cssi/SciSciGPT-SciSciNet huggingface dataset:
In Vitro Reconstitution of an Escherichia coli RNA-guided Immune System Reveals Unidirectional, ATP-dependent Degradation of DNA Target

Many prokaryotes utilize small RNA transcribed from clustered, regularly interspaced, short palindromic repeats (CRISPRs) to protect themselves from foreign genetic elements, such as phage and plasmids. In Escherichia coli, this small RNA is packaged into a surveillance complex (Cascade) that uses the RNA sequence to direct binding to invasive DNA. Once bound, Cascade recruits the Cas3 nuclease-helicase, which then proceeds to progressively degrade the invading DNA. Here, using individually purified Cascade and Cas3 from E. coli, we reconstitute CRISPR-mediated plasmid degradation in vitro. Analysis of this reconstituted assay suggests that Cascade recruits Cas3 to a single-stranded region of the DNA target exposed by Cascade binding. Cas3 then nicks the exposed DNA. Recruitment and nicking is stimulated by the presence, but not hydrolysis, of ATP. Following nicking and powered by ATP hydrolysis, the concerted actions of the helicase and nuclease domains of Cas3 proceed to unwind and degrade the entire DNA target in a unidirectional manner. Background: The CRISPR-Cas immune system protects E. coli against invasive DNA. Results: We have reconstituted this immune system in vitro using recombinant proteins. Conclusion: Degradation of invasive DNA is tightly regulated and unidirectional. Significance: Reconstitution provides an invaluable tool for understanding the CRISPR-Cas immune system.
Acute physiological and behavioral effects of oral cocaine in humans: a dose-response analysis.

Abstract The present study was designed to assess the acute physiological and behavioral effects of a wide range of doses of oral cocaine HCL (placebo, 50, 100, 200, and 300 mg). Nine volunteers (eight males and one female) with recent histories of cocaine use resided on a general inpatient psychiatry unit while they participated. Drug doses were administered in a double-blind fashion under medical supervision, but for safety purposes, they were administered in ascending order. The physiological, subject-rated, and performance effects of oral cocaine HCL were assessed before drug administration and periodically afterwards for 5 h. Oral cocaine HCL increased heart rate and blood pressure as a graded function of dose, but the magnitude of these effects were not clinically significant. Oral cocaine HCL produced positive subject-rated drug effects (e.g. increased ratings of good effects, like drug, and willing to take again), but did not affect performance. Consistent with the pharmacokinetics of oral cocaine HCL, drug effects were generally discernible from placebo 0.5–1 h after administration, peaked approximately 1 h after administration, and progressively abated during the remainder of the experimental session. The results of this experiment demonstrate that across a six-fold range of doses oral cocaine HCL is well tolerated by individuals with recent histories of cocaine use and can be safely administered under controlled laboratory and medical conditions.
Progress towards a service-oriented universal access telerehabilitation platform

This paper addresses how UniTherapy, a telerehabilitation platform developed primarily for computer-assisted motivating rehabilitation applications, is being turned into an accessible service. This process has involved transformation to a service-oriented universal access infrastructure that also supports intelligent context-aware user interface generation that is dependent on current and emerging standards such as the V2 standard for universal remote consoles. It also has involved support for a steadily increasing, diverse menu of approaches for performance assessment, and of interfaces for promoting universal access. Progress and key issues are discussed.
Defining Preparation and Professional Development for the Future.

This article provides an overview of principal and superintendent preparation in the past and offers suggestions for the future development of such leaders. Implications for prin- cipal and superintendent preparation are that many essential skills and much important knowledge cannot be delivered by a traditional university-based program. Although the authors continue to support the preparation of principals and superintendents in university-based programs for these harsh and demanding times, they recommend that the programs (a) attend to belief, attitude, and philosophy; (b) deal with problems in practice; and (c) foster institutional arrangements to allow for coordination of efforts with schools. Preparation must be redesigned to reflect the findings of research on the advancement of professional practice. Preparation programs must be reorganized to reflect what we have learned from large-scale school improvement efforts. There must be closer association between higher education, the professional organizations, and dis- tricts themselves to provide preparation outside conventional classroom settings. This article reports on the current thinking about the position of principals and superintendents in America's schools. The article also provides conclu- sions on how we might restructure both the preparation and continued profes- sional development of these educational leaders. At the heart of this work are some fundamental notions about what superintendents and principals are obliged to do when children come to school under conditions of compulsory
Abstract C106: Discovery and characterization of INCB024360, a potent and selective inhibitor of indoleamine 2,3‐dioxygenase (IDO1) as a novel agent for cancer immunotherapy

