cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhaled Corticosteroids for Asthma

1. Edward W. Fong, MD* 2. Robert H. Levin, PharmD† 1. *Pediatric Pulmonologist, Children's Hospital and Research Center Oakland, Oakland, Calif., and California Pacific Medical Center, San Francisco, Calif 2. †Professor Emeritus of Clinical Pharmacy, University of California San Francisco School of Pharmacy, San Francisco, Calif Asthma is an inflammatory disease of the respiratory tract. It is the most common chronic disorder in children and adolescents, with more than 3 million asthma attacks occurring in more than 5% of all children each year. Asthma creates significant morbidity and is the leading cause of school absences. Costs attributed to asthma are in the billions of dollars each year. All levels of persistent asthma require daily anti-inflammatory treatment, and the safest, most effective treatment for patients who have persistent asthma is inhaled corticosteroids (ICSs). Although steroids may be given orally or parenterally, and numerous nonsteroidal medications are available for treating persistent asthma, ICSs are the treatment of choice. Even when ICSs are given daily over a long period of time, they have less toxicity than oral or parenteral steroids administered only occasionally. This article reviews the currently available ICSs, devices and techniques for optimal administration, and potential adverse effects. The data and recommendations are based on the National Asthma Education and Prevention Program (NAEPP) guidelines (1991 and 1997) and Update 2002, which are available at http://www.nhlbi.nih.gov/guidelines/asthma. Asthma is a complex disorder whose pathogenesis is not fully understood. Current thinking is that susceptible individuals develop asthma because of an imbalance between the T-helper (Th)1 and Th2 lymphocytes. Th1 cells produce interleukin-2 (IL-2) and interferon-gamma, which act as a cellular defense mechanism, and Th2 cells produce cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13), which mediate allergic inflammation. According to this current “hygiene hypothesis,” the Th1 cellular defense mechanism is reduced, while Th2 cellular activity increases. This imbalance predisposes the individual to episodes of chronic inflammatory asthma. Whatever triggers the pathogenesis sets up an inflammatory process in which many cellular components participate, including mast cells, T lymphocytes, eosinophils, neutrophils, and epithelial cells. The result is inflammation, hyperresponsiveness (bronchospasm), and in …
Plectin-1 as a Novel Biomarker for Pancreatic Cancer

Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed. Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC. Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver. Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging. Clin Cancer Res; 17(2); 302–9. ©2010 AACR.
Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells.

Abstract Microarray analysis is a powerful tool to identify the biological effects of drugs or chemicals on cellular gene expression. In this study, we compare the relationships between traditional measures of genetic toxicology and mutagen-induced alterations in gene expression profiles. TK6 cells were incubated with 0.01, 0.1, or 1.0 μM ±anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) for 4 h and then cultured for an additional 20 h. Aliquots of the exposed cells were removed at 4 and 24 h in order to quantify DNA adduct levels by 32 P post-labeling and measure cell viability by cloning efficiency and flow cytometry. Gene expression profiles were developed by extracting total RNA from the control and exposed cells at 4 and 24 h, labeling with Cy3 or Cy5 and hybridizing to a human 350 gene array. Mutant frequencies in the Thymidine Kinase and Hypoxanthine Phosphoribosyl Transferase genes were also determined. The 10α-(deoxyguanosin-N2-yl)-7α,8β,9β-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (dG-N2-BPDE) adduct increased as a function of dose and was the only adduct identified. A dose-related decrease in cell viability was evident at 24 h, but not at 4 h. Cell death occurred by apoptosis. At 4 h, analysis of the gene expression profiles revealed that Glutathione Peroxidase and Gadd45 were consistently upregulated (greater than 1.5-fold and significantly (P
Phase I Trial of Carboplatin and Etoposide in Combination with Panobinostat in Patients with Lung Cancer

A phase I trial consisting of panobinostat (a HDAC inhibitor), carboplatin and etoposide was condacted in patients with lung cancer. Patients and Methods: Patients received carboplatin AUC5 on day 1 and etoposide 100 mg/m2 on days 1, 2 and 3, every 21 days. Concurrent oral panobinostat was given 3 times weekly on a 2-weeks-on and 1-week-off schedule during the 4–6 cycles of chemotherapy and then continued as maintenance therapy. Results: Six evaluable patients were treated at the first dose level of panobinostat (10 mg). Dose-limiting toxicity occurred in two patients (33%) during the first cycle. One patient developed grade 4 thrombocytopenia and another grade 4 febrile neutropenia. Therefore, the study was suspended based on the pre-specified study design. No recommended phase II starting dose was established. Conclusion: The addition of panobinostat to carboplatin and etoposide was not tolerable at the lowest dose level tested in this trial. Further research and development into this combination is not recommended.
Evidence-Based Diabetes Care

