cssi/SciSciGPT-SciSciNet huggingface dataset:
[11C]Dimebon as a new PET agent for imaging of Alzheimer's disease and Huntington's disease

1510 Objectives Dimebon is an antihistamine drug that has been developed and used in Russia since 1983. This old drug has been recently proposed to be useful for treating neurodegenerative disorders such as Alzheimer’s disease (AD) and Huntington’s disease (HD). This study was designed to develop [11C]Dimebon as a new PET agent for imaging of AD and HD. Methods The reference standard Dimebon {2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole} and its corresponding desmethylated precursor 8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole were synthesized from p-toluidine, 2-methyl-5-vinylpyridine and substituted piperidin-4-one in 4 steps including 1,2-addition, nitration, reduction and condensation reactions. The target tracer [11C]Dimebon was prepared from its precursor with [11C]CH3OTf under basic condition through N-[11C]methylation and isolated by HPLC method. Results The overall chemical yields for the target compound and the precursor in 4 steps were 33% and 30% respectively. The radiochemical yield for the target tracer was 30-40%, decay corrected to end of bombardment (EOB), based on [11C]CO2. The specific activity was 222-296 GBq/μmol at EOB. Conclusions A new synthetic route to labeling precursor and Dimebon has been described, and an efficient and convenient synthesis of [11C]Dimebon has been well-developed for the first time. Research Support The Indiana Genomics Initiative (INGEN) of Indiana University, which is supported in part by Lilly Endowment Inc
A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

Mutations in the gene NR0B1 have been associated with several clinical phenotypes of X-linked adrenal hypoplasia congenita (AHC). The degree and onset of adrenal insufficiency and involvement of hypogonadotropic hypogonadism is variable and may not be concordant with the identified mutation. We review a patient with AHC in which prenatal estriol levels were low, presenting with early-onset mineralocorticoid deficiency in the newborn period followed by glucocorticoid deficiency 2 years later. The reported child is hemizygous for a novel mutation that is deemed de novo in the ligand-binding site of the protein (DAX1) expressed by NR0B1. The identified frameshift mutation results in a T407N/fs protein change. Low prenatal estriol levels may represent a sensitive marker of potentially fatal disorders associated with adrenal insufficiency and should be utilized more frequently. Additionally, accurate reporting of mutations in NR0B1 and the associated phenotype are important to eventually establish a genotype-phenotype correlation that may help anticipate guidance in AHC.
Cross-limb communication during Xenopus hindlimb regenerative response: non-local bioelectric injury signals.

ABSTRACT Regeneration of damaged body parts requires coordination of size, shape, location and orientation of tissue with the rest of the body. It is not currently known to what extent injury sites communicate with the remaining soma during repair, or what information may emanate from the injury site and reach other regions. We examined the bioelectric properties (resting potential gradients in the epidermis) of Xenopus laevis froglets undergoing hindlimb amputation and observed that the contralateral (undamaged) limb exhibits apparent depolarization signals immediately after the opposite hindlimb is amputated. The pattern of depolarization matches that of the amputated limb and is correlated to the position and type of injury, revealing that information about damage is available to remote body tissues and is detectable non-invasively in vivo by monitoring the bioelectric state. These data extend knowledge about the electrophysiology of regenerative response, identify a novel communication process via long-range spread of injury signaling, a phenomenon that we call bioelectric injury mirroring, and suggest revisions both to regenerative medicine and diagnostic strategies that are focused entirely on the wound site, and to the use of contralateral limbs as controls.
Unexpected Role of Ru(II) Orbital and Spin Contribution on Photoinduced Ligand Exchange: New Mechanism To Access the Photodynamic Therapy Window

A series of 12 Ru(II) complexes of the type [Ru(tpy)(L)(CH3CN)]n+, 1–12, containing the tridentate tpy ligand (tpy = 2,2′:6′,2″-terpyridine) and various bidentate ancillary ligands, L, were synthesized and evaluated for their ability to photodissociate CH3CN, a model for nitrile-containing drugs. Although the bidentate ligands chosen display a similar degree of steric bulk around the metal center in the ground state, the photosubstitution efficiencies of 1–12 vary by approximately an order of magnitude. The complexes containing the most electron-donating bidentate ligands, 8–11, exhibit the larger quantum yield values for ligand exchange in water. Complexes 8–11 also possess the smallest energy gap between the ground state and the lowest energy triplet metal-to-ligand charge transfer (3MLCT) excited state. In addition, density functional theory calculations indicate that a large degree of ligand character is present in their highest occupied molecular orbitals (HOMOs) and in their 3MLCT excited states. Th...
Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation.

