cssi/SciSciGPT-SciSciNet huggingface dataset:
US Prescription Drug User Fee Act (PDUFA): An Introduction for the Pharmaceutical Physician

Originally enacted to address the delays in US Food and Drug Administration (FDA) new drug review due to chronic understaffing and outdated systems, the Prescription Drug User Fee Act (PDUFA) of 1992, with its 5-year reauthorization cycle, enabled rapid rigorous review and ushered in a new era of continuing program innovation, evaluation, and improvement. This has resulted in a scientifically and financially strong program with transparent stakeholder engagement as a routine way of doing business. The enhancements to the process of human drug review, conducted in the FDA Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), originally focused on the FDA review of a new drug application, have evolved and expanded to include extensive communication and consultation between drug sponsors and FDA throughout drug development, advances in regulatory science applied to drug development and regulatory oversight, strengthening and innovating approaches to post-market safety, increasing patient focus and modernizing supporting informatics. These enhancements, identified and supported in successive rounds of user fee negotiation with regulated industry, have enabled the USA to sustain global leadership in drug innovation, and earlier patient access to safe and effective new medicines.
Phasee I Biological Study of IV and SQ Azacitidine (Vidaza®) to Determine the Optimal Biological Dose in Hematologic Malignancies

Azacitidine (5-azacytidine, Vidaza) is a DNA methylation inhibitor that has been shown to have a survival benefit in patients with high-risk myelodysplastic syndrome and is under investigation in other cancers. The purpose of this study was to determine the optimal dose and route of administration for azacitidine to inhibit DNA methylation in patients with hematologic malignancies. Eligibility included patients with hematologic malignancy who provided informed consent. Enrollment criteria varied depending on the type of cancer. Patients were enrolled into 5 escalating dose levels for the first course of therapy (25mg, 50mg, 75mg, 100mg or 150mg IV per m2 per day for 5 days). On day 28 all patients received 75mg/m2/day IV for 5 days. For course 3 patients received 75mg/m2/day SQ × 5 days. Beyond course 3 patients received 75mg/m2/day either SQ or IV × 5 days every 4 weeks. Peripheral blood was collected on days 1, 3 and 5 for each course and LINE1 DNA methylation was measured using bisulfite-PCR Pyrosequencing to measure global DNA methylation changes induced by azacitidine. To date, 17 patients have been treated (3 at 25mg, 4 at 50mg, 4 at 75mg, 3 at 100mg, and 3 at 150mg/m2). Diagnosis included 6 patients with MDS, 9 patients with AML (3 untreated older patients, 6 relapsed or refractory patients), 1 patient with CML (imatinib refactory), and 1 patient with non-Hodgkin’s lymphoma (relapsed disease). At the time of submission (August 2008) 12 patients were evaluable for response with 1 CR, 3 PR, 7 SD and 1 PD reported. The median number of cycles given was 2 (range 0–12+). LINE1 DNA methylation decreased by 1.4, 2.3, 4.8, 1.9 and 4.0% on day 5 for the 25mg, 50mg, 75mg, 100mg, and 150mg/m2 dose levels respectively. Mean decrease in LINE1 DNA methylation with 75mg/m2 IV was 3.7% and only 2.6% by 75mg/m2 of azacitidine SQ. There was a large amount of inter-patient variability but less intra-patient variability in DNA methylation response to azacitidine. DNA methylation and data analysis is ongoing. Azacitidine is effective at inhibiting DNA methylation at multiple dose levels for both IV and SQ routes of administration. There is a high degree of patient-to-patient variability in DNA methylation changes, but 75mg/m2 lead to the greatest mean decrease in DNA methylation by a 5 day IV regimen. Updated analysis for this study will be presented.
Group Work with African American Men Who Batter: Toward more Ethnically Sensitive Practice

The literature on counseling the African American man who batters is sparse. Some researchers have noted an underrepresentation of this population in domestic violence treatment programs. One possi...
Bioengineering cardiac constructs using 3D printing

To date, 3D bioprinting has found many actual and potential applications in medicine through assembling cells, biomaterials and supporting factors into living tissues. In particular, the combination of bioprinting and tissue engineering has emerged as a new promising strategy to address the growing need for tissues and organs for both transplantation and basic research. This review summarizes the current progress in the design and printing of bioengineered cardiac tissues for various applications. We highlight the specific biological and technical complexities such as the choice of cells and biomaterials, cell viability and function, vasculature design and tissue architecture. Current challenges and future perspectives in the field of cardiovascular tissue printing are also discussed.
Pharmacokinetic and Pharmacodynamics Relationships

PET imaging is likely to be a valuable tool for informing multi-compartment PK analysis by directly providing tissue drug concentration as a function of time, enabling a better understanding of the quantitative relationship between drug doses, time, and drug concentrations at the site of infection. Improved PK models coupled with real-time noninvasive PET imaging will support the design of drug regimens and allow the effect of drug dose on tissue drug concentrations to be directly monitored.
Patient compliance for postoperative radiotherapy and survival outcome of women with stage I endometrioid endometrial cancer.

