, of stability and flux, have furnished continuing challenges to human understanding since the origins of intellectual life. For over two thousand years, philosophers, theologians, poets, and scientists have struggled with the implications of this dichotomy. For the most part, treatises devoted to this topic have been characterized by a strong and consistent evaluative stance. The fluctuating and the ephemeral have typically emerged as problematic aspects of human experience, to be overcome by intellectual ingenuity or spiritual transcendence. In contrast, the search for permanence has often been invested with sanctity, whether it be in philosophy, science, religion, or the arts. In John Dewey’s words, “The conceptions that had reigned in the philosophy of nature and knowledge for two thousand years ... rested on the assumption of the superiority of the fixed and the final; they rested upon treating change and origin as signs of defect and unreality. (They laid) hands upon the sacred arc of absolute permanency” (1910, p. 46).
Phase Velocity and Attenuation of SH Waves in a Fiber-Reinforced Composite

We consider SH wave propagation in a fiber-reinforced composite which consists of a homogeneous, isotropic matrix, containing long, parallel, randomly distributed circular fibers of identical properties. The scattering of waves in the elastically inhomogeneous medium results in a frequency dependent velocity and attenuation of the coherent wave.
Pharmacotherapy of Down syndrome.

Introduction: Comorbid psychiatric disorders are common in Down syndrome (DS). Evidence for pharmacotherapy of psychiatric co-morbidity in DS is limited.Areas covered: This article reviews the lite...
The Psychology of Authenticity

Perceptions of authenticity (or, inauthenticity) have been shown to affect people’s judgments and behavior across a wide variety of domains. However, there is still ambiguity about how the concept ...
What Happened to the American Middle Class

This chapter surveys the literature exploring the decline of the American middle class from a variety of disciplinary perspectives, ranging from economic to political to social. It lays the groundwork for a policy agenda that integrates these approaches to address this pressing issue tugging at the heart of American democracy.
Blinatumomab As a Successful Bridge to Hematopoietic Stem Cell Transplant in a Down Syndrome Patient with Relapsed B-Precursor Acute Lymphoblastic Leukemia

Introduction Children with Down syndrome (DS) carry a 20-fold higher risk of developing acute lymphoblastic leukemia (ALL) than other children and have increased rates of treatment-related mortality (TRM) and relapse. The prognosis for relapsed DS-ALL patients is grim with long-term survival rates of 20%. Blinatumomab, a CD19/CD3 bispecific antibody, is FDA approved for relapsed pediatric pre-B ALL, and recently approved for patients with minimal residual disease (MRD). However there are few reports of the use of blinatumomab in DS-ALL patients, and no reports of blinatumomab as a bridge to stem cell transplant (SCT) in this population. Case Description A 19 year old male with DS presented with thrombocytopenia and was diagnosed with pre-B ALL. Upfront therapy included fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, pegaspargase, and rituximab for 8 cycles, and he achieved complete remission (CR). Maintenance therapy included 26 months of 6-mercaptopurine, vincristine, methotrexate, and prednisone. He relapsed 5 months after completion of therapy and was found to have a P2RY8-CRLF2 fusion. IgH gene rearrangement analysis by next generation sequencing (LymphoTrack assay) demonstrated clonal rearrangement. Re-induction therapy included vincristine, pegaspargase, and prednisone. He completed 2 additional courses of chemotherapy but continued to have MRD both by flow cytometry and LymphoTrack. Given persistent MRD with CD19+ lymphoblasts, he was treated with blinatumomab at the FDA recommended dosing; he had no signs of toxicity. He achieved negative MRD by flow cytometry and LymphoTrack after 1 cycle. He then proceeded to a T-cell depleted peripheral blood SCT from a 10/10 matched sibling after conditioning with total body irradiation, thiotepa, and cyclophosphamide. Post-SCT course was uncomplicated and he is now 1 year post-SCT with no evidence of leukemia and 100% donor chimerism. Conclusion Blinatumomab is clinically effective and safe for patients with relapsed/refractory pre-B ALL, yet there is limited information on its use in DS-ALL patients. These patients have been largely excluded from blinatumomab trials given their altered immune system and unknown level of innate T cell dysfunction, potentially altering the efficacy of blinatumomab. We present here the case of a 22 year old male with relapsed DS-ALL who remained MRD positive after several cycles of re-induction chemotherapy, but achieved a CR following 1 cycle of blinatumomab with no toxicities, and safely proceeded to SCT. Although this is a single case, it demonstrates clinical efficacy of blinatumomab in relapsed DS-ALL, suggesting that these patients' T cells can be engaged to recognized CD19-positive leukemic blasts. Furthermore, blinatumomab represents a particularly attractive bridging therapy to SCT for DS-ALL patients who experience high rates of TRM with traditional agents.
Do Long Term Outcomes Justify Third Time Redo Lung Transplantation

Purpose Graft failure remains a significant obstacle to long-term survival in lung transplantation (LT), however, the reported outcomes of reoperative LT are inferior to primary LT, and there is controversy of how best to manage a scarcity of donor allografts for candidates likely to derive maximum benefit. The outcomes of third-time LT have not been described in detail. Methods Review of UNOS database was performed. 3rd time recipients of LT were identified and compared to first-time and second-time LT recipients. Survival was estimated with Kaplan Meier method and compared using log-rank test. Influence of 2nd and 3rd LT was performed using univariate and multivariate analyses. Results 28 recipients of 3rd LT were compared to 1,252 2nd LT and 32,703 primary recipients. Patients of 3rd LT were younger (38.1 ± 16.0 years vs 44.4 ± 16.8 for 2nd LT, 52.6 ± 14.6 for primary LT), and have shorter wait list times (37.0 days [95% CI 9.0-67.5] vs 45.5 days [13.0-57.5] for 2nd LT and 112.0 [30.0- 329.0] for primary LT. Median survival was 60 months for primary LT, 32 months for 2nd LT, and 19 months for 3rd LT (log-rank p Conclusion Reoperative LT has significantly lower long-term survival compared to primary LT, and survival after 3rd LT appears to be worse than 2rd LT. Further work is needed to define which candidates are likely to benefit most from reoperative LT.
A breast cancer case-control study of polybrominated diphenyl ether (PBDE) serum levels among California women.

Abstract Purpose Polybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study. Methods Participants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100), and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders. Results The OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results. Conclusions Our findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.
I’ll Know One When I See It: Using Social Network Analysis to Define Comprehensive Institutions Through Organizational Identity

Comprehensive institutions (CIs) have long been characterized as middling universities with a confused identity and purpose. Yet, their historical origins demonstrate that they have served as an important point of access into higher education for marginalized student groups. Still, there remains little consensus over which institutions are CIs and what organizational characteristics are associated with being an CI. This study uses novel data on institutional comparison groups and a network approach to determine which institutions other U.S. colleges and universities define as CIs. The analysis provides a method for detecting culturally-defined organizational categories and clarifies the definition of a CI. Creating analytical clarity about which institutions are CIs has important implications for future research on these institutions and for policy that affects these institutions.
History of the Four Volumes of Decisions of the United States District Court for the Territory of Hawaii 1903-1917

The so-called "Estee's Reports," named for Judge Morris March Estee was an early case reporter in the Hawaiian Territory. Only four volumes of decisions of the United States District Court (USDC) for the Territory of Hawaiʻi were ever printed. They span the years 1903-1917. The decisions in these volumes do not appear in the Federal Reporter covering the same time frame. The Federal Supplement, a West Publishing created reporter of decisions of the federal district courts began in 1933. Prior to 1933, federal district court decisions appeared in the Federal Reporter.
Addressing bias in healthcare: Confrontation as a tool for bias reduction and patient and provider self-advocacy

Abstract The individual biases of health-care providers may be one contributor to the persistence of health disparities. Evidence suggests that health-care professionals, like members of the broader community, hold implicit biases, and furthermore that these biases are related to the quality of doctor–patient interactions. In this chapter, we propose that patient confrontation of physician bias may serve as a self-advocacy tool that reduces physician bias and improves quality of patient care. We discuss unique challenges and considerations for effective confrontation in the health-care setting. We also discuss the possibility of confrontation as a strategy that health-care providers may use to reduce expressions of bias from their patients. Finally, we discuss evidence on whether confrontation-based training effectively reduces bias in this setting.
Mechanosensitive pathways controlling translation regulatory processes in skeletal muscle and implications for adaptation

The ability of myofibers to sense and respond appropriately to mechanical signals is one of the primary determinants of the skeletal muscle phenotype. In response to a change in mechanical load, mu...
Robust determinants of income inequality

While economic theory suggests a wide range of potential determinants of income inequality, there is little consensus regarding the most relevant ones. Such a lack of consensus reflects, to an important extent, the impact of model uncertainty. Using model-averaging techniques—specifically WALS (weighted-average least squares)—to get at a robust set of determinants, our results underscore the multiplicity of factors behind rising national-level inequalities. In the cross-section, the level of development and demographics, as well as unemployment and globalization, seem to be key drivers. Trade and financial globalization have asymmetric effects, with trade integration associated with lower inequality, and financial globalization with higher inequality. Financial deregulation and technological change seem to be important drivers of inequality, particularly in advanced economies.
Transplanted interneurons improve memory precision after traumatic brain injury

Repair of the traumatically injured brain has been envisioned for decades, but regenerating new neurons at the site of brain injury has been challenging. We show GABAergic progenitors, derived from the embryonic medial ganglionic eminence, migrate long distances following transplantation into the hippocampus of adult mice with traumatic brain injury, functionally integrate as mature inhibitory interneurons and restore post-traumatic decreases in synaptic inhibition. Grafted animals had improvements in memory precision that were reversed by chemogenetic silencing of the transplanted neurons and a long-lasting reduction in spontaneous seizures. Our results reveal a striking ability of transplanted interneurons for incorporating into injured brain circuits, and this approach is a powerful therapeutic strategy for correcting post-traumatic memory and seizure disorders.
Acceleration of adjoint-based adaptation through sub-iterations

Abstract In this paper, we introduce an algorithm for reducing the cost of output-based error estimation and mesh adaptation through the use of a sub-iteration algorithm. A single sub-iteration is an adaptation iteration in which the most expensive solves—the primal and fine-space adjoint—are calculated only approximately. We intersperse sub-iterations with standard full-solve iterations to obtain accurate error estimates. The use of sub-iterations in between full-solves reduces the computational cost while improving solution accuracy per full-solve iteration. We demonstrate this method for steady, compressible Euler and Navier-Stokes simulations, discretized with the discontinuous Galerkin (DG) finite-element method. Because the acceleration in the output-based method is based on sub-iterations of the adaptation cycle, regardless of the discretization, the idea is not specific to DG and can be applied to general discretizations.
Communities Healing And Transforming Trauma (CHATT): A Trauma-Informed Speakers' Bureau for Survivors of Violence.

There is increasing recognition of the value of consumer participation in advocacy and community activism. Among trauma survivors, finding a sense of purpose and a way to make meaning from the trau...
Correlates of sexually transmitted infection testing following women’s release from jail: Correlates of STI testing following incarceration

Given incarcerated women’s frequent transitions between jail and community, it is important to seize opportunities to provide comprehensive health care. A potential time to provide care might be wh...
Specialized immune responses in the peritoneal cavity and omentum

The peritoneal cavity is a fluid filled space that holds most of the abdominal organs, including the omentum, a visceral adipose tissue that contains milky spots or clusters of leukocytes that are organized similar to those in conventional lymphoid tissues. A unique assortment of leukocytes patrol the peritoneal cavity and migrate in and out of the milky spots, where they encounter Ags or pathogens from the peritoneal fluid and respond accordingly. The principal role of leukocytes in the peritoneal cavity is to preserve tissue homeostasis and secure tissue repair. However, when peritoneal homeostasis is disturbed by inflammation, infection, obesity, or tumor metastasis, specialized fibroblastic stromal cells and mesothelial cells in the omentum regulate the recruitment of peritoneal leukocytes and steer their activation in unique ways. In this review, the types of cells that reside in the peritoneal cavity, the role of the omentum in their maintenance and activation, and how these processes function in response to pathogens and malignancy will be discussed.
Abstract 12527: Serum Amyloid A, Inflammasome Activation and Stroke

Serum amyloid A (SAA) proteins are critical to the regulation of inflammation in systemic as well as neurological diseases. Studies have shown that during an acute phase response (APR), SAA levels ...
Aberrant expression of HMB45 and negative PRAME expression in halo nevi

Background Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). Methods PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. Results Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. Conclusion Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.
Enhanced Two-photon Absorption with Deep Learning-based Computer Generated Holography

We propose a new algorithm for 3D computer-generated holography with deep learning. Experiments in a two-photon microscope show that our method outperforms alternate algorithms and can optically stimulate cells with significantly less tissue heating.
Endoscopic resection of juvenile nasopharyngeal angiofibromas

Juvenile nasopharyngeal angiofibromas (JNAs) are a rare, highly vascular benign tumor affecting adolescent males. Recent advances in endoscopic visualization and technique have allowed for complete extirpation of these tumors endoscopically. Proponents of this approach find benefit in the lack of facial incisions, decreased intraoperative blood loss, and excellent tumor control. This chapter describes the endoscopic approach to JNAs.