Indoleamine 2,3‐dioxygenase (IDO or IDO1) mediates the oxidation of tryptophan, an amino acid essential for cell proliferation and survival. Inhibition of IDO activity or expression has shown therapeutic potential in preclinical models of immunodeficiency‐associated abnormalities including cancer. Here we report the identification of INCB024360, a novel, potent and selective small molecule inhibitor of IDO1, and the investigation of its effects on the proliferation and activation of various immune cells in vitro as well as its anti‐tumor activity in preclinical tumor models. In multiple cell‐based assays, INCB024360 potently inhibits human IDO1 with an IC50 of approximately 10 nM ‐ the most potent IDO1 inhibitor published thus far. INCB024360 is IDO1 selective and has little activity against other related enzymes including IDO2, TDO or tryptophan transporters. In co‐culture systems of human allogeneic lymphocytes with either dendritic cells or tumor cells, inhibition of IDO1 by INCB024360 increases the proliferation of T and NK cells, as well as IFN‐ production. INCB024360 addition also reduces the generation of regulatory T cells. Interestingly, IDO1 expression promotes dendritic cell apoptosis while addition of INCB024360 reverses this and increases the number of CD86high cells within the IDO+ DC population, potentially representing a novel mechanism by which IDO1 inhibition can promote T cell activation. In vivo, INCB024360 inhibits tryptophan catabolism in tumors and tumor draining lymph nodes and controls tumor growth either alone or in combination with chemotherapeutic agents in multiple tumor models. The ability to reduce tumor growth is dependent on a functional immune system, consistent with the proposed mechanism of action. Finally, an analysis of kynurenine/tryptophan levels in patient blood samples affirms that the IDO activity is elevated in multiple tumor types. Collectively, these data suggest that INCB024360, a potent IDO1 selective inhibitor, has the potential to be a novel and effective immunotherapeutic agent for cancer treatment. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C106.
Chemotherapy and targeted therapy combinations in advanced melanoma

For three decades, clinical trials with chemotherapy in melanoma have failed to show superiority of any one regimen over another. Dacarbazine remains the only "standard" agent. With response rates of <10% and median progression-free survival of 2 months or less in contemporary trials, there is a need to improve systemic therapy. Combination chemotherapy is associated with higher response rates than single-agent therapy but this has not translated into improved survival. An increasing number of potential therapeutic targets have been identified. For some, pharmacologic inhibitors are available, including sorafenib for BRAF, farnesyltransferase inhibitors for NRAS, PD-0325901 for mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, rapamycin analogues for mammalian target of rapamycin, and agents that inhibit either vascular endothelial growth factor or its receptors. Several multitargeted kinase inhibitors have potency against the fibroblast growth factor receptor, c-kit, and platelet-derived growth factor receptor. Small-molecule inhibitors of c-met and Akt are in preclinical development. Another class of agents indirectly affect aberrant signaling, including inhibitors of chaperones and proteasomes. Several targeted agents seem to enhance the cytotoxicity of chemotherapy in preclinical models. The mechanism by which signaling inhibition might synergize with chemotherapy requires more study so that rational combinations move forward. Very few targeted agents have been studied rigorously in this fashion.
Driving rural energy access: a second-life application for electric-vehicle batteries

Building rural energy infrastructure in developing countries remains a significant financial, policy and technological challenge. The growth of the electric vehicle (EV) industry will rapidly expand the resource of partially degraded, ‘retired’, but still usable batteries in 2016 and beyond. These batteries can become the storage hubs for community-scale grids in the developing world. We model the resource and performance potential and the technological and economic aspects of the utilization of retired EV batteries in rural and decentralized mini- and micro-grids. We develop and explore four economic scenarios across three battery chemistries to examine the impacts on transport and recycling logistics. We find that EVs sold through 2020 will produce 120–549 GWh in retired storage potential by 2028. Outlining two use scenarios for decentralized systems, we discuss the possible impacts on global electrification rates. We find that used EV batteries can provide a cost-effective and lower environmental impact alternative to existing lead-acid storage systems in these applications.
Selective Attention and Transfer Phenomena in L2 Acquisition: Contingency, Cue Competition, Salience, Interference, Overshadowing, Blocking, and Perceptual Learning

If first language is rational in the sense that acquisition produces an end-state model of language that is a proper reflection of input and that optimally prepares speakers for comprehension and production, second language is usually not. This paper considers the apparent irrationalities of L2 acquisition, that is the shortcomings where input fails to become intake. It describes how ‘learned attention’, a key concept in contemporary associative and connectionist theories of animal and human learning, explains these effects. The fragile features of L2 acquisition are those which, however available as a result of frequency, recency, or context, fall short of intake because of one of the factors of contingency, cue competition, salience, interference, overshadowing, blocking, or perceptual learning, which are all shaped by the L1. Each phenomenon is explained within associative learning theory and exemplified in language learning. Paradoxically, the successes of L1 acquisition and the limitations of L2 acquisition both derive from the same basic learning principles.
Magnetic resonance imaging defines structural brain injury acquired during critical illness