Background and Objectives To examine characteristics and survival outcome of women with endometrial cancer who declined postoperative radiotherapy. Methods A retrospective study was conducted to examine surgically-treated grade 1-2 stage IB and grade 3 stage IA-IB endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results Program between 1983 and 2013 (n = 10 613). Associations of patient declination for guideline-based postoperative radiotherapy and clinico-pathological demographics or survival outcome were examined on multivariable analysis. Results There were 323 (3.0%) women who declined adjuvant radiotherapy. Women who declined postoperative radiotherapy were more likely to be older, White, Western U.S. residents, and register in recent years (all, adjusted-P < 0.05). On multivariable analysis, patient declination for guideline-based postoperative radiotherapy remained an independent prognostic factor for decreased endometrial cancer-specific survival in unstaged grade 1-2 stage IB or staged/unstated grade 3 stage IA-IB diseases (adjusted-hazard ratio 1.84, 95% confidence interval 1.34-2.51, P = 0.001). Association of patient declination for guideline-based postoperative radiotherapy and decreased overall survival remained independent in the entire cohort on multivariable analysis (adjuvant-hazard ratio 1.71, 95% confidence interval 1.44-2.02, P < 0.001). Conclusions Our study suggested that patient compliance to guideline-based postoperative radiotherapy is a prognostic factor for women with stage I endometrioid endometrial cancer.
Auditory Processing of Echoes: Representation of Acoustic Information from the Environment in the Bat Cerebral Cortex

Clues to understanding information processing by the auditory system are hidden in the differences in response properties of single neurons within and among individual auditory nuclei. In order to explore neural mechanisms for signal processing, we thus focus our research on differences in response properties among neurons as well as response properties per se. All the acoustic information of use to an animal is contained in the activity of its auditory nerve. In mammals, all nerve fibers with identical best frequencies show nearly the same response pattern and frequency-tuning curve. In bats, all these primary auditory neurons respond to both emitted orientation sounds (also called pulses) and echoes by discharging multiple action potentials to each. The role of the central auditory system is to process this activity and send appropriate information to regulate the motor system, if necessary.
Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women.

Objective: To conduct the first longitudinal study examining whether trauma exposure and PTSD are associated with increased risk of incident SLE in a civilian cohort. Methods: We examined the association of trauma exposure and PTSD symptoms with SLE incidence over 24 years of follow-up in a U.S. longitudinal cohort of women (N=54,763). Incident SLE with ≥4 American College of Rheumatology criteria was ascertained by self-report and confirmed by medical record review. PTSD and trauma exposure were assessed with the Short Screening Scale for DSM-IV PTSD and the Brief Trauma Questionnaire. Women were categorized as having: no trauma, trauma and no PTSD symptoms, subclinical PTSD (1-3 symptoms), or probable PTSD (4-7 symptoms). We examined whether longitudinally assessed health risk factors (e.g., smoking, body mass index (BMI), oral contraceptive (OC) use) accounted for increased SLE risk among women with versus without trauma exposure and PTSD. Results: During follow-up, 73 cases of SLE occurred. Compared to women with no trauma, probable PTSD was associated with increased SLE risk (HR4-7 symptoms =2.94, 95% CI=1.19-7.26, p<0.05). Subclinical PTSD was associated with increased SLE risk, though this did not reach statistical significance (HR1-3 symptoms =1.83, 95% CI=0.74-4.56, p=0.19). Smoking, BMI and OC use slightly attenuated associations (e.g., probable PTSD adjusted HR=2.62, 95% CI=1.09-6.48, p<0.05). Trauma exposure, regardless of PTSD symptoms, was strongly associated with incident SLE (HR=2.87, 95% CI=1.31, 6.28, p<0.01). Conclusions: This study contributes to growing evidence that psychosocial trauma and associated stress responses may lead to autoimmune disease. This article is protected by copyright. All rights reserved.
International Production Location and 'Pro Forma' Hedging of Exchange Rate Risk

Of the many considerations in a firm's choice of a country in which to locate a production facility, one of the least understood is the implication of foreign exchange risk. In addition to the concept of operational hedging, there is economic exposure and maybe competitive exposure to consider. A firm's competitive exposure depends upon a firm's own production country, as well as that of its competition. Some of these concepts are developed in this article in hypothetical scenarios. Also, the scenarios demonstrate the "pro forma" financial hedging of currency exposure in simple "3-outcome" examples. The hedging analysis provides a straightforward way to evaluate the production location alternatives by implicitly adjusting for the market's pricing of exchange rate risk. This version corrects a numerical error in the published article.
Refining Classification of Heart Failure Based on Ejection Fraction