Gerstein HC, Haynes RB. Evidence-Based Diabetes Care . Hamilton, Ontario: BC Decker, 2001. Evidence-Based Diabetes Care aims to compile evidence from applied clinical research about the diagnosis, prognosis, and treatment of a comprehensive list of diabetes-related medical problems. Although the target audience is primarily healthcare providers, the editors suggest that the text could also serve as a resource to those developing or evaluating current clinical practice guidelines. In the first chapter, the editors explicitly define the criteria used throughout the text for seeking and appraising clinical evidence. These criteria are based on those used by the Canadian Diabetes Association in developing their clinical practice guidelines, and they are rational and cogent. Although the editors explicitly state that this resource was not intended to present …
Study of Beam-Beam Effects at PEP-II

Using a self-consistent three-dimensional simulation running on parallel supercomputers, we have modeled the beam-beam interaction at the PEP-II asymmetric e + e − collider. To provide guidance for luminosity improvement, we scanned the tunes and currents in both rings and computed their impact on the luminosity and transverse beam sizes. We also studied the effects of colliding the beams with a small crossing angle. Where possible, the code was benchmarked against experimental measurements of luminosity and beam sizes, yielding an acceptable agreement.
Modified anti-windup compensators for stable linear systems

In this paper, we use the Small Gain Theorem to study the stability, and develop appropriate convex L2 gain LMIs for synthesis, of static anti-windup gains. The main contribution of this paper is investigating the effects of delaying the activation of anti-windup by allowing actuators to remain in the saturated regime longer, on their own. The basic idea is to apply anti-windup when the performance of saturated system faces substantial degradation. For this, we present a modified anti-windup scheme along with the appropriate convex LMIs to obtain the gains. For two well-known examples, we show that the modified anti-windup scheme renders better performance than the case of immediate application of anti-windup.
Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome

This study examined the cross-sectional medical and social characteristics of children diagnosed with congenital central hypoventilation syndrome (CCHS). A detailed questionnaire was mailed to all families with a child with CCHS who are affiliated with a family network or support group. The questionnaire response rate was >75% (n=196). Mean age was 10.22 years +/- 6.6 years (SD) (range, 0.4-38 years), with a 1:1 sex ratio. Multisystem involvement was almost universal among the cohort, with Hirschsprung's disease (HD) present in 16.3%; 61.7% of the children had a tracheotomy, but 14.3% were never tracheotomized, with 77 subjects (39.3%) not having a tracheostomy tube at time of survey. Respiratory support approaches varied but clearly reflected the trend towards earlier and more widespread transition to noninvasive ventilatory modalities. Significant developmental problems were noted, but attendance in regular classes occurred in the majority. Significant deficiencies in routine periodic evaluation and management were reported. In addition, the presence of CCHS was associated with a significant financial and psychosocial burden to the families. In conclusion, a comprehensive survey of 196 CCHS children and their families revealed a cross-sectional picture of substantial medical and psychosocial complexities associated with this disorder, and pointed out substantial inadequacies in routine preventive care that appear to impose stress on the families. The emerging trend of earlier transition to noninvasive ventilatory support warrants future studies. Implementation of recommended guidelines for diagnosis and multidisciplinary follow-up of CCHS should ultimately ameliorate the long-term outcome of this lifelong condition.
Uncoupling hypoxia signaling from oxygen sensing in the liver results in hypoketotic hypoglycemic death

