bluuebunny/crossref_metadata_2025 huggingface dataset:
PRIVACY, THE INDIVIDUAL AND GENETIC INFORMATION: A BUDDHIST PERSPECTIVE
Authors: HONGLADAROM SORAJ
Published: April 2009

Bioinformatics is a new field of study whose ethical implications involve a combination of bioethics, computer ethics and information ethics. This paper is an attempt to view some of these implications from the perspective of Buddhism. Privacy is a central concern in both computer/information ethics and bioethics, and with information technology being increasingly utilized to process biological and genetic data, the issue has become even more pronounced. Traditionally, privacy presupposes the individual self but as Buddhism does away with the ultimate conception of an individual self, it has to find a way to analyse and justify privacy that does not presuppose such a self. It does this through a pragmatic conception that does not depend on a positing of the substantial self, which is then found to be unnecessary for an effective protection of privacy. As it may be possible one day to link genetic data to individuals, the Buddhist conception perhaps offers a more flexible approach, as what is considered to be integral to an individual person is not fixed in objectivity but depends on convention.
641. ROSA LONGICUSPIS
Authors: Rix Martyn
Published: April 2009

The climbing rose, Rosa longicuspis Bertol. is described and illustrated and its distribution and ecology are outlined. The status of Rosa sinowilsonii Hemsl. is discussed.
645. PAULOWNIA KAWAKAMII
Authors: Kirkham Tony , Fay Michael F.
Published: April 2009

Paulownia kawakamii Ito (Paulowniaceae) is illustrated and described. Its habitat in the wild and conservation status in Taiwan are covered. The relationship of the family Paulowniaceae to the Scrophulariaceae sensu lato is discussed.
A Novel Application of a Bivariate Regression Model for Binary and Continuous Outcomes to Studies of Fetal Toxicity
Authors: Najita Julie S. , Li Yi , Catalano Paul J.
Published: April 2009

Public health concerns over the occurrence of birth defects and developmental abnormalities that may occur as a result of prenatal exposure to drugs, chemicals and other environmental factors has led to an increasing number of developmental toxicity studies. Because fetal pups are commonly evaluated for multiple outcomes, data analysis frequently involves a joint modelling approach. We focus on modelling clustered binary and continuous outcomes in the setting where both outcomes are potentially observable in all offspring but, owing to practical limitations, the continuous outcome is only observed in a subset of offspring. The subset is not a simple random sample but is selected by the experimenter under a prespecified probability model. Although joint models for binary and continuous outcomes have been developed when both outcomes are available for every fetus, many existing approaches are not directly applicable when the continuous outcome is not observed in a simple random sample. We adapt a likelihood-based approach for jointly modelling clustered binary and continuous outcomes when the continuous response is missing by design and missingness depends on the binary trait. The approach takes into account the probability that a fetus is selected in the subset. Through the use of a partial likelihood, valid estimates can be obtained by a simple modification to the partial likelihood score. Data involving the herbicide 2,4,5-trichlorophenoxyacetic-acid are analysed. Simulation results confirm the approach.
MONEY, CREDIT, AND BUSINESS CYCLE COMOVEMENT
Authors: Jin Yi , Zeng Zhixiong
Published: April 2009

Abstract.  We developed a two‐sector general equilibrium model with money and credit to study cross‐sector comovement over the business cycle. Through a working capital channel, both money and productivity shocks can generate procyclicality of sectoral activities and positive cross‐sector correlations of output, employment and investment. In our model, firms in each sector borrow in the credit market to finance their purchase of labour inputs, part of which are used in the adjustment process of capital stock. The shocks affect sectoral employment and investment through their impacts on interest rates and external finance premia.
IMPROVING FORECAST ACCURACY BY COMBINING RECURSIVE AND ROLLING FORECASTS*
Authors: Clark Todd E. , McCracken Michael W.
Published: April 2009

This article presents analytical, Monte Carlo, and empirical evidence on combining recursive and rolling forecasts when linear predictive models are subject to structural change. Using a characterization of the bias–variance trade‐off faced when choosing between either the recursive and rolling schemes or a scalar convex combination of the two, we derive optimal observation windows and combining weights designed to minimize mean square forecast error. Monte Carlo experiments and several empirical examples indicate that combination can often provide improvements in forecast accuracy relative to forecasts made using the recursive scheme or the rolling scheme with a fixed window width.
SHAREHOLDERS' UNANIMITY WITH INCOMPLETE MARKETS*
Authors: Carceles‐Poveda Eva , Coen‐Pirani Daniele
Published: April 2009

When markets are incomplete, shareholders typically disagree on the firm's optimal investment plan. This article studies the shareholders' preferences with respect to the firm's investment in a model with aggregate risk, incomplete markets and heterogeneous households who trade in firms' shares instead of directly accumulating physical capital. If the production function exhibits constant returns to scale and borrowing limits are not binding, a firm's shareholders unanimously agree on its optimal level of investment. In contrast, with binding borrowing constraints, constrained shareholders prefer a higher level of investment than unconstrained ones.
Increased visual cortex glucose metabolism contralateral to angioma in children with Sturge—Weber syndrome
Authors: Batista Carlos E A , Juhasz C , Muzik O , Chugani D C , Chugani H T
Published: April 2009