The complex clinical syndrome of heart failure (HF) is associated with a wide spectrum of left ventricular functional abnormalities [(1)][1]. These range from preserved left ventricular ejection fraction (EF) and normal left ventricular size to severely reduced EF and marked dilation of the left
PLANE ELASTOSTATIC ANALYSIS OF AN INFINITE PLATE WITH A DOUBLY PERIODIC ARRAY OF HOLES OR RIGID INCLUSIONS

An approximate analysis is developed for evaluation of stresses and displacements in a plate with a rectangular grid of holes which have symmetry axes directed along the rectangular grid. The holes are either uniformly pressurized or are bonded to rigid inclusions. The plate is loaded in a manner such that the principal stresses at infinity are directed along the rectangular grid. Stress distribution curves are presented for circular and elliptic holes which are load free or contain inclusions. Close agreement is shown with existing literature.
Quantization of high dimensional Gaussian vector using permutation modulation with application to information reconciliation in continuous variable QKD

This paper is focused on the problem of Information Reconciliation (IR) for continuous variable Quantum Key Distribution (QKD). The main problem is quantization and assignment of labels to the samples of the Gaussian variables observed at Alice and Bob. Trouble is that most of the samples, assuming that the Gaussian variable is zero mean which is de-facto the case, tend to have small magnitudes and are easily disturbed by noise. Transmission over longer and longer distances increases the losses corresponding to a lower effective Signal-to-Noise Ratio (SNR) exasperating the problem. Quantization over higher dimensions is advantageous since it allows for fractional bit per sample accuracy which may be needed at very low SNR conditions whereby the achievable secret key rate is significantly less than one bit per sample. In this paper, we propose to use Permutation Modulation (PM) for quantization of Gaussian vectors potentially containing thousands of samples. PM is applied to the magnitudes of the Gaussian ...
On the Supposed Utility of a Folk Theory of Pain

What follows raises objections to some arguments that claimthat a “principle of applicability” of ordinary pain talkconstrains developments in the pain sciences. A more apt pictureof lay use of pain language shows its non-theoretic character.Since instrumentalism and eliminativism are philosophical viewsabout the status of theories of pain, neither is a threatto clinical use of standard pain lingo. Perfected pain theoryis likely to enhance and improve pain language in clinicalsettings, should such theory find its way into popular ideasand talk of pain.
The Psychological Cost of College Math: Digital Learning Behaviors, Outcomes, and Genders Differences

Students’ perception of the costs of engaging in learning has only recently been the focus of empirical study. Perceived costs include effort cost, opportunity cost, and psychological cost. This study focuses on the implications of psychological cost – the perceived negative psychological consequence of participating in a learning task –for learning behavior, performance, and the potentially greater prevalence of cost for women learning math. Research questions include: (1) Does perceived psychological cost of engaging in a calculus course predict undergraduates’ behavior in the learning management system (LMS)? (2) Does psychological cost of engaging in a calculus course predict students’ academic performance? (3) Which digital learning behaviors predict final exam score? (4) Do females perceive greater psychological cost than males? (5) Are there differences in course achievement by gender? And (6) Do male and females’ digital learning behaviors differ? Contrasting theory and prior findings, psychological cost did not predict learning behavior or course performance. Students’ use of policy documents and a tool to organize study sessions predicted final exam performance. Females perceived greater psychological costs than males when studying calculus, consistent with prior research. Female students also scored lower than males on the final exam. Results suggest that costs may differ by gender and may mediate gender differences in performance.
Frontline Treatment for Older Patients with Mantle Cell Lymphoma

The natural history of mantle cell lymphoma (MCL) undergoing chemotherapy is a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. The median age of the occurrence of MCL is 65 years, so half of the newly diagnosed MCL patients are considered "elderly." The tolerance to long-term chemotherapy in elderly patients is decreased; hence, the response to frontline therapy used is of paramount importance. We hope that our review may guide clinicians in treating such populations in a more personalized and evidence-based manner.In the older patients with risk variables, frontline treatment is determined according to different body status of fit, unfit or compromised, and frail. In the fit patients, the pursuit of remission and prolongation of survival might currently justify the use of more intense and toxic therapies. For unfit or compromised older patients, disease control needs to be prioritized, maintaining a balance between the benefits and toxicities of the treatment. For frail patients, tolerance of treatment and minimizing myelotoxicity should be the primary focus. "Chemotherapy-free" regimens are likely to be considered as the first-line strategy for this population. On the other hand, in the older MCL population without risk variables, observation or "watch and wait" can prevent overtreatment. Furthermore, more clinical trials and research studies on novel agents and targeted therapies need to be translated into the general population to provide optimal treatment and to guide personalized treatment. IMPLICATIONS FOR PRACTICE: This review emphasizes the importance of frontline therapies for older MCL patients. MCL patients commonly experience a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. As a special population, elderly patients have various comorbidities and decreased organ function, which may reduce the chances of undergoing treatment for recurrent disease. Thus, this older population of patients with MCL should be treated separately and exceptionally. So far, systematic reviews with regard to frontline treatment for older patients with MCL have not been encountered, but the hope is that this review may guide clinicians in treating such populations in a more personalized and evidence-based manner.
Prodrome and Non-prodrome Phenotypes of Bladder Pain Syndrome/Interstitial Cystitis.