Objective To examine the hypothesis that atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation (AF) by comparing atrial fibrosis burden between patients with embolic stroke of undetermined source (ESUS), patients with AF, and healthy controls. Methods We used late-gadolinium-enhancement MRI to compare atrial fibrosis in 10 patients with ESUS against 10 controls (no stroke, no AF) and 10 patients with AF. Fibrosis was compared between groups, controlling for stroke risk factors. Results Mean age was 51 ± 15 years, and 43% of participants were female. Patients with ESUS had more atrial fibrosis than controls (16.8 ± 5.7% vs 10.6 ± 5.7%, p = 0.019) and similar fibrosis compared to patients with AF (17.8 ± 4.8%, p = 0.65). Odds ratios of ESUS per quartile of fibrosis were 3.22 (95% CI [CI] 1.11–9.32, p = 0.031, unadjusted) and 3.17 (95% CI 1.05–9.52, p = 0.041, CHA2DVASc score adjusted). Patients with >12% fibrosis had a higher percentage of ESUS (77.8% vs 27.3%, p = 0.02), and patients with >20% fibrosis had the highest proportion of ESUS (4 of 5). Conclusions Patients with ESUS exhibit similar atrial fibrosis compared to patients with AF and more fibrosis than healthy controls. Fibrosis is associated with ESUS after controlling for stroke risk factors, supporting the hypothesis that fibrosis is in the causal pathway of cardioembolic stroke independently of AF. Prospective studies are needed to assess the role of anticoagulation in primary and secondary stroke prevention in patients with high atrial fibrosis.
Sjögren-Larsson syndrome: a complex metabolic disease with a distinctive ocular phenotype.

Purpose: Sjogren-Larsson Syndrome (SLS) is a rare genetic disorder characterized by a distinctive crystalline maculopathy, congenital ichthyosis, spasticity and intellectual disability. We review the genetic, biochemical and clinical aspects of SLS with a particular focus on the ophthalmologic features of the disease.Methods: Published reports of SLS are combined with clinical experience to provide an overview of this disease.Results: SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase, a key enzyme needed for the metabolism of long-chain aliphatic aldehydes and alcohols. SLS patients display perifoveal crystalline inclusions (glistening white dots) that appear in early childhood, vary from sparse to florid and are located in the inner retina. Other findings include retinal thinning, cystic macular degeneration, retinal pigment epithelium atrophy and deficiency of macular pigment. Photophobia is common. Visual evoked potentials are often absent or delayed, whereas electroretinography studies are usually normal. Mild-moderate deficits in visual acuity are common but vision is usually preserved into adulthood. The maculopathy is thought to be due to the accumulation of fatty aldehydes and/or alcohols, which alter membrane function. Defective macular pigment metabolism may also contribute to a unique susceptibility to photo-oxidative damage in the retina.Conclusions: The distinctive retinal phenotype, together with the neurologic and cutaneous symptoms, allows the ophthalmologist to reliably diagnose SLS. Although no effective treatment exists for the ocular symptoms, emerging insight into the pathogenic mechanisms at play in the eye promises to bring effective therapy for SLS in the future.
BP Components in Advanced CKD and the Competing Risks of Death, ESRD, and Cardiovascular Events

CKD is a prevalent disorder found in over 13% of the population ([1][1]), making it more common than even diabetes mellitus. Similar to diabetes, the presence of CKD is strongly associated with cardiovascular disease ([2][2]). Because hypertension is a common complication of CKD, and, also, a major
Real-time prediction of public bike sharing system demand using generalized extreme value count model

Abstract Public Bike Sharing Systems (BSSs) are becoming increasingly popular in recent times. Both the BSS operators and the customers can benefit from the large digital data portals that continuously record the state of the BSS. In this context, the current study developed generalized extreme value (GEV) count models that can predict hourly bike arrivals and departures at each station while accounting for time-of-day, weather, built environment, infrastructure, temporal, and spatial dependency factors. The proposed models were used to analyze the demand patterns in the Capital Bikeshare system and were found to predict the demand at both aggregate and disaggregate levels with reasonable accuracy. Specifically, the total demand in the entire system was predicted within 5% margin of error whereas 75% of the station-level arrival and departure predictions in the next one hour were within a margin of one from the observed counts. The proposed modeling system is useful (a) to BSS customers to better plan their travel based on expected bike and dock availability at the origin and destination ends of their BSS trips, and (b) to BSS operators to anticipate the future demand and optimize their rebalancing plans.
Experiential Learning: Justice System Officials as Co-Educators

Most students are interested in the operation of our courts. They want to know how crimes are investigated, how criminals are prosecuted, convicted and sentenced, and how (and how well) prisons operate. Unfortunately, the people with the best experience to address these topics are not usually found on campus. But with some advanced planning, they can become partners in a meaningful experiential education collaboration. This paper briefly reviews the experiential theory behind this undergraduate field class, and the mechanics of its operation.
Lexical frequency and morphological regularity as sources of heritage speaker variability in the acquisition of mood

The present investigation examines intra-speaker variability in heritage speakers (HSs) of Spanish by focusing on the potential effects of two variables in their acquisition of mood: lexical freque...
The impact of information disclosure on consumer purchase behavior on sharing economy platform Airbnb