As the ultimate electron acceptor in oxidative phosphorylation, oxygen plays a critical role in metabolism. When oxygen levels drop, heterodimeric hypoxia-inducible factor (Hif) transcription factors become active and facilitate adaptation to hypoxia. Hif regulation by oxygen requires the protein von Hippel-Lindau (pVhl) and pVhl disruption results in constitutive Hif activation. The liver is a critical organ for metabolic homeostasis, and Vhl inactivation in hepatocytes results in a Hif-dependent shortening in life span. While albumin-Cre;Vhl(F/F) mice develop hepatic steatosis and impaired fatty acid oxidation, the variable penetrance and unpredictable life expectancy has made the cause of death elusive. Using a system in which Vhl is acutely disrupted and a combination of ex vivo liver perfusion studies and in vivo oxygen measurements, we demonstrate that Vhl is essential for mitochondrial respiration in vivo. Adenovirus-Cre mediated acute Vhl disruption in the liver caused death within days. Deprived of pVhl, livers accumulated tryglicerides and circulating ketone and glucose levels dropped. The phenotype was reminiscent of inborn defects in fatty acid oxidation and of fasted PPARα-deficient mice and while death was unaffected by pharmacologic PPARα activation, it was delayed by glucose administration. Ex vivo liver perfusion analyses and acylcarnitine profiles showed mitochondrial impairment and a profound inhibition of liver ketone and glucose production. By contrast, other mitochondrial functions, such as ureagenesis, were unaffected. Oxygen consumption studies revealed a marked suppression of mitochondrial respiration, which, as determined by magnetic resonance oximetry in live mice, was accompanied by a corresponding increase in liver pO(2). Importantly, simultaneous inactivation of Hif-1β suppressed liver steatosis and rescued the mice from death. These data demonstrate that constitutive Hif activation in mice is sufficient to suppress mitochondrial respiration in vivo and that no other pathway exists in the liver that can allow oxygen utilization when Hif is active precluding thereby metabolic collapse.
Cardiovascular disease and chronic renal disease: a new paradigm.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal disease (CRD). Despite improvement in treatment for CVD over the past 30 years, CVD mortality is approximately 15 times higher in dialysis patients than in the general population. The high prevalence of CVD among incident dialysis patients suggests that CVD begins in earlier stages of CRD, and that implementation of risk factor reduction strategies earlier in the course of CRD may provide an opportunity to prevent CVD in CRD. Based on parallels between CVD and renal disease progression, we have proposed a paradigm that CVD and CRD are outcomes of the same underlying disorders. We propose that risk factor reduction strategies used to prevent CVD in the general population also be applied to patients with CRD, with the hope of preventing progression of renal disease, as well as preventing CVD.
PERSPECTIVES ON ADVERTISING RESEARCH: Views from Winners of the American Academy of Advertising Outstanding Contribution to Research Award

To gather insights about the current state and future directions of advertising research, as well as to obtain a glimpse of its evolvement over time, testimony was compiled from experts in the field. The experts were selected from individuals who have won the American Academy of Advertising Outstanding Contribution to Research Award. Their responses provide a chronicle of advertising research that is marked by thoughtful observation, personal introspection, and careful speculation. This paper represents a snapshot of advertising research that is panoramic and clear due to the diversity and contemporaneous comments of the participants. Summary comments are offered that bring attention to general themes that emerge from the contributors' thoughts. It is hoped that this paper will serve as a signpost and catalyst for advertising research both now and in the years to come.
An Overview of Protestant Education in Africa

This chapter gives an overview of Protestant educational practices and challenges in a variety of nations in the African continent. The author notes that Protestant education is on the rise in Africa, particularly because Christianity generally and Protestantism specifically are on the rise in Africa. The chapter considers both the history of Protestant education and the contemporary situations in a various African countries. In 1900 only about 3–4% of Africans were Christians, but today that percentage is nearly 50%. The chapter highlights the fact that more than any other inhabited continent in the world, Africa often falls victim to vast generalizations and attempts to dispel those generalizations. The author notes that while there are commonalities among these nations, considerable differences exist between the various African nations generally and this truism holds to the more specific expressions of Protestant education. The author notes that one of the reasons why Africans have become open to Christianity is because they believe that following Christian edicts brought prosperity to Europe and eventually to North America. The author addresses a wide range of issues faced by Protestant education in Africa, which will provide an excellent resource for many readers.
Measuring Science Instructional Practice: A Survey Tool for the Age of NGSS

Ambitious efforts are taking place to implement a new vision for science education in the United States, in both Next Generation Science Standards (NGSS)-adopted states and those states creating their own, often related, standards. In-service and pre-service teacher educators are involved in supporting teacher shifts in practice toward the new standards. With these efforts, it will be important to document shifts in science instruction toward the goals of NGSS and broader science education reform. Survey instruments are often used to capture instructional practices; however, existing surveys primarily measure inquiry based on previous definitions and standards and with a few exceptions, disregard key instructional practices considered outside the scope of inquiry. A comprehensive survey and a clearly defined set of items do not exist. Moreover, items specific to the NGSS Science and Engineering practices have not yet been tested. To address this need, we developed and validated a Science Instructional Practices survey instrument that is appropriate for NGSS and other related science standards. Survey construction was based on a literature review establishing key areas of science instruction, followed by a systematic process for identifying and creating items. Instrument validity and reliability were then tested through a procedure that included cognitive interviews, expert review, exploratory and confirmatory factor analysis (using independent samples), and analysis of criterion validity. Based on these analyses, final subscales include: Instigating an Investigation, Data Collection and Analysis, Critique, Explanation and Argumentation, Modeling, Traditional Instruction, Prior Knowledge, Science Communication, and Discourse.
Attachment and maintenance of adult rabbit cardiac myocytes in primary cell culture