Objective To test the hypothesis that risk factors for bladder pain syndrome/interstitial cystitis (BPS/IC) in women differ between those with and without the BPS/IC prodrome. Materials and Methods Incident cases of BPS/IC and healthy controls were recruited nationally. More than half the BPS/IC cases reported subsyndromal urinary symptoms for decades before onset of BPS/IC and were identified as having the prodrome. Risk factors for BPS/IC were examined separately for cases with and without the prodrome using a set of matched controls. Results Two risk factors distinguished 178 prodrome from 134 non-prodrome cases. One was “UTIs” in the year before BPS/IC onset, possibly a manifestation of the prodrome itself. The other was the presence of the maximal number of nonbladder syndromes (NBSs): prodrome cases were 12 times more likely than non-prodrome cases to have ≥4 NBSs. Additional risk factors for prodrome and/or non-prodrome cases were the direct association of exogenous female hormones, as well as 3 inverse associations: type 2 diabetes mellitus, multiple pregnancies, and current daily smoking. Conclusion Prodrome cases developed urinary symptoms in their early 20s (ie, the prodrome) and were at very high risk of numerous NBSs. Non-prodrome cases developed urinary symptoms in their early 40s (ie, full-blown BPS/IC) and were no more likely than controls to have the maximal number of NBSs. These findings are consistent with recent suggestions of two BPS/IC phenotypes: one with systemic and psychosocial manifestations and the other more specific to the bladder. Additionally, several risk factors identified here might be hints of related or causal nervous system pathophysiologies.
Proof Without Words: Pythagorean Runs

(2000). Proof Without Words: Pythagorean Runs. Mathematics Magazine: Vol. 73, No. 1, pp. 59-59.
Photopolymers for holography and other applications

Recent advances in DuPont's OmniDex® holographic recording materials are discussed. A mechanism for holographic recording is presented along with a description of physical and holographic properties. Several applications including holographic optical elements are mentioned which can utilize the unique properties of these materials.
Identification of Microbiota-Induced Gene Expression Changes in the Drosophila melanogaster Head

Symbiotic microorganisms exert multifaceted impacts on the physiology of their animal hosts. Recent discoveries have shown the gut microbiota influence host brain function and behavior, but the host and microbial molecular factors required to actuate these effects are largely unknown. To uncover molecular mechanisms that underlie the gut-microbiota-brain axis, we used Drosophila melanogaster and its bacterial microbiota as a model to identify microbiota-dependent gene expression changes in the host brain and head. Specifically, we employed RNA-seq and nanoString nCounter technology to identify Drosophila genes that exhibit altered transcript levels in fly heads upon elimination of the microbiota. The identified genes, some of which exhibited sex-specific differences, have demonstrated or inferred functional roles in the immune response, metabolism, neuronal activity, and stress resistance. Overall, this study reveals microbiota-responsive genes in the fly head, an anatomical structure not previously investigated in this context. Our results serve as a foundation for future investigations of how microbe-driven gene expression changes impact Drosophila biology.
Extractive practices, oil corporations and contested spaces in Nigeria

Abstract In 2003, Nigeria voluntarily joined the Extractive Industries Transparency Initiative (EITI), implementing a Nigerian Extractive Industries Transparency Initiative (NEITI). This paper maps the various contestations----contestations over ownership of oil, state control of the verse oil resources and the lack of benefits by communities where the oil is located---around oil exploration in the Niger Delta region of Nigeria, suggesting that the establishment and enactment of the NEITI is a clear response to many of the contestations that have bedeviled the oil industry for decades. In mapping these contestations, I situate NEITI within a global system of extractive practices that have over several decades entangled extractive enclaves with corporations and the state. The paper suggests that while EITI/NEITI focuses on transparency and accountability in the revenue stream of the state in the extractive industries, it neglects how extractive practices impact the daily, lived experiences of the people who live in extractive enclaves. My argument is that the idea of transparency being promoted by NEITI is emblematic of a particular neoliberal frame that centers at its core a particular form of extractive practices whose goal is maximization of profit. This neoliberal frame is not particular to Nigeria, but rather shaped by a global order that connects local actors with transnational networks, promoting an alliance that reconfigures power and forms of knowledge production that privilege the state and its business partners, the oil corporations
Forests as pathways to prosperity: Empirical insights and conceptual advances

