cssi/SciSciGPT-SciSciNet huggingface dataset:
Evolution of a longitudinal, multidisciplinary, and scalable patient navigation matrix model

This Longitudinal patient navigation Matrix Model was developed to overcome barriers across the cancer care continuum by offering prepatients, patients, and their families with support services. The extraordinary heterogeneity of patient needs during cancer screening, risk assessment, treatment, and survivorship as well as the vast heterogeneity of oncology care settings make it nearly impossible to follow a static navigation model. Our model of patient cancer navigation is unique as it enhances the traditional model by being highly adaptable based on both patient and family needs and scalable based on institutional needs and resources (eg, clinical volumes, financial resources, and community-based resources). This relatively new operational model for system-wide and systematic navigation incorporates a carefully cultivated supportive care program that evolved over the last decade from a bottom up approach that identified patient and family needs and developed appropriate resources. A core component of this model includes shifting away from department-centric operations. This model does not require a patient to opt in or independently be able to report their needs or ask for services-it is an opt out model. The multidisciplinary "cross-training" model can also facilitate reimbursement and sustainability by clarifying the differentiating actions that define navigation services: identification of barriers to quality care and specific actions taken to overcome those barriers, across the full continue of cancer care from community engagement to survivorship or end-of-life care.
Chronic Kidney Disease and Acute Kidney Injury Outcomes Post Left Ventricular Assist Device Implant

Introduction Left ventricular assist devices (LVAD) are used as a bridge to heart transplant or destination therapy for patients with the New York Heart Association (NYHA) class 3 or 4 heart failure. Acute kidney injury (AKI) or need for renal replacement therapy (RRT) post-LVAD implant can lead to poor outcomes. Identifying risk factors of AKI post-LVAD implant can help stratify potential LVAD candidates. Methods This is a retrospective study of all patients who received continuous-flow LVAD at our institution from January 2015 until August 2017. We calculated the incidence of AKI and the need for RRT post-LVAD implant, as well as the rate of renal recovery and survival rates at 30 days and 1-year post-LVAD implant. The presence of chronic kidney disease (CKD) and proteinuria was assessed, and kidney ultrasound results were reviewed on all patients, if available. CKD was present if estimated glomerular filtration rate (eGFR) was <60 mL/min per 1.73m2 for ≥3 months preceding LVAD implant and/or presence of proteinuria ≥ 20 mg/dL on two or more urine samples prior to LVAD implant and/or an abnormal kidney ultrasound with increased echogenicity, small size <9 cm or scarring. AKI was defined as per the current Kidney Disease Initiative Global Outcomes (KDIGO) guidelines. Results A total of 137 patients received LVAD during this time period. There were 112 males and 25 females with a mean age of 59.2 years. Incidence of AKI and the need for RRT post-LVAD implant were 64% and 19.7%, respectively. Sub-group analysis was performed based on the presence of CKD, advanced CKD stage (Stage 1-2 vs 3-5), proteinuria and abnormal kidney ultrasound. The incidence of AKI post-LVAD implant was significantly higher if baseline CKD was present (P = 0.028), and patient had an advanced CKD stage (P = 0.008). The need for RRT post-LVAD implant was significantly higher if baseline CKD was present (P = 0.015), and the patient had an abnormal kidney ultrasound (P = 0.04). Thirty-day and one-year mortality rates post-LVAD implants were 4.3% and 21.1%, respectively for the entire cohort. Out of the 27 patients requiring RRT, nine (33.3%) came off RRT before one year. Compared to the eGFR on the day of LVAD implant, eGFR at 30 days post-LVAD implant was higher in 57% and lower in 42% patients. At one year, this eGFR improvement reversed and eGFR was lower in 67% and higher in 32% patients. Conclusion The incidence of AKI and need for RRT post-LVAD implant are very high. The presence of CKD, advanced CKD stage, and an abnormal kidney ultrasound are statistically significant risk factors of AKI post-LVAD implant and/or need for RRT. Identifying these renal risk factors can help stratify the potential LVAD candidates. Only one out of three patients requiring RRT achieved dialysis independence by one-year post-LVAD implant.
Organ-on-a-Chip Engineered Microenvironments for Safety and Efficacy Testing

The need to improve testing platforms for current and new pharmaceuticals has helped generate studies involving “organs-on-a-chip” technologies in recent years. This text, aimed at a readership including biomedical engineers, entrepreneurs, design engineers, new drug investigators, etc., attempts to survey the current state of the art in this area of endeavor. It does this well, with 15 chapters from 36 contributors from eight countries. The text covers the many justifications for this work, multiple examples of platforms involving one or more lines of organ cells, discussion of the technologies involved in system design, and one chapter giving an example of a multi-organ-on-a-chip design.
Abusing Surrealism: Pynchon's V . and Breton's Nadja