Patients with non-neurological critical illness commonly develop cerebral dysfunction, which may take the form of delirium, coma, and long-term cognitive impairment. Delirium in the ICU is associated with increased mortality and prolonged mechanical ventilation and hospital stay, and is commonly attributed to metabolic derangements. Tests such as brain computed tomography (CT) and cerebrospinal fluid analysis are frequently nondiagnostic. We hypothesized that brain magnetic resonance imaging (MRI) is a valuable tool in the diagnosis of delirium and coma acquired in the ICU.
Low power circuit design based on heterojunction tunneling transistors (HETTs)

The theoretical lower limit of subthreshold swing in MOSFETs (60 mV/decade) significantly restricts low voltage operation since it results in a low ON to OFF current ratio at low supply voltages. This paper investigates extremely-low power circuits based on new Si/SiGe HEterojunction Tunneling Transistors (HETTs) that have subthreshold swing
TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells

The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Global gene expression profiling after downregulation of TLX1 and inhibition of the NOTCH pathway in ALL-SIL cells revealed that TLX1 synergistically regulated more than 60% of the NOTCH-responsive genes. Structure-function analysis demonstrated that TLX1 binding to Groucho-related TLE corepressors was necessary for maximal transcriptional regulation of the NOTCH-responsive genes tested, implicating TLX1 modulation of the NOTCH-TLE regulatory network. Comparison of the dataset to publicly available biological databases indicated that the TLX1/NOTCH-coregulated genes are frequently targeted by MYC. Gain- and loss-of-function experiments confirmed that MYC was an essential mediator of TLX1/NOTCH transcriptional output and growth promotion in ALL-SIL cells, with TLX1 contributing to the NOTCH-MYC regulatory axis by posttranscriptional enhancement of MYC protein levels. Functional classification of the TLX1/NOTCH-coregulated targets also showed enrichment for genes associated with other human cancers as well as those involved in developmental processes. In particular, we found that TLX1, NOTCH and MYC coregulate CD1B and RAG1, characteristic markers of early cortical thymocytes, and that concerted downregulation of the TLX1 and NOTCH pathways resulted in their irreversible repression. We found that TLX1 and NOTCH synergistically regulate transcription in T-ALL, at least in part via the sharing of a TLE corepressor and by augmenting expression of MYC. We conclude that the TLX1/NOTCH/MYC network is a central determinant promoting the growth and survival of TLX1+ T-ALL cells. In addition, the TLX1/NOTCH/MYC transcriptional network coregulates genes involved in T cell development, such as CD1 and RAG family members, and therefore may prescribe the early cortical stage of differentiation arrest characteristic of the TLX1 subgroup of T-ALL.
Nested designs with multivariate measurement : An illustration of the structural approach to random effects multivariate analysis of variance

Dawid's structural approach [1]to modeling is illustrated through balanced nested designs with multivariate measurement. The usual multivariate covariance component model is justified based on the exchangeability of sampling units. Likelihood based and Bayesian inference are described assuming multivariate normality. Generalization to a unified theory of multivariate random effects analysis of variance is outlined.
Developing and evaluating instructionally sensitive assessments in science

The purpose of this article is to address a major gap in the instructional sensitivity literature on how to develop instructionally sensitive assessments. We propose an approach to developing and evaluating instructionally sensitive assessments in science and test this approach with one elementary life-science module. The assessment we developed was administered to 125 students in seven classrooms. The development approach considered three dimensions of instructional sensitivity; that is, assessment items should: represent the curriculum content, reflect the quality of instruction, and have formative value for teaching. Focusing solely on the first dimension, representation of the curriculum content, this study was guided by the following research questions: (1) What science module characteristics can be systematically manipulated to develop items that prove to be instructionally sensitive? and (2) Are the instructionally sensitive assessments developed sufficiently valid to make inferences about the impact of instruction on students' performance? In this article, we describe our item development approach and provide empirical evidence to support validity arguments about the developed instructionally sensitive items. Results indicated that: (1) manipulations of the items at different proximities to vary their sensitivity were aligned with the rules for item development and also corresponded with pre-to-post gains; and (2) the items developed at different distances from the science module showed a pattern of pre-to-post gain consistent with their instructional sensitivity, that is, the closer the items were to the science module, the larger the observed gains and effect sizes. © 2012 Wiley Periodicals, Inc. J Res Sci Teach 49: 691–712, 2012
The treated prevalence of bipolar disorder in a large staff-model HMO