Functional reorganization after focal brain injury can lead to altered cerebral metabolism of glucose. Sturge‐Weber syndrome (SWS) with unilateral involvement is a clinical model for evaluating the effects of early focal brain injury on brain metabolism and function. In this study, 2‐deoxy‐2[18F]fluoro‐D‐glucose (FDG) positron emission tomography (PET) was used to measure glucose metabolism in cortex and basal ganglia, both ipsilateral and contralateral to the angioma, in 17 children (eight males, nine females; age range 1y 8mo‐10y 4mo; mean 5y 7mo [SD 2y 11mo]) with unilateral SWS and epilepsy. The PET findings were compared with those of a control group of 11 age‐matched children (four males, seven females; age range 3y‐10y 8mo; mean 6y [SD 2y 10mo]) with partial epilepsy but normal magnetic resonance imaging and PET scans. In the SWS group, visual and parietal cortex showed decreased glucose metabolism on the side of the angioma (p=0.001) but increased metabolism on the contralateral side (p=0.002). In particular, glucose metabolism was very high in contralateral visual cortex of childrenwith SWS, showing severe occipital hypometabolism on the side of the angioma. Eight children with visual field defect showed increased metabolism in the contralateral visual cortex (p=0.012). These findings indicate that early, severe unilateral cortical damage in SWS may induce increased glucose metabolism in the contralateral visual cortex, probably reflecting reorganization.
Direct evidence for axonal transport defects in a novel mouse model of mutant spastin‐induced hereditary spastic paraplegia (HSP) and human HSP patients
Authors: Kasher Paul R. , De Vos Kurt J. , Wharton Stephen B. , Manser Catherine , Bennett Ellen J. , Bingley Megan , Wood Jonathan D. , Milner Roy , McDermott Christopher J. , Miller Christopher C. J. , Shaw Pamela J. , Grierson Andrew J.
Published: April 2009

Mutations in spastin are the most common cause of hereditary spastic paraplegia (HSP) but the mechanisms by which mutant spastin induces disease are not clear. Spastin functions to regulate microtubule organisation, and because of the essential role of microtubules in axonal transport, this has led to the suggestion that defects in axonal transport may underlie at least part of the disease process in HSP. However, as yet there is no direct evidence to support this notion. Here we analysed axonal transport in a novel mouse model of spastin‐induced HSP that involves a pathogenic splice site mutation, which leads to a loss of spastin protein. A mutation located within the same splice site has been previously described in HSP. Spastin mice develop gait abnormalities that correlate with phenotypes seen in HSP patients and also axonal swellings containing cytoskeletal proteins, mitochondria and the amyloid precursor protein (APP). Pathological analyses of human HSP cases caused by spastin mutations revealed the presence of similar axonal swellings. To determine whether mutant spastin influenced axonal transport we quantified transport of two cargoes, mitochondria and APP‐containing membrane bound organelles, in neurons from mutant spastin and control mice, using time‐lapse microscopy. We found that mutant spastin perturbs anterograde transport of both cargoes. In neurons with axonal swellings we found that the mitochondrial axonal transport defects were exacerbated; distal to axonal swellings both anterograde and retrograde transport were severely reduced. These results strongly support a direct role for defective axonal transport in the pathogenesis of HSP because of spastin mutation.
Normal protein composition of synapses in Ts65Dn mice: a mouse model of Down syndrome
Authors: Fernandez Fabian , Trinidad Jonathan C. , Blank Martina , Feng Dong‐Dong , Burlingame Alma L. , Garner Craig C.
Published: April 2009

Down syndrome (DS) is the most prevalent form of intellectual disability caused by the triplication of ∼230 genes on chromosome 21. Recent data in Ts65Dn mice, the foremost mouse model of DS, strongly suggest that cognitive impairment in individuals with DS is a consequence of reduced synaptic plasticity because of chronic over‐inhibition. It remains unclear however whether changes in plasticity are tied to global molecular changes at synapses, or are due to regional changes in the functional properties of synaptic circuits. One interesting framework for evaluating the activity state of the DS brain comes from in vitro studies showing that chronic pharmacological silencing of neuronal excitability orchestrates stereotyped changes in the protein composition of synaptic junctions. In the present study, we use proteomic strategies to evaluate whether synapses from the Ts65Dn cerebrum carry signatures characteristic of inactive cortical neurons. Our data reveal that synaptic junctions do not exhibit overt alterations in protein composition. Only modest changes in the levels of synaptic proteins and in their phosphorylation are observed. This suggests that subtle changes in the functional properties of specific synaptic circuits rather than large‐scale homeostatic shifts in the expression of synaptic molecules contribute to cognitive impairment in people with DS.
Health Insurance Coverage and Mortality Revisited
Authors: Kronick Richard
Published: April 2009

Objective. To improve understanding of the relationship between lack of insurance and risk of subsequent mortality.

Data Sources. Adults who reported being uninsured or privately insured in the National Health Interview Survey from 1986 to 2000 were followed prospectively for mortality from initial interview through 2002. Baseline information was obtained on 672,526 respondents, age 18–64 at the time of the interview. Follow‐up information on vital status was obtained for 643,001 (96 percent) of these respondents, with approximately 5.4 million person‐years of follow‐up.

Study Design. Relationships between insurance status and subsequent mortality are examined using Cox proportional hazard survival analysis.

