cssi/SciSciGPT-SciSciNet huggingface dataset:
High-volume providers and brachytherapy practice: A Medicare provider utilization and payment analysis.

Abstract Purpose Brachytherapy is an important component of the treatment of gynecologic and prostate cancers, with data supporting its impact on clinical outcomes. Prior data have suggested that brachytherapy tends to be focused at high-volume centers. Medicare reimbursement data can provide an understanding of the distribution of brachytherapy cases among billing providers. The objective of this study is to quantify the distribution of brachytherapy cases and high volume providers. Methods and Materials The Medicare Physician and Other Supplier Public Use File was queried for individual physicians who had performed brachytherapy for more than 10 patients with gynecologic or prostate cancer in the years 2012–2015. Aggregate data were also queried. Trends were identified, and basic summary statistics were tabulated. Results During the study period, there was an increase in vaginal brachytherapy (3328 unique cases in 2012–4308 in 2015) but a decrease in intrauterine implants, such as tandem placements (1522 in 2012–1307 in 2015) and prostate brachytherapy (8860 in 2012–6527 in 2015). High-volume providers treating more than 10 patients represented a disproportionate number of patients treated, particularly with intra-uterine brachytherapy, representing no more than 1.2% of the active providers in a given year but up to 11.1% of intra-uterine brachytherapy cases. Conclusions Among Medicare claims, a small number of providers accounted for a significant proportion of gynecologic and prostate brachytherapy cases, particularly in the case of intrauterine implants. The vast majority of brachytherapy providers perform limited cases in this population. Efforts toward improving access to intrauterine implants in Medicare patients should be a national priority.
Critical reasoning

Model-based diagnosis algorithms face a combinatorial explosion. To combat this explosion, this paper presents a fundamentally new architecture, IMPLODE, which constructs an abstract representation of the environment, the conflict, and the diagnosis spaces using a sensitivity analysis of assumptions. Experimental results show that the most dramatic improvement is obtained for circuits which are the most difficult to diagnose using previous algorithms. Moreover, typical sources of combinatorial explosion, such as reconvergent fanout, are a source of combinatorial implosion for IMPLODE.
Socio-economic differences in fertility control. Is there an early warning system at the village level?

This article is about identifying the origins of fertility limitation in a way designed to overcome the constraints which require that fertility control be discovered only after it is undeniable. The analysis is based on data from the Belgian commune of La Hulpe, covering the period from 1846–1880. It shows (using hazard models) that the clearest signs of fertility control were visible among literate women and the bourgeoisie.
Assessment of body weight for age determination in kittens

ObjectivesThe objective of this study was to assess the utility of using body weight for age determination in kittens.MethodsMedical records were reviewed for serial body weight measurements collec...
Robust decision making method for adaptive ordered-statistics CFAR technique using information elasticity

Some performance characteristics of ordered-statistics CFAR (OS-CFAR), such as probability of false alarm (PFA) and probability of detection (PD), are controlled by many parameters. Some of these parameters can be considered decision parameters, since they are user defined to achieve a fixed PFA, and an optimized PD. However, other parameters that control these probabilities have the tendency to fluctuate based on the radar environment and operating conditions. These environmental variables can sometimes be difficult to predict and may affect performance. In this paper, a robust decision making method is presented, which selects decision parameters that provide robust performance even in the presence of these variations. The relevant environmental variables investigated in this paper are the number of interfering targets within the detection window and the signal-to-noise ratio (SNR). The Forward Automatic Order Selection Ordered Statistics Detector (FAOSOSD) is used to provide an estimate for the number of interfering targets, and the accuracy of this estimate is observed as a function of SNR. The proposed method defines a performance metric and observes its mean and variance over the uncertain parameter SNR. A trade-off behavior is shown between this mean and variance, and using information elasticity analysis, a decision is selected.
The current systems assessment and the clinical care process. A tool for clinical supervision and the design of clinical information systems.

A side benefit of a current systems assessment carried out prior to automation was the development of a systematic picture of the clinical care system as captured in the system flow chart. The results of this assessment provided clinical administrators with ablueprint identifying the current system's strengths and weaknesses, which could be used both to introduce improvements and to measure the effect of such changes totally apart from the initial question of automation.
Using Power-Anomalies to Counter Evasive Micro-Architectural Attacks in Embedded Systems