Abstract Via the empirical evidences from Airbnb from eight major cities in U.S., we examine the role of information disclosure in influencing consumers' purchase behavior on this sharing economy platform. We analyze information disclosure from four aspects – namely, what information (i.e., information content), from where (i.e., information source), in what format (information presentation format), and how much (the quantity of information). We find all three information sources – providers, platform, and peer consumers – influence consumer purchase behavior. Regarding information posted by providers, we find a concave relationship between room information (i.e. the number of photos and the length of description) and consumer purchase behavior. However, no significant relationship between providers' self-description (texts and photos) and consumer purchase behavior is found. Regarding information posted by platform, both the recommendation from platform and provider verification information positively influence consumer purchase behavior. For provider-consumer interactions information, the providers' high response rate and fast response speed enhance consumer purchase behavior. However, providing connections to providers' social media profiles negatively influences consumers' purchasing behavior. Regarding the information from peer consumers, we find although consumers' overall ratings positively affect consumer purchase behavior, such influence diminishes when the ratings exceed certain thresholds. Our study provides implications for platform owners to optimize information presentation layout directly through the platform design or indirectly through the guidance to the providers' information disclosure to facilitate consumers’ information search and acquisition to reduce the perceived risk, enhance trust on providers and the platform, and thus enhance their purchase intention and behavior.
The impact of investor-level taxation on mergers and acquisitions

Abstract When capital gains are taxed at a lower rate than dividends, the difference in rates creates a tax discount on mergers and acquisitions. The intuition is that if a target firm's assets are subject to the higher dividend tax rate, but the proceeds from the sale of these assets are taxed at the lower capital gains rate, there is a tax preference to be acquired. Using quasi-experimental variation created by the Jobs Growth and Tax Relief Reconciliation Act of 2003, we show that this tax discount increases the quantity and decreases the quality of acquisitions made by dividend-paying firms with taxable shareholders. Our estimates suggest that re-implementing the same wedge between dividend and capital gains rates that the 2003 reform eliminated would destroy approximately $59 billion of the value of mergers and acquisitions in the U.S. annually.
National Assessment of Bicycle Friendliness Using a Spatial Approach: Focus on Universities and Communities

Abstract Bicycle mobility as a sustainable form of transportation has been increasing, particularly as a result of the COVID-19 pandemic. As a result, evaluating bicycle friendly areas, including c...
Natural Language Processing Enabling COVID-19 Predictive Analytics to Support Data-Driven Patient Advising and Pooled Testing.

Objective The COVID-19 pandemic response at MUSC included virtual care visits for patients with suspected SARS-CoV-2 infection. The telehealth system used for these visits only exports a text note to integrate with the EHR, but structured and coded information about COVID-19 (e.g., exposure, risk factors, symptoms) was needed to support clinical care and early research as well as predictive analytics for data-driven patient advising and pooled testing. Methods To capture COVID-19 information from multiple sources, a new data mart and a new Natural Language Processing (NLP) application prototype were developed. The NLP application combined reused components with dictionaries and rules crafted by domain experts. It was deployed as a web service for hourly processing of new data from patients assessed or treated for COVID-19. The extracted information was then used to develop algorithms predicting SARS-CoV-2 diagnostic test results based on symptoms and exposure information. Results The dedicated data mart and NLP application were developed and deployed in a mere 10-day sprint in March 2020. The NLP application was evaluated with good accuracy (85.8% recall and 81.5% precision). The SARS-CoV-2 testing predictive analytics algorithms were configured to provide patients with data-driven COVID-19 testing advices with a sensitivity of 81-92% and to enable pooled testing with a negative predictive value of 90-91% reducing the required tests to about 63%. Conclusion SARS-CoV-2 testing predictive analytics and NLP successfully enabled data-driven patient advising and pooled testing.
How K-12 Teachers Adapt Problem-Based Learning Over Time

Teachers adapt their instructional strategies over time based on a variety of contextual constraints. In response to these challenges, teachers often have to make changes to their PBL approaches. While the literature has documented generally positive results of initial PBL implementations, less is known about the degree to which teachers adapt their usage of PBL over time. Some adaptations include a refined approach to teaching strategies, while others include significant diversions from the original PBL model. A better understanding of the changes teachers enact provides important insight as to fidelity and thus the expected learning outcomes of PBL. To address this gap, this research conducted semi-structured interviews with experienced K-12 educators who employed PBL over multiple years. In terms of preparing for PBL, themes that emerged from the interviews included more emphasis on reimagining the problem scope and design thinking. During classroom time, teachers described shifting perspectives in terms of the following: problem-solving skills over content knowledge, student control and teacher facilitation, and embracing failure. Relating to technology, teachers described more adoption trends towards collaborative tools, while also describing opportunities and challenges with digital literacy. Finally, teachers described strategic approaches to assessment in light of the ill-structured problems posed by PBL. Implications for practice and theory are discussed.
Gradient in refractive index reveals denser near free surface region in thin polymer films