The present observations demonstrate that quiescent calcium-tolerant adult rabbit cardiac myocytes can be isolated by collagenase-hyaluronidase perfusion and maintained in primary culture for at least 2 wk. Culturing large numbers of myocytes requires that the freshly isolated cells be attached to a suitable substratum such as laminin, type IV collagen, or fetal bovine serum. The cultured myocytes retain their rod-like morphology for approximately 7 days before gradually spreading into a flattened conformation by 14 days. During the 1st wk of culture, contaminating interstitial cells rapidly proliferate, making cultures unsuitable for long-term study. Pure myocyte populations can be established and maintained if freshly isolated cells are cultured in the presence of cytosine arabinoside (Ara-C, 10 microM). This antimetabolite does not appear to adversely affect high-energy phosphates, since ATP and creatine phosphate (CrP) content of the myocytes is maintained at levels normally found in biopsy samples of rabbit myocardium. These results illustrate that an energetically stable population of adult cardiac myocytes can be maintained in primary culture in sufficient numbers to make them useful for future investigations of myocyte function.
Climate Change Decisions: International Influences on Argentina's Foreign Policy Decision Making

This paper aims to contribute to both environmental and Latin American foreign policy decision making literatures, both of which are comparatively underrepresented areas of study. Specifically, it analyzes the factors affecting former Argentine President Carlos Saul Menem when he chose to join the Kyoto Protocol in 1998 and, thus, the international climate change regime. President Menem made a bold announcement that his country would voluntarily reduce its greenhouse gas emissions, a pledge well beyond what was required of the developing nation (as prescribed by the Protocol). This paper suggests that international factors, specifically Menem’s desire to align his nation with the United States, critically influenced the president’s decision, thereby advancing the argument that in this instance international (and individual), and not domestic factors, determined the president’s behavior. The paper concludes with a discussion of the boarder implications of the importance of international variables in the decision making processes of Latin American leaders and environmental foreign policy.
On the Temperature Dependence of Resistivity of Polycrystalline Silicon Films

It is shown that the grain boundary (GB) in polycrystalline-silicon (poly-Si) films need not be modeled as a temperature-dependent potential barrier or as an amorphous region to explain the temperature (T) dependence of resistivity ( ρ ) in p-type poly-Si films at low T. Specifically, we consider that QB defect states allow for the tunneling component of current to occur by a two-step process. Incorporation of the two-step process in a numerical calculation of ρ vs. T results in excellent agreement with available data from 100 K to 300 K.
Rabies: Laboratory Diagnosis and Postexposure Treatment

Rabies in wildlife, such as is found in bats, coyotes, foxes, raccoons, and skunks, is a much more important source of infection in man in the United States than that found in any domesticated species, including the dog. The best postexposure treatment to prevent rabies in man is the administration of a single dose of antirabies serum, followed by 21 daily doses of rabies vaccine, followed by booster closes of vaccine given 10 and 20 or more days later.
Psychological Efficacy of Religiosity in Late Adolescence

The purpose of the present study was to assess the relationship berween frequency of church attendance, perhaps the most commonly used social index of religious fervor, and ocher dimensions of religiosity in late adolescence. Since the spiritual efficacy of religious ritual might be assessed empirically via some measure of humane-benevolent deeds, the relation of frequency of church atrendance and magnitude of altruistic-humane activity was emphasized. To assess the dimensions of religiosity, an expanded form of Ligon's Religious Participation Scale (3) was administered to 161 introductory psychology students. Correlations between frequency of church attendance and other dimensions of religiosiry were: frequency of praying (.363), extent of reading religious literamre (.439), longevity of Sunday school attendance (.378), and indices of altruistic-benevolent deeds (.465). These rs (p = .001) should not be accepted prematurely as a corroboration of the efficacy of church attendance in producing moral-humane integrity. Computation of mean scores indicated that the average S was attending public church services three times monthly but infrequently (less than once monthly) performing alrruisric deeds as a function of his religious convictions. Therefore, although a significant T was obtained between measures of church attendance and humane-beneficent concern, scores were consistently lower for the latter variable. The obtained rs plus the low level of humane-altruistic activity suggest that church attendance may have limited spiritual efficacy. In many instances church attendance may provide more social-psycholog~cal reinforcement than spiritual stimulation. Attending church in many settings is a bas~c avenue of manifesting one's moral fiber to the community and thus maintaining social and business status. Ic also affords opportunities to cultivate friendships, manifest skills (such as singing. playing an instrument, presenting a discourse, etc.) and exhibit material affluence. Although perhaps nor consciously recognized, one's basic incentive for church atrendance may be social approval rather than spirirual edification.
Compositions of analytic functions of the form f n ( z )= f n-1 ( f n ( z )), f n ( z )—> f ( z )