Principal Findings. Adjusted for demographic, health status, and health behavior characteristics, the risk of subsequent mortality is no different for uninsured respondents than for those covered by employer‐sponsored group insurance at baseline (hazard ratio 1.03, 95 percent confidence interval [CI], 0.95–1.12). Omitting health status as a control variable increases the estimated hazard ratio to 1.10 (95 percent CI, 1.03–1.19). Also omitting smoking status and body mass index increases the hazard ratio to 1.20 (95 percent CI, 1.15–1.24). The estimated association between lack of insurance and mortality is not larger among disadvantaged subgroups; when the analysis is restricted to amenable causes of death; when the follow‐up period is shortened (to increase the likelihood of comparing the continuously insured and continuously uninsured); and does not change after people turn 65 and gain Medicare coverage.

Conclusions. The Institute of Medicine's estimate that lack of insurance leads to 18,000 excess deaths each year is almost certainly incorrect. It is not possible to draw firm causal inferences from the results of observational analyses, but there is little evidence to suggest that extending insurance coverage to all adults would have a large effect on the number of deaths in the United States.
How Bad Is Depression? Preference Score Estimates from Depressed Patients and the General Population
Authors: Pyne Jeffrey M. , Fortney John C. , Tripathi Shanti , Feeny David , Ubel Peter , Brazier John
Published: April 2009

Objective.To compare depression health state preference scores across four groups: (1) general population, (2) previous history of depression but not currently depressed, (3) less severe current depression, and (4) more severe current depression.

Data Sources.Primary data were collected from 95 general population, 163 primary care, and 83 specialty mental health subjects.

Study Design.Stratified sampling frames were used to recruit general population and patient subjects. Subjects completed cross‐sectional surveys. Key variables included rating scale and standard gamble scores assigned to depression health state descriptions developed from the Patient Health Questionnaire‐9 (PHQ‐9) and SF‐12.

Data Collection/Extraction Methods.Each subject completed an in‐person interview. Forty‐nine subjects completed test/retest reliability interviews.

Principal Findings.Depressed patient preference scores for three of six SF‐12 depression health states were significantly lower than the general population using the rating scale and two of six were significantly lower using standard gamble. Depressed patient scores for five of six PHQ‐9 depression health states were significantly lower than the general population using the rating scale and two of six were significantly lower using standard gamble.

Conclusions.Depressed patients report lower preference scores for depression health states than the general population. In effect, they perceived depression to be worse than the general public perceived it to be. Additional research is needed to examine the implications for cost‐effectiveness ratios using general population preference scores versus depressed patient preference scores.
Pericardial effusion and cardiac tamponade caused by intrapericardial granulation tissue in a dog
Authors: Parra Joshua L. , Mears Erick A. , Borde Davin J. , Levy Mark S.
Published: April 2009

Objective
–
To describe and report successful surgical management of pericardial effusion and cardiac tamponade in a dog caused by intrapericardial granulation tissue.

Case Summary
–
An 8‐month‐old, intact male, Greater Swiss Mountain Dog was referred for cardiac evaluation following 2 weeks of progressive lethargy, abdominal distention, and difficulty breathing. On the day of presentation, the dog had an episode of acute collapse. A 14‐cm multilocular pericardial cystic lesion causing collapse of the right atrial free wall and resulting in pericardial tamponade was observed on echocardiogram. After the dog subsequently experienced two acute episodes of pericardial effusion, a subtotal pericardectomy was performed and clinical signs resolved. The histopathologic diagnosis of the mass was inflammation and granulation tissue, likely caused by a resolving hematoma or abscess.

New or Unique Information Provided
–
This is the first report of intrapericardial granulation tissue as the cause of pericardial effusion and cardiac tamponade.
A tale of two cancers: Collision presentation of ovarian carcinoma and lymphoma
Authors: SINGHAL Nimit , QUILTY Simon , GEORGE Matthew , DAVY Margaret , SELVA NAYAGAM Sid
Published: April 2009

Synchronous malignancies are rare diagnostic and treatment challenges. Here we present three cases of synchronous ovarian cancer and lymphoma. Both malignancies were recognised in the same histopathology sections. This report discusses diagnosis and management dilemmas with a brief literature review. The simultaneous presentation of ovarian cancer and lymphoma has not previously been reported.
ASDIN: Banding of Hemodialysis Access to Treat Hand Ischemia or Cardiac Overload
Authors: Van Hoek Frank , Scheltinga Marc , Luirink Martin , Pasmans Huub , Beerenhout Charles
Published: April 2009