Abstract The role of forests in supporting current consumption and helping people cope with seasonal, climatic, and other stressors is increasingly well understood. But can forests help rural households climb out of poverty? And can forests provide a pathway to prosperity that includes more widely shared economic benefits and improvements in other aspects of human well-being? This introduction to the Special Issue on “Forests as Pathways to Prosperity” reviews the literature on forest livelihoods in developing countries to synthesize evidence relating to these questions. We find that available research primarily examines poverty mitigation aspects of forests rather than the potential role of forest conservation, management, and use in alleviating poverty or promoting broader prosperity. To increase understanding of forest-livelihood relationships we propose a framework based on the concept of prosperity, which draws particular attention to human well-being beyond economic and material dimensions. We argue that explicitly taking a more expansive view can enable better accounting for the diverse ways forests contribute to human welfare, expand the constituency for forests, and inform policies to more sustainably manage forests within wider landscapes. Together, our review and the other articles in this volume advance these objectives by providing new analytical frameworks, empirical insights, and theoretical understanding to build knowledge on linkages between forests, poverty, and broader prosperity.
Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer.

Background HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear. Methods 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3). Results 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002). Conclusions There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).
CHAPTER 2 – Vector Spaces

Publisher Summary This chapter describes vector spaces. The concept of a vector space is fundamental for a linear associative algebra. A vector space is a special case of a general algebraic discipline, called a module over a ring. The notion of a vector space can be generalized in various ways. Every vector space with more than one element has a basis. Isomorphism is an equivalence relation in any set of vector spaces over the same field. However, two isomorphic vector spaces are algebraically indistinguishable. If a vector space is not finite dimensional then it is called an infinite dimensional vector space.
Abstract LB-352: CD4+ follicular helper-like T cells are key players in anti-tumor immunity

CD4+ T helper cells (TH) are central orchestrators of an efficient immune response. However, within the tumor microenvironment (TME), it is unknown what type of CD4+ TH cells or CD4 helper-derived signals are essential to generate robust CD8+ CTL and TRM anti-tumor immune responses, which are positively associated with patient prognosis. To determine the nature of CD4+ T cells that provide ‘help9 for generating robust anti-tumor CD8+ CTL responses, we profiled the transcriptomes of patient-matched CD4+ and CD8+ T cells present in the TME of treatment-naive patients with lung cancer and analyzed them jointly using a novel approach, integrated weighted gene correlation network analysis. We found that the follicular helper T cell (TFH) program in CD4+ T cells was strongly associated with proliferation and tissue-residency in CD8+ CTLs. Single-cell transcriptomic analysis demonstrated the presence of tumor-infiltrating TFH-like cells, a subset of which lacked CXCR5 expression but displayed superior functional properties such as provision of CD8+ ‘help9, cytotoxicity and proliferation. Because these anti-tumor functions were not previously ascribed to TFH cells which are known to support B cell responses, we validated our findings using independent in vitro and in vivo approaches. Multi-parametric immunohistochemistry showed co-localization of TFH cells with CD8+ TRM cells within tumors, the density of which was positively correlated with that of TFH cells. Adoptive transfer or induction of TFH cells in mouse tumor models resulted in augmented CD8+ CTL responses and impairment of tumor growth, indicating an important role of TFH-like CD4+ T cells in anti-tumor immunity. Furthermore, tumor-infiltrating TFH-like cells expressed PD-1 and were enriched in tumors following checkpoint blockade, suggesting that they may respond to anti-PD-1 therapy in addition to CD8+ CTLs. Our findings provide insights into the molecular identity and functional status of CD4+ T cells within tumors that mount robust CTL responses and uncover potential targets for tumor immunotherapy. Citation Format: Anusha Preethi Ganesan. CD4+ follicular helper-like T cells are key players in anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-352.
Both analysis and feelings? The influence of risk beliefs on holistic risk judgments through dual systems using the ESSA model

Considerable previous research has examined factors that make up risk perception (its content), and the mechanisms through which risk is perceived (the process(es)). Content-based models have the a...
Stress Training in the Classroom: Evidence of Learning Transfer and Gains in Psychological States an

Stress is ubiquitous in life. Learning effective stress responses is necessary for any life domain. In this study, we attempt to address these concerns to understand how students respond to their l...
Detection of opioid effect with pupillometry

Abstract Background Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic brain insults. We undertook this study to determine which pupillary responses are most profoundly and consistently affected by a progressive infusion of remifentanil. Methods We studied the effect of remifentanil on the pupil using two portable infrared pupillometers in 18 volunteers. One pupillometer measured pupillary unrest in ambient light (PUAL) and the other pupillometer measured neurological pupillary index (NPi), constriction velocity (CV), pupil diameter (PD), latency, and % reflex (% reflex) following a transient light flash. Remifentanil was administered at predetermined weight-adjusted rates to raise opioid effect site concentration up to a range known to produce respiratory depression and oxyhemoglobin desaturation, based on a previously published pharmacokinetic model. Results PUAL was ablated by remifentanil, declining 94 ± 6% from baseline at the time of maximum drug effect. Other pupillary measurements decreased 50–65% from baseline. NPi was unchanged. At the time of oxyhemoglobin desaturation, deviations in PD, CV, and % reflex were widely scattered, whereas PUAL consistently approached zero. Conclusion PUAL is a highly specific indicator of central opioid effect. As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids.
Therapeutic Targeting of Hypoxia-A2-Adenosinergic Pathway in COVID-19 Patients.