In his introduction to Slow Learner, Pynchon mentions two aesthetic movements which influenced his own writing: that of the Beats, and Surrealism. While he says the effect of the Beat writers was "exciting, liberating, and strongly positive" (7), he also positions his own writing as "post-Beat" (9). In contrast, he says he has "abuse[d]" Surrealism even more extensively than other influences in the years since writing his early stories in the late 1950s and early 1960s (20). This remark suggests that the influence of Surrealism continued to grow rather than wane as Pynchon wrote V. and his other novels, and that Surrealism may be an even more important influence on Pynchon than the Beats. Although the Beats share certain narrative techniques with the Surrealists, as exemplified by works like Burroughs's Naked Lunch and Ginsberg's Howl, the focus in this essay will be on the Surrealist techniques advanced by Andre Breton as they are manifested in V.
Early Versus Delayed Pacemaker for Heart Block After Valve Surgery: A Cost-Effectiveness Analysis.

Abstract Background A significant percentage of patients who acutely develop high-grade atrioventricular block after valve surgery will ultimately recover, yet the ability to predict recovery is limited. The purpose of this analysis was to evaluate the cost-effectiveness of two different management strategies for the timing of permanent pacemaker implantation for new heart block after valve surgery. Methods A cost-effectiveness model was developed using costs and probabilities of short- and long-term complications of pacemaker placement, short-term atrioventricular node recovery, intensive care unit stays, and long-term follow-up. We aggregated the total expected cost and utility of each option over a 20-y period. Quality-adjusted survival with a pacemaker was estimated from the literature and institutional patient-reported outcomes. Primary decision analysis was based on an expected recovery rate of 36.7% at 12 d with timing of pacemaker implantation: early placement (5 d) versus watchful waiting for 12 d. Results A strategy of watchful waiting was more costly ($171,798 ± $45,695 versus $165,436 ± $52,923; P Conclusions Watchful waiting for pacemaker insertion is a cost-effective management strategy compared with early placement for acute atrioventricular block after valve surgery. Although this is cost-effective from a population perspective, clinical risk scores predicting recovery will aid in personalized decision-making.
Information sharing via electronic health records in team-based care: the patient perspective.

PURPOSE Team-based care offers potential improvements in communication, care coordination, efficiency, value and satisfaction levels of both patients and providers. However, the question of how to balance the need for information in team-based care without disregarding patient preferences remains unanswered. This study aims to determine patients' perceptions of information sharing via electronic health records (EHRs) in team-based care. METHODS This qualitative study used a focus group approach. Participants were primary care patients and representative members from minority groups (ethnic, racial or social). Audio recordings of the sessions were transcribed and coded consistent with thematic analyses. RESULTS The analysis revealed that the participants in the focus groups had diverging levels of understanding and personal beliefs around five major themes including (i) patient's understanding of the care team, (ii) perceptions of electronic health records, (iii) defining basic health care information, (iv) sharing information with the health care team and (v) patient's trust in doctors and the health care system. CONCLUSIONS The participants of our focus groups value team-based care and view patients as a critical part of those teams. With respect to electronic health records, our participants recognized their importance but had concerns about inaccuracies and limited options to correct errors in their records. In general, participants were willing to share basic information but disagreed about what information should be considered to be basic. Moreover, based on their trust and comfort level, many participants want to control what information is recorded and shared in the electronic health record.
Burden of Ionizing Radiation in the Diagnosis and Management of Necrotizing Pancreatitis.