High-assurance embedded systems are deployed for decades and expensive to re-certify – hence, each new attack is an unpatchable problem that can only be detected by monitoring out-of-band channels such as the system’s power trace or electromagnetic emissions. Micro-Architectural attacks, for example, have recently come to prominence since they break all existing software-isolation based security – for example, by hammering memory rows to gain root privileges or by abusing speculative execution and shared hardware to leak secret data. This work is the first to use anomalies in an embedded system’s power trace to detect evasive micro-architectural attacks. To this end, we introduce power-mimicking micro-architectural attacks – including DRAM-rowhammer attacks, side/covert-channel and speculation-driven attacks – to study their evasiveness. We then quantify the operating range of the power-anomalies detector using the Odroid XU3 board – showing that rowhammer attacks cannot evade detection while covert channel and speculation-driven attacks can evade detection but are forced to operate at a 36× and 7× lower bandwidth. Our power-anomaly detector is efficient and can be embedded-of-band into (e.g.,) programmable batteries. While rowhammer, side-channel, and speculation-driven attack defenses require invasive code- and hardware-changes in general-purpose systems, we show that power-anomalies are a simple and effective defense for embedded systems. Power-anomalies can help future-proof embedded systems against vulnerabilities that are likely to emerge as new hardware like phase-change memories and accelerators become mainstream.
Replies to My Critics

This is a revised version of a paper presented at the APA Eastern Division's 115th annual meeting in New York on Monday January 07, 2019. It was presented at session 2O Author Meets Critics: Michael Jacovides, Locke’s Image of the World. The session chair was Antonia LoLordo (University of Virginia), the critics were Robert Pasnau (University of Colorado Boulder) and Kathryn Tabb (Columbia University), and the author was Michael Jacovides (Purdue University).
The role of depression and suicidal cognitions as contributors to suicide risk among active duty soldiers reporting symptoms of posttraumatic stress disorder

Abstract Background Military suicide rates have risen across all service branches, with the overall rate surpassing that of the general population for the first time in history in 2008. Service members with posttraumatic stress disorder (PTSD) are at a substantially higher risk for suicidal ideation, suicide attempts, and death by suicide than their peers without PTSD. While the link between PTSD and suicide is well established in the literature, less is known about the precise nature of that connection. Several constructs have been implicated as potential mediators of this relation, such as depression, alcohol use, suicidal cognitions, and sleep disturbance. Yet, to our knowledge, these constructs have never been examined simultaneously in a single model to determine mediational influence for suicide risk among soldiers with PTSD. Methods A sample of 172 active duty Army soldiers completed a series of measures targeting the aforementioned constructs. Data were analyzed using mediation model analyses. Results Suicidal cognitions fully mediated the relation between PTSD symptoms and current suicide risk severity. The indirect effect for suicidal cognitions was significantly larger than indirect effects for alcohol use, depression, and sleep disturbance. Exploratory analyses suggest serial mediation of the relation between PTSD and current suicide risk by depression and suicidal cognitions. Limitations These results should be interpreted within the context of study limitations, to include use of self-report data and inability to firmly establish temporal sequencing assumed in mediation. Conclusions Implications of this study include the improvement of suicide risk assessment and individualized treatment planning for suicidal military personnel with PTSD.
Seismic harmonic response of inhomogeneous soil: scaling analysis

The study of the seismic response of inhomogeneous soil deposits, underlying rigid bedrock, has traditionally been framed as a one-dimensional wave propagation problem in a linear viscoelastic medi...
The microRNA target site landscape is a novel molecular feature associating alternative polyadenylation with immune evasion activity in breast cancer

Alternative polyadenylation (APA) in breast tumor samples results in the removal/addition of cis-regulatory elements such as microRNA (miRNA) target sites in the 3'-untranslated region (3'-UTRs) of genes. Although previous computational APA studies focused on a subset of genes strongly affected by APA (APA genes), we identify miRNAs of which widespread APA events collectively increase or decrease the number of target sites [probabilistic inference of microRNA target site modification through APA (PRIMATA-APA)]. Using PRIMATA-APA on the cancer genome atlas (TCGA) breast cancer data, we found that the global APA events change the number of the target sites of particular microRNAs [target sites modified miRNA (tamoMiRNA)] enriched for cancer development and treatments. We also found that when knockdown (KD) of NUDT21 in HeLa cells induces a different set of widespread 3'-UTR shortening than TCGA breast cancer data, it changes the target sites of the common tamoMiRNAs. Since the NUDT21 KD experiment previously demonstrated the tumorigenic role of APA events in a miRNA dependent fashion, this result suggests that the APA-initiated tumorigenesis is attributable to the miRNA target site changes, not the APA events themselves. Further, we found that the miRNA target site changes identify tumor cell proliferation and immune cell infiltration to the tumor microenvironment better than the miRNA expression levels or the APA events themselves. Altogether, our computational analyses provide a proof-of-concept demonstration that the miRNA target site information indicates the effect of global APA events with a potential as predictive biomarker.
Rapid Discrete Optimization via Simulation with Gaussian Markov Random Fields

Inference-based optimization via simulation, which substitutes Gaussian process (GP) learning for the structural properties exploited in mathematical programming, is a powerful paradigm that has be...
Flutter and Limit Cycle Oscillations of Cantilevered Plate in Supersonic Flow

Research interest is growing for theoretical models of highly deflected structures in aeroelastic settings. Presented here is a model of a cantilevered plate subjected to axial supersonic flow to d...
Neutrino Astrophysics and Galactic Cosmic Ray Anisotropy in IceCube

The IceCube Observatory is a kilometer-cube neutrino telescope under construction at the South Pole and planned to be completed in early 2011. When completed it will consist of 5,160 Digital Optical Modules (DOMs) which detect Cherenkov radiation from the charged particles produced in neutrino interactions and by cosmic ray initiated atmospheric showers. IceCube construction is currently 90% complete. A selection of the most recent scientific results are shown here. The measurement of the anisotropy in arrival direction of galactic cosmic rays will also be presented and discussed.
How to outlive the university

The author reflects on the historical and present systemic violence of universities; highlighting the experience of graduate student exploitation within the academy and the field of communication s...
Pulmonary manifestations and outcomes in paediatric ANCA-associated vasculitis: a single-centre experience.