The Hypoxia-HIF-1a-A2-adenosinergic pathway protects tissues from inflammatory damage during anti-pathogen immune responses. The elimination of this physiological tissue-protecting mechanism by supplemental oxygenation may contribute to the high mortality of oxygen ventilated COVID-19 patients by exacerbating inflammatory lung damage. Engagement of this pathway using hypoxia-adenosinergic drugs may improve outcomes of these patients.
Opportunity, Willingness and the Diffusion of War, 1816–1965

Using borders and alliances as indicators of opportunity and willingness, respectively, we test the relationship between these and the diffusion of war during the 1816–1965 period.
Genome Sequence of the Thermophilic Soil Bacterium Ureibacillus terrenus ATCC BAA-384T.

Ureibacillus terrenus TH9AT (=ATCC BAA-384T) was isolated from uncultivated soil in Italy in 1995. We present a draft genome sequence for the type strain, with a predicted genome length of 2,936,851 bp, containing 2,766 protein-coding genes, 82 RNA genes, and 5 CRISPR arrays, with a G+C content of 42.5%.
Prosthetic Aortic Valves and Diagnostic Challenges

Stenosis of bioprosthetic or mechanical aortic valves can occur due to valve degeneration, pannus formation, thrombosis, and endocarditis. Prosthetic valve stenosis is characterized by elevated trans-aortic velocities and gradients; however, it is imperative to realize that the mere presence of an elevated gradient across an aortic valve prosthesis is not sufficient to diagnose prosthesis stenosis. This chapter will review the valve design and types, causes of prosthetic aortic valve stenosis, approach to evaluate patients with elevated trans-aortic prosthesis gradient, as well as the complimentary role of CT and MRI.
Extra Dimensions and More

One of the most stimulating recent ideas in particle physics involves a possibility that our universe has additional compactified spatial dimensions, perhaps as large as 1 mm. In this review, we discuss the results of recent experimental searches for such large extra dimensions, as well as new developments in this field.
Magnetic rotation spectrum of singlet-triplet transitions: Part II. Pyrazine

Abstract Nine vibrational bands have been found in the magnetic rotation spectrum (MRS) of the 3 B 1u ← 1 A g transition in pyrazine near 3700 A; no MRS was observed for the region ascribed to the 1 B 1u ← 1 A g transition near 3200 A. The origin band at 3727 A exhibits a very sharp spike of negative sign near the band center and clearly resolvable rotational structure extending into the wings. Both the location and sign of rotation of the resolved structure are consistent with a case (b) model of the triplet state. The sign of the sharp spike is not explicable in terms of this model and suggests a different coupling scheme or more subtle effects in the MRS. This study provides the first clear correlation of sign of rotation in MRS with the rotational structure of a polyatomic electronic transition.
A New Class of Stochastic Volatility Models with Jumps: Theory and Estimation

The purpose of this paper is to propose a new class of jump diffusions which feature both stochastic volatility and random intensity jumps. Previous studies have focused primarily on pure jump processes with constant intensity and log-normal jumps or constant jump intensity combined with a one factor stochastic volatility model. We introduce several generalizations which can better accommodate several empirical features of returns data. In their most general form we introduce a class of processes which nests jump-diffusions previously considered in empirical work and includes the affine class of random intensity models studied by Bates (1998) and Duffie, Pan and Singleton (1998) but also allows for non-affine random intensity jump components. We attain the generality of our specification through a generic Levy process characterization of the jump component. The processes we introduce share the desirable feature with the affine class that they yield analytically tractable and explicit option pricing formula. The non-affine class of processes we study include specifications where the random intensity jump component depends on the size of the previous jump which represent an alternative to affine random intensity jump processes which feature correlation between the stochastic volatility and jump component. We also allow for and experiment with different empirical specifications of the jump size distributions. We use two types of data sets. One involves the S&P500 and the other comprises of 100 years of daily Dow Jones index. The former is a return series often used in the literature and allows us to compare our results with previous studies. The latter has the advantage to provide a long time series and enhances the possibility of estimating the jump component more precisely. The non-affine random intensity jump processes are more parsimonious than the affine class and appear to fit the data much better.
Interpolating fields for elementary particles in the Lee model