A hemodialysis access may lead to cardiac overload (CO) or hand ischemia [hemodialysis access induced distal ischemia (HAIDI). Surgical banding restricts access flow and promotes distal perfusion. Aim of the study was to investigate short‐ and long‐term clinical success of banding in these patient groups. After evaluation using a standard protocol, banding procedures (n = 19) were performed in patients (n = 17) with a hemodialysis access flow ≥2 l/minute or with refractory HAIDI. Various parameters including access flow, digital brachial index (DBI), and symptomatology of hand ischemia using a standard scoring system were determined before and after the operation. Surgical banding in CO patients (n = 9) lowered access flows by 2 l (Flowpreop 3.2 ± 0.3 l/minute vs. Flowpostop 1.2 ± 0.1 l/minute, p < 0.001). Banding in HAIDI patients (n = 10) increased DBI from 0.52 ± 0.08 to 0.65 ± 0.08 (p = 0.05), whereas ischemic symptomatology was attenuated (153 ± 33 to 42 ± 15, p < 0.02). All patients successfully continued dialysis, and immediate access occlusions (<3 months) were not observed. Access flows remained at acceptable levels after a mean follow‐up of 30 months in surviving patients (n = 11, flow: 1.0 ± 0.1 l/min). Two patients were reoperated for recurrent CO (one and 28 months postoperatively). Surgical banding monitored by measurement of flow and finger pressures is an effective short‐ and long‐term treatment modality for hemodialysis access related CO or distal ischemia.
ASDIN: An Interesting Case: Bilateral Superior Vena Cava in a Patient with End Stage Renal Disease
Authors: Orija Abiodun , Rajan James , Degenhard Anthony
Published: April 2009

A left superior vena cava, which is present in 0.5% of the population, is the result of persistence of the embryonic left anterior cardinal vein and is usually considered a normal variant. We present our experience of an incidental discovery of bilateral superior vena cava during routine evaluation of suspected intra‐fistula stenosis in a dialysis‐dependent patient with end stage renal disease. Our images were consistent with a left‐sided venous structure draining into the heart with an independent right side superior vena cava as evidenced by fluoroscopy. There was also evidence of a 60% intra‐fistula stenosis. To conclude, twin superior vena cava may be present as draining vessels independent of each other or as part of a duplicate caval drainage. While cases of persistent left superior vena cava have been associated with disturbances of cardiac impulse formation and conduction no such significant associations have been found in patients with bilateral superior vena cava. However, the variant anatomy may confound efforts during central venous catheterization as well as alter flow characteristics, such that one could postulate that the anatomy may also affect the maturation of an arteriovenous fistula.
High‐Alcohol Preferring Mice Are More Impulsive Than Low‐Alcohol Preferring Mice as Measured in the Delay Discounting Task
Authors: Oberlin B. G. , Grahame N. J.
Published: April 2009

Background: Repeated studies have shown that high impulsivity, when defined as the tendency to choose small immediate rewards over larger delayed rewards, is more prevalent in drug addicts and alcoholics when compared with nonaddicts. Assessing whether impulsivity precedes and potentially causes addiction disorders is difficult in humans because they all share a history of drug use. In this study, we address this question by testing alcohol‐naïve mice from lines showing heritable differences in alcohol intake.

Methods: Replicated selected lines of outbred high‐alcohol preferring (HAP) mice were compared to a low‐alcohol preferring (LAP) line as well as the low‐drinking progenitor line (HS/Ibg) on an adjusting amount delay discounting (DD) task. The DD task employs 2 levers to present subjects with a choice between a small, immediate and a large, delayed saccharin reward. By adjusting the quantity of the immediate reward up and down based on choice behavior, the task allows an estimate of how the subjective value of the delayed reinforcer decreases as delays increase. Latency to respond was also measured for each trial.

Results: Both HAP2 and HAP1 lines of mice were more impulsive than the LAP2 and HS/Ibg lines, respectively. Hyperbolic curve‐fitting confirmed steeper discounting in the high‐alcohol drinking lines. In addition, the high‐alcohol drinking lines demonstrated greater within‐session increases in reaction times relative to the low‐alcohol drinking lines. No other differences (consumption of saccharin, total trials completed) consistently mapped onto genetic differences in alcohol drinking.

Conclusions: Alcohol‐naïve outbred mice selected for high‐alcohol drinking were more impulsive with saccharin reinforcers than low‐alcohol drinkers. These data are consistent with results seen using inbred strain descendents of high‐alcohol drinking and low‐alcohol drinking rat lines, and suggest that impulsivity is a heritable difference that precedes alcoholism.
Risk Factors for Community‐Acquired Pneumonia in Immunocompetent Seniors
Authors: Jackson Michael L. , Nelson Jennifer C. , Jackson Lisa A.
Published: April 2009

OBJECTIVES: To identify risk factors for developing community‐acquired pneumonia (CAP) in seniors.

DESIGN: Nested case‐control study.

SETTING: Group Health, a health maintenance organization in Washington state.

PARTICIPANTS: One thousand one hundred seventy‐three immunocompetent seniors with CAP and 2,346 age‐ and sex‐matched controls, sampled during influenza seasons and pre‐influenza periods of 2000/01 and 2002/03. CAP cases were presumptively identified according to diagnosis codes assigned to outpatient and inpatient encounters and validated according to review of chest radiograph reports or medical records.

MEASUREMENTS: Medical records were used to assess body mass, the presence and severity of cardiopulmonary and other chronic diseases, and the presence of functional or cognitive impairments. Use of prescription medications and inpatient, outpatient, and home medical services were identified from administrative databases.

RESULTS: Independent predictors of CAP include the presence and severity of cardiopulmonary disease, low weight and recent weight loss, and poor functional status; 42.0% of pneumonia cases can be attributed to underlying cardiopulmonary disease.