OBJECTIVES ANCA-associated vasculitis (AAV) usually involves the renal and respiratory systems, but the paediatric literature on pulmonary manifestations and outcomes is limited. We aimed to describe pulmonary manifestations and outcomes after therapy in a cohort of paediatric AAV (pAAV) patients. METHODS A retrospective chart review of all patients <19 years presenting to our institution with AAV between 1/2008 and 2/2018 was conducted. Patient demographics, clinical presentation, diagnostic testing, therapy and pulmonary outcomes over the first 3 years after presentation were evaluated. RESULTS A total of 38 patients were included; all had ANCA positivity by immunofluorescence. A total of 23 had microscopic polyangiitis (MPA), 13 had granulomatosis with polyangiitis and 2 had eosinophilic granulomatosis with polyangiitis. A total of 30 (79%) had pulmonary manifestations, with cough (73%) and pulmonary haemorrhage (67%) being the most common. Abnormalities were noted in 82% of chest CT scans reviewed, with nodules and ground-glass opacities being the most common. At 6, 12 and 36 months follow-up, respectively, 61.8%, 39.4% and 29% of patients continued to show pulmonary manifestations. Five MPA patients with re-haemorrhage are described in detail. CONCLUSION MPA was more common than granulomatosis with polyangiitis, with pulmonary involvement being common in both. MPA patients had more severe pulmonary manifestations. Chest CT revealed abnormal findings in a majority of cases. A subgroup of young MPA patients experienced repeat pulmonary haemorrhage. Treatment modality and response were comparable in different subtypes of AAV, except for this young MPA group. Additional prospective studies are needed to better understand the different phenotypes of pAAV.
Impact of cerebrospinal fluid flow study in patients undergoing intrathecal chemotherapy via ventricular catheter reservoir

Leptomeningeal carcinomatosis (LMC) is a form of CNS cancer metastasis with severe morbidity. Intrathecal chemotherapy (ITC) administration through an implanted ventricular catheter reservoir (IVCR) is often utilized. Additionally, a nuclear imaging flow study can be performed prior to ITC administration to assess cerebrospinal fluid (CSF) flow. The clinical impact of a CSF flow study is unclear. A retrospective chart review identified 31 patients with LMC that underwent IVCR placement between 2011 and 2019. Data extracted included patient demographics, nuclear imaging flow study, surgical complications, ITC toxicities and outcomes. Potential drug-induced neurologic toxicities (headache, nausea/vomiting, altered mental status, etc.) were noted in (n = 4/16) 25% of patients who underwent a flow study prior to initiation of ITC, compared to (n = 1/15) 6.6% of patients who did not undergo a flow study. Median overall survival (OS) was 4.0 and 32.8 months for the patients that underwent a flow study versus patients who did not, respectively (p < 0.01). The mean interval from IVCR implantation to initiation of ITC was 15.2 ± 8.5 days and 3.3 ± 3.0 days in patients who underwent CSF flow study and patients that did not, respectively (p < 0.0001). A flow study can provide information regarding CSF flow dynamics prior to initiation of ITC; however this might delay initiation of ITC which may negatively impact OS. Additionally, in our study patients that underwent a flow study had more ITC induced drug toxicity events compared to those that did not. Further studies are needed to clarify the role of CSF flow study in these patients.
Journey to a Big Data Analysis Platform: Are we there yet?

Data warehousing and analytics are going through a metamorphosis. Corporations are transforming their data warehousing capabilities, centralizing data analytics, and leveraging cloud technologies. Eight years ago, at ASMC 2013, we presented our approach to big data solutions and asked the industry leaders to help unify technologies to enable our big data transformations more seamlessly for the industry. This paper will cover what does, what did not, and what will not in the future work, where data and analytics are heading, and what the semiconductor industry needs to do to address big data challenges. The material will present clear reasons for leveraging big data solutions including up to 20× performance improvements analysis, cloud to cloud sharing options, ways to easily scale and handle data growth and centralizing information. There will also be a few areas where it will be shown how better integration from the factory floor to the modern data analysis platforms could be possible but cannot be fully addressed without the help from vendors.
Enhanced characterization of the thyA system for mutational analysis in Escherichia coli: Defining mutationally "hot" regions of the gene.