Author(s): Thiruvengadam, Nikhil R; Miranda, Janille; Kim, Christopher; Behr, Spencer; Corvera, Carlos; Dai, Sun-Chuan; Kirkwood, Kimberly; Harris, Hobart W; Hirose, Kenzo; Nakakura, Eric; Ostroff, James W; Kochman, Michael L; Arain, Mustafa A | Abstract: IntroductionA step-up endoscopic or percutaneous approach improves outcomes in necrotizing pancreatitis (NP). However, these require multiple radiographic studies and fluoroscopic procedures, which use low-dose ionizing radiation. The cumulative radiation exposure for treatment of NP has not been well defined.MethodsWe conducted a retrospective study of consecutive patients with NP admitted to University of California San Francisco Medical Center from January 2011 to June 2019. We calculated effective doses for fluoroscopic procedures using the dose area product and used the National Cancer Institute tool for computed tomography studies. The primary outcome was the cumulative effective dose (CED). Multivariable logistic regression was used to evaluate risk factors of high exposure (CED g 500 mSv).ResultsOne hundred seventy-one patients with NP (mean follow-up 40 ± 18 months) underwent a median of 7 (interquartile range [IQR] 5-11) computed tomography scans and 7 (IQR 5-12) fluoroscopic procedures. The median CED was 274 mSv (IQR 177-245) and 30% (51) of patients received high exposure. Risk factors of high exposure include multiorgan failure (aOR 3.47, 95%-CI: 1.53-9.88, P = 0.003), infected necrosis (adjusted odds ratio [aOR] 3.89 95%-CI:1.53-9.88, P = 0.005), and step-up endoscopic approach (aOR 1.86, 95%-CI: 1.41-1.84, P = 0.001) when compared with step-up percutaneous approach.DiscussionPatients with NP were exposed to a substantial amount of ionizing radiation (257 mSv) as a part of their treatment, and 30% received more than 500 mSv, which corresponds with a 5% increase in lifetime cancer risk. Severity of NP and a step-up endoscopic approach were associated with CED g 500 mSv. Further studies are needed to help develop low-radiation treatment protocols for NP, particularly in patients receiving endoscopic therapy.
“Stop the Murders of Our Children”: Mothers and the Battle for Hearts and Minds

In honor of Mother's Day 1957, thirty-seven Cuban mothers who had lost a rebel son or daughter claimed, on the basis of “tears and innocent blood shed,” the right to speak and be heard, calling on Cuban women “to safeguard Cuba, to protect other mothers from suffering this agony”: For a woman there is nothing that can be compared to the life of a son, a brother, a husband, and this is the time to prove it. Thus we appeal to our sisters to aid in the crusade for redemption which will detain the river of blood and tears which drown us … It is essential that this Mother's Day should set the date on which the Cuban mothers join together to raise their voices as one and say to the government: ENOUGH. In an insurrection so closely associated with bearded young men in olive green fatigues, this maternal call to action is a dramatic counterpoint. Given that two decades later, the Nicaraguan and Salvadoran revolutionary movements would include robust maternal organizations, and the mothers of the disappeared in Chile and Argentina would help bring down dictatorships, it is not surprising to find middle-aged Cuban women mobilized in the insurrection, particularly as mothers. However, apart from a few photos and anecdotes, revolutionary Cuba has not included maternal protest as a prominent part of its war story, nor have these protests or the middle-aged and older women marching in them received much attention in the literature. A variety of factors converge to create this gap: the Cuban revolution idealized youth; guerrilla warfare in the Sierra was privileged over the llano and the war of ideas; and men's contributions were valued over women's. By exploring women rebels over the age of thirty-five – their backgrounds, their paths to activism, and their modes of participation – this chapter challenges these dominant narratives, revealing an insurrection that was generationally diverse, waged significantly through ideas, and with valuable contributions by women. Drawing from testimonials, memoirs, rebel propaganda, US State Department communiques, and post-1958 Cuban media interviews, this chapter examines these women from three angles.
Perception of Curvature and Object Motion via Contact Location Feedback

We describe a new tactile display for use in dexterous telemanipulation and virtual reality. Our system renders the changing location of a remote or virtual contact by moving a tactile element along the user’s fingertip. Mounted at the endpoint of a haptic mechanism, our thimble-sized device concurrently displays contact location and interaction forces. We believe such a design will enable more versatile object manipulation for haptic interactions. To evaluate this display concept, we conducted two perceptual experiments. First, human subjects judged object curvature though direct manipulation of physical models and virtual manipulation with the device. Results show similar levels of discrimination in real and virtual interactions, indicating the device can effectively portray contact information. Second, we investigated virtual interactions with rolling and anchored objects and demonstrated that users can distinguish the interaction type using our device. These experiments provide insight into the sensitivity of human perception and suggest that even a simple display of the contact centroid location may significantly enhance telerobotic and virtual grasping tasks.
How to Play the Majority Game with Liars

The Majoritygame is a two player game with a questioner Q and an answerer A . The answerer holds nelements, each of which can be labeled as 0 or 1. The questioner can ask questions comparing whether two elements have the same or different label. The goal for the questioner is to ask as few questions as possible to be able to identify a single element which has a majority label, or in the case of a tie claim there is none. We denote the minimum number of questions Q needs to make, regardless of A 's answers, as q*. In this paper we consider a variation of the Majority game where A is allowed to lie up to ttimes, i.e., Q needs to find an error-tolerantstrategy. In this paper we will give upper and lower bounds for q*for an adaptive game (where questions are processed one at a time), and will find q*for an oblivious game (where questions are asked in one batch).
Administration of l-3,4-dihydroxyphenylalanine to rats after complete hepatectomy—II: Excretion of metabolites