CONCLUSION: Seniors with cardiopulmonary disease, poor functional status, low weight, or recent weight loss have a greater risk of developing CAP. Preventative efforts should be targeted toward these individuals.
Development of the Risk Appraisal Measure: A Brief Screen to Identify Risk Areas and Guide Interventions for Dementia Caregivers
Authors: Czaja Sara J. , Gitlin Laura N. , Schulz Richard , Zhang Song , Burgio Louis D. , Stevens Alan B. , Nichols Linda O. , Gallagher‐Thompson Dolores
Published: April 2009

OBJECTIVES: To develop and validate a brief screening measure for use in research, healthcare, and community settings to systematically assess well‐being and identify needed areas of support for caregivers of patients with dementia.

DESIGN: This study used data from Resources for Enhancing Alzheimer's Caregiver Health (REACH II), a multisite randomized clinical trial of a behavioral intervention designed to improve the quality of life of caregivers in multiple domains.

SETTING: REACH II.

PARTICIPANTS: Two hundred twelve Hispanic, 211 black, and 219 white family caregivers providing in‐home care to patients with dementia.

MEASUREMENT: Based on conceptual and psychometric analyses, a 16‐item measure was developed that assesses six domains linked to caregiver risk and amenable to intervention: depression, burden, self‐care and health behaviors, social support, safety, and patient problem behaviors. The reliability and validity of the instrument was evaluated with 642 dementia caregiver dyads from the REACH II program.

RESULTS: The measure was found to have acceptable internal consistency for a multidimensional scale and similar measurement properties for each of the racial and ethnic groups. Concurrent validity was also demonstrated for the measure.

CONCLUSION: The REACH Risk Appraisal Measure developed in this study shows promise as an assessment tool that can be used in research, clinical, and community settings to guide, prioritize, and target needed areas of support for caregivers of patients with dementia.
Color Difference Thresholds of Maxillofacial Skin Replications
Authors: Paravina Rade D. , Majkic Goran , Del Mar Perez Maria , Kiat‐amnuay Sudarat
Published: April 2009

Purpose: The purpose of this study was to determine perceptibility and acceptability thresholds for color differences in light and dark skin‐colored maxillofacial elastomers.

Materials and Methods: A total of 15 pairs of light specimens (mimicking white, Asian, and Hispanic skin) and 15 pairs of dark specimens (mimicking African‐American skin) were made using skin‐colored maxillofacial silicone elastomers, combined with opacifiers and pigments. Color match/mismatch and acceptable/unacceptable mismatch of each pair of specimens were visually evaluated by 45 evaluators under controlled conditions of a viewing booth. Color differences were calculated using CIELAB and CIEDE2000 formulae. After calculating the model parameters, receiver operating characteristics (ROC) curves and area under the ROC curve (AUC) were analyzed. Repeated measures ANOVA and Tukey's HSD test were used in a statistical analysis (α= 0.05)

Results: CIELAB/CIEDE2000 perceptibility and acceptability thresholds for light specimens were 1.1/0.7 and 3.0/2.1, respectively. Corresponding values for dark specimens were 1.6/1.2 and 4.4/3.1, respectively. Differences in primary specimen color and type of threshold were found to be significant (p < 0.001). Only the primary specimen color effect was found to be significant in AUC comparisons.

Conclusions: Within the limitations of this study, both main effects of threshold type (perceptibility and acceptability) and primary color (light and dark) on 50:50% color‐difference thresholds of colored maxillofacial elastomers were found significant for both color‐difference formulae used (CIELAB, CIEDE2000). In addition, significant interaction between the two main effects was found, indicating a stronger effect of skin type on acceptability than perceptibility thresholds. Primary specimen color (light vs. dark) was found to be the only significant main effect on the AUC of ROC curves constructed from logistic regression.
Effect of Incorporation of Disinfectant Solutions on Setting Time, Linear Dimensional Stability, and Detail Reproduction in Dental Stone Casts
Authors: Lucas Matheus Guilherme , Arioli‐Filho João Neudenir , Nogueira Sergio Sualdini , Batista André Ulisses Dantas , Pereira Rodrigo De Paula
Published: April 2009

Purpose: The aim of this paper was to analyze the influence of incorporation of disinfectants during the cast die stone‐setting time. Setting time, linear dimensional stability, and reproduction details on casts were measured.

Materials and Methods: Die stone type IV specimens with disinfection solutions (sodium hypochlorite 1%, glutaraldehyde 2%, chlorhexidine 2%) were incorporated in two concentrations (50%, 100%). The detail reproduction, dimensional stability, and setting time were tested in accordance with ADA recommendations.

Results: Disinfecting solutions promoted an increase in setting time compared to control; sodium hypochlorite was responsible for the highest setting time. The addition of undiluted sodium hypochlorite 1.0% led to contraction during setting, but the groups with 50% diluted sodium hypochlorite 1.0% and undiluted chlorhexidine 2.0% resulted in intermediate values compared to the other groups, thus matching the control. The others did not demonstrate any effect on expansion. For detail reproduction, it was observed that the control group presented results similar to the others, except those where sodium hypochlorite was added.

Conclusions The addition of sodium hypochlorite in both dilutions significantly altered, negatively, all the evaluated properties. But the addition of glutaraldehyde and chlorhexidine did not promote any significant alterations in the evaluated properties.
Retrospective analysis of autologous blood use in bimaxillary repositioning osteotomy surgery: a quality improvement study
Authors: Böttger Sebastian , Streckbein Philipp , Hartmann Bernd , Schaaf Heidrun , Howaldt Hans Peter , Junger Axel
Published: April 2009

BACKGROUND: Multiple studies have considered the necessity of preoperative autologous blood donation before bimaxillary orthognathic osteotomies. In the context of a quality improvement project, this topic was also investigated in our institution. Furthermore, the transfusion practice was analyzed and the correlations between patient, operative variables, and blood loss were studied.