Abstract We have extensively characterized base substitution mutations in the 795 base pair (bp) long E. coli thyA gene to define as many of the base substitution mutational sites that inactivate the gene as possible. The resulting catalog of mutational sites constitutes a system with up to 5 times as many sites for monitoring each of the six base substitution mutations as the widely used rpoB/Rifr system. We have defined 75 sites for the G:C -> A:T transition, 68 sites for the G:C -> T:A transversion, 53 sites for the G:C -> C:G transversion, 49 sites for the A:T -> G:C transition, 39 sites for the A:T -> T:A transversion, and 59 sites for the A:T -> C:G transversion. The system is thus comprised of 343 base substitution mutations at 232 different base pairs, all of which can be sequenced with a single primer pair. This allows for the examination of mutational spectra using a more detailed probe of known mutations, while still allowing one to compare the number of repeated occurrences at specific sites. We have examined several mutagens and mutators with this system, and show its utility by looking at the spectrum of cisplatin, that has a single hotspot, underscoring the value of having as large an array of sites as possible at which one can monitor repeat occurrences. To test for regions of the gene that might be hotspots for a number of mutagens, or “hot” (mutaphilic) regions, we have looked at the ratio of mutations per set of an equal number of mutational sites throughout the gene. The resulting graphs suggest that there are “hot” regions at intervals, and this may reflect aspects of secondary structures, of the higher order structure of the chromosome, or perhaps the nucleoid structure of the chromosome plus histone-like protein complexes.
The Bilingual Language Diversity of Latino Preschoolers: A Latent Profile Analysis

Purpose This study describes the language diversity (the within-group variability in dual-language skills) of a sample of Latino dual-language learners (preschoolers, 3–5 years of age) and how lang...
Tissue Culture Techniques: Introduction

Cell culture techniques were developed as a way to study animal cells in vitro. The behavior of single cells, organ culture and monolayer cells can be studied without the in vivo influences arising from physiological and environmental variations among experimental animals. Cell culture or tissue culture as the technique is widely known, was first described in 1907 (Freshney 1987) and through the decades has undergone extensive developments. These include the introduction of defined media, the development of continuous cell lines, cell fusion techniques and the extension of animal cell culture techniques to plant, insect and lower vertebrate cell culture.
The uptake of dissolved organic material by the sea cucumber Parastichopus californicus (Stimpson) and its potential role in visceral regeneration

The sea cucumber Parastichopus californicus atrophies and regenerates its internal organs on an annual cycle. Previous research has suggested that during the period of maximal regeneration (January–March) no movement or feeding occurs; however metabolic rate is doubled compared to non-regenerative periods (June–August). Uptake of dissolved organic material (DOM) from the aqueous environment could provide an external source of biosynthetic materials for regeneration of the internal organs. P. californicus were collected in the summer (actively moving and feeding, not degenerating or regenerating), winter (inactive, degenerating), and spring (inactive, regenerating). Animals were incubated in seawater containing a mixture of amino acids labeled with 15N and 13C. Incorporation of 15N (summer, winter, spring) and 13C (summer, spring) by the respiratory trees was significantly higher than incorporation by other types of tissues. Additionally, dorsal and ventral epidermis, oral tentacles, digestive tract, muscle, and tube feet incorporated 15N and/or 13C during at least one season. These results demonstrate that certain tissues, especially the respiratory trees, of P. californicus assimilate free amino acids from the sea water which could be used as biosynthetic materials for regeneration. These results also indicate that the respiratory trees may have a role in nutrition as well as respiration.
Portal radiography in veterinary radiation oncology: options and considerations.

Portal radiography involves the acquisition of images to visualize radiation treatment field(s) using the radiation treatment source. The standard has been the use of film-based systems with improvements over the years in film–screen technology providing near diagnostic quality images. More recent advances have included the development of digital systems with such notable improvements including ability to window/level images to enhance viewing and readability, and significant shortening of the time required to acquire images.
Nuclear Magnetic Resonance Studies of the Biosynthesis of Vitamin B12 THE ORIGIN OF THE METHYL GROUPS ON THE CORRIN RING