Abstract The excretion of metabolites of l -[3- 14 C]dihydroxyphenylalanine ( l -[3- 14 C]DOPA) was studied after its injection into rats with complete hepatectomies and into control rats. Approximately 60 per cent of the dose (11 mg/kg; 20 μCi) of injected [ 14 C]DOPA was excreted in urine in 24 hr by the control rats, and 11 per cent in bile. Although a similar percentage of the dose (69.4 per cent) was excreted by the hepatectomized rats into urine, excretion was at a slower rate. Decarboxylation of injected [ 14 C]DOPA within 24 hr appeared to be as great in the hepatectomized rats as in the controls, but metabolism of 3,4-dihydroxyphenylethylamine (dopamine, DA) to norepinephrine was less. In the operated animals most of the DA was metabolized to 3,4-dihydroxyphenylacetic acid or to homovanillic acid. Little radioactivity was present in tissues at 24 hr after injection of l -DOPA into control rats or into hepatectomized rats; however, some radioactivity appeared to be bound to protein in some tissues in both groups of rats.
Screen printed MWCNT/PDMS based dry electrode sensor for electrocardiogram (ECG) measurements

This paper reports on the development of a novel printed and flexible dry electrode sensor consisting of multi-walled carbon nanotube (MWCNT)/ polydimethylsiloxane (PDMS) composite for electrocardiogram (ECG) measurements. The sensor was screen printed using silver (Ag) flake ink on flexible polyethylene terephthalate (PET) substrate. MWCNT/PDMS was then bar coated on the screen printed electrode. The capability of the printed sensor, which is conformal enough to have a better electrode-skin contact without the use of wet gel and skin preparation, was demonstrated. The response of the flexible dry electrode sensor is analyzed and presented in this paper.
Civil Unions Reconsidered

Civil unions were introduced in 2000, as a way forward in the marriage equality battle. By conferring all the benefits of marriage but withholding the word from same-sex couples, states signaled both their commitment to legal equality and their willingness to consign gay and lesbian couples to second-class status. The article examines both the practical limitations of the civil union and the deeper problem that no new institution, whatever its name, can capture the rich social and historical meaning of marriage. It nonetheless recognizes the civil union as an important step forward, and notes that the creation of this institution has been instrumental in triggering a discussion about the true meaning of marriage – and the consequences of deliberate exclusion from it. The article also offers a few observations about how the availability of civil unions for opposite-sex couples in a few states has begun to open up a dialogue about marriage’s negative associations for some people. Whether this modest movement away from marriage by a small number of opposite-sex couples becomes a more substantial threat to that institution remains to be seen.
Measuring rater judgment within learning assessments—Part 1: Why the number of categories matters in a rating scale

Abstract Assessments will focus learning, and so it should be aligned with desired educational outcomes. Frequently human raters (content experts) are needed to judge many abilities of advanced learners. To use subjective human judgments effectively, both the number of categories in a rating scale and the design of rubrics are important. This first article of the Methodology Matters section discusses cognitive limits in rater judgments, rating scales, and their applications. The second part of this article considers use of a “mixed approach” to rubric creation; holistic and analytic rubrics are described, as is dual-processing theory to help explain the advocated mixed approach. After reading part 1 of this article, readers should be able to (a) discuss why a four-point rating scale is often preferred (using cognitive psychology, avoiding a middle category, and rating scale performance from Rasch Measurement), and (b) create a preferred rating scale application for a learning assessment in pharmacy education. After reading part 2 of this article, the readers should be able to: (a) recognize the differences between holistic and analytic rubrics, (b) discuss integration with cognition and dual-processing theory, and (c) create a rubric for a learning assessment using a mixed approach.
Pivaloyloxymethyl-modified isoprenoid bisphosphonates display enhanced inhibition of cellular geranylgeranylation

Nitrogenous bisphosphonate inhibitors of farnesyl disphosphate synthase have been used clinically for treatment of bone disease. Because many of their effects may be mediated by depletion of geranylgeranyl diphosphate, our group has sought compounds that do this more directly through inhibition of geranylgeranyl diphosphate synthase and we have discovered a number of isoprenoid-containing bisphosphonates that selectively inhibit this enzyme. These compounds have a high negative charge at physiological pH which is necessary for inhibition of the enzyme but may limit their ability to enter cells. Therefore, chemical modifications that mask this charge may enhance their cellular potency. We now have synthesized novel pivaloyloxymethyl-modified isoprenoid bisphosphonates and investigated their ability to inhibit protein geranylgeranylation within cells. We have found that addition of pivaloyloxymethyl moieties to isoprenoid bisphosphonates increases their potency towards cellular geranylgeranylation even though this modification decreases their in vitro inhibition of geranylgeranyl diphosphate synthase. Pivaloyloxymethyl modifications more effectively increase the cellular activity of the more polar isoprenoid bisphosphonates. These results reveal structural relationships between in vitro and cellular activity which may serve as the basis for future development of more potent and/or drug-like inhibitors of geranylgeranyl diphosphate synthase.
The Status of the Testing Effect for Complex Materials: Still a Winner.