OBJECTIVE: The treated prevalence of bipolar disorder was examined in a large staff-model health maintenance organization (HMO) in western Washington state. METHODS: Automated data for all 294,284 adults enrolled in the HMO or treated by HMO providers were used to determine the number of patients treated for bipolar disorder between July 1, 1995, and June 30, 1996. Patients with bipolar disorder were identified using computerized records of inpatient diagnoses, outpatient visit diagnoses, and outpatient prescriptions of mood stabilizers. Validity of the identification procedure was confirmed by review of a random sample of outpatient records. RESULTS: The treated prevalence of bipolar disorder in the HMO was .42 percent. Somewhat higher treated-prevalence rates were found for women, younger enrollees, family members of HMO subscribers, enrollees in some of the individual plans within the HMO, and enrollees in the state's Basic Health Plan program for low-income residents. Of the 1,236 adults treated for b...
Effects of kinship care on behavioral problems by child age: A propensity score analysis

Abstract When a child must be removed from the family home, placement with a relative is often sought because kinship care is the least restrictive and most family-like out-of-home placement. Although kinship care has become a preferred option in most U.S. child welfare systems, this preference is often based on “soft evidence” rather than rigorous evaluation of the risks and benefits of kinship care. Therefore, an evaluation of the impact of kinship care on child behavioral problems is needed to guide child welfare practice and policy. In addition, given that children of different ages and in different developmental stages are likely to have varying placement experiences, the evaluation of kinship care should explore the effect of kinship care on child behavioral problems across age groups. To fill these knowledge gaps, we compare the behavioral problems of 584 children in kinship care with those of 470 children in non-kinship care. Moreover, we examine the impact of kinship care on behavioral problems in 2 age groups: younger children (0 to 5 years) and older children (6 to 17.5 years). The analysis uses data from Waves 1 and 2 of the National Survey of Child and Adolescent Wellbeing, and applies propensity score methods to account for selection bias. Results show that older children in kinship care had significant lower levels of externalizing, internalizing, and total behavior problems. However, for younger children, the effects of kinship care on child behavioral problems did not reach statistical significance. The implications for practice, research and policy are discussed.
Altering Nursing Student and Older Adult Attitudes Through a Possible Selves Ethnodrama.

The purpose of this mixed method study is to evaluate the effects of participation in the development and implementation of ethnodrama about possible selves on nursing student attitudes toward older adults and older adult attitudes to aging. Twelve nursing students and 12 older adult long-term care residents collaborated in a transformational learning experience involving interviews on the topic of possible selves culminating in the presentation of an ethnodrama developed from these data. Longitudinal data from student surveys about attitudes toward older adults were analyzed using growth modeling, whereas older adult pre–post data on attitudes toward aging were analyzed with a paired samples t test. Video of group discussions and open-ended feedback on the overall experience were analyzed to provide qualitative understanding of change in student attitudes over time. Although positive overall, student attitudes varied in initial status and rate of change. Students who interacted most frequently with older adults had more neutral attitudes. Older adult attitudes surrounding psychosocial loss improved over the course of the intervention. Normalizing attitudes may be as important as improving attitudes; neutrality may be more representative of realistic perceptions of older adults and late-life potential.
A nonlinear counts to antenna temperature algorithm for a total power radiometer with external calibration and noise diode injection

The newest innovation to passive microwave remote sensing technology is the inclusion of noise diodes for radiometric calibration of total power radiometers. Instead of the usual two-point calibration using passive black body sources, now there are four-calibration noise levels, which allow system nonlinearities to be corrected. Conventional approaches linearize the radiometer output "rad_counts" (using the four-point calibration correction) and use a linear transfer function to calculate the antenna temperature (TA) at the radiometer input. This paper presents a novel approach of using a quadratic radiometer transfer function (with nonlinear rad_counts) to derive (TA). This algorithm is tested using on-orbit satellite measurements from the Global Precipitation Measurement (GPM) Microwave Imager (GMI). Empirical results are presented, which show only mille-Kelvin differences between this TA algorithm and the standard TA product provided by NASA.
Near-infrared spectroscopy provides continuous monitoring of compromised lower extremity perfusion during cardiac surgery

Near-infrared spectroscopy (NIRS) is more frequently used to monitor regional oxygenation/perfusion of the cerebral and somatorenal vascular bed during congenital heart surgery. However, NIRS probes can be placed elsewhere to assess regional perfusion. We report the intraoperative use of NIRS probes on both calves of an infant to continuously monitor changes in the regional oxygenation/perfusion of a lower extremity whose perfusion was compromised after femoral arterial line placement. The NIRS trend of the compromised limb was compared with the contralateral limb throughout congenital heart surgery including the period on cardiopulmonary bypass (CPB). Our case report illustrates that NIRS technology can be used to monitor ongoing lower extremity vascular compromise during congenital heart surgery when it is not practical to directly access and continuously assess the limb. Transient vascular compromise after invasive femoral arterial line or sheath placement for cardiac catheterization in small infants is not infrequent. NIRS technology in such circumstances may help to decide whether watchful waiting is acceptable or immediate interventions are indicated. Continuous NIRS monitoring showed that limb regional oxygenation remained depressed during CPB but dramatically increased in the post-CPB period.
Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells

This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells, allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of α-cells (5%), β-cells (92%), δ-cells (1%), and pancreatic polypeptide cells (2%). We identified cell-type-specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability, low sequencing quality, or contamination resulting in the detection of more than one islet hormone. Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system.
Crystal and molecular structure oftrans-dichlorobis(oxazole)palladium(II)

The crystal and molecular structure oftrans-dichlorobis(oxazole)palladium-(II), Pd(C3H3ON)2Cl2, has been determined by single-crystal X-ray diffraction techniques using counter methods and has been refined by full-matrix least-squares procedures to a finalR index of 0.022. The complex crystallizes in the triclinic space groupP¯1 with unit cell dimensions ofa = 6.957(1),b = 7.506(1),c = 5.538(1) A, α = 109.22(1), β = 91.37(1), and γ = 115.09(1) °, withZ = 1. The palladium(II) ion, located at an inversion center, is coordinated in a regular square-planar manner to two chloride ions at 2.293(1) A and, at 2.016(2) A, to the nitrogen atoms of two oxazole ligands. The planar oxazole rings are tilted 33 ° with respect to the PdN2Cl2 plane. Further verification of the presence of oxazole in the complex was obtained by high-resolution mass spectrometry. Crystals of Pd(C3H3ON)2Cl2 resulted irreproducibly from attempts to prepare single crystals of a previously reported dimeric palladium(II) disulfide complex by treating Pd(CH3CN)2Cl2 with a slight excess of diphenyl disulfide in benzene in the atmosphere. The source of the oxazole is not understood.
Successful Limb Salvage of a "Too-Short Segment" of the Proximal Part of the Femur with Use of a Compression Osseointegration Implant: A Case Report.

After resection of a bone tumor, reconstruction can be performed with use of a variety of techniques, including large-segment allografts, allograft-prosthetic composites, endoprostheses, and other types of tissue-transfer procedures1-5. All of these options rely on healthy native bone and soft tissues. The difficulty of achieving a successful outcome increases as the segment of remaining normal bone decreases6,7. For example, endoprosthetic implants with stems require a sufficient length of bone to achieve either press-fit or cemented fixation. Similarly, allografts and vascularized bone transfers require healthy bone to achieve adequate fixation8. When short segments of bone remain after tumor resection, traditional implants will not fit, and the surgeon has to rely on alternatives such as allograft-prosthetic composites, custom implants, or replacement of the entire bone (as with total replacement of the femur). Determining what constitutes sufficient bone to perform a reconstruction is not known and depends on the surgeon’s experience, the implants that are available, the patient’s acceptance of surgical risks, and the resources available for postoperative rehabilitation. To the best of our knowledge, there are no studies in the literature that specifically provide information or guidance on how to perform an endoprosthetic reconstruction of the femur when only the proximal metaphysis is intact. We present a case of a seventy-five-year-old man who underwent successful endoprosthetic replacement of the entire femur, distal to the lesser trochanter and including the knee joint, after complications associated with a chondrosarcoma resection. This case demonstrates a novel technique with use of a compression osseointegration implant for preservation of the native hip joint while replacing almost the entire femur. The patient was informed that data concerning the case would be submitted for publication, and he provided consent. A seventy-five-year-old man presented with a four-to-six-month history of pain …
Functional sex ratio in the carmine spider mite

Functional sex ratio (no. sexually capable males : no. available females) of T. cinnabarinus was monitored throughout a colonizing episode. The results were compared with a model constructed from life table data. Because males are sexually capable throughout their adult lives and individual females are available only briefly, the functional sex ratio becomes markedly skewed towards males, particularly during the period of maximum dispersal from the host plant. Even when males are in abundance, guarding behavior is concentrated on those female deutonymphs nearest to emergence. These factors combine to (1) increase male competition for the few available females and (2) ensure that nearly all females are fertilized at or shortly after emergence.
Peer review in cardiothoracic radiology.

A variety of peer review methods can be used as part of quality assurance and quality improvement in cardiothoracic radi- ology. Traditionally, peer review in radiology is a retrospective process relying primarily on review of previously interpreted studies at the time of follow-up or additional imaging. However, peer review can be enhanced with other methods such as double reads, focus practice review, practice audit, and correlation with operative and pathologic findings. Furthermore, feedback from referring physicians can be extremely useful in improving the quality of a radiology practice. This article discusses peer review in radiology with a focus on cardiothoracic imaging. Types of peer review, advantages and shortcomings, and future challenges are addressed.
Hyperhomocysteinemia exacerbates Alzheimer's disease pathology by way of the β‐amyloid fibrinogen interaction