A gradient in refractive index that is linear in magnitude with depth into the film is used to fit ellipsometric data for thin polymer films of poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(2-vinyl pyridine) (P2VP). We find that the linear gradient model fits provide more physically realistic refractive index values for thin films compared with the commonly used homogeneous Cauchy layer model, addressing recent reports of physically unrealistic density increases. Counter to common expectations of a simple free volume correlation between density and dynamics, we find that the direction of refractive index (density) gradient indicates a higher density near the free surface, which we rationalize based on the observed faster free surface dynamics needed to create vapor deposited stable glasses with optimized denser molecular packings. The magnitude of refractive index gradient is observed to be three times larger for PMMA than for PS films, while P2VP films exhibit a more muted response possibly reflective of a decoupling in free surface and substrate dynamics in systems with strong interfacial interactions.
Equivalence of arterial and venous blood for 11CO2-metabolite analysis following intravenous administration of 11C-acetate and 11C-palmitate

1501 Objectives Sampling of arterial blood for metabolite correction is often required to define a true radiotracer input function in quantitative modeling of PET data. However, arterial puncture for blood sampling is often undesirable. To establish whether venous blood could substitute for arterial blood in quantitative PET studies with 11C-acetate and 11C-palmitate, we compared the results of 11CO2-metabolite analyses performed on simultaneously collected arterial and venous blood samples. Methods Paired arterial and peripheral venous blood samples were drawn from anesthetized pigs at 1, 3, 6, 8, 10, 15, 20, 25 and 30 minutes after i.v. administration of 11C-acetate and 11C-palmitate. Blood radioactivity present as 11CO2 was determined using a validated method. Briefly, total blood 11C-radioactivity was counted in alkalinized 11C-blood, and non-11CO2 radioactivity was counted after the 11C-blood was acidified and bubbled with air for 10-minutes to quantitatively remove 11CO2. Results For both 11C-acetate and 11C-palmitate, a total of 34-pairs of arterial and venous samples were analyzed from four resting-state pigs. Over the 1-30 minute period, the fraction of total blood 11C present as 11CO2 rose from 4% to 64% for acetate, and 0% to 24% for palmitate. An excellent correlation was found between concurrent arterial and venous 11CO2 levels. For the 11C-acetate study, the regression equation derived to estimate the venous 11CO2 from the arterial values was: y = 0.9943x + 0.0042 (R2=0.97, p Conclusions Venous 11CO2 values appear suitable as substitutes for arterial blood samples in 11CO2 metabolite analysis after administration of 11C-acetate or 11C-palmitate
RELATIONSHIP BETWEEN TISSUE-SPECIFIC HYDROCARBON PROFILES AND LIPID MELTING TEMPERATURES IN THE COCKROACH Blattella germanica

Hydrocarbons (HC) are the most important waterproofing barrier on the cuticle of most terrestrial insects. Yet, the relationships among the type, amount, biophysical properties, and water retardation capacity of constituent HC are poorly understood. Melting temperatures and gas chromatographic profiles of HC of German cockroach tissues of various ages and stages were compared. The melting temperature (Tm) of oothecal HC was highest, Tm of epicuticular HC was substantially lower, and that of hemolymph HC was lowest. The epicuticular HC of older nymphs and adults had higher Tm than HC of the same sex and stage soon after the molt. The HC of females had higher Tm than did male HC. Principal components analysis suggested that normal and 3and 5-methylalkanes, which were more prevalent on the epicuticle, were associated with higher Tm, implicating these components of the HC blend in waterproofing roles. The cockroach ootheca is particularly well protected by an abundance of n-alkanes and its external HC exhibit the highest Tm of any HC blend. The methyl ketone sex pheromone components, which are derived from HC, appear to only slightly reduce the Tm of the epicuticular HC, probably because the methyl ketones represent only 1.12% of the mass of epicuticular HC. We suggest that the evolution of polar epicuticular chemical signals may be constrained by their tendency to increase water transpiration.
Dissolved organic carbon lability increases with water residence time in the alluvial aquifer of a river floodplain ecosystem

We assessed spatial and temporal patterns of dissolved organic carbon (DOC) lability and composition throughout the alluvial aquifer of the 16 km2 Nyack Floodplain in northwest Montana, USA. Water influx to the aquifer derives almost exclusively from the Middle Fork of the Flathead River, and water residence times within the aquifer range from days to months. Across seasons and channel discharge conditions, we measured DOC concentration, lability, and optical properties of aquifer water sampled from 12 wells, both near and ~3 m below the water table. Concentrations of DOC were typically low (542 ± 22.7 µg L−1; mean ± se), and the percentage of labile DOC averaged 18 ± 12% during 3 day laboratory assays. Parallel factor analysis of fluorescence excitation-emission matrices revealed two humic-like and two amino acid-like fluorescence groups. Total DOC, humic-like components, and specific UV absorbance decreased with water residence time, consistent with sorption to aquifer sediments. However, labile DOC (both concentration and fraction) increased with water residence time, suggesting a concurrent influx or production of labile DOC. Thus, although the carbon-poor, oxygen-rich aquifer is a net sink for DOC, recalcitrant DOC appears to be replaced with more labile DOC along aquifer flow paths. Our observation of DOC production in long flow paths contrasts with studies of hyporheic DOC consumption along short (centimeters to meters) flow paths and highlights the importance of understanding the role of labile organic matter production and/or influx in alluvial aquifer carbon cycling.
Resistance of Candida albicans to direct lethal miconazole action induced by low-level miconazole.