The target articles in the special issue address a timely and important question concerning whether practice tests enhance learning of complex materials. The consensus conclusion from these articles is that the testing effect does not obtain for complex materials. In this commentary, I discuss why this conclusion is not warranted either by the outcomes reported in the target articles or by the available evidence from prior research. Importantly, the weight of the available evidence does not alter the prescription for teachers and students to use practice testing to enhance learning of complex materials. However, the special issue highlights the need for more empirical and theoretical work on test-enhanced learning for complex materials, to further examine when and why these effects may be limited and to inform efforts to optimize test-enhanced learning for educationally relevant materials and tasks.
Development of the FMT chemical transport simulator : coupling aqueous density and mineral volume fraction to phase compositions

The Fracture-Matrix Transport (FMT) code couples saturated porous medium advection and diffusion with mechanistic chemical models for speciation and interphase reactions. Previous versions of FMT simulated double-porosity transport in two dimensions on the continuum from advection- to diffusion-dominated, with a user-specified velocity field to allow double-porosity transport. However, aqueous density was assumed constant, and reactive minerals were assumed to occupy negligible volume. Both of these assumptions can be considered poor for evaporite systems, where large changes in porosity and aqueous density can result from high mineral solubilities. Further development of FMT has relaxed these restrictions, allowing aqueous density to vary with phase composition, and allowing void volume to change as minerals dissolve and precipitate. This paper describes the additional mathematical complexity and code modifications required to simulate such systems. The sensitivity of advection-dominated transport to these variables is explored briefly in a one-dimensional example.
13C n.m.r. spectroscopy in living cells of Pseudomonas oleo vorans

Abstract Natural abundance solution 13 C nuclear magnetic resonance (n.m.r.) spectroscopy was used to monitor the intracellular production and degradation in vivo of two poly(3-hydroxyalkanoates) (PHAs), produced by Pseudomonas oleovorans , poly(3-hydroxynonanoate), (PHN), poly(3-hydroxyphenylvalerate) (PHPV) and a blend of both PHN and PHPV. PHN was produced and degraded faster than PHPV when it was either the sole intracellular polyester or a component of a blend with PHPV. However, the rate of PHPV degradation was increased dramatically when PHN was present. Comparison of the n.m.r. method for quantitative monitoring of the PHAs with that of extracting and weighing the polymers from freeze-dried cells, showed that the 13 C n.m.r. method was faster, easier, non-destructive (to the cells) and more accurate, while giving additional valuable information on the mobility and the composition of the PHAs present. This method was also particularly useful for determining optimal harvest times because PHPV formation continued long after the maximum optical density was reached.
Thinking Complexly About Men, Gender Role Conflict, and Counseling Psychology

The influential nature of this Major Contribution makes commenting a daunting task. However, after reviewing some of the likely consequences of this article, the author offers his sense of areas in which the research on male gender role conflict needs to grow.
Prediction of porosity and lithology in siliciclastic sedimentary rock using cascade neural assemblies

Abstract A novel approach to porosity and lithology prediction in siliciclastic sedimentary rocks is discussed here. It is based on the use of multi-element neural assembly with multiple inputs and a single output. In experiments with porosity prediction, the writers used one-, two- and three-dimensional input vector-parameters with coordinates (1) Vp or Vs; (2) Vp and Vs, and (3) petrophysical group index, Vp and Vs. When the neural assembly was trained to predict lithology, the input parameters were: (1) Vp or Vs; (2) Vp and Vs, and (3) Vp, Vs, and porosity. The writers utilized the training data-sets containing only 20 to 30 elements. To be able to work efficiently with such small training sets the writers used cascading neural assemblies specifically designed to work with small training data-sets. Each element of the neural assembly is a neural network of a simple structure. The elements of the assembly are combined in such a way that the approximation error of the assembly obtained during training session decreases with increasing number of elements. This allows for a simple and a well-defined methodology of estimating of a necessary number of neural elements in the assembly. The cost function of each element of neural assembly was taken as a sum of two terms. The first term was an estimate of the prediction error (a standard cost function of the predictive neural net), whereas the second term was a regularization term equal to the weighted sum of the squared norms of the transform matrixes. The neural network-based prediction of rock parameters was tested on a variety of training and test data-sets. Best results were achieved when the training data-set included representatives of all lithologies (petrophysical groups) contained in the test data-set and when the input parameters included independent data on the type of lithology or porosity in addition to seismic velocities.
A chebyshev collocation method for moving boundaries, heat transfer, and convection during directional solidification