Essentials Evidence suggests a comorbidity between hyperhomocysteinemia (HHC) and Alzheimer's disease (AD). Homocysteine (HC) could affect the β-amyloid (Aβ)-fibrinogen interaction in AD pathology. AD patients with concomitant HHC have increased fibrin and Aβ deposits in their brains. HC contributes to AD pathology via the Aβ-fibrinogen interaction. SummaryBackground Accumulating clinical evidence suggests that hyperhomocysteinemia (HHC) is correlated with Alzheimer's disease (AD) and vascular dementia. Objective This study was carried out to elucidate the specific role of elevated homocysteine (HC) levels in AD pathophysiology. Methods Immunohistochemistry was used to examine β-amyloid (Aβ) deposition along blood vessels, also known as cerebral amyloid angiopathy (CAA), fibrin(ogen) deposition, and their correlation to each other in the brains of AD patients with and without HHC. To study AD-HHC co-morbidity in detail, an AD mouse model was administered a high methionine diet for several months. Parenchymal Aβ plaques, CAA-positive vessels and fibrin deposits were then assessed by immunohistochemistry at different stages of AD progression. Memory deficits were evaluated with contextual fear conditioning and the Barnes maze. Additionally, the effect of HC and its metabolite, homocysteine thiolactone (HCTL), on the Aβ–fibrinogen interaction was analyzed by pull-down, ELISA and fibrin clot formation and fibrinolysis assays in vitro. Results We found increased fibrin(ogen) levels and Aβ deposits in the blood vessels and brain parenchyma of AD patients with HHC. We demonstrate that HC and HCTL enhance the interaction between fibrinogen and Aβ, promote the formation of tighter fibrin clots and delay clot fibrinolysis. Additionally, we show that diet-induced HHC in an AD mouse model leads to severe CAA and parenchymal Aβ deposition, as well as significant impairments in learning and memory. Conclusions These findings suggest that elevated levels of plasma HC/HCTL contribute to AD pathology via the Aβ–fibrin(ogen) interaction.
Pseudomeningitis again. Association with cytocentrifuge funnel and Gram-stain reagent contamination.

Objective To report an "epidemic" of pseudomeningitis related to cytocentrifuge funnel and Gram-stain reagent contamination, and our evaluation and responses. Design Investigation was stimulated by the recognition of Gram-stained, smear-positive, culture-negative cerebrospinal fluid (CSF) specimens. Cytofunnels, glass slides, Gram-staining reagents, and an automated Gram-staining apparatus were subjected to repeated staining and culture. Control stains and cultures using fetal bovine serum (simulated CSF) were performed for comparison. Setting The clinical microbiology laboratory of Parkland Memorial Hospital, a large acute-care teaching hospital. Specimens Cerebrospinal fluid specimens were submitted to the clinical microbiology laboratory in the course of routine patient care. Main outcome measures Gram's stains and cultures of test and control preparations. Results Most of the smear-positive, culture-negative, original CSF specimens contained Gram-positive bacilli or Gram-negative bacilli. Smears of cytofunnels revealed similar organisms, and cultures revealed Bacillus species. Cytofunnels from several lots were culture-positive. Glass slides were not contaminated. Of 25 CSF specimens stained during the initial week of investigation, 23 were negative by culture and two grew Cryptococcus neoformans (from acquired immunodeficiency syndrome patients). Control stains and cultures of simulated CSF were negative. Gram-stain reagents were frequently smear-positive, and cultures repeatedly yielded Flavimonas oryzihabitans from the crystal violet well of an automated Gram-staining apparatus. These latter contaminants could not be eliminated consistently. Interventions No alternative sources of cytofunnels were found. The Gram-staining apparatus was cleaned and reagents changed frequently. Cytocentrifugation and use of automated Gram staining was discontinued for CSF and other normally sterile fluids. The laboratory staff was repeatedly educated about the problem. Conclusions Contamination of cytocentrifuge funnels and an automated Gram-staining apparatus contributed to an "epidemic" of pseudomeningitis. The problem was corrected by education of the laboratory staff and by altered management of CSF and other sterile body fluid specimens.
The Moral Original Position

Chapter 4 showed that the Categorical-Instrumental Imperative — a principle that I have argued solves the problem of possible future selves — can be restated as follows: The Kingdom of Human and Sentient Ends Formulation: voluntarily aim for its own sake, in every relevant action, to abstract away from the interests (or ends) of particular human or nonhuman sentient being(s), acting instead on interests (or ends) it is instrumentally rational for all human and nonhuman sentient beings to universally agree to share given their different voluntary, involuntary, and semivoluntary interests, where relevant actions are determined recursively as actions it is instrumentally rational for one’s present and possible future selves to universally agree upon as such in cases where one’s present self wants to know and advance their future interests — and then, when the future comes, voluntarily choose your having acted as such.
Writing the Voices of Our Participants

Our voice is not the only voice in our ethnographies. Our participants should have voice as well, distinct from our own, with their own quicks and speech patterns–with their own howls. Since we are engaging in ethnographic practice, we also want to call on the voices of our participants; ours should not be the only voice in the tale.
Comparison of total artificial heart and biventricular assist device support as bridge-to-transplantation.