A general class of local interpolating fields consistent with the quantum numbers of the elementary V-particle in the Lee model is constructed. We assume that this class of interpolating fields converge weakly to the in and out fields associated with the V-particle. The matrix elements of the V-particle are then calculated. It is shown that the physical properties of the V-particle are independent of the form of the interpolating field.
Disability as Socio-Rhetorical Action: Towards a Genre-Based Approach

In many respects, the reconceptualization of genre over the past few decades mirrors that of disability. Just as disability scholars and activists reject rigid categories of fixed difference based solely on individual deviations from some supposedly neutral norm, so too have contemporary genre theorists rejected the traditional view of genre as static categories of discourse that share certain objective conventional features. Such a view is unsatisfactory because, in casting genres as decontextualized, ahistorical forms or receptacles, it fails to adequately reflect the inherently social nature of discourse and texts. Instead, genre theorists now (re)conceive genres as dynamic sites of social action. Disability is also a form of social action, a rhetorical convention used to construct and regulate human actions and interactions, and, as such, can be viewed and analysed in generic terms. Conceiving disability as genre (and metagenre) provides an additional theoretical lens for examining and transcending, among other things, the reductive and oppressive categorization deployed by the medical model of disability. A perspective informed by genre theory helps to shift critical attention from description to explanation, a necessary step in deconstructing hegemonic discourses.
Homenet: A Control Network for Consumer Applications

Homenet fills the need for a low cost network for the exchange of control information among a broad spectrum of consumer applications in the home. Just as cablevision and telephone media are stimulating delivery of new services the home, Homenet's purpose is to provide a standardized control network within the home for innovative consumer products and to complement these and other external delivery systems. Homenet is designed to handle applications ranging from rudimentary functions like on-off remote controls to complex non-data-intensive functions like energy management, security, entertainment module coordination, and clock synchronization.
Ontogeny of guinea pig liver cholesterol 7α-hydroxylase: Unexpected inverse correlation of enzyme activity with expanding bile acid pool

Abstract Changes in the activity of guinea pig liver cholesterol 7α-hydroxylase (rate limiting enzyme of cholesterol catabolism) from birth to adult life was investigated using a microsomal acetone extraction method (to remove endogenous cholesterol). Contrary to the previously held notion, it was noted that while the total bile acid pool increased progressively with age after birth, hepatic cholesterol 7α-hydroxylase specific activity declined. Neonatal hepatic cholesterol 7α-hydroxylase showed an increase in enzyme activity in response to cell supernatant factors (100,000 xg supernatant) from neonatal livers, but not from adult livers.
Abrupt climate change in southeast tropical Africa influenced by Indian monsoon variability and ITCZ migration

[1] The timing and magnitude of abrupt climate change in tropical Africa during the last glacial termination remains poorly understood. High-resolution paleolimnological data from Lake Tanganyika, Southeast Africa show that wind-driven seasonal mixing in the lake was reduced during the Younger Dryas, Inter-Allerod Cool Period, Older Dryas, and Heinrich Event 1, suggesting a weakened southwest Indian monsoon and a more southerly position of the Inter-Tropical Convergence Zone over Africa during these intervals. These events in Lake Tanganyika, coeval with millennial and centennial-scale climate shifts in the high latitudes, suggest that changes in ITCZ location and Indian monsoon strength are important components of abrupt global climate change and that their effects are felt south of the equator in Africa. However, we observe additional events in Lake Tanganyika of equal magnitude that are not correlated with high-latitude changes, indicating the potential for abrupt climate change to originate from within tropical systems.
Nuclear excitation in the reaction 207Pb(μ−, ν6n) 201Tl☆

Abstract A probability of roughly 1% has been measured for the formation of the first excited state of 201Tl following muon capture on 207Pb. A probability of this magnitude for 6 neutron may indicate structure in the nuclear excitation function near 54 MeV. An alternative interpretation is provided by muon capture on a correlated np pair in analogy with pion absorption.
Large-amplitude quantum fluctuations and subgap optical absorption in trans-polyacetylene.

We show that in the frequency regime of the subgap tail, large-amplitude fluctuations of the (CH${)}_{\mathrm{x}}$ chain are involved in the optical absorption process. A recently developed semiclassical technique is applied to calculate the absolute absorption coefficient which is related to multidimensional tunneling of soliton pairs. We include the renormalization effects of weak electron-electron interactions and background transverse phonons. Good agreement with recent experimental data is found. Experimental predictions are made concerning the isotope dependence and the effect of the soliton shape mode on the absorption coefficient.
A modified bronchial anastomosis technique for lung transplantation