Free and moving boundary problems require the simultaneous solution of unknown field variables and the boundaries of the domains on which these variables are defined. There are many technologically important processes that lead to moving boundary problems associated with fluid surfaces and solid-fluid boundaries. These include crystal growth, metal alloy and glass solidification, melting and name propagation. The directional solidification of semi-conductor crystals by the Bridgman-Stockbarger method is a typical example of such a complex process. A numerical model of this growth method must solve the appropriate heat, mass and momentum transfer equations and determine the location of the melt-solid interface. In this work, a Chebyshev pseudospectra collocation method is adapted to the problem of directional solidification. Implementation involves a solution algorithm that combines domain decomposition, finite-difference preconditioned conjugate minimum residual method and a Picard type iterative scheme.
Neurohypophyseal peptide action on andenylate cyclase and hydro-osmotic properties of toad urinary bladder epithelium

The relationship between increase in water permeability in intact urinary bladder of toad, Bufo marinus, and activation of its membrane-bound adenylate cyclase preparation in response to neurohypophyseal peptides was examined. All of the peptides tested produced a maximal hydro-osmotic response in the intact bladder; in the adenylate cyclase assay the intrinsic activities of peptides varied greatly. While there is a positive qualitative correlation (rs = 0.85, P < 0.01) between the apparent affinity parameters (pD2) of the peptides obtained in the adenylate cyclase and hydro-osmotic assays, there is a difference in peptide sensitivity between the two assays of one to four orders of magnitude. The magnitude of this difference increases as the intrinsic activity of the peptides increases. The differences in peptide affinity observed in the two assay systems as well as the lack of correlation between intrinsic activities as measured in subcellular and membrane preparations can in part be explained on the basis that maximal hormonal response in intact tissue may require only a small franction (5% or less) of the cyclic AMP produced in response to maximally stimulating concentrations of hormone or analog. On this basis, the greater the potency of a peptide in generating cyclic AMP, the greater will be the discrepancy between the peptide concentration required to produce half-maximal responsens in the two assays.
Clinically Important Changes in Acute Pain Outcome Measures: A Validation Study

The purpose of this study was to validate the changes in acute pain measurement scales that are most strongly associated with a patient-determined indicator of clinical importance. Measures of pain intensity and pain relief are commonly used outcomes in therapeutic clinical trials. Recent studies of the properties of acute pain measures have provided data defining the cut-off points that are best associated with clinically important differences. Validation of these findings in another clinical trial data set is important. Data were obtained from the titration phase of a recently conducted randomized controlled clinical trial of oral transmucosal fentanyl citrate (OTFC), which compared OTFC to immediate release morphine sulfate (MSIR) for the treatment of cancer-related acute breakthrough pain. Changes in pain intensity and pain relief were recorded every 15 minutes for 60 minutes and global medication performance recorded at the end of each study pain episode. At any titration step, if the patient felt that the first dose of the study medication did not provide adequate relief within 30 minutes, an additional rescue medication could be taken. To find the level of each pain scale best associated with this measure of the adequacy of pain relief, the calculated sensitivity, specificity, and accuracy for different cut-off points of the measured pain scales were compared to whether or not the patient needed rescue medication. The overall ability of the pain measures to discriminate episodes for which a rescue was not needed was calculated using area under the receiver operating characteristics (ROC) curves. Data were analyzed from 134 OTFC-naive patients who collected data on 1307 episodes of breakthrough pain. Using the criteria of a balanced sensitivity and specificity, the best cut-off points were determined to be: 33% for the percent pain intensity difference; > or =2 for the raw pain intensity difference on a 0-10 numeric rating scale; > or =2 (i.e., moderate or better) for pain relief; > or =33% for the percent maximum total pain relief; and > or =2 (good or better) for global medication performance. ROC area under the curve ranged from 0.839 to 0.862 for each of the pain measures listed above, calculated at 60 minutes. These data indicate that the pain scale cut-off points that are best associated with a patient-derived measure of a clinically important difference closely approximate those found in an earlier study. ROC analysis provided evidence that the overall pain measures were strongly associated with not requiring an "additional dose of rescue medication." Thus, the cut-off points determined for these pain scales provide a good surrogate measure of a patient-determined clinically important response. This provides support for the usefulness of these values in future clinical trials of pain therapy.
Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts

Abstract Background . Severe myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion. Methods . Banding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion. Results . 2-Deoxyglucose uptake ( 31 P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts. Conclusions . These data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.
Visual Pathway Axonal Loss in Benign Multiple Sclerosis: A Longitudinal Study