Summary. Logarithmic phase cells of Candida albicans are susceptible to physicochemical damage by ≥ 2 times 10-5mol miconazole resulting in direct lethal action (DLA). Stationary phase yeasts are resistant to such action. At low levels (i.e. < 10-5mol), miconazole can inhibit synthesis of cell membrane components and can also revert DLA-susceptible cells to DLA resistance. Reversion was studied in relation to low-level miconazole exposure time. DLA was assessed by viable count determinations. Most cells in susceptible cultures reverted to resistance within 30 to 60 min of exposure to 2.0 times 10-6mol miconazole. The rapidity of this shift suggested subtle alterations in existing cell membrane material in response to low-level miconazole. Saturation of membrane fatty acids might explain the shift. Zusammenfassung. Candida albicans-Zellen in logarithmischer Wachstumsphase werden durch ≥ 2 times 10-5mol Miconazol physikochemisch direkt le-tal geschadigt (DLA). Die stationare Hefephase ver-halt sich gegenuber dieser Wirkung resistent. In ge-ringerer Dosierung (< 10-5mol) kann Miconazol die Synthese von Zellmembranbestandteilen hem-men und auch DLA-empfindliche Zellen in DLA-resistente umwandeln. Diese Reversion wurde in Abhangigkeit zur Miconazol-Niedrigdosis-Exposi-tionszeit untersucht. Die DLA wurde durch Le-bendkeimzahl-Bestimmungen bewertet. In emp-findlichen Kulturen revertierten die meisten Zellen innerhalb von 30 bis 60 min Exposition gegenuber 2,0 times 10-6mol Miconazol zur Resistenz. Die Schnelligkeit dieses Uberganges last subtile Ande-rungen im vorhandenen Zellmembranmaterial in-folge der Niedrigdosis-Miconazol-Exposition ver-muten. Der Sattigungsgrad der Membranfettsauren konnte diesen Ubergang erklaren.
Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer.

PURPOSEEnhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated.PATIENTS AND METHODSFUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN-a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography.RESULTSThe maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose-limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +...
Evaluation of methods for preservation of water samples for nutrient analysis

Mercuric ion, sulfuric acid, and chloroform were examined as preservatives for nitrogen and phosphorus species in water samples containing biologically active microorganisms. Chilling at 4°C without addition of a chemical preservative also was examined. Chilling alone at 4°C was an adequate preservation technique for 8‐day storage for the water samples used in this study. However, for samples analyzed after 16‐day storage, the addition of 40 milligrams per liter of mercuric ion plus chilling at 4°C, appeared to be the preservation technique of choice. Neither chloroform nor sulfuric acid, coupled with chilling, were adequate as preservation techniques for all analytes determined during the 16‐day study period.
Impossibility of steady flow of a Maxwell liquid in a porous cylindrical annulus with circular cross-section

In this note it is pointed out that for a Maxwell liquid with one relaxation time, steady flows in a porous cylindrical annulus with circular cross-section are impossible. The solution given by Rao is not valid except in the case of either a Newtonian liquid or no cross-flow.
Evaluating the impact of medical treatment on the quality of life: A 5-year update

A comparison of the studies investigating the impact of medical care on quality of life over a recent 5-year period (1980-1984) with those appearing during the preceding 5 years from 1975 to 1979 [1]reveals; that (a) 3 times as many (69 as compared to 23) appeared during the time span, that (b) almost two-thirds (60%) of the recent studies included a subjective measure of quality of life as compared to only 1 in 10 for the previous 5-year period, but that (c) one-shot, case studies designs still predominate. On the other hand, (d) the use of control groups doubled from 1981 to the present, although (c) the majority of studies continues to use samples of convenience (e.g. consecutive patients or treatment survivors) rather than employing random assignments or random sampling. Nevertheless, (f) the average size of samples has doubled from 90 to 178, and (g) whereas almost all of the studies in the earlier review concluded that the intervention being studied improved quality of life, now approx. 1 in 5 report negative outcomes with another 30% reporting mixed results. It is concluded that in spite of increasing methodological sophistication, investigation of the impact of medical care on quality of life will be hindered until there is better agreement as to what constitutes adequate assessment of the construct. Suggestions for how a consensus might be attained are discussed.
Intake, performance, and blood parameters in young goats offered high forage diets of lespedeza or alfalfa hay