Abstract Frequently, in applications, a function is iterated in order to determine its fixed point, which represents the solution of some problem. In the variation of iteration presented in this paper fixed points serve a different purpose. The sequence { F n ( z )} is studied, where F 1 ( z ) = f 1 ( z ) and F n ( z ) = F n −1 ( f n ( z )), with f n → f . Many infinite arithmetic expansions exhibit this form, and the fixed point, α, of f may be used as a modifying factor ( z = α) to influence the convergence behaviour of these expansions. Thus one employs , rather than seeks the fixed point of the function f .
Bronchoalveolar lavage of flexible bronchoscopy in the diagnosis and treatment of children with Mycoplasma pneumoniae pneumonia

Objective To investigate the application of bronchoalveolar lavage of flexible bronchoscopy in diagnosis and treatment of children with Mycoplasma pneumoniae pneumonia(MPP).Methods Clinical data of 155 pneumonia patients(57 cases of MPP and 98 cases of non-MPP),who had examination in flexible bronchoscopy, MP-DNA of bronchoalveolar larlavage fluid(BALF),and the traditional blood serological test of Mycoplasma pneumoniae,were retrospectively analyzed from Aug.2011 to Apr.2012 in Anhui Provincial Children's Hospital.Results Mycoplasma pneumoniae pneumonia often occur red in children over the age of 5 or with lobar pneumonia or atelectasis in the left lung. The accu-racy of MP-DNA in BALF was higher than that of the blood serological test. After alveolar wash and administration of medicines, 95.7% of the atelectasis cases were cured.Conclusions Flexible bronchoscopy and bronchoalveolar lavage should be applied to MPP and atelectasis cases as soon aspossible topromote lung recruitment and improve the outcome.
Signaling and Immune Regulation in Melanoma Development and Responses to Therapy

Melanoma is a complex and genomically diverse malignancy, and new genes and signaling pathways involved in pathogenesis continue to be discovered. Mechanistic insights into gene and immune regulation in melanoma have led to the development of numerous successful and innovative pharmacologic agents over recent years. Multiple targeted therapies and immunotherapies have already entered the clinic, becoming new standards of care and transforming the prognosis for many patients with malignant melanoma. In this review, we provide an overview of the current understanding of signaling and immune regulation in melanoma and implications for responses to treatment, organized in the framework of hallmark characteristics in cancer.
Induction of rat small intestinal cytochrome P-450 2J4.

Cytochrome P-450 (CYP) 2J4 is a member of the recently identified CYP2J subfamily-part of the CYP superfamily-and is primarily expressed in rat small intestinal epithelium (enterocytes). Studies to determine small intestinal CYP2J4 inducibility by prototypic CYP inducers have been undertaken. Immunoblot analysis of enterocyte microsomes from rats treated with beta-naphthoflavone, dexamethasone, or phenobarbital revealed unchanged, diminished, or slightly increased levels of CYP2J4 protein, respectively, relative to vehicle-treated rats, whereas rats treated with pyrazole (200 mg/kg) had 3- to 4-fold increased levels of CYP2J4. Pyrazole administration also increased CYP2J4 metabolic activity, as probed by retinoic acid formation from retinal, approximately 3-fold, and the activity was inhibited by 90% by a polyclonal anti-CYP2J4 antibody. CYP2J4 mRNA levels were increased 2.5-fold by pyrazole administration. The route of pyrazole administration-oral or i.p.-did not affect the extent or time course of intestinal CYP2J4 induction. However, at >300 mg/kg pyrazole, oral administration produced higher levels of CYP2J4 activity than i.p. administration. Pyrazole also produced increased hepatic and olfactory mucosal levels of CYP2J4. We speculate, based on our data and on published mechanisms of pyrazole induction, that pyrazole induces rat intestinal CYP2J4 by stabilization of mRNA primarily, and by stabilization of protein to a lesser extent. This study documents for the first time the induction of a CYP2J subfamily member by a xenobiotic and provides the basis for a mechanism by which xenobiotics could modulate biological processes.
Hematologic findings in Southeast Asian immigrants with particular reference to hemoglobin E

Recent immigrants from Southeast Asia were screened for hematologic abnormalities using a multichannel cell counter (Coulter S), peripheral smear, free erythrocyte protoporphyrin (FEP), isoelectric focusing, and a qualitative screen for glucose-6-phosphate dehydrogenase deficiency. Hematologic abnormalities were further defined by hemoglobin electrophoresis, globin electrophoresis, HbA2 levels, and HbF levels. Of the 189 adults studied, 68 (36 percent) were hematologically abnormal, including 28 hemoglobin E (HbE) heterozygotes, six HbE homozygotes, 14 with alpha-thalassemia minor, and 10 with presumptive iron deficiency. Of the 54 people with microcytic (MCV less than 80fl) red blood cells (RBC), 52 had evidence of HbE or thalassemia and two had iron deficiency alone; five had both iron deficiency and a hemoglobinopathy. Homozygosity for HbE results in an asymptomatic condition similar to thalassemia minor with microcytic RBC, large numbers of target cells, normal or slightly reduced hematocrit and greater than 90 percent HbE. People heterozygous for HbE are asymptomatic and have hematologic findings similar to thalassemia minor with slightly reduced or low normal MCV and 25 to 35 percent HbE.
A 90nA quiescent current 1.5V–5V 50mA asynchronous folding LDO using dual loop control