Multiple sclerosis (MS) is characterized by a wide range of clinical presentations (1). Patients with limited neurological signs and symptoms have been described as having a milder or benign form of MS (2-13). Benign MS has been traditionally defined as an Expanded Disability Status Score (EDSS) score ≤3 with ≥15 years disease duration (14). However, a recent consensus definition suggested using an EDSS score ≤2 and disease duration ≥10 years (12). Ultimately, the diagnosis of benign MS can only be made in retrospect (2-14). It is exceedingly difficult to predict which patients will continue to follow a benign clinical trajectory after 10-15 years (6). As few as 20% of patients categorized as having benign MS at 10 years of disease duration, will continue to follow this same course after 20 years of follow-up (2,7). Despite relatively preserved motor function, patients with benign MS have a similar or even greater MRI T2 lesion burden compared to typical MS (14-27). Possible explanations include sparing of clinically eloquent regions (14-19), paucity of tissue damage in and around MS lesions (19-24), and effective compensatory mechanisms (25-27). EDSS scores do not adequately reflect the frequent and often disabling component of MS associated cognitive impairment, an important feature that correlates with increased MRI lesion burden in benign MS (28-32). Vision is also not well-captured by the EDSS, yet is as important as walking is to patients with early MS (33-38). Optical coherence tomography (OCT) has brought visual function to the forefront as a model for testing new MS therapies (33-35). We determined the extent of visual pathway axonal loss by OCT retinal nerve fiber layer (RNFL) thickness in a benign MS cohort, and assessed how visual function, history of acute optic neuritis (ON), and QOL differ for benign vs. typical MS. While primary analyses used the traditional definition of EDSS ≤3 and disease duration ≥15 years, the recently revised consensus definition (EDSS ≤2, ≥10 years duration) was also examined.
Properties of the HUI and Walter and Related Methods for Estimating Prevalence Rates and Error Rates of Diagnostic Testing Procedures

When a confirmatory test is completely accurate or has known low error rates, the sensitivity and the specificity of a screening test can be estimated. When the error rates for the confirmatory test are unknown, Hui and Walter (2) presented a method for estimating the sensitivity and specificity of both the screening and the confirmatory tests using the tests on two populations with different prevalence rates of the infection. The method requires that the tests have equal error rates in the two populations. When this requirement is not met, we show that the estimated prevalence rates are robust when the difference in the prevalence rates of the two subpopulations is large. An alternative design, requiring only one population, but other assumptions, is also described.
The development of an enduring commitment to service work.

The authors examine factors that motivate and sustain young professionals' commitment to those in need and discuss how individuals come to see service as their life's mission.
Interfacial Properties of the a-Si ∕ Cu :Active–Inactive Thin-Film Anode System for Lithium-Ion Batteries

Amorphous silicon thin films deposited on copper foil have been observed to exhibit near theoretical capacity for a limited number of cycles. The films, however, eventually delaminate, leading to failure of the anode. In order to better understand the mechanism of capacity retention and the ultimate failure mode of a model brittle active:elastic/plastic inactive anode system, the films were subjected to in situ adhesion tests while observing the film surface using scanning electron microscopy. Atomic force and transmission electron microscopy, and electrochemical cycling were conducted to analyze the emerging morphology of the films during cycling. The adhesion of the as-deposited Si film to the Cu substrate was measured to ∼7.7 J/m 2 , reflecting a weak interface adhesion strength. Plastic deformation of the underlying Cu substrate combined with a ratcheting mechanism is proposed to occur in the Si:Cu system, with delamination failure mode occurring only after the formation of an interface imperfection. From the analysis of slow rate cycling experiments, nucleation of a lithium compound based on the interdiffusion of Si and Cu is identified as the most probable cause of the ultimate delamination failure of the deposited film.
Musculoskeletal recovery following hindlimb immobilization in adult female rats

Abstract Bone loss during immobilization is well known. Common medical treatments of aged individuals that involve temporary immobilization may create an iatrogenic medical problem, a permanently increased risk of fracture. The goal of this article is to understand recovery of musculoskeletal tissues from temporary immobilization. Six-month-old female Sprague-Dawley retired breeder rats were used. A baseline group was killed; half the rest were immobilized (unilateral right hindlimb taping). After six weeks, groups of immobilized and control rats were killed and the immobilized rats were released from taping. After six more weeks, all remaining rats were killed. All rats received in vivo dual fluorochrome labeling. Lower leg muscles and tibiae and femurs were collected. Histomorphometric analysis of the proximal tibial metaphysis and cortical bone near the tibio fibula junction was completed. During immobilization, cancellous bone mass and trabecular number declined. Cortical bone mass did not change, but formation was lower and resorption was higher. Muscle weight fell. During the recovery period, bone mass rose, but did not exhibit complete recovery. The same was true for muscle weight. This model seems adequate for studying musculoskeletal recovery following immobilization. Both muscle and bone require a time period longer than the period of immobilization in order to make a complete recovery from the temporary deterioration. Bone structure deteriorates markedly during immobilization and recovers poorly. Longer studies are necessary to evaluate the ability of the adult skeleton to make a full recovery without intervention.
Theory of vectorcardiography: A review of fundamental concepts