July-born F1 Boer x Spanish (BoerX), Nubian, and Spanish buck kids (n = 18) were used in an experiment to evaluate the use of lespedeza hay in goat diets. Bucklings were weaned at 60 d of age and maintained on pasture and in pens, before being assigned to the experiment at 6 months of age. Kids were randomly assigned to six pens and stratified by breed. The two diets were ad libitum: (1) sericea lespedeza [Lespedeza cuneata (Dum.-Cours) G. Don; LESP] hay, or (2) alfalfa (Medicago sativa L.; ALF) hay. All animals received a 16% crude protein (CP) corn/cottonseed-based supplement offered at 0.5% of body weight (BW) per head/d. Total dry matter intake (DMI) was higher (P 0.10) in ADG (mean 79 g/d). Bucks offered the ALF-based diet had higher (P < 0.001) plasma concentrations (mg/dl) of blood urea nitrogen (BUN; 21.1 versus 10.7) and glucose (67.7 versus 59.5) and lower (P < 0.001) creatinine (0.53 versus 0.62 mg/dl) compared to kids offered the LESP-based diet. Blood glucose concentrations were highest (P < 0.001) for Nubian (66.3 mg/dl) and lowest for Boer cross (60.9 mg/dl); Spanish was intermediate (63.6 mg/dl). Creatinine levels were similar among breeds (mean 0.57 mg/dl). More research is needed to evaluate goat breed, forage species, stage of forage maturity, condensed tannins, and supplementation effects on nutrient utilization by finishing goats.
Possible survival benefit from concomitant beta-but not calcium-antagonist therapy during reperfusion for acute myocardial infarction.

Abstract To test the hypothesis that long-term β- or calciumantagonist therapy begun before the time of myocardial infarction and coronary reperfusion might improve patient in-hospital survival compared with reperfusion alone, 424 consecutive patients successfully reperfused with coronary angioplasty within 12 hours of infarct symptom onset were carefully and retrospectively characterized. Forty-seven patients (11%) were taking β antagonists and 74 patients (17%) were taking calcium antagonists at the time of infarction. Patients receiving β antagonists had a more frequent history of hypertension (p ≤ 0.001) and prior infarction (p ≤0.01) than those not so treated and patients receiving calcium antagonists had a more frequent history of prior infarction, prior angina, hypertension and diabetes (all p ≤ 0.001) than their nontreated counterparts. Stepwise logistic regression analysis found significant independent correlations between inhospital death and the following variables: recurrent ischemia (p ≤ 0.001); proximal left anterior descending coronary infarct (p ≤ 0.001); 3-vessel disease (p = 0.002); patient age (p = 0.004); and initial total occlusion of the infarct artery (p = 0.022). After adjustment for these factors, β antagonist use (mortality = 0 vs 8% without treatment) was still significantly correlated with improved survival (p = 0.048), whereas calcium-antagonist therapy made no difference in survival. Heart rate and left ventricular end-diastolic pressure upon presentation were significantly lower in patients treated with β antagonists. Thus, β-antagonist therapy, but probably not calcium-antagonist therapy, taken before reperfusion for acute myocardial infarction, may improve early survival compared to reperfusion alone. Larger studies will be required to confirm or refute these observations.
Simultaneous reference allocation in code generation for dual data memory bank ASIPs

We address the problem of code generation for DSP systems on a chip. In such systems, the amount of silicon devoted of program ROM is limited, so application software must be sufficiently dense. Additionally, the software must be written so as to meet various high-performance constraints, which may include hard real-time constraints. Unfortunately, current compiler technology is unable to generate high-quality code for DSPs, whose architectures are highly irregular. Thus, designers often resort to programming application software in assembly—a time-consuming task. In this paper, we focus on providing support for architectural feature of DSPs that makes code generation difficult, namely multiple data memory banks. This feature increases memory bandwith by permitting multiple data memory accesses to occur in parallel when the referenced variables belong to different data memory banks and the registers involved conform to a strict set of conditions. We present an algorithm that attempst to maximize the benefit of this architectural feature. While previous approaches have decoupled the phases of register allocation and memory bank assignment, thereby compromising code quality, our algorithm performs these two phases simultaneously. Experimental results demonstrate that our algorithm not only generates high-quality compiled code, but also improves the quality of completely-referenced code.
Counting subrings of Z n of index k

We consider the problem of determining the number of subrings of the ring Z^n of a fixed index k, denoted f"n(k). We present a decomposition theorem for these subrings and calculate explicit expressions for the Dirichlet series generating function F"n(s)=@?"k"="1^~f"n(k)k^-^s for n=<4 and for the generating function @F"p(x,y)=@?"e"="0^~@?"n"="0^~f"n(p^e)x^ey^n/n! modulo p. We also calculate f"n(k) when k is not divisible by the sixth power of any prime.
FRAX®: a fracture risk-assessment tool

There is a need to identify patients with osteopenia who are at high risk of sustaining fractures and who would benefit from treatment, since many patients with osteopenia do not sustain fractures. In 2008, the WHO unveiled the fracture risk-assessment tool (FRAX®), which calculates the 10-year probability of a patient sustaining a fracture. It is available on the internet free of charge, and represents a major step forward since it takes into account a number of risk factors and allows clinicians to focus on those patients at high risk of sustaining fractures, in whom the benefits of treating a silent disease outweigh the potential adverse effects and cost. In the USA, the National Osteoporosis Foundation has suggested a fracture threshold to recommend treatment. In this article, the various risk factors included in the FRAX tool are briefly reviewed, and the advantages, potential limitations and possible future developments are discussed.
Prevalence of type 2 diabetes mellitus in patients with primary hyperparathyroidism.