STUDY DESIGN AND METHODS: In accordance with the recommendations of the Federal Medical Association and the Federal Ministry for Health and Social Security, a transfusion demand list was compiled using data of 82 patients who underwent bimaxillary orthognathic surgery between 1997 and 2005. The maximum blood loss tolerable without transfusion (MBL) was calculated for each patient on the basis of sex, weight, height, and preoperative hematocrit (Hct). This was compared with the actual transfusion and blood loss data.

RESULTS: An autologous blood donation was carried out in 65 of 82 patients (79.3%). Sixty‐two of 65 autologous blood donors (95.4%) and 2 of 17 patients (11.8%) without autologous blood donation received transfusion. The actual blood loss did not exceed the calculated MBL in 48 of the 82 cases. Nevertheless, 31 of these 48 patients (64.6%) received transfusions. For patients with a low calculated MBL, only a trend to a higher transfusion rate was observed, although the actual blood loss in these cases more often exceeded the individually calculated MBL (p < 0.01). In addition, transfusion triggers (Hct ≤0.22 or hemoglobin ≤7.5 g/dL) were also more often seen in cases with low calculated MBL (p < 0.05).

CONCLUSIONS: In this study, an inappropriate transfusion practice in patients undergoing bimaxillary orthognathic osteotomies after preoperative autologous blood donation was detected. Calculation of the individual MBL should be used to help identify patients at high risk for transfusion and guide adequate methods to decrease the need of homologous blood.
Immunophenotypical, morphologic, and functional characterization of maturation‐associated plasmacytoid dendritic cell subsets in normal adult human bone marrow
Authors: Martín‐Martín Lourdes , Almeida Julia , Hernández‐Campo Pilar María , Sánchez María Luz , Lécrevisse Quentin , Orfao Alberto
Published: April 2009

BACKGROUND: Information about maturation of plasmacytoid dendritic cell precursors (pre‐pDCs) in normal bone marrow (BM) remains limited.

STUDY DESIGN AND METHODS: Immunophenotypical, morphologic, and functional changes associated with maturation of pre‐pDCs were analyzed in adult normal human BM (n = 45).

RESULTS: Three pre‐pDC maturation stages, with an increasingly higher degree of maturity, were systematically identified: CD34++/HLA‐DR++/+++/CD123++/CD45+/++ (Stage I), CD34+/HLA‐DR+/++/CD123++/+++/CD45+/++ (Stage II), and CD34−/HLA‐DR++/CD123++/+++/CD45++ (Stage III) cells. Lymphoid‐ and early myeloid‐associated molecules, as well as CD86, were coexpressed in Stage I pre‐pDCs, being down regulated afterward. CD304 and CD85j appeared in Stage I, progressively increasing their levels thereafter. Interestingly, cutaneous lymphocyte‐associated antigen was heterogeneously expressed throughout the maturation, particularly in Stage I pre‐pDCs. The morphologic appearance of Stage I pre‐pDCs was consistent with their undifferentiated stage, while Stage II/III cells showed morphologic features of more differentiated cells. From the functional point of view, only Stage II and Stage III pre‐pDCs were capable of inducing allogeneic T‐cell proliferation, the later subset also showing interferon‐γ secretion; in contrast, Stage I pre‐pDCs showed the highest endocytic ability.

CONCLUSION: In summary, three maturation stages of pre‐pDCs can be identified in adult normal BM, which show unique phenotypical, morphologic, and functional characteristics; these results provide a frame of reference for a better understanding of pDC malignancies.
Long‐term cryopreservation of autologous stem cell grafts: a clinical and experimental study of hematopoietic and immunocompetent cells
Authors: Liseth Knut , Ersvær Elisabeth , Abrahamsen Jenny Foss , Nesthus Ingerid , Ryningen Anita , Bruserud Øystein
Published: April 2009

BACKGROUND: Autologous stem cell transplantation (ASCT) is used in the treatment of several malignancies. Harvesting sufficient peripheral blood progenitor cells (PBPCs) for a potential second autotransplantation at the time of relapse several years after diagnosis is becoming an increasingly common practice.

STUDY DESIGN AND METHODS: Cryopreserved PBPCs were prepared with different concentrations of dimethyl sulfoxide (DMSO; 2, 4, 5, and 10%) and stored for at least 5 years before the recovery of CD34+ cells and various T‐ and natural killer (NK)‐cell subsets were analyzed by flow cytometry. Furthermore, clinical variables for myeloma patients having a second autotransplantation with long‐term‐stored autografts were evaluated.

