bluuebunny/crossref_metadata_2025 huggingface dataset:
A Double‐Blind, Placebo‐Controlled Trial of Magnesium Sulfate in the Ethanol Withdrawal Syndrome
Authors: Wilson Allan , Vulcano Brent
Published: February 2008

One hundred alcoholics treated for ethanol withdrawal were assigned randomly according to a double‐blind protocol to receive four intramuscular injections of 2 g of magnesium sulfate at 6‐hr intervals or an equivalent amount of normal saline. All patients were treated for signs of withdrawal according to a standardized protocol using orally‐administered chlordiazepoxide for sedation. Three observers rated each patient for signs of withdrawal. There was no statistically significant difference between magnesium sulfate and placebo groups on any of the variables measured. The groups required equivalent amounts of chlordiazepoxide for control of withdrawal. The authors concluded that the routine administration of magnesium sulfate is not indicated for the management of alcohol withdrawal unless accompanied by cardiac arrhythmias.
Long Term Outcome in Working and Homemaking Alcoholic Women
Authors: Herr Barbara M. , Pettinati Helen M.
Published: February 2008

Retrospective and outcome data were examined for 48 homemaking and 24 working women who came for treatment for alcoholism to an Addiction Recovery Unit at an inpatient psychiatric hospital. Outcome was assessed at the end of each of 4 years following treatment via personal interview by an experienced social worker and was corroborated by at least one source. At admission, the homemakers had been drinking for significantly more years (p < 0.05) than working women. Occupation at admission did not directly relate to outcome. However, for a small subgroup comprised of both homemaking and working women, a change in occupation following treatment was associated with improvement.
Effect of Severe Alcoholic Liver Disease on the Disposition of Methadone in Maintenance Patients
Authors: Novick David M. , Kreek Mary Jeanne , Ams Patricia A. , Lau Lisa L. , Yancovitz Stanley R. , Gelb Alvin M.
Published: February 2008

We studied methadone disposition in 11 maintenance patients with alcoholic liver disease of such severity that liver biopsy was con‐traindicated. Nine methadone‐maintained patients with recent alcohol abuse