INTRODUCTION To determine the prevalence of type 2 diabetes mellitus (DM) in patients with primary hyperparathyroidism. METHODS Prevalence of type 2 DM in 609 patients with surgically verified primary hyperparathyroidism presenting between 1992 and 2003 in a tertiary care hospital setting was assessed retrospectively and compared with published data of type 2 DM prevalence in Michigan's general population. Diagnosis of type 2 DM was made on the basis of documentation in the medical record of fasting or random blood glucose level thresholds according to the 1997 American Diabetes Association criteria, history of diabetes mellitus, or therapy with antidiabetic medications. RESULTS The crude prevalence rate of type 2 DM in patients with primary hyperparathyroidism was significantly higher than the prevalence in the Michigan general population (15.9% vs 7.8%, respectively; P<.001). However, this difference was not significant after age stratification except for the age group of 64 to 75 years. Because of the differential distribution of participants across age categories in the 2 groups, a standardized prevalence ratio (SPR) was estimated to account for the variance. After adjustment, there was no significant difference in the prevalence of DM between patients with primary hyperparathyroidism and the control population (SPR, 1.19 [95% confidence interval, 0.96-1.45]) except in men. CONCLUSION The reported higher prevalence of type 2 DM in patients with primary hyperparathyroidism could not be confirmed in this large cohort of patients except for in older patients and in men. Because of the retrospective nature the study and the lack of appropriate controls, further studies are needed to confirm or refute these findings.
Most probable number quantification of hypophosphite and phosphite oxidizing bacteria in natural aquatic and terrestrial environments.

Concentrations of hypophosphite and phosphite oxidizing bacteria were found to be high, relative to bacterial concentrations growing on phosphate, in sediment and soil during winter and summer seasons from 12 common terrestrial and aquatic sites using a most probable number method. The percent of total culturable bacterial concentrations that could use these reduced phosphorus compounds as a sole source of phosphorus were as follows: hypophosphite, 7–100%; phosphite, 10–67%; aminoethylphosphonate, 34–270%. The average MPN/g (±SEM) was as follows: phosphate, 6.19 × 106 (±2.40 × 106); hypophosphite, 2.61 × 106 (±1.35 × 106) phosphite, 1.91 × 106 (±1.02 × 106); aminoethylphosphonate, 3.90 × 106 (± 1.95 × 106). Relatively high concentrations of reduced phosphorus oxidizing bacteria were found in both pristine sites and sites with urban and agricultural disturbance. Concentrations of reduced phosphorus oxidizing bacteria in anoxic sediments and soil were equivalent. Our data indicate that reduced phosphorus oxidizing bacteria are abundant in the environment and provide strong evidence for the importance of bacterial P oxidation in nature.
A long life after exploitation and exploration

Purpose – The purpose of this paper is to investigate the longevity implications of exploitation and exploration. It examines the main effect of exploitation, the main effect of exploration, and the interaction effect of exploitation and exploration on organizational longevity. Design/methodology/approach – This study employs Cox Proportional Hazard Model in analyzing 20-year data from the hard disk drive industry. Findings – Exploitation, independent of exploration, has a positive impact on organizational longevity. Exploration, independent of exploitation, has a curvilinear impact on organizational longevity. Jointly, exploitation weakens the curvilinear relationship between exploration and organizational longevity. Research limitations/implications – This study challenges the dualistic view that exploitation is for “current viability” and exploration is for “future viability.” It suggests that firms need to actively engage in (instead of compromise) both exploitation and exploration in order to prolong...
Some unusual properties of the nucleic acid in bacteriophages S13 and phi X174.

Abstract Phages ∅X174 (and S13), labeled with P 32 , are inactivated by decay of their incorporated radioactive atoms with approximately 100% efficiency, even at −196° C (assuming the DNA content of ∅X174 to be as determined by Sinsheimer). The high sensitivity to P 32 decay suggests an unusual structure and function of the DNA in these phages. One possibility is a single-stranded DNA. The efficiency of inactivation of ∅X174 is measured at temperatures up to 37°. The rate of death of the phage at the elevated temperatures is too great to be entirely due to decay of the incorporated P 32 atoms. This suggests a technical difficulty in studying the effects of temperature on the lethality of phage-incorporated P 32 atoms. The resemblance of S13 and ∅X174 to some plant and animal viruses is discussed.
Magnetic order in three rare-earth elpasolite compounds Cs2NaRCl6.