Abstract Background Low rates of major complications have been reported for the intussuscepting bronchial anastomotic technique but stenosis, malacia, and granulation tissue at the anastomosis may cause clinically important morbidity. We hypothesized that a modification of the telescoping technique that improves bronchial wall apposition might be associated with improved bronchial healing and clinical outcomes. Methods The telescoping horizontal mattress "U-stitch" suture technique was modified to incorporate figure-of-eight sutures placed in the cartilaginous wall between each of three intussuscepting U stitches. Serial videotape records of 152 individual anastomoses (99 modified, 53 telescoped) in 118 consecutive operative survivors were retrospectively reviewed by examiners blinded with respect to technique used. Stenosis, airway instability, mucosa quality, and devascularized luminal tissue were graded at 4 to 14 days (initial), 4 to 12 weeks (early), and 6 to 12 months (late) after transplantation. Results The incidence of anastomotic stenosis was significantly lower using the modified technique at the initial ( p = 0.025) and late ( p = 0.015) observations. In the initial phase airway instability ( p = 0.015) and devascularization grades ( p = 0.001) were also significant lower in the modified group. There were no significant differences in mucosal condition between techniques. The modified telescoping technique was associated with significant survival advantage (mean 17.7%; p = 0.029) by multivariate analysis. The incidence of major airway complications (dehiscences and stenoses required stents) tended to be lower (3% versus 6%) in the modified group. Conclusions The modified telescoping bronchial anastomosis technique is associated with improved early and late bronchial healing and higher 5-year survival without increased major airway complications.
Letter to the Editor of Pain on Jørum et al: Catecholamine-induced excitation of nociceptors in sympathetically maintained pain; Pain 2007;127:296-301.

The pearl in this “neuropathic” pain patient, studied by Jorum et al, is activation of three nociceptors in hyperalgesic skin by reflex sympathetic maneuvers and by ID norepinephrine. What does it mean?
Motion of a tank-treading ellipsoidal particle in a shear flow

A theoretical model is developed for the motion of a human red blood cell in a shear field. The model consists of a tank-treading ellipsoidal membrane encapsulating an incompressible Newtonian liquid immersed in a plane shear flow of another incom- pressible Newtonian liquid. Equilibrium and energy considerations lead to a solution for the motion of the particle that depends on the ellipsoidal-axis ratios and the ratio of the inner- to outer-liquid viscosities. The effect of variation in these parameters is explored and it is shown that, depending on their values, one of two types of overall motion is exhibited: a steady stationary-orientation motion or an unsteady flipping motion. A qualitative agreement of the predicted behaviour of the model with experi- mental observations on red blood cells is found.
Prosthetic intervention effects on activity of lower-extremity amputees.

Abstract Klute GK, Berge JS, Orendurff MS, Williams RM, Czerniecki JM. Prosthetic intervention effects on activity of lower-extremity amputees. Objective To investigate the effect of prosthetic interventions on the functional mobility of lower-extremity amputees. Design Crossover with repeated measures. Setting Household and community environment. Participants Twelve transtibial and 5 transfemoral amputees. Interventions For transtibial amputees, shock-absorbing versus rigid pylons. For transfemoral amputees, C-Leg versus Mauch SNS knees. Main Outcome Measures Daily activity level (step count) and duration (minutes of activity). Results Pylon type had no effect on the daily activity level or duration of transtibial amputees. Knee type had no effect on the daily activity level or duration of transfemoral amputees. Transtibial amputees were more active on weekdays (3079±1515 steps/d) than weekends (2386±1225 steps/d) ( P =.007). In general, lower-extremity amputees perform numerous short-duration bouts of activity (1−2min) consisting of fewer than 17 steps/min, but activities of more than 15 minutes in duration were relatively rare ( Conclusions Intervention had no effect on amputee activity level and duration. Higher weekday activity levels of transtibial amputees suggest their vocational activities are more demanding than recreational activities. The fitting, alignment, and design of prosthetic components should be optimized for 1 to 2 minute bouts of activity consisting of only a few dozen steps.
Unsupervised Discovery of Subspace Trends

This paper presents unsupervised algorithms for discovering previously unknown subspace trends in high-dimensional data sets without the benefit of prior information. A subspace trend is a sustained pattern of gradual/progressive changes within an unknown subset of feature dimensions. A fundamental challenge to subspace trend discovery is the presence of irrelevant data dimensions, noise, outliers, and confusion from multiple subspace trends driven by independent factors that are mixed in with each other. These factors can obscure the trends in conventional dimension reduction & projection based data visualizations. To overcome these limitations, we propose a novel graph-theoretic neighborhood similarity measure for detecting concordant progressive changes across data dimensions. Using this measure, we present an unsupervised algorithm for trend-relevant feature selection, subspace trend discovery, quantification of trend strength, and validation. Our method successfully identified verifiable subspace trends in diverse synthetic and real-world biomedical datasets. Visualizations derived from the selected trend-relevant features revealed biologically meaningful hidden subspace trend(s) that were obscured by irrelevant features and noise. Although our examples are drawn from the biological domain, the proposed algorithm is broadly applicable to exploratory analysis of high-dimensional data including visualization, hypothesis generation, knowledge discovery, and prediction in diverse other applications.