Abstract The origin of the methyl group on carbon atom 1 of Ring A of the corrin ring of vitamin B12 was investigated by 13C and 1H magnetic resonance spectroscopy. Recently we found by the same technique that this methyl group does not originate from the 5-carbon atom of δ-aminolevulinic acid. This was of considerable interest, for it has been considered that in the fusion of Rings A and D the potential δ-methine bridge found in porphyrins, which does arise from δ-aminolevulinic acid, is converted to the methyl group found on carbon atom 1 of the corrin ring. Since the methyl group of methionine was previously found to be the source of at least six other methyl groups on the corrin ring, methionine was tested as a possible precursor of the methyl group on carbon atom 1. l-[methyl]-13C]Methionine was added to a growing culture of Propionibacterium shermanii and vitamin B12 was isolated. The 13C magnetic resonance spectra of the vitamin B12 in H2O, in 0.1 m KCN, and in aqueous HCl (pH l 1) showed seven methyl-13C resonances. Single frequency decoupling experiments enabled us to assign a 13C resonance to the C-1 methyl group. It appears, therefore, that in the synthesis of the corrin ring the aminomethyl group on Ring A or Ring D, which is the potential δ-methine bridge carbon atom found in the porphyrin ring, is eliminated and that carbon atom 1 (C-1) of the corrin ring accepts a methyl group provided by l-methionine. This finding should aid in the elucidation of the mechanism of synthesis of the functional isomers of vitamin B12 and of porphyrins. Analysis of our spectra also enabled us to make other resonance assignments and to differentiate between the relative positions in space of the two geminal methyl groups on carbon atom 12 of the corrin ring which arise by different mechanisms.
Novel Approaches to Examine Passage, Student, and Question Effects on Reading Comprehension

Reading comprehension is influenced by sources of variance associated with the reader and the task. To gain insight into the complex interplay of multiple sources of influence, we employed crossed random-effects item response models. These models allowed us to simultaneously examine the degree to which variables related to the type of passage and student characteristics influenced students' (n = 94; mean age = 11.97 years) performance on two indicators of reading comprehension: different types of comprehension questions and passage fluency. We found that variables related to word recognition, language, and executive function were influential across various types of passages and comprehension questions and also predicted a reader's passage fluency. Further, an exploratory analysis of two-way interaction effects was conducted. Results suggest that understanding the relative influence of passage, question, and student variables has implications for identifying struggling readers and designing interventions to address their individual needs.
A Hybrid Approach to Unsupervised Relation Discovery Based on Linguistic Analysis and Semantic Typing

This paper describes a hybrid approach for unsupervised and unrestricted relation discovery between entities using output from linguistic analysis and semantic typing information from a knowledge base. We use Factz (encoded as subject, predicate and object triples) produced by Powerset as a result of linguistic analysis. A particular relation may be expressed in a variety of ways in text and hence have multiple facts associated with it. We present an unsupervised approach for collapsing multiple facts which represent the same kind of semantic relation between entities. Then a label is selected for the relation based on the input facts and entropy based label ranking of context words. Finally, we demonstrate relation discovery between entities at different levels of abstraction by leveraging semantic typing information from a knowledge base.
Linguistic Variation as Social Practice: The Linguistic Construction of Identity in Belten High

Linguistic Variation as Social Practice: The Linguistic Construction of Identity in Belten High. Penelope Eckert. Maiden, MA: Blackwell Publishers, 2000. 240 pp.
Communicator credibility and persuasian.

Prior research has usually found a positive relationship between a communicator’s perceived credibility and his persuasiveness. An experiment was designed to test the hypothesis that the perceived vested interest of a speaker, the position the speaker advocated, and the social similarity between audience and speaker would influence attributions of credibility and affect the speaker’s persuasiveness. Three variables were manipulated in a 2 by 2 by 2 factorial design. Ss read a speech that either favored (pro) or opposed (con) student voting rights; the speech was attributed to a speaker who was either similar (student) or dissimilar (townie) to the stndent audience and who either had a vested interest (running for elective office) or had no vested interest (merely giving his opinion) :in the position he advocated. As predicted, the similarity of the speaker to the audience, the vested interest of the speaker, and the position advocated in the speech strongly influenced attributions of credibility. However, in contrast to much previous research, persuasion was found to be relatively independent of the variation in the speaker’s perceived credibility. It was suggested that the failure of attributions of credibility to relate to persuasion may have been due to the high degree of ego involvement for the Ss in the topic of student voting rights.
TREATMENT STRATEGIES FOR PATIENTS WITH AN INTERMACS I PROFILE

Treatment of patients with INTERMACS class I heart failure can be very challenging, and temporary long-term device support may be needed. In this article, we review the currently available temporary support devices in order to support these severely ill patients with decompensated heart failure. Strategies of using a temporary assist as a bridge to long-term device support are also discussed.
Phosphorylation of the receptor for PTH and PTHrP is required for internalization and regulates receptor signaling.

We have previously shown that agonist-dependent phosphorylation of the PTH/PTHrP receptor occurs on its carboxyl-terminal tail. Using site- directed mutagenesis, phosphopeptide mapping, and direct sequencing of cyanogen bromide-cleaved fragments of phosphoreceptors, we report here that PTH-dependent phosphorylation occurs on the serine residues at positions 491, 492, 493, 495, 501, and 504, and that the serine residue at position 489 is required for phosphorylation. When these seven sites were mutated to alanine residues, the mutant receptor was no longer phosphorylated after PTH stimulation. The phosphorylation-deficient receptor, stably expressed in LLCPK-1 cells, was impaired in PTH-dependent internalization and showed an increased sensitivity to PTH stimulation; the EC50 for PTH-stimulated cAMP accumulation was decreased by 7-fold. Furthermore, PTH stimulation of the phosphorylation-deficient PTH/PTHrP receptor caused a sustained elevation in intracellular cAMP levels. These data indicate that agonist...
Transient nucleation following pulsed-laser melting of thin silicon films.