BACKGROUND The use of left ventricular assist devices (LVAD) has increased significantly in the last decade. However, right heart dysfunction remains a problem despite the improved outcomes with continuous-flow LVADs. Surgical options for bridge to transplantation (BTT) in patients with biventricular failure are total artificial heart (TAH) or biventricular support (BiVAD). This study examines the differences in pre- and post-transplantation outcomes and survival in patients with TAH or BiVAD support as BTT. METHODS The United Network of Organ Sharing database was retrospectively queried from January 2005 to December 2014 to identify adult patients undergoing heart transplantation (n = 17,022). Patients supported with either TAH (n = 212) or BiVAD (n = 366) at the time of transplantation were evaluated. Pre- and post-transplantation Kaplan–Meier survival curves were examined. Cox regression model was used to study the hazard ratios of the association between TAH versus BiVAD support and post-transplant survival. RESULTS The median age of the study groups was 49.8 ± 12.9 (TAH) and 47.2 ± 13.9 (BiVAD) years (range 18–74 years). There were more men, 87% versus 74%, in the TAH group (p < 0.0001) with greater body mass index, 27.3 ± 5.2 versus 25.6 ± 4.7 (p < 0.0001), compared to those with BiVADs. Creatinine was higher, 1.7 + 1.2 versus 1.3 + 0.8 mg/dL (p < 0.0001), in the TAH group before transplant. The 30-day, one-, and three-year post-transplantation survival was 88%, 78%, and 67%, respectively, for patients with TAH support versus 93%, 83%, and 73% (p = 0.06) for patients with BiVAD support. Cox regression model shows pre-transplant creatinine (HR = 1.21, p = 0.008) is associated with a lower post-transplant survival. TAH is not associated with a worse post-transplant survival (p = 0.1). There was no difference in wait-list survival in patients supported with TAH or BiVAD (p = 0.8). CONCLUSION Although there has been a recent increase in the use of the TAH as BTT, BiVAD support remains a viable option with similar post-transplant survival.
Photo Quiz: Frontal Brain Abscesses in an Immunocompetent Patient

A 59-year-old male with a past medical history of chronic obstructive pulmonary disease, hyperlipidemia, and gastroesophageal reflux disease and a recent history of upper left molar pain and right-sided body numbness was found by his wife to be having seizure activity while asleep. Upon arrival to
Design and Analysis of Two-Way Limited Feedback Beamforming Systems

Limited feedback beamforming is a simple technique to supply channel state information at the transmitter (CSIT) of a multiple-input-multiple-output (MIMO) system using beamforming. Feedback relies on the existence of a two-way communication system, which has two users conveying data to each other. As resources allocated to feedback and to transmitting data assist transmissions in two different directions, a fundamental tradeoff exists between the achievable rates in both directions. In this paper, we focus on beamforming systems with limited feedback where all transmissions, including feedback, use beamforming. We propose an anlytical framework to analyze such a system using simple effective SNR expressions. Closed- form results for the local tradeoff boundary for each user are found. Simulations illustrate system behavior for various configurations. The system becomes less coupled as available power on each side increases.
Reactivation of occult HBV infection in an HIV/HCV Co-infected patient successfully treated with sofosbuvir/ledipasvir: a case report and review of the literature

Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV. The patient is a Caucasian 54-years old female, with HIV/HCV co-infection (genotype 4), and a previous exposure to HBV, documented by negativity of HBsAg and positivity of HBsAb and HBcAb. Her medical history included: myocardial infarct, chronic kidney disease stage 3, chronic obstructive pulmonary disease, and mild pulmonary hypertension. HCV had not been treated with interferon (IFN)-based regimens and liver stiffness was 10.5 KPa (Metavir stage F3) at hepatic elastography. Because of CKD, she was prescribed with a nucleoside reverse transcriptase (NRTI)-sparing regimen including darunavir/ritonavir plus etravirine, and thereafter with sofosbuvir/ledipasvir for 12 weeks. Four weeks after DAA termination, the patient was hospitalized with symptoms of acute hepatitis. Blood tests showed HCV RNA <12 IU/ml, but positivity of HBAg, HBeAg, and of anti-core antibodies (IgM and IgG), while anti-HBs and anti-HBe antibodies were negative. HBV DNA was 6.06 Log10 IU/ml. Entecavir was started obtaining resolution of symptoms, normalization of liver enzymes, as well as reduction of HBV DNA and of quantitative HBV surface antigen. This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.
The pediatric sedation unit: a mechanism for safe pediatric sedation.

To the Editor. As an anesthesiologist, a pediatric intensive care physician, but most of all as a Fellow of the American Academy of Pediatrics (AAP), I read with great interest the article by Lowrie et al1 that appeared in the September 1998 issue of Pediatrics electronic pages . I certainly hope that the publication of this article represents an attempt by Pediatrics and the AAP to initiate a controversy and bring to light questionable and unsafe practices in the sedation of children, rather than an endorsement of an institutional practice that violates the standards established by the AAP,2 the American Society of Anesthesiologists,3 and many if not all state laws and regulations governing the scope of practice of nursing. Dr Lowrie describes a “sedation service” in which general anesthesia is induced and maintained using the intravenous anesthetic propofol (Diprivan) by pediatric intensive care physicians. Although the package insert of Diprivan recommends limiting the use of this agent to those with training in general anesthesia, it is not the controversial use of this agent by pediatricians without such training that I wish to criticize in this letter. Rather it is the egregious practice by Lowrie to then send children under propofol anesthesia to remote areas of her hospital attended not by an anesthesiologist, indeed not by any physician, not even by a nurse anesthetist, but rather by unsupervised critical care staff nurses whose training and credentials do not qualify them to administer general anesthetic agents. This practice is inherently unsafe, exposes both Dr Lowrie and her hospital to significant liability, and puts children at significant risk. Dr Lowrie states that “only” 2.5% of cases needed to be cancelled because of complications. This number may at first blush seem small to pediatricians reading this journal, but it must be …
Extracorporeal Shock Wave Lithotripsy in Children

AbstractExtracorporeal shock wave lithotripsy has proved to be an effective method of treating upper urinary tract calculi. We report on 14 patients 17 years old or younger who were treated with the Dornier lithotriptor. Special adjustments of the gantry and water level, as well as shielding of the lungs, were necessary in those children less than 135cm. in height or 30kg. in weight. Hospital stay averaged 2.5 days and ranged from 1 to 6 days. There were no major intraoperative complications. Postoperative pulmonary edema developed in 1 patient and only 3 required parenteral analgesics for postoperative pain control. Of the 12 patients for whom a 3-month followup is available 10 are free of stone. One patient required ureterolithotomy for removal of impacted stone fragments. We conclude that extracorporeal shock wave lithotripsy is a safe and effective method of treating renal calculi in children.
From private to public ordering: An expanding federal role for regulating privacy and data security?

This article discusses recent legislative issues in the United States affecting privacy and data security and assesses prospects for new measures affecting businesses and their customers, including the impact of private ordering and market forces on the scope and content of government regulation.
Why Shading Matters along Contours

Shape from shading is a classical inverse problem in computer vision. It is inherently ill-defined and, in different formulations, it depends on the assumed light source direction. In contrast to these mathematical difficulties, we introduce a novel mathematical formulation for calculating local surface shape based on covariant derivatives of the shading flow field, rather than the customary integral minimization or P.D.E approaches.Working with the shading flow field rather than the original image intensities is important to both neurogeometry and neurophysiology. To make the calculations concrete we assume a Lambertian model for image formation, butwe do not make global light source positional assumptions. In particular, for smooth surfaces in generic position, we show that second derivatives of brightness are independent of the light sources and can be directly related to surface properties. We use these measurements to define the matching local family of surfaces that could result from a given shading patch. In total our results change the emphasis from seeking a single, well-define solution to an ill-posed problem to characterizing the ambiguity in possible solutions to this problem. The result is relevant both mathematically and perceptually, because we then show how the equations simplify and the ambiguity reduces are certain critical points of intensity. We conclude with a discussion of image reconstruction at these critical points.
Pudrición negra en raicillas de palto (Persea americana Mill.) por Cylindrocarpon destructans: patogenicidad y aspectos epidemiológicos

En un vivero comercial de Quillota (V Region, Chile), durante los anos 1994 y 1995 se produjo en plantas de de palto ( Persea americana Mill.) un subito decaimiento de estas, caracterizado por sintomas iniciales de marchitez, perdida de turgor de las hojas, asociada a clorosis y necrosis marginal y al mismo tiempo, a nivel de las raices, se observo una pudricion severa de color cafe oscuro a negro. Solo por concepto de estos problemas, se destruyeron 22.000 plantas en dos anos. A partir de la zona de avance de las lesiones radiculares, se aislo en forma consistente colonias de Cylindrocarpon destructans , no detectandose representantes del genero Phytophthora . Con el proposito de determinar la posible fuente de inoculo, se efectuaron aislamientos desde el sustrato empleado, sus diferentes componente y de semillas, recuperandose este patogeno solo desde la arena de rio y suelo de tranque. De acuerdo con los resultados obtenidos a partir de los diferentes aislamientos, las pruehas de patogenicidad y los sintomas observados, se considera a C. destructans como el agente causal de una nueva enfermedad que afecta a plantas de palto en vivero.