This paper presents a 90 nA quiescent current 1.5V–5.0V LDO regulator in a 0.35 um BiCMOS process. A new dual-loop (asynchronous digital loop and an analog loop) LDO is proposed. The digital loop (D-Loop) boosts the loop response speed under fast switching clock frequencies and the analog loop (Α-Loop) provides a clean output voltage with an ultra-low current consumption. The prototype IC achieves 90 nA of quiescent current during steady state with a power supply of up to 5.0 V. It has a drop-out voltage of 200 mV and a 50 mA output current capability. This prototype is implemented using a 0.35 um BiCMOS process and the active chip area is 0.25 mm2.
Parametric System Identification of Resonant Nonlinear Micro/Nanosystems

The parametric system identification of macroscale resonators operating in a nonlinear response regime can be a challenging research problem, but at the micro- and nanoscales, experimental constraints add additional complexities. For example, due to the small and noisy signals micro/nanoresonators produce, a lock-in amplifier is commonly used to characterize the amplitude and phase response of the system. While the lock-in enables detection, it prohibits the use of established methods which rely upon time-domain measurements. As such, the only methods that can be used for parametric system identification are those based on fitting experimental data to an approximate solution of a reduced-order model. This work summarizes a much longer effort (Sabater and Rhoads in Mech Syst Signal Process 2016, [13]) that proposes that the parametric system identification of micro/nanosystem operating in a nonlinear response regime can be treated as the amalgamation of four coupled sub-problems. The theoretical foundations of these coupled sub-problems are discussed. To provide context, an electromagnetically-transduced microresonator is used as an example.
How Much Does it Cost to Search a Laptop in Canada? A Cost-Benefit Analysis

The Canadian government has a policy of searching laptop computers at airports and other border crossings. It is considered an outrageous policy by those who have been subjected to this gross invasion of privacy, and it has drawn some press attention. The Canadian courts have yet to rule on the constitutionality of this policy. The present article reports on one person’s experience (the author’s) and makes a conservative estimate of the cost of this policy to the Canadian people, both monetary and nonmonetary. The conclusion is that the cost of searching laptop computers is high while the benefits of doing so are low or nonexistent.
Negotiating Leadership Positions

How do you become a leader? What road do you need to follow to get to leadership? If you do decide to make the trip, where do you start the journey? And what about organizations seeking leadership? What road should they follow to obtain the leadership that they need? What is the best way of making that journey? What are the potential pitfalls and traps along the way? For both people seeking to be leaders and for organization that want leadership, the ultimate goal is to negotiate a leadership deal that will meet their respective interests. In reality, however, the two sides must negotiate two deals, not just one. The first is a negotiation that secures the leadership position for a particular person; the second concerns the specific leadership role that the person selected will play in the organization. Both deals have to be struck if the organization is to obtain the effective leadership it seeks and the chosen leader is to be empowered to lead effectively.
Comparison of general versus isolated regional anesthesia in total shoulder arthroplasty: A retrospective propensity-matched cohort analysis.

Background Intraoperative anesthetic typically consists of either general anesthesia (GA) or isolated regional anesthesia (RA).
Renewable Energy and Sum-Zero Energy Buildings

In the past few decades the diminishing resources and consequently the higher prices of fossil-based energy, and also increasing public awareness and understanding of the massive damages that utilizing the common fossil-based energy resources such as coal and gas impose to the environment have made the engineers to investigate new and clean resources of energy. These new and clean resources mainly are known as renewable energy. The renewable energy (sustainable energy) is commonly defined as resources of energy that can be reused time after time without short changing the future generations from reliable resource of energy and would not create harmful residuals that can threat the people health and the environment cleanness.
The 26S Proteasome as a Therapeutic Target in Cancer: Beyond Protease Inhibitors?

The 26S proteasome is a multi-subunit complex that has a barrel-shaped peptidase core (CP) whose proteolytic activity is sequestered from the cellular milieu by two regulatory particles (RP) that are docked on either end. The RP confers ubiquitin and ATP dependence to the proteolytic process. The CP can also be regulated by the REGγ complex, and can, in some instances, catalyze the degradation of proteins independent of ATP and ubiquitin. The peptidase activity of the 20S CP has been validated as a therapeutic target for cancers such as multiple myeloma by the development of inhibitors such as VELCAID. Since the peptidase activity is so central to 26S proteasome function, inhibitors of this class are generally toxic. Alternative therapeutic targets within the 26S proteasome can be explored, given the multistep nature of regulated degradation. Specifically, the recognition, and deubiquitination, of the polyubiquitin chain, and the unfolding and gating steps can be targeted.
Cerebral palsy of the upper extremity.

