cssi/SciSciGPT-SciSciNet huggingface dataset:
Benchmarking Observational Analyses Against Randomized Trials: a Review of Studies Assessing Propensity Score Methods

Observational analysis methods can be refined by benchmarking against randomized trials. We reviewed studies systematically comparing observational analyses using propensity score methods against randomized trials to explore whether intervention or outcome characteristics predict agreement between designs. We searched PubMed (from January 1, 2000, to April 30, 2017), the AHRQ Scientific Resource Center Methods Library, reference lists, and bibliographies to identify systematic reviews that compared estimates from observational analyses using propensity scores against randomized trials across three or more clinical topics; reported extractable relative risk (RR) data; and were published in English. One reviewer extracted data from all eligible systematic reviews; a second reviewer verified the extracted data. Six systematic reviews matching published observational studies to randomized trials, published between 2012 and 2016, met our inclusion criteria. The reviews reported on 127 comparisons overall, in cardiology (29 comparisons), surgery (49), critical care medicine and sepsis (46), nephrology (2), and oncology (1). Disagreements were large (relative RR 1.43) in 68 (54%) and statistically significant in 12 (9%) of the comparisons. The degree of agreement varied among reviews but was not strongly associated with intervention or outcome characteristics. Disagreements between observational studies using propensity score methods and randomized trials can occur for many reasons and the available data cannot be used to discern the reasons behind specific disagreements. Better benchmarking of observational analyses using propensity scores (and other causal inference methods) is possible using observational studies that explicitly attempt to emulate target trials.
Retrospective Analysis of HER2+ Breast Cancer Outcomes at a County Hospital: Do Published Outcomes Hold up in the Real World?

Introduction Landmark trials repeatedly demonstrate that pertuzumab and trastuzumab plus standard chemotherapy have the best outcomes in human epidermal growth factor receptor 2 (HER2) positive breast cancer in the neoadjuvant, adjuvant, and metastatic setting. However, many of these multicenter landmark trials lack diversity and studied largely Caucasian populations. Our goal is to address this under-representation of minorities, and compare pathologic complete response (pCR) rates in our predominantly Hispanic population with HER2 positive breast cancer receiving the same neoadjuvant chemotherapy (NACT) at Olive View-UCLA Medical Center (OVMC) to that of pCR rates observed in the TRYPHAENA trial. Methods For this retrospective cohort study, we compiled a list of 53 patients aged 18 and older, 52 female and 1 male, with HER2 positive breast cancer identified by fluorescence in situ hybridization treated at OVMC from December 2015 to May 2018. Our population was 57% Hispanic, 13% white, 13% Filipino, 11% Asian, 2% black, and 4% other. The complete list included patients receiving standard neoadjuvant, adjuvant, and metastatic chemotherapy regimens. We analyzed 23 female patients with HER2 positive breast cancer staged I to IIIC, receiving standard NACT (docetaxel, carboplatin, trastuzumab, and pertuzumab). Metastatic HER2 positive breast cancer patients were excluded. The primary outcome studied was pCR rates after receiving NACT. pCR was defined as the absence of invasive cancer cells from tissue samples removed after surgery. Secondary outcomes measured were side effects of chemotherapy. pCR rates and side effects were compared to TRYPHAENA. Data regarding insurance status, breast cancer detection modality, and time to seek medical attention were recorded. Results 50% of our patients who received NACT achieved pCR. Our pCR rates mirrored those observed in the TRYPHAENA trial (51.9%). The most common side effect observed in our population was diarrhea. A higher proportion (37.5%) of our patients had liver function test (LFT) elevation compared to the TRYPHAENA trial (3.9%). Baseline LFTs were normal prior to treatment in 96% of patients. In terms of modality of detection, 70% were self-palpated, 26% were detected through routine mammography, and 4% were found incidentally. Average time from mass discovery to seeking medical attention was 3.4 months. Only 26% had medical insurance at diagnosis. Although not included in our study, 28% of our patients were initially diagnosed with stage IV metastatic disease. Conclusion: Our study found that pCR rates in our primarily Hispanic population compared well to the response rates observed in landmark trials with largely Caucasian populations. Genetic variations in chemo-sensitivity may have a minimal influence on cancer care outcomes in this population.
The National Death Index as a Source of Homicide Data: A Methodological Exposition of Promises and Pitfalls for Criminologists.