Thin Si films on thermally grown ${\mathrm{SiO}}_{2}$ layers were completely melted by pulsed-laser irradiation. The molten films cool very rapidly (g${10}^{9}$ K/s) until bulk nucleation initiates solidification. The quench rate was varied by changing the thickness of the Si or the ${\mathrm{SiO}}_{2}$ layers. For quenches below \ensuremath{\sim}${10}^{10}$ K/s the supercooling prior to nucleation was constant and \ensuremath{\sim}500 K; however, for more rapid quenches, the supercooling increases significantly. This increase is attributed to embryo distributions that fall out of steady state during rapid quenches.
Patient-derived tumour xenografts as models for oncology drug development

Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
Evolution of repeated hippocampal seizures in the cat

In unanesthetized cats, with permanent intracerebral electrodes, as many as 100 repeated hippocampal after-discharges (HAD's) were evoked during a period of 15–30 days. In addition, four cats were trained in conditioned avoidance, and the tests were repeated during HAD's. In other cats, after several HAD's had been evoked, ablations were made of the motor areas, fornix and amygdala, and then the HAD's were studied. Results were as follows: 1. 1. Repetition of HAD's did not modify local thresholds, but considerably increased the behavioral disturbances according to a pattern which was repeated in different animals. 2. 2. Conditioned avoidance response was very little impaired during the first 10 sec of the evoked HAD, but was considerably disturbed at the height of the HAD. Repetition of the HAD's decreased the responses even during the first 10 sec of each HAD, with responses dropping to zero at the height of the HAD. Controls, however, showed that repetition of the HAD's did not produce lasting deficits in avoidance performance. Hippocampal stimulations which were not followed by HAD's did not modify the conditioned responses. 3. 3. During HAD's, thresholds and effects evoked by stimulation of the reticular mesencephalic substance were not modified. Hypothalamic thresholds were also kept constant. The septum excitability increased with a drop in threshold to about half of the control values, without modification of the pattern of response. 4. 4. Ablation of the motor areas had no effect on the electrical or clinical pattern of the HAD. Bilateral destruction of the fornix did not modify the clinical symptomatology, but affected the electrical pattern of the HAD's. After unilateral destruction of the amygdala, the ipsilateral facial motor manifestation which accompanied the HAD's disappeared, and did not return even during the generalized seizure produced after many repeated HAD's. 5. 5. Repetition of the seizures increased the duration of the HAD's two to five times, producing also an increase in the duration of “clonic” activity and short, irregular spikes. In general, however, the configuration of each pattern was not modified. 6. 6. A clear correlation was established between motor participation of the face and 4–6 c/sec activity of the amygdala. Other possible clinical EEG correlations are discussed in this paper. 7. 7. Two different classes of spread from the hippocampus to the amygdala are considered: (a) propagated: in which the pattern of the amygdala after-discharge corresponds to and seems to depend on the pattern of the hippocampal seizure; (b) reactive: in which the amygdala showed 4–6 c/sec waves, which were independent of, but triggered by HAD's. The propagated spread was asymptomatic while the reactive spread was associated with ipsilateral motor manifestations of the face. Similar examples have previously been recorded in other parts of the limbic system of the monkey, and the distinction between the two kinds of spread may have functional and perhaps diagnostic implications.
Effects of constant environmental temperatures of 10°C and 31°C on serum biochemical and hematologic measurements of heat-tolerant and cold-tolerant cattle☆

Abstract 1. 1. Serum biochemical and hematologic measurements were determined on heat- and cold-tolerant cattle subjected to constant environmental temperature-relative humidity (RH) treatments of 10°C–50%RH and 31°C–50%RH. 2. 2. Significant breed × temperature interactions were found for creatinine, inorganic phosphorus, glutamic-oxaloacetic transaminase, leucocyte count and per cent lymphocytes and neutrophils. 3. 3. Significant temperature effects but no breed × temperature interactions were found for chloride, potassium, glucose, cholesterol, urea nitrogen, total bilirubin, alkaline phosphatase, erythrocyte count, packed cell volume, hemoglobin concentration, anisocytosis and poikilocytosis. 4. 4. Breed differences were similar to those found previously.
Transfer Student Engagement: Blurring of Social and Academic Engagement.

Transfer students are a distinct population. Their characteristics lead to a qualitatively different student experience. Drawing on interviews with a cross-sectional sample of transfer students at ...
Therapeutic advances in small cell lung cancer.