RESULTS: The number of viable CD34+ cells in long‐term‐stored grafts was higher when autografts were cryopreserved with 4 or 5% than with 2 and 10% DMSO. The number of viable CD34+ cells was reduced by 13.9% after 5 years of cryostorage in 5% DMSO. Lymphocyte viability was also higher with 4 or 5% DMSO. However, the frequencies of several T‐cell subsets showed DMSO‐dependent differences, whereas NK‐cell subsets did not. Furthermore, after a second autotransplantation with long‐term‐stored PBPC grafts at the time of myeloma relapse (median storage time, 42 months) all 17 patients reached neutrophil counts exceeding 0.5 × 109/L and platelet counts exceeding 20 × 109/L within 15 days. There was no difference in engraftment between patients receiving autografts preserved with 5 and 10% DMSO.

CONCLUSION: PBPC autografts can safely be stored for at least 5 years in 5% DMSO and used for ASCT.
The Correlation Structure of Unexpected Returns in U.S. Equities
Authors: Balyeat R. Brian , Muthuswamy Jayaram
Published: April 2009

We examine the correlations between unexpected market moves and unexpected equity portfolio moves conditional on market performance. We derive unexpected returns from a two‐stage regime switching model. The model allows for time‐varying expected returns where the market portfolio alone dictates the regime switching process. Portfolios exhibit a natural hedge where correlations during extreme unexpected market downturns are generally negative. During unexpected market upswings, correlations increase. Using the unconditional analysis would lead to overhedging during market downturns and underhedging during market upswings. The adjustments to the unconditional hedging strategy conditional on extreme market movements frequently exceed ±10%.
Continuing Medical Education Program in Journal of Cardiovascular Electrophysiology
Authors: HAMMILL STEPHEN C. , SOEJIMA KYOKO , YADA HIROTAKA
Published: April 2009

Article Title:  The Work‐Up and Management of Patients with Apparent or Subclinical Cardiac Sarcoidosis: With Emphasis on the Associated Heart Rhythm Abnormalities.
NF‐κB regulation: the nuclear response
Authors: Mankan Arun K. , Lawless Matthew W. , Gray Steven G. , Kelleher Dermot , McManus Ross
Published: April 2009

Introduction

Activation of NF‐κB

Regulators of NF‐κB activation

Nuclear regulation of NF‐κB

B cell lymphoma 3 (Bcl‐3)

Post‐translational modification of NF‐κB complex in the nucleus

Phosphorylation

Nuclear regulators of NF‐κB: potential molecular chaperones

Conclusion

Nuclear factor κB (NF‐κB) is an inducible transcription factor that tightly regulates the expression of a large cohort of genes. As a key component of the cellular machinery NF‐κB is involved in a wide range of biological processes including innate and adaptive immunity, inflammation, cellular stress responses, cell adhesion, apoptosis and proliferation. Appropriate regulation of NF‐κB is critical for the proper function and survival of the cell. Aberrant NF‐κB activity has now been implicated in the pathogenesis of several diseases ranging from inflammatory bowel disease to autoimmune conditions such as rheumatoid arthritis. Systems governing NF‐κB activity are complex and there is an increased understanding of the importance of nuclear events in regulating NF‐κB's activities as a transcription factor. A number of novel nuclear regulators of NF‐κB such as IκB‐ζ and PDZ and LIM domain 2 (PDLIM2) have now been identified, adding another layer to the mechanics of NF‐κB regulation. Further insight into the functions of these molecules raises the prospect for better understanding and rational design of therapeutics for several important diseases.
Metabolic modulation and cellular therapy of cardiac dysfunction and failure
Authors: Revenco Diana , Morgan James P.
Published: April 2009

Introduction

Metabolic modulation

Medications that influence metabolism in heart failure (Table 2)

Cell therapy

Mechanisms of stem cell mediated myocardial regeneration

Clinical applications of stem cells

Potential metabolic modulators in heart failure

(1) Long‐chain 3‐ketoacyl coenzyme A thiolase inhibitor

 Trimetazidine

(2) CPT I inhibitors

 Perhexiline

 Etomoxir

 Oxfenicin

(3) PPAR‐γ activators

 Rosiglitazone

 Pioglitazone

At present the prevalence of heart failure rises along with aging of the population. Current heart failure therapeutic options are directed towards disease prevention via neurohormonal antagonism (β‐blockers, angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers and aldosterone antagonists), symptomatic treatment with diuretics and digitalis and use of biventricular pacing and defibrillators in a special subset of patients. Despite these therapies and device interventions heart failure remains a progressive disease with high mortality and morbidity rates. The number of patients who survive to develop advanced heart failure is increasing. These patients require new therapeutic strategies. In this review two of emerging therapies in the treatment of heart failure are discussed: metabolic modulation and cellular therapy. Metabolic modulation aims to optimize the myocardial energy utilization via shifting the substrate utilization from free fatty acids to glucose. Cellular therapy on the other hand has the goal to achieve true cardiac regeneration. We review the experimental data that support these strategies as well as the available pharmacological agents for metabolic modulation and clinical application of cellular therapy.
Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasures
Authors: RÖLLE ALEXANDER , OLWEUS JOHANNA
Published: April 2009