Abstract Five factors which determine the accuracy of representing the electrical field of the heart by means of a spatial vectorcardiogram are: 1. 1. The validity of representing multiple dipole centers within the heart as a single resultant dipole. 2. 2. The variability of the location of the assumed single resultant dipole center during the cardiac cycle. 3. 3. The degree of eccentricity of the assumed single resultant dipole center. 4. 4. The lack of electrical homogeneity of tissues forming the volume conductor. 5. 5. The irregularity of the limiting boundary of the volume conductor. The last three factors influence the validity of utilizing reference frames devised according to anatomic considerations but can be eliminated by the use of reference frames, the electrical properties of which are determined experimentally and expressed in terms of the lead vector concept. The latter has been explained and illustrated in a detailed manner. The first factor involves an assumption which becomes increasingly tenous, the more closely one or more electrodes forming a lead approach the heart. Various methods, reviewed in detail, have been devised to assess the validity of this assumption. Such studies have indicated limitations of applying the concept of a single resultant dipole to precordial leads, although, in general, it would appear that such limitations are not as stringent as would be predicted from anatomic considerations. A possible explanation for this is discussed. The second factor, migration of the assumed single resultant dipole center during the cardiac cycle, is related to and, from a practical standpoint, inseparable from, the first factor. It contributes to the shortcomings involved in applying the single resultant dipole concept to any electrocardiographic lead and is involved in the experimental evaluation of the validity of this concept. A method is suggested for devising a spatial reference frame formed by remote leads which may obviate the last three factors and reduce to a minimum the influence of the first two. In view of the limitations inherent in the single resultant dipole concept, alternate methods of representing the manner in which the electromotive forces arising in the heart influence an electrocardiographic lead are discussed. These comprise a mathematical representation consisting of multiple lead vectors, one for each point in the myocardium generating an electromotive force, and its physical counterpart consisting of “flow lines” or “tubes of influence” to depict the electrical characteristics of the lead field at each myocardial point. A method is outlined in Appendix II for the application of the multiple lead vector concept to the experimental determination of the relative extent to which various portions of the heart contribute potentials to precordial leads.
Bifurcation theory and the type numbers of marston morse.

Abstract Let H be a real Hilbert space and f(x,λ) be a C2 operator mapping a small neighborhood U of (x0,λ0) e (H × R1) into itself. We investigate the solutions of the equation f(x,λ) = 0 near a solution (x0,λ0), assuming that f(x,λ) is a gradient mapping and 0 < dim Ker fx(x0,λ0) < ∞. In particular, we show that the type numbers of Marston Morse for an isolated critical point can be used to prove the existence of a point of bifurcation at (x0,λ0). An application of this result is given to the discovery of periodic motions near a stationary point for a large class of nonlinear Hamiltonian systems in “resonant” cases.
Tissue distribution of IgA receptor-bearing cells in mouse and guinea pig with special reference to the lymphoid population of the gastrointestinal tract.

Abstract The presence and relative number of cells bearing IgA and IgG receptors in various mouse and guinea pig lymphoid tissues was determined using rosetting techniques. Both types of cells were found to be widely distributed, with cells binding IgG (range 10 to 45%) being more common than cells binding IgA (range 2 to 6%) in all tissues examined. In the mouse, cells bearing IgA receptors were not more prevalent in the intestinal lymphoid organs, Peyer's patches and mesenteric lymph nodes, as compared to the systemic lymphoid organs, spleen and peripheral lymph nodes, although PP contained the highest percentage. In addition, the percentage of cells with IgA or IgG receptors in a given murine tissue did not directly correlate with the capacity of lymphocytes from that tissue to synthesize immunoglobulin of the same isotype upon LPS stimulation. In the guinea pig, cells with IgA receptors were found in both lamina propria and intraepithelial lymphocyte populations isolated from small intestinal mucosa. However, their number there was only marginally higher than that found in other guinea pig tissues, such as spleen. Thus, cells bearing IgA receptors are not preferentially localized in tissues which are active in the secretory (IgA) immune system.