Criminologists largely rely on national deidentified data sources to study homicide in the United States. The National Death Index (NDI), a comprehensive and well-established database compiled by t...
Four-Dimensional Anisotropic Mesh Adaptation

Abstract Anisotropic mesh adaptation is important for accurately simulating physical phenomena at reasonable computational costs. Previous work in anisotropic mesh adaptation has been restricted to studies in two- or three-dimensional computational domains. However, in order to accurately simulate time-dependent physical phenomena in three dimensions, a four-dimensional mesh adaptation tool is needed. This work develops a four-dimensional anisotropic mesh adaptation tool to support time-dependent three-dimensional numerical simulations. Anisotropy is achieved through the use of a background metric field and the mesh is adapted using a dimension-independent cavity framework. Metric-conformity – in the sense of edge lengths, element quality and element counts – is effectively demonstrated on four-dimensional benchmark cases within a unit tesseract in which the background metric is prescribed analytically. Next, the metric field is optimized to minimize the approximation error of a scalar function with discontinuous Galerkin discretizations on four-dimensional domains. We demonstrate that this four-dimensional mesh adaptation algorithm achieves optimal element sizes and orientations. To our knowledge, this is the first presentation of anisotropic four-dimensional meshes.
Simulating Exposure-Related Health Effects: Basic Ideas

This is the first of four chapters that explain and apply the dynamic simulation approach to health risk assessment modeling introduced in Chap. 2. The exposition in this chapter is motivated by an observation made by toxicologist Julie Goodman of Gradient, who coauthored the article on which this chapter is based (Cox Jr et al. 2020): most of the key ideas of the dynamic simulation approach can be explained through relatively simple diagrams, without going through the underlying equations. This chapter undertakes such a high-level diagrammatic exposition. It returns to two of the diagrams used in Chap. 2 to introduce simulation modeling, and adds further discussion and diagrams to help understand and visualize the dynamic responses of internal doses to different time patterns of exposure. Chapters 4, 5, and 6 and their appendices then cover the same material in much greater depth, providing the underlying systems of equations used to model biological responses to exposures to inhaled respirable crystalline silica (Chap. 4) and asbestos (Chap. 5) and highlighting the importance of nonlinearities in these responses for risk assessment and risk management (Chap. 6).
The Bibliographic Work: History, Theory, and Practice

The bibliographic work has assumed a great deal of importance in modern cataloging. But the concept of the work has existed for over a century, and even some of the earliest catalog codes different...
The Impact of Under-triage on Trauma Outcomes in Older Populations ≥65 Years:

BackgroundUndertriage of older trauma patients is implicated as a cause for outcome disparities. Undertriage is defined by an Injury Severity Score (ISS) ≥16 without full trauma activation. We hypo...
Artificial Neural Networks Applied to Stabilization of 81-beam Coherent Combining

An artificial neural network is used to stabilize 2D, diffractive, 81-beam coherent combining. Simulations demonstrate a neural network can predict phase errors based on pattern recognition of the uncombined beams and can correct them in one step.
Diverse computer simulation models provide unified lessons on university operation during a pandemic

Despite the ongoing COVID-19 pandemic, many US universities decided to open their campuses, invite students to the dorms, and hold in-person instruction, relying on various policies for mitigating the chance of experiencing an outbreak. The policies cover a wide range including on-campus testing, contact tracing, isolation and quarantine, encouraging mask use and social distancing, and redesigning class environments to provide enough space between individuals. The authors of this viewpoint have been involved in an intense 5-month modeling of the spread of COVID-19 in universities, applying various modeling techniques, including network analysis, system dynamics, differential-equation modeling, agent-based stochastic simulations, and statistical approaches. For several reasons, including the financial viability of academic institutions and the social and pedagogical benefits of having students on campus, many universities decided to follow the path of opening campuses and providing the option of in-person or hybrid classes. In preparation for reopening of in-person instruction, academic institutions across the country spent significant time and effort to keep their campus and classrooms safe. The simulation models show that tests are necessary, but in order to effectively contain the disease, several stringent criteria should be met about how testing is implemented;otherwise, testing and isolation are ineffective to contain sizeable outbreaks. First, testing of the majority of the university community on arrival to the community is crucial in order to minimize importation and, therefore, slow down the early spread of the disease. Second, comprehensive testing of everyone, including faculty and staff members, should continue for the duration of the academic term at a high frequency;otherwise, the initial missed cases are enough to cause a substantial outbreak. However, a significant portion of the overall university community faculty and staff members are much more likely to fall in high-risk populations. The spread of the disease among students and the broader community comes with high likelihood of fatalities among this population. Universities must accept that the implementation of policies sufficient to prevent or curtail an outbreak will be challenging, costly, and fraught with setbacks.
Youth and parent report of sleep-based interventions and utilization of technology resources in the treatment of pediatric mood disorders.