Human cytomegalovirus (HCMV) is a β‐herpesvirus that infects the majority of the population during early childhood and thereafter establishes life‐long latency. Primary infection as well as spontaneous reactivation usually remains asymptomatic in healthy hosts but can, in the context of systemic immunosuppression, result in substantial morbidity and mortality. HCMV counteracts the host immune response by interfering with the recognition of infected cells. A growing body of literature has also suggested that the virus evades the immune system by paralyzing the initiators of antiviral immune responses – the dendritic cells (DCs). In the current review, we discuss the effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate and adaptive immune responses. The impact of HCMV on DCs has mainly been investigated using monocyte‐derived DCs, which are rendered functionally impaired by infection. In mouse models, DCs are targets of viral evasion as well, but the complex cross‐talk between DCs and natural killer cells has, however, demonstrated an instrumental role for DCs in the control and clearance of viral infection. Fewer studies address the role of peripheral blood DC subsets, plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs, rather than being paralyzed by HCMV, are largely resistant to infection, mount a vigorous first‐line defense and induce T‐cell responses to the virus. This possibly provides a partial explanation for an intriguing conundrum: the highly efficient control of viral infection and reactivation in immunocompetent hosts in spite of multi‐layered viral evasion mechanisms.
The hepatitis C virus enigma
Authors: MYRMEL HELGE , ULVESTAD ELLING , ÅSJØ BIRGITTA
Published: April 2009

Hepatitis C virus (HCV) has a high propensity to establish chronic infection with end‐stage liver disease. The high turnover of virus particles and high transcription error rates due to lack of proof‐reading function of the viral polymerase imply that HCV exists as quasispecies, thus enabling the virus to evade the host immune response. Clearance of the virus is characterized by a multispecific, vigorous and persistent T‐cell response, whereas T‐cell responses are weak, narrow and transient in patients who develop chronic infection. At present, standard treatment is a combination of pegylated interferon‐α and ribavirin, with a sustained viral response rate of 40–80%, depending on genotype. The mechanisms for the observed synergistic effects of the two drugs are still not known in detail, but in addition to direct antiviral mechanisms, the immunomodulatory effects of both drugs seem to be important, with a shift from Th2‐ to Th1‐cytokine profiles in successfully treated patients. This article describes virus–host relations in the natural course of HCV infection and during treatment.
The role of costimulation in antibody deficiencies: ICOS and common variable immunodeficiency
Authors: Yong Patrick F. K. , Salzer Ulrich , Grimbacher Bodo
Published: April 2009

Summary:  The identification of mutations in the inducible costimulator (ICOS) gene in nine patients with common variable immunodeficiency (CVID) was a major breakthrough. CVID is a complex, highly heterogeneous primary immunodeficiency disease, and the discovery of these mutations revealed a molecular basis. ICOS belongs to the CD28 family of costimulatory molecules and is expressed exclusively on activated T cells. It has at least three critical functions: germinal center formation, isotype class switching, and the development of memory B cells. The discovery of human ICOS deficiency showed that a monogenic disorder could account for the full spectrum of manifestations seen in childhood and adulthood‐onset CVID, including autoimmune, inflammatory, and malignant disease complications, as well as recurrent infections. Moreover, this discovery showed that a disorder which had previously been perceived as a B‐cell disease might in fact have its genetic origin in human T cells. In this article, we review the role of ICOS in the mammalian immune system and human disease, as well as the discovery and characteristics of patients with ICOS deficiency. Finally, we also discuss how these ‘human knockouts’ have contributed to our understanding of ICOS functions and have suggested potential avenues for using therapeutic ICOS manipulation to treat other diseases.
PD‐1 signaling in primary T cells
Authors: Riley James L.
Published: April 2009

Summary:  Programmed death‐1 (PD‐1) is a cell surface molecule that regulates the adaptive immune response. Engagement of PD‐1 by its ligands PD‐L1 or PD‐L2 transduces a signal that inhibits T‐cell proliferation, cytokine production, and cytolytic function. While a great deal is known concerning the biologic roles PD‐1 plays in regulating the primary immune response and in T‐cell exhaustion, comparatively little is known regarding how PD‐1 ligation alters signaling pathways. PD‐1 ligation is known to inhibit membrane‐proximal T‐cell signaling events, while ligation of the related inhibitory molecule cytotoxic T‐lymphocyte antigen‐4 appears to target more downstream signaling pathways. A major obstacle to an in‐depth understanding of PD‐1 signaling is the lack of physiologic models in which to study signal transduction. This review focuses on: (i) signaling pathways altered by PD‐1 ligation, (ii) factors recruited upon PD‐1 phosphorylation, and (iii) exploring the hypothesis that PD‐1 ligation induces distinct signals during various stages of immune‐cell differentiation. Lastly, we describe models to dissect the function of the PD‐1 cytoplasmic tail using primary cells in the absence of agonist antibodies.
The costimulatory role of TIM molecules
Authors: Rodriguez‐Manzanet Roselynn , DeKruyff Rosemarie , Kuchroo Vijay K. , Umetsu Dale T.
Published: April 2009

Summary:  The T‐cell immunoglobulin domain and mucin domain (TIM) family, including TIM‐1, TIM‐2, TIM‐3, and TIM‐4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T‐cell activation, induction of T‐cell apoptosis and T‐cell tolerance, and the clearance of apoptotic cells. TIM‐1 costimulates T‐cell activation and enhances cytokine production. In humans, TIM‐1 also serves as a susceptibility gene for allergy and asthma. TIM‐3, expressed on T cells and dendritic cells, regulates T‐cell apoptosis and immune tolerance. By contrast, TIM‐4, which is expressed primarily on antigen‐presenting cells and which is a receptor for phosphatidylserine, regulates T‐cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.