SUMMARY The care of patients with spastic cerebral palsy requires the dedicated attention of a surgeon who is interested in the upper extremity, in association with therapists and other medical personnel who have a similar interest. The difficult problems of the upper extremity have often been overlooked by concerns related to the other skeletal manifestations in the spine and lower extremities. However, a pessimistic view of surgical results in the upper extremity is unwarranted, as even small gains in severely affected patients often result in an improved life. The surgical concepts related to this complex neurologic problem must be kept rather simple, and include principally the release of spastic deforming muscles, and, secondly, the use of augmentation tendon transfers to maintain an improved functional position. In order to allow the augmentation tendon transfers to function with minimal postoperative muscle re-education, tendon transfers that use muscles that contribute to the deformity are preferred; in the transferred position, these will function to correct the deformity and fire in phase without extensive postoperative training. Such muscle transfers are usually available to correct the more common pattern of spastic deformities. The most important aspect of surgical planning is to determine whether or not the individual is attempting to voluntarily use the upper extremity. In such cases, surgical procedures can reposition the deformed limb and enable the individual to function more effectively. On the other hand, it is most important to realize that an operative procedure will not stimulate an individual to begin to use a previously functionless limb.
Puberty in the Last 25 Years: A Retrospective Bibliometric Analysis

Puberty research has been highly productive in the past few decades and is gaining momentum. We conducted an analysis of bibliographic data, including titles, abstracts, keywords, indexing terms, and citation data to assess the sheer numbers, audience and reach, publication types, and impact of puberty-related publications. Findings suggest that puberty-related publications are increasing in sheer numbers, and have reach in many fields as befits an interdisciplinary science. Puberty-related publications typically have higher impact in terms of citations than the journal averages, among the journals that published the most studies on puberty. Limitations of the field and recommendations for researchers to improve the impact and reach of puberty-related publications (e.g., clear conclusions in abstracts, highlighting the importance of puberty) are discussed.
Exposure to fine particulate matter and temporal dynamics of episodic memory and depressive symptoms in older women.

Abstract Background Emerging data suggests PM2.5 (particulate matter with aerodynamic diameter Methods Older women (n = 2,202; aged 67–83 in 1999) enrolled in the Women’s Health Initiative Study of Cognitive Aging completed up to eight annual assessments of depressive symptoms (15-item Geriatric Depression Scale) and EM (California Verbal Learning Test). A nationwide spatiotemporal model (1999–2010) was used to estimate ambient PM2.5 exposure at residential locations. Univariate and bivariate structural equation models (SEMs) for latent-change scores were used to examine how 3-year average PM2.5 preceding each assessment affects the temporal dynamics and bidirectional relations of annual changes in depressive symptoms and EM. Results In univariate SEMs, one inter-quartile (4.04 μg/m3) increment of 3-year PM2.5 was significantly (p Conclusions Findings suggest that PM2.5 neurotoxicity may damage brain areas implicated in EM, followed by manifestation of depressive symptoms. Our data did not support depressive symptoms as the neuropsychological mediator of accelerated brain aging associated with PM2.5 exposure.
Impact of ultrasound processing on some milk-borne microorganisms and the components of camel milk

Inactivation of pathogenic bacteria Escherichia coli O157: H7 and Salmonella Typhimurium in camel milk was investigated using ultrasound processing (900 W, 20 kHz, 100% power level). In addition, the effect of ultrasound treatment on raw camel milk components was studied to detect changes in fatty acid profile, lipid peroxides, protein fractions, and volatile compounds. Bacterial strains (106 CFU/ml) were added to pasteurized camel milk samples (70 ml) and transferred into a sterile aluminum container (30 mm x 120 mm, 100-ml total capacity) and then subjected to continuous ultrasound processing for 15 min in an ice water bath using a 13-mm diameter probe. The standard plate count (SPC) agar method and the in vivo imaging system (IVIS) were used to evaluate the viability of bioluminescence-transformed bacteria (E. coli O157: H7 and S. Typhimurium). The continuous ultrasound processing of camel milk resulted in significant (P 0.05) by the ultrasound processing. The TBAR values, a marker of lipid peroxidation, and milk protein fractions were also similar (P>0.05) between the sonicated and unsonicated raw camel milk. A total of 24 volatile compounds (VC) were identified including 8 aldehydes, 3 ketones, 5 acids, 5 esters, 2 aromatic hydrocarbonate, and 1 sulfo compound. Of these 24 VC, eleven VC increased (P<0.05) and seven decreased (P<0.05) after sonication. In conclusion, the results of this study showed that ultrasound processing of camel milk was efficient in inactivating subsets of milk-borne pathogens without detrimental effects on camel milk fatty acids, lipid peroxides, and protein fractions. However, there were some changes in milk VC which may affect the sensory quality of milk.
Telemedicine in Oncology: Delivering on an Overdue Promise in the COVID-19 Era