The apparently undistorted fcc rare-earth salts ${\mathrm{Cs}}_{2}$${\mathrm{NaDyCl}}_{6}$ and ${\mathrm{Cs}}_{2}$${\mathrm{NaErCl}}_{6}$ display susceptibilities characteristic of dipolar ferromagnetism in the ordered state. This agrees with the predictions of both classical and quantum-mechanical spin-wave theories. We do not observe a predicted quantum-mechanical anisotropy due to zero-point motion of the spins. ${\mathrm{Cs}}_{2}$${\mathrm{NaGdCl}}_{6}$ behaves in a manner consistent with a slight tetragonal distortion of its lattice, with a crystal containing many tetragonal domains oriented randomly along the fourfold axes of the cubic phase, and exhibiting anisotropic dipolar ferromagnetic order.
Efficient algorithms for sequence assembly

Sequencing genomes is one of the most fundamental problems in modern biology and has immense impact on biomedical research. De novo sequencing is computationally more challenging when compared to sequencing with a reference genome. Repeats, for instance, make genome assembly extremely difficult. Locations of reads shorter than the repeat length cannot be resolved uniquely. On the other hand the existing sequencing technology is not mature enough to identify/read the entire sequence of the genome - especially for complex organisms like mammals. However small fragments of the genome can be read with acceptable accuracy. The shotgun sequencing employed in many sequencing projects breaks the genome randomly at many places and generates a large number of small fragments (called reads) of the genome. The problem of reassembling all the fragmented reads into a sequence close to the original sequence is known as the Sequence Assembly (SA) problem. Sequence assembly is complex for various reasons including short reads, errors in sequencing, the presence of repeats, etc. In this talk we survey some of the algorithms (specifically [1, 2, 3]) that have been proposed for SA. Both de Bruijn and overlap graph based algorithms will be discussed. We also summarize a recent algorithm we have come up with for the problem of scaffolding.problem.
Non-viral endostatin plasmid transfection of mesenchymal stem cells via collagen scaffolds

Angiogenesis is critical in the early stage of reparative processes and tissue regeneration, but the persistence of a vascular network may interfere with later transformation/maturation in naturally avascular tissues such as articular cartilage. Our supposition is that the timed delivery of an anti-angiogenic factor in cartilage tissue engineering may facilitate the formation of hyaline cartilage by inducing the regression of vascularization. To this end our overall goal is to prepare an off-the-shelf scaffold containing the gene for a potent anti-angiogenic factor. The objective of this study was to investigate the use of a type I/III collagen scaffold for the non-viral transfection of marrow stromal cells (MSCs, also referred to as mesenchymal stem cells) with the plasmid encoding endostatin. Caprine MSCs were transfected by the naked plasmid alone and plasmid incorporated into a cationic lipid complex in three experiments: 1) cells were transfected in monolayer; 2) monolayer-transfected cells were grown in a collagen sponge-like scaffold; and 3) non-transfected cells were grown in a collagen scaffold containing the naked plasmid and endostatin lipoplex. Independent variables were the passage number of the cells and the plasmid loading. The amount of endostatin released by the cells into the medium was measured using an ELISA. The results demonstrated the overexpression of endostatin by MSCs growing in the endostatin lipoplex-supplemented collagen scaffolds. Endostatin released by the cell-seeded scaffolds reached a peak of 13 ng/ml for scaffolds incorporating as little as 20 μg of plasmid, at the 3-day collection period ending 5 days post-seeding. The accumulated endostatin synthesis over a 2-week period began to achieve what may be a therapeutic level. MSCs transfected with the endostatin gene in monolayer continued to express the gene when grown in the collagen scaffolds. The results demonstrate the promise of the non-viral delivery of the gene for this potent anti-angiogenic protein to MSCs via a collagen scaffold.
Summing one-loop graphs at multiparticle threshold

It is shown that the technique recently suggested by Brown for summing the tree graphs at threshold can be extended to calculate the loop effects. An explicit result is derived for the sum of one-loop graphs for the amplitude of threshold production of $n$ on-mass-shell particles by one virtual particle in the unbroken $\ensuremath{\lambda}{\ensuremath{\varphi}}^{4}$ theory. It is also found that the tree-level amplitude of production of $n$ particles by two incoming on-mass-shell particles vanishes at the threshold for $ng4$.
T-cell regulation of renal immune responses.

Advances in basic immunology have markedly enhanced our understanding of immune-mediated renal disease, particularly in view of the growing recognition of the importance of T-cells in mediating renal injury. Recent milestones in investigative technology, including cell-culture techniques supporting T-cell clones and renal-derived cell populations, and genetic inbreeding of both recombinant and transgenic mice, provide a unique opportunity to study specific mechanisms of cell-mediated responses that target the kidney. In the past year the role of major histocompatibility complex molecule expression and T-cell repertoire selection has been better defined in some models of autoimmune renal disease. In addition, new observations regarding mechanisms that down regulate injurious T-cell-mediated responses may direct further studies that develop new therapeutic modalities.
Support Vector Machine (SVM) pattern recognition to AVO classification

[1] The purpose of this paper is to present a learning algorithm to classify data with nonlinear characteristics. The Support Vector Machine (SVM) is a novel type of learning machine based on statistical learning theory [Vapnik, 1998]. The support vector machine (SVM) implements the following idea: It maps the input vector X into a high-dimensional feature space Z through some nonlinear mapping, chosen a priori. In this space, an optimal separating hyperplane is constructed to separate data groupings. The support vector machine (SVM) learning method can be used to classify seismic data patterns for exploration and reservoir characterization applications. The SVM is particularly good at classifying data with nonlinear characteristics. As an example the SVM method is applied to AVO classification of gas sand and wet sand.