Small cell lung cancer (SCLC) is characterised by neuroendocrine differentiation, early metastatic potential and initial responsiveness to cytotoxic therapy. Unfortunately, despite recent therapeutic advances, most patients relapse and the overall five-year survival rate is only 5%. Standard treatment of SCLC consists of platinum-based combination chemotherapy, with thoracic irradiation added for patients with limited-stage disease. Several newer chemotherapeutic drugs have recently been shown to have significant activity in patients with untreated or relapsed SCLC. These agents include: the topoisomerase I inhibitors, topotecan and irinotecan; the taxanes, paclitaxel and docetaxel; the pyrimidine analogue, gemcitabine; and the vinca alkaloid, vinorelbine. Recent advances in our understanding of the molecular events involved in the pathogenesis and progression of SCLC have led to the identification of a variety of potential targets for novel therapeutic interventions. Strategies aimed at inhibiting the myriad of growth factor pathways that control the proliferation of SCLC cells, include: broad spectrum neuropeptide antagonists (e.g., substance P analogues); growth factor/receptor-specific inhibitors (e.g., anti-GRP monoclonal antibodies, bradykinin antagonist dimers); and a variety of selective protein kinase inhibitors. The importance of cell death pathways in carcinogenesis and treatment-resistance has led to several novel strategies targeting apoptotic mediators, such as bcl-2, that are frequently dysregulated in SCLC (e.g., bcl-2 antisense). Our current challenges are to further refine these promising therapeutic strategies, efficiently evaluate their activity in the clinical setting and integrate them into more effective treatment regimens to improve the overall prognosis of patients with SCLC.
Estimation in two-parameter exponential distributions

Exponential distributions are used extensively in the field of life-testing. Estimation of parameters is revisited in two-parameter exponential distributions. A comparison study between the maximum likelihood method, the unbiased estimates which are linear functions of the maximum likelihood method, the method of product spacings, and the method of quantile estimates are presented. Finally, a simulation study is given to demonstrate the small sample properties
RGS expression rate-limits recovery of rod photoresponses.

Signaling through G protein-coupled receptors (GPCRs) underlies many cellular processes, yet it is not known which molecules determine the duration of signaling in intact cells. Two candidates are G protein-coupled receptor kinases (GRKs) and Regulators of G protein signaling (RGSs), deactivation enzymes for GPCRs and G proteins, respectively. Here we investigate whether GRK or RGS governs the overall rate of recovery of the light response in mammalian rod photoreceptors, a model system for studying GPCR signaling. We show that overexpression of rhodopsin kinase (GRK1) increases phosphorylation of the GPCR rhodopsin but has no effect on photoresponse recovery. In contrast, overexpression of the photoreceptor RGS complex (RGS9-1·Gβ5L·R9AP) dramatically accelerates response recovery. Our results show that G protein deactivation is normally at least 2.5 times slower than rhodopsin deactivation, resolving a long-standing controversy concerning the mechanism underlying the recovery of rod visual transduction.
Using emulators as vehicles for instruction in systems programming: prospective consideration

Microprogramming is a technique for implementing machine language instruction sets —it is critical in today's computer architectures and operating systems. An emulator is a set of microprograms that implements the architecture of one machine on another; microprogramming is often used in emulation to make one computer system appear as if it were another. This paper presents the architecture for a microprogrammed computer system, the VSEM. The simulated virtual computer system, its monitor and a simulated concurrent PASCAL are discussed. The usefulness of the VSEM, its monitor and the concurrent PASCAL as vehicles for instruction in systems programming is addressed.
Validation of a scheme for assessing argumentative writing of middle school students

Abstract Two studies tested factors influencing ratings of argumentative essays in order to develop a scheme for assessing essays written by middle school students. Study CLAIM-CLARITY assessed the effect of: 1. (a) claim clarity, 2. (b) reason strength, 3. (c) strength of rebuttals to counterarguments, 4. (d) the rater's personal values, and 5. (e) the rater's topic knowledge. These factors explained a third of the variance in holistic scores. There was a significant interaction between raters' topic knowledge and the validity of evidential statements. Raters' values were not significant with respect to the range of topics included in this study. Study DEVELOPMENT assessed the effect of: 1. (a) development, 2. (b) voice, and 3. (c) conventions. The factors explained 63 percent of the variance in holistic ratings. This result was attributed to an assessment scheme that fostered integrated rather than isolated consideration of argument elements.
The effects of multicultural links on reading and writing performance and cultural awareness of fourth and fifth graders

Abstract This exploratory study was designed to examine the effects of a hypermedia program, Multicultural Links, on vocabulary development, reading and writing performance, and attitudes toward writing, culture, and computers. The major objectives of the study were to determine whether fourth and fifth graders using Multicultural Links with the Multicultural Literacy Program (a) improve their vocabulary development, reading performance, and writing performance; and (b) improve their attitudes toward writing, culture, and computers more than fourth and fifth graders using either the Multicultural Literacy Program alone or a traditional reading program. The Multicultural Literacy Program, which was funded by a grant through the Department of Education, Funds for Improvement and Reform of Schools and Teaching, is a program that integrates multicultural literature and literature-based activities with the reading/writing curriculum. Examples of multicultural literature-based activities might include: interactive reading and writing activities; choral reading; readers' theater; semantic mapping and knowledge-generating activities; writing responses to literature; interactive discussion; cooperative literacy learning activities; thematic learning approaches; and creative responses to literature through drama, art, music, and folk dancing (for more information about the program, see Diamond & Moore, 1995).
Lyophilization‐induced protein denaturation in phosphate buffer systems: Monomeric and tetrameric β‐galactosidase