Telemedicine has historically been underutilized in medicine broadly, and specifically in oncology, despite the general availability of the needed infrastructure to offer it as a platform for remote care. The COVID-19 pandemic posed new risks of infection exposure and potentially life-threatening complications, particularly in patients with cancer, created a new setting for cancer care ideally suited for the rapid roll-out of telemedicine for patients with cancer who need regular follow up but in whom live visits may not be critical. In the months since the upheaval of our health care system and wider society in the United States, as well as other countries, our early experience with telemedicine has demonstrated the feasibility of telemedicine for a subset of patients with cancer, facilitated by a removal of regulatory hurdles and payment parity, at least temporarily. At the same time, however, many patients still need to return to the clinic for routine infusions of anti-cancer therapy that obviate much of the value of remote clinic visits, and many patients remain limited by access to hardware, fast and reliable internet, and technical expertise. While we need to address these shortcomings and ensure training of health care professionals in "webside manner" with patients, as well as to work to develop ways to incorporate remote care in the conduct of clinical trials, telemedicine is poised to emerge not merely as an interim solution to a transient challenge but as a valuable tool ideally suited to deliver cancer care efficiently for a subset of patients well suited to adopt this platform.
Adenosine modulates extracellular glutamate levels via adenosine A2A receptors in the delayed-ethanol induced headache.

Abstract Identifying the mechanism behind delayed ethanol-induced headache (DEIH), otherwise known as the hangover headache, may provide insight into the mechanisms behind common headache triggers. Acetate was previously shown to be the key ethanol metabolite behind DEIH in the recurrent inflammatory stimulation (IS) rat model of headache. The reversal of trigeminal sensitivity following ethanol exposure with caffeine previously suggested a role of adenosine in DEIH. To characterize this, behavioral analysis and measurement of brainstem adenosine and glutamate with microdialysis and HPLC was performed while pharmacologically manipulating adenosine signaling in the IS and Spontaneous Trigeminal Allodynia (STA) rat models of headache. Blocking adenosine A2A receptor activation with istradefylline or acetate transport into astrocytes with the monocarboxylate transporter competitive inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), prevented acetate-induced trigeminal sensitivity. Blocking adenosine A1, A2B, and A3 receptor signaling did not prevent trigeminal sensitivity. Compared to control rats, IS rats had greater increases in extracellular adenosine and glutamate within the trigeminal nucleus caudalis (TNC) of the brainstem during local acetate perfusion. Blocking transport of acetate into astrocytes with 4-CIN prevented the increase in adenosine and glutamate. Blocking A2A receptor activation prevented the increase in extracellular glutamate, but not adenosine in the TNC. These data are the first to demonstrate the physiological consequence of acetate on adenosinergic systems within trigeminal pain by suggesting that acetate-induced trigeminal sensitivity in DEIH is mediated by adenosine A2A receptor activation which modulates extracellular glutamate levels in the TNC. Significance Statement It is unknown how several common headache triggers induce headache pain. Since migraineurs are more sensitive to these triggers, studying the mechanisms behind their effects may reveal unique migraine pathophysiology. In this study, we explored the common headache trigger, ethanol, which migraineurs are particularly sensitive to. When ethanol is ingested, its quickly metabolized to acetaldehyde and subsequently into acetate. We find that acetate increases brainstem adenosine and causes trigeminal sensitivity, which is exacerbated in the rat headache model. Blocking either acetate uptake or adenosine signaling prevents trigeminal sensitivity and brainstem glutamatergic signaling, suggesting that adenosine is involved in the hangover headache and that differences in acetate metabolism may account for the increased sensitivity to ethanol in migraineurs.
Safety, Efficacy, and Long-Term Outcomes of Anticoagulation in Cirrhotic Portal Vein Thrombosis

The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear. We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not. Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan–Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals. A total of 214 patients were followed for a median 27 months (IQR 12–48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p = 0.0007), (multivariable HR for CRR with AC; 2.49 (1.54–4.04, p = 0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p = 0.0013), (multivariable HR for RCO with AC; 4.86 (1.91–12.37, p = 0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p = 0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68–2.46, p = 0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p = 0.1362), (HR for death with AC; 0.69 (0.38–1.28, p = 0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence). AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.