Objectives:Mood disorders in youth are associated with social and academic impairment, and difficulties within the family system. Engagement in sleep hygiene, and family- and technology-based treat...
Reducing Unjust Convictions: Plea Bargaining, Trial, and Evidence Suppression/Disclosure

We develop a dynamic model of the disposition of a criminal case, allowing for the potential discovery of exculpatory evidence by prosecutors (who choose whether to disclose this evidence) and by defendants, as the case proceeds from arrest through plea bargaining and (possibly) trial. We characterize equilibrium behavior by prosecutors and defendants, under three different disclosure regimes: (1) no disclosure is required; (2) disclosure is required before trial; and (3) disclosure is required from the point of arrest onward. A prosecutor who has (resp., has not) privately observed exculpatory evidence is called an “informed” (resp., “uninformed”) prosecutor. When no disclosure is required, an informed prosecutor makes a lower plea offer than one who is uninformed; no case is dropped voluntarily. When disclosure is required only prior to trial, then an informed prosecutor makes the same offer as an uninformed prosecutor, but an informed prosecutor will disclose and drop the case following a rejected plea offer. Finally, when the prosecutor is required to disclose prior to plea bargaining, then an informed prosecutor discloses and drops the case, whereas an uninformed prosecutor makes the same offer as in the no-disclosure regime, and never voluntarily drops the case. In all regimes, some innocent defendants accept the plea offer and others reject it (and similarly for guilty defendants). We find that both regimes requiring some disclosure, as compared with a no-disclosure regime, are (at least weakly) more likely to convict the guilty and less likely to convict the innocent (regardless of whether the prosecutor is informed or uninformed). However, the more-limited disclosure regime, as compared to the more-extensive regime, leads to a higher likelihood of conviction for innocent defendants facing an informed prosecutor, but a lower likelihood of conviction of innocent defendants facing an uninformed prosecutor and a lower likelihood of conviction of guilty defendants.
A rare description of pure partial trisomy of 16q12.2q24.3 and review of the literature

Trisomy 16 is the most common autosomal trisomy in humans, which is almost uniformly embryonic lethal. Partial trisomy 16 including a segment of the long arm of chromosome 16 is occasionally compatible with life and has been associated with severe congenital defects, growth retardation, and early lethality. Segmental trisomy of 16q is usually described concomitantly with partial monosomy of another chromosome, often resulting from a parental balanced translocation. Pure partial chromosome 16q trisomy is exceedingly rare. About nine children with 16q12→qter and 16q13→qter duplication have been reported in the literature, almost all described with monosomy of a second chromosome, and highlighting very few long-term survivors. A single individual with pure partial distal 16q12.1q23.3 duplication has been reported in an infant, underscoring complexities of genetic counseling and management, especially in view of life-limiting congenital anomalies in rare survivors. Here, we present a 12-month-old child with pure 16q12.2q24.3 trisomy, having continued morbidity related to pulmonary hypertension and chronic lung disease. The features of intrauterine growth retardation, facial dysmorphism, hypotonia, congenital heart defect, distal contractures, urogenital abnormalities, and hearing loss support the association with 16q partial trisomy, as in previous studies. This report expands our current understanding related to the survival of infants with large segmental aneusomy of the long arm of chromosome 16.
The Effect of Sorghum Polyphenols on DNA Methylation and Histone Acetylation in Colon Cancer

Objectives Colorectal cancer (CRC) is a major public health issue, accounting for nearly 150,000 cases annually. Because CRC correlates with oxidative stress, exploiting the antioxidative nature of bioactive components in our diet that could potentially inhibit cancer promotion might be beneficial. New varietals of the grain Sorghum bicolor contain high amounts of polyphenols, which may contribute to CRC prevention due to their strong antioxidative and anti-carcinogenic properties. Because gene expression of enzymes may be mediated by epigenetic mechanisms, we are interested in DNA methylation and histone acetylation patterns of genes, including those enzymes that play a role in the promotion or prevention of CRC. Our objective is to examine how high-polyphenol sorghum varietals impact epigenetic mechanisms in human colon cancer cells.
WS5.5. Electroencephalographic Monitoring

Electroencephalographic (EEG) monitoring was one of the first neurophysiologic techniques to be used in the operating room. EEG helps assess cerebral function during surgical procedures. It is different than evoked potential monitoring in the operating room as there is no stimulus used to elicit the waveforms, rather ongoing “spontaneous” activity is assessed. One of the earliest applications of EEG in the operating room was to determine adequacy of cerebral perfusion during carotid endarterectomy surgery. Subsequently, many other uses have been realized for EEG monitoring. In this presentation, the specifics of EEG recording techniques in the operating room will be discussed. Anesthetics can greatly affect the EEG, and these effects will be reviewed. How and why the EEG changes during surgery will be discussed as well. Finally, the clinical applications for EEG monitoring will be reviewed.
Rolling-Circle Replication

Plasmids that replicate by a rolling-circle (RC) mechanism are ubiquitous in gram-positive bacteria and are also found in gram-negative bacteria as well as in Archaea. This chapter discusses the general anatomy of rolling-circle replicating (RCR) plasmids, architecture of the double-strand origin (dso), the single-strand origin (sso), the initiator proteins and their structure-function relationship, key events during the initiation and termination process, and the role of host proteins in plasmid RC replication. It highlights the gaps in the current understanding of the replication of RCR plasmids and possible future lines of research that may uncover these gaps. The first of the RCR plasmids to be identified were native to the gram-positive bacterium, Staphylococcus aureus. The Rep proteins of the pT181 family act as dimers and utilize Tyr-191 of the two monomers in the initiation and termination events. Biochemical analyses using heterodimers of the pT181 RepC protein have provided insights into the role of individual monomers in plasmid RC replication. Elucidation of the three-dimensional structure of plasmid Rep proteins should considerably increase the understanding of the mechanistic aspects of plasmid RC replication. The availability of crystal structures of the initiators of various plasmid families should provide major insights into the mechanisms of initiation and termination of plasmid RC replication.
The mechanism of evagination of imaginal discs of Drosophila melanogaster. III. Evidence for cell rearrangement.

The shape and arrangement of cells in leg discs of Drosophila melanogaster at different stages of evagination were examined by scanning electron microscopy. The observations indicate that the change in shape of the disc during evagination is largely a result of cell rearrangement. This process involves small movements of many cells within the disc epithelium while close associations between neighboring cells are maintained.
The American Adoption of Indian Children from Mother Theresa's Orphanages: The Parents.

ABSTRACT This study explores the family backgrounds and personal motives of 70 families who adopted Indian children from Mother Theresa's orphanages in the late 1970s and 1980s. We ask what kind of people seek to adopt children of another ethnic group and color who also are highly likely to have chronic disabilities -physical, emotional, behavioral, intellectual. Our inquiry, while without formal hypotheses, was informed by depictions of altruists and rescuers of Holocaust victims. We found a strong resemblance between the adoptive parents, altruists and rescuers in the following respects: (1) the description of their backgrounds and their own life choices as ordinary; (2) the description of early development and early family relationships as extremely mentally healthy; (3) the highly ethical orientation of their lives combined with a lack of specific ideological commitments.
Differentiating service tasks for IT application

This research investigates the study of service operations and information technology (IT) in order to observe the interaction between these two constructs. Phase I utilizes a Delphi study, involving 31 participants from 11 organizations, to provide initial specification of a service typology based on task requirements. Phase II of the research is a multiple case study that further refines the construct specifications and analyzes the dynamics of the interaction between components of the service task and IT. Results of the Delphi and case analysis suggest that differentiation within the service task construct occurs along an expertise‐based continuum that incorporates four primary task requirements. These requirements include knowledge‐base, level of standardization and two databased elements, data configuration and data interpretation. The case analyses further indicate the presence of three primary levels of task requirements – transaction processing, request fulfillment and problem resolution. Early results from the task‐IT interaction analysis suggest that the task‐IT relationship affects critical operations factors such as process innovation, IT diffusion rates, achievement of informational and operational advantage, performance measurement and elements of service quality.
CHILD DEVELOPMENT: A BASIC SCIENCE FOR PEDIATRICS

ALTHOUGH I have considered presenting some of the work of our group on this occasion, I have elected, rather, to discuss an issue which I feel to be of importance not alone to those of us interested in child development, but to all pediatricians (and indeed to all interested in child welfare). I refer to the role of child development in pediatrics—most particularly academic pediatrics. To the members of this section it is no surprise to observe that teaching and research in child development have not been integrated into the mainstream of academic pediatrics. It continues, with rare exceptions, to be treated as a minority group in the academic community, even though a knowledge of child development is a major concern of the practicing pediatrician. This relative neglect causes me to inquire as to whether we are to have two cultures or one in pediatrics. At the outset I wish to indicate that my bias is clearly in favor of a unitarian view. For, I believe we continue this dichotomy at our peril in pediatric teaching and research. Perhaps we can deal with this problem better if we understand how we came to be this way. I will, therefore, attempt to develop my thesis from an historical perspective. These periods are arbitrarily defined; although starting dates are given, there are no end points, since each new period is telescoped into the rich history of its antecedents (Fig. 1). The prescientific era in pediatrics (prior to 1900) was rich in contributions to our understanding of child development.
Treatment of Overactive Bladder in the Elderly Female: The Case for Trospium, Oxybutynin, Fesoterodine and Darifenacin

Overactive bladder (OAB) is a common constellation of lower urinary tract storage symptoms that causes a significant impact on a person's quality of life. The elderly may be disproportionally impacted by these symptoms due to concomitant poor mobility, comorbid conditions such as diabetes and heart failure, and polypharmacy. While behavioral modification and pelvic floor muscle training should be considered first-line treatment options, pharmacotherapy remains the backbone of the therapeutic regimen. Trospium, oxybutynin, fesoterodine, and darifenacin all have unique properties that may confer certain advantages in the elderly population. The hydrophilicity and quaternary amine structure of trospium may limit its ability to cross the blood-brain barrier and thus minimize impact on cognition in the elderly. In its oral form, oxybutynin may have the most significant effect on cognition; however, the transdermal preparations may be favorable in the elderly population due to the ability to avoid first-pass metabolism and its limited antimuscarinic adverse effects. Fesoterodine may be the most extensively studied OAB medication in the elderly population. Darifenacin has a strong affinity for the M3 receptor in the bladder, while having a weak affinity for the M1 receptor commonly found in the brain. It must be noted that all muscarinic receptor antagonists are associated with common adverse effects to some degree, and frequent re-evaluation of the elderly patient is necessary to confirm the proper benefit-to-risk profile.
Use of C1 Inhibitor for Angiotensin-Converting Enzyme (ACE) Inhibitor-Induced Angioedema Decreases Mechanical Ventilation Time

Abstract Background Angiotensin-converting enzyme (ACE) inhibitor–induced angioedema is a rare, albeit serious emergency that can result in airway compromise and potentially death if not treated promptly. Currently, there are no agents approved by the Food and Drug Administration to target ACE inhibitor angioedema and to prevent intubation. C1 inhibitors are approved for hereditary angioedema but may show promise in alleviating inflammation associated with ACE inhibitor angioedema. Case Report A 41-year-old man presented to the emergency department with swelling of his lips a few days after starting lisinopril for hypertension. Despite receiving diphenhydramine, ranitidine, and methylprednisolone, the swelling progressed to the patient's tongue. A C1 inhibitor was ordered in an effort to prevent intubation. Before the arrival of the medication, the patient was intubated emergently for airway protection. After receipt of the C1 inhibitor, the swelling dramatically improved, and the patient was successfully extubated after less than 18 hours from presentation. Why Should an Emergency Physician Be Aware of This? This case illustrates a potential role for C1 inhibitors in the emergency setting for treating drug-induced angioedema, which may prevent or minimize mechanical ventilation time.
Highly Reliable High Power Diode Laser for Laser Radar Application

In 1997, we have applied laser technology to the world's first practical adaptive cruise control (ACC) system. The ACC system is based on 2-dimensional scanning laser-radar-sensor technology that is supported by highly reliable high power diode laser. Now, we have developed 34W output power multiple-quantum-well (MQW) diode laser. The power of 870nm near IR diode laser is twice as high as conventional one, thus it meets the strong needs for robust detection of the reflective laser beams from the moving vehicle ahead. Furthermore, Au-Sn-Ni a new alloy solder has been employed to sustain high degree of vibration and thermal shock to raise reliability. The acceleration life-tests at high temperature pulsed operation demonstrate the high reliability of developed 34W high power diode laser.
Electron-phonon interaction and scattering in Si and Ge: Implications for phonon engineering

We report ab-initio results for electron-phonon (e-ph) coupling and display the existence of a large variation in the coupling parameter as a function of electron and phonon dispersion. This variation is observed for all phonon modes in Si and Ge, and we show this for representative cases where the initial electron states are at the band gap edges. Using these e-ph matrix elements, which include all possible phonon modes and electron bands within a relevant energy range, we evaluate the imaginary part of the electron self-energy in order to obtain the associated scattering rates. The temperature dependence is seen through calculations of the scattering rates at 0 K and 300 K. The results provide a basis for understanding the impacts of phonon scattering vs. orientation and geometry in the design of devices, and in analysis of transport phenomena. This provides an additional tool for engineering the transfer of energy from carriers to the lattice.
An Integrated Development Of A Dynamic Software-Fault Monitoring System

The problems being solved by today's software systems are becoming more complex and are requiring the integration of knowledge from multiple domains. As a result, traditional verification and validation techniques may not be sufficient to identify the existence of software faults. Augmenting these techniques with runtime software-fault monitoring can ensure that software behaves in accordance with constraints elicited from domain experts in varying areas or fields. Previous approaches to software-fault monitoring require the developer to specify pre- and post-conditions on modules, specify constraints on data types, and/or insert constraints at appropriate execution points. The approach described in this paper, Dynamic Monitoring with Integrity Constraints (DynaMICs), addresses issues that have hindered adoption of previous approaches by limiting human intervention to constraint definition and justification and minimizing performance degradation. Unlike other software-fault monitoring systems, DynaMICs captures domain-specific and implementation-independent knowledge through integrity constraints. This paper describes the techniques and knowledge that must be integrated in order to realize this system.
Development of thin-film plastic scintillator detectors for use in in-beam fission studies

Abstract Thin-film plastic scintillators have been developed for use as fission detectors in direct-reaction-induced fission experiments. The method of detector fabrication is described. Typical response to fission fragments produced both by a 252 Cf source and by charged-particle-induced fission of natural uranium is shown and discussed.
Food viscosity influences caloric intake compensation and body weight in rats.

Objective: To determine the effects of food viscosity on the ability of rats to compensate for calories in a dietary supplement. Research Methods and Procedures: In a series of four experiments, rats consumed dietary supplements equated for caloric and nutritive content but differing in viscosity. Experiments 1 to 3 examined the ability of the rats to compensate for the calories consumed in low- compared with high-viscosity premeals by reducing intake of a subsequent test meal. Caloric compensation was assessed with a wide range of premeal viscosity levels and with two different non-nutritive thickening agents. Experiment 4 assessed the effects of consuming daily a low-viscosity compared with an equicaloric high-viscosity dietary supplement on longer term body weight gain. Results: Consuming a lower viscosity premeal was followed by significantly more caloric intake (i.e., less caloric compensation) compared with consuming premeals with higher viscosity levels. This effect was not specific to one thickening agent. Furthermore, rats given a low-viscosity supplement daily gained significantly more weight over a 10-week period compared with rats given a high-viscosity supplement. Discussion: The results of these experiments suggest that food viscosity may be an important determinant of short-term caloric intake and longer term body weight gain.
In vitro and in vivo immune responses in neonatally thymectomized holstein-friesian calves exposed to bovine viral diarrhea virus☆

Abstract Neonatally thymectomized and normal Holstein-Friesian calves were exposed to bovine viral diarrhea virus and challenged 22 days later. Baseline values in non-specific mitogen induced lymphocyte blastogenesis and serologic responses to tetanus toxoid and Brucella abortus strain 19 were established in neonatally thymectomized and normal calves. Neither viral recovery nor protective antibody production followed the very low level primary exposure to bovine viral diarrhea virus. The expected clinical response to an appropriate challenge inoculum did not occur, however, suggesting an immune response to bovine viral diarrhea virus had been initiated by the primary exposure. Five of eight calves developed protective serum levels of bovine viral diarrhea antibody. This may represent an example of immunologic priming. Exposure to low levels of bovine viral diarrhea virus also has potential implications in the pathogenesis of chronic bovine viral diarrhea wherein low level exposure may interfere with the development of protective levels of bovine viral diarrhea antibody as was observed in three calves. Circulating lymphocyte concentrations and results of non-specific mitogen stimulation of lymphocytes revealed a reduced phytohemagglutinin response in conjunction with a slightly increased response to bacterial lipopolysaccharide and pokeweed mitogen in the presence of moderate lymphopenia. The capacity of lymphocytes to respond to phytohemagglutinin was unchanged but an increased total response, as occurred in control thymectomized and intact calves, did not occur. The response to tetanus toxoid, a thymus-independent antigen, was increased following exposure to bovine viral diarrhea virus, perhaps reflecting an alteration in thymic-independent regulation. The lack of a differential response to Brucella abortus strain 19 implied competence in thymus-dependent helper cells.
Transport of Bacillus anthracis from the lungs to the draining lymph nodes is a rapid process facilitated by CD11c+ cells

Inhalational anthrax is established after inhaled Bacillus anthracis spores are transported to the lung associated lymph nodes. Dendritic cells (CD11c+ cells) located in the lungs are phagocytes that maintain many capabilities consistent with transport. This study investigates the role of dendritic cells as conduits of spores from the lung to the draining lymph nodes. The intratracheally spore-challenged mouse model of inhalational anthrax was utilized to investigate in vivo activities of CD11c+ cells. FITC labeled spores were delivered to the lungs of mice. Subsequently lung associated lymph nodes were isolated after infection and CD11c+ cells were found in association with the labeled spores. Further investigation of CD11c+ cells in early anthrax events was facilitated by use of the CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice in which CD11c+ cells can be transiently depleted by treatment with DT. We found that the presence of CD11c+ cells was necessary for efficient traffic of the spore to lung associated lymph nodes at early times after infection. Cultured dendritic cells were used to determine that these cells are capable of B. anthracis spore phagocytosis, and support germination and outgrowth. This data demonstrates that CD11c+ cells are likely carriers of B. anthracis spores from the point of inhalation in the lung to the lung associated lymph nodes. The cultured dendritic cell allows for spore germination and outgrowth supporting the concept that the CD11c+ cell responsible for this function can be a dendritic cell.
NONLINEAR OPTICAL STUDIES OF BACTERIORHODOPSIN

We report interesting results on nonlinear optics at low powers in bacteriorhodopsin films with applications in all-optical switching and modulation. Chemically stabilized films of bacteriorhodopsin in a polymer matrix for which the lifetime of the excited M state is 3 to 4 orders of magnitude longer than that of water solutions of wild-type bR were used in these experiments. Due to the sensitivity of the films, very small powers of order microwatts are required for optical phase conjugation. The influence of the fast photochemical M to B transition induced by blue light on the saturation intensity, phase conjugate intensity and switching time was established. We also report our measurements of the intensity dependence of the self-focusing and self-defocusing properties of wild-type bR in water solution using the Z-scan technique with low power cw lasers at two wavelengths on either side of the absorption band. Our measurements indicate that the sign of the nonlinearity depends on the wavelength and the magnitude depends on the fluence of the incident laser beam. The observed self-focusing and defocusing is not due to the intrinsic electronic nonlinearity. The observations can be explained in terms of the Kramers-Kronig dispersion relation that relates the real and imaginary parts of the complex index of refraction.
Mean field limits by population acceleration

Mean field or large population limits are useful analytical tools that provide well justified approximations to finite systems. Motivated by problems in Game Theory and Queueing Theory we provide a framework to develop mean field limits that emerge from finite population systems in a very general setting. Our results prove new generalizations of the standard Glivenko-Cantelli and Donsker's Theorems. We prove these limits by making use of an analytical technique called population acceleration first introduced in [1] to study transtitory queueing models.
Novel, complex interruptions of the GAA repeat in small, expanded alleles of two affected siblings with late‐onset Friedreich ataxia

Friedreich ataxia (FA) is an autosomal recessive disorder associated with expanded GAA repeats in intron 1 of the FRDA gene. Two siblings presented with a mild form of FA at >60 years of age. Both had a large expansion (>600 repeats) and a small expansion (120 repeats) by long-range PCR. Sequence analysis of the small allele revealed multiple, complex interruptions in the GAA repeat. These 2 patients presented later than predicted from their allele size alone, when compared with a large cohort of FA patients. Accounting for the interruptions in the GAA repeat, though, did not make the age of onset consistent with that noted in other patients. Three additional patients with late onset FA and small expanded alleles also exhibited interrupted GAA repeats that were not associated with inappropriately late onset. Our observations suggest that interrupted GAA repeats do not clearly impact the age of onset in FA.
Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

Chronic exposure to cocaine is associated with neuroadaptions in stress and reward circuits that may increase susceptibility to relapse. We examined whether there are alterations in stress response and craving in abstinent cocaine-dependent individuals compared with a demographically matched group of non-addicted socially drinking community controls. Forty treatment-engaged abstinent cocaine patients (17F/23M) and 40 controls (19F/21M) were exposed to a brief 5 min guided imagery of individually calibrated stressful situations, personal drug/alcohol-related situation and a neutral-relaxing situation, one imagery per session, presented in random order. Craving, anxiety, emotion rating scales, and physiological measures were assessed. Cocaine patients reported significantly higher and more persistent stress- and cue-induced drug/alcohol craving, negative emotions, and physiological responses compared with social drinkers. In cocaine patients, stress- and cue-induced drug craving was accompanied by increased anger, fear, sadness, heart rate, and SBP. Controls reported minimal stress-induced craving and only increases in anxiety and SBP during stress exposure. Cue-induced alcohol craving was accompanied only by an increase in relaxed state. Females reported increased stress-induced anxiety and sadness compared with males, while males were emotionally and physiologically more reactive in the cue condition. These findings are the first to document functional alterations in stress- and reward-related affect and physiology in recently abstinent cocaine patients that is marked by an enhanced sensitivity to stress- and drug-related cue exposure. These data suggest that recovery from chronic cocaine abuse could be hampered by a hyper-responsive stress- and drug-craving state that increases cocaine relapse susceptibility.
Some further observations on the stimulation by high external potassium of the sodium efflux in barnacle muscle fibers

A study has been made in single barnacle muscle fibers of the mechanism underlying the stimulatory response of the ouabain-insensitive Na efflux to high K0. Fibers poisoned with ouabain and preinjected with GTPNa2 show a biphasic stimulatory response to 100 mK K0 which is practically abolished by exposure of these fibers to verapamil. Prior or post-injection of cAMP-protein kinase type II regulatory subunits reduces the size of the response to 100 mK K0. Prior injection of cAMP-protein kinase catalytic subunits (CSU) attenuates the response to 100 mM K0 in fibers showing moderate sensitivity to CSU. In fibers showing extreme sensitivity to injected CSU, elevation of K0 partially reverses the sustained stimulatory response to CSU. Prior injection of Mg2+ leads to almost complete abolition of the response to 100 mM K0. External and internal application of F− reduces the response to 100 mM-K0. Injection of KF following decay of the response to high K0 results in a sustained stimulatory response. The drugs, chlorpromazine, trifluoperazine, imipramine and diphenylhydantoin are able to appreciably reduce the response to 100 mK K0. Taken together, these observations support the idea that the stimulatory response to high K0 is primarily due to activation by newly formed cAMP of cAMP-protein kinase, and that the transitory nature of the response and variable sensitivity of these fibers to high K0 is closely linked to the activity of a putative Mg2+-dependent protein phosphatase.
Molecular composites based on thermosetting matrix polymers: Poly(p‐phenyleneterephthalamide)‐epoxy

Poly(p-phenyleneterephthalamide) (PPTA) reinforced molecular composites that utilize a thermosetting epoxy as the matrix polymer have been prepared by an in situ polymerization process. The properties of these molecular composites were compared with those of Kevlar pulp-filled composites that utilized the same matrix formulation. Study of the curing reactions of these systems using Fourier transform infrared, dynamic mechanical analysis, and nuclear magnetic resonance spectroscopy indicated some differences in the reactivity and ultimate polymer structure of these two systems. A comparison of the properties indicated increased tensile strength, modulus, and heat resistance for the molecularly reinforced material over the conventional fiber-filled system. Examination of the morphology of the molecular composite system showed that aggregated PPTA molecules are formed during the insitu polymerization process. This aggregation phenomenon was found to be due to formation of a liquid crystalline polymer solution during processing and final cure. These findings indicate the possibilities that exist in molecular composite processing for simultaneous control of the properties of the matrix and the reinforcement.
Adnexal torsion.: Can the adnexa be saved?

Abstract OBJECTIVE: Our purpose was to identify which cases of adnexal torsion may be managed with adnexal conservation. STUDY DESIGN: A retrospective chart review was conducted on all patients diagnosed with adnexal torsion between Feburary 1983 and February 1993 at four hospitals in the Emory University system. RESULTS: Fifty-nine patients ranging in age from 23 months to 73 years- (mean 31.9 years) were reviewed. Almost half of the patients were nulliparous. Lower abdominal pain (83%) and an adnexal mass (72%) were the most common presenting findings, but in general clinical findings were nonspecific. Most patients were treated with-extirpative therapy of the affected adnexa. Untwisting of the adnexa was performed in 10 patients; however, adnexal conservation was accomplished in only one patient. There were no thromboembolic complications in any of the patients. CONCLUSIONS: Adnexal torsion is a diagnostic challenge, often with nonspecific symptoms. There is growing evidence that untwisting the involved adnexa to observe for tissue reperfuslon and viability is safe. However, significant delay in surgical intervention may result in irreversible tissue necrosis, rendering the adnexa unsalvageable.
Realizing ‘Political’ Neutrality

Political liberalism is supposed to be neutral among reasonable comprehensive doctrines, including comprehensive liberalism. Some critics think that it implicitly assumes comprehensive liberalism. I argue that political liberalism has the resources to avoid this charge and chart a path between sectarianism and unprincipled accommodation that allows a range of policy justifications onto the political agenda of a scope that honors the ideal of neutrality.
Connexin Diversity: Discriminating the Message

In cardiac electrophysiology, gap junctions are often conceptualized as passive resistors that allow for electrical charge to move between cells. From that standpoint, gap junctions seem like rigid structures that sit idle between cells as small ions traverse across. Yet, although the importance of gap junctions in electrical synchronization is not questioned, it is generally accepted that these structures are more than electrical elements. Indeed, gap junctions are highly regulable molecular complexes present in the vast majority of cells in the body, including many cell types that are electrically nonexcitable. In addition to allowing the passage of ions, gap junctions allow the passage of small molecules as well. Hence, gap junctions provide not only electrical coupling to excitable cells but also metabolic coupling to all cell types where they are present.1 Yet, although the nature of the message that carries electrical information is rather well understood (ions carrying charge), the nature of the molecule(s) providing metabolic coupling is mostly unknown. The answer to the obvious question remains elusive: what goes through gap junctions in living cells? The answer to this question is complicated by the fact that not all gap junctions are exactly the same. Gap junctions are formed by the oligomerization of a protein called connexin (Figure). Six connexin subunits noncovalently bind to form a hemichannel (or connexon); two connexons, one provided by each cell, dock their extracellular domains and open a hydrophilic pore into the neighboring cytoplasmic spaces, forming a gap junction channel. Twenty connexins have been identified in the human genome.2 Each …
The interaction of human neutrophils and Entamoeba histolytica increases cytopathogenicity for liver cell monolayers

The in vitro interaction of neutrophils and virulent axenic Entamoeba histolytica trophozoites on Chang liver cells was studied to determine if the presence of neutrophils enhanced destruction of liver cell monolayers. Axenic amoebae (strain HM1:IMSS) destroy liver cell monolayers in a dose-dependent manner (P less than .001). Human neutrophils had no effect on the liver cell monolayers; however, when neutrophils were added to amoebae, destruction of monolayers was enhanced (P less than .05 compared with amoebae alone). Similar results were obtained when Chinese hamster ovary (CHO) cells were substituted for Chang cells (P less than .01). In this in vitro model, neutrophils were lysed by amoebae, as determined by release of 111Indium oxine from labeled neutrophils (P less than .001). The augmentation of cytopathogenicity for Chang cells was not inhibited by catalase (3,000 U/ml) and was observed with neutrophils from a patient with chronic granulomatous disease. N-Acetyl-D-galactosamine (45.0 mM) decreased monolayer destruction due to amoebae, with or without the presence of neutrophils (P less than .01). These studies establish that in vitro lysis of human neutrophils by E. histolytica enhances destruction of liver or CHO cell monolayers and that this effect is not due to release of neutrophil oxidative products.