During freezing in phosphate buffers, selective precipitation of a less soluble buffer component and subsequent pH shifts may induce protein denaturation. Previous reports indicate significantly more inactivation and secondary structural perturbation of monomeric and tetrameric beta-galactosidase (beta-gal) during freeze-thawing in sodium phosphate (NaP) buffer as compared with potassium phosphate (KP) buffer. This observation was attributed to the significant pH shifts (from 7.0 to as low as 3.8) observed during freezing in the NaP buffer (1). In the current study, we investigated the impact of the additional stress of dehydration after freezing on the recovery of active protein on reconstitution and the retention of the native structure in the dried state. Freeze-drying monomeric and tetrameric beta-gal in either NaP or KP buffer resulted in significant secondary structural perturbations, which were greatest for the NaP samples. However, similar recoveries of active monomeric protein were observed after freeze-thawing and freeze-drying, indicating that most dehydration-induced unfolding was reversible on reconstitution of the freeze-dried protein. In contrast, the tetrameric protein was more susceptible to dehydration-induced denaturation as seen by the greater loss in activity after reconstitution of the freeze-dried samples relative to that measured after freeze-thawing. To ensure optimal protein stability during freeze-drying, the protein must be protected from both freezing and dehydration stresses. Although poly(ethylene glycol) and dextran are preferentially excluded solutes and should confer protection during freezing, they were unable to prevent lyophilization-induced denaturation. In addition, Tween did not foster maintenance of native protein during freeze-drying. However, sucrose, which hydrogen bonds to dried protein in the place of lost water, greatly reduced freezing- and drying-induced denaturation, as observed by the high retention of native protein in the dried state as well as the complete recovery of active beta-gal on reconstitution. These results indicate that addition of an effective stabilizer, such as sucrose, may minimize protein denaturation during freeze-drying in phosphate buffers, even if there are large-scale changes in solution pH during freezing.
Auditory role of the suprabranchial chamber in gourami fish.

Fish hearing specialists (e.g., goldfish, holocentrids, clupeoids, mormyrids) have evolved specialized structures (e.g., Weberian ossicles, swimbladder diverticulae, gas-filled bullae) to enhance their auditory frequency range and threshold sensitivity. The inner ears of anabantoid fish are encased in membranous cranial bones and are protruded into air-filled suprabranchial chambers. This research was intended to test the hypothesis that the gas bubbles inside the suprabranchial chambers may modulate the hearing abilities of anabantoid fish because of their proximity to the membranous bone-encased inner ears. Three species of gourami (blue gourami Trichogaster trichopterus; kissing gourami Helostoma temminckii; dwarf gourami Colisa lalia) were examined. Using the auditory brainstem response recording technique, baseline audiograms tested at 300, 500, 800, 1500, 2500, 4000 Hz were obtained. The air bubbles in the suprabranchial chambers were replaced by water, and the audiograms were remeasured. Thresholds were elevated in all three species. When three blue gouramis were allowed to replenish air into the suprabranchial chambers their hearing abilities returned to baseline levels. These results support the hypothesis that air bubbles in the suprabranchial chambers can affect hearing abilities of gouramis by lowering the thresholds.
Diagnostic errors: central to patient safety, yet still in the periphery of safety's radar screen1).

1)Note from the Editors: The article was originally presented in Dr. Wachter’s blog at http://community.the-hospitalist. org/2013/10/09/diagnostic-errors-central-to-patient-safety-yetstill-in-the-periphery-of-safetys-radar-screen/. *Corresponding author: Robert M. Wachter, MD, Box 0120, 505 Parnassus Ave, Moffitt M994, University of California, San Francisco, CA, USA, Phone: +415 476‐5632, Fax: +415 502‐5869, E-mail: bobw@medicine.ucsf.edu
Strategies of clarification in judges’ use of language: From the written to the spoken

The present study examines judges’ strategies in clarifying their verbal explanations of constitutional rights to criminal defendants. Nine Superior Court judges of Pima County, Arizona were observed and tape recorded as they presided over taking of guilty pleas, and they were interviewed about their reasons for speaking as they did. Six clarification strategies are identified, and these strategies are compared with other studies of clarification processes and with the properties of simplified registers, particularly speech addressed to first and second language learners.
Synthesis of sulfenic acids: Flash vacuum pyrolysis of aryl and alkyl t-butyl sulfoxides

Bei der Pyrolyse der Sulfoxide (I) entstehen primar die Sulfensauren (II), die uber (III) teilweise zu den Disulfiden (IV) und Thiosulfonsauren (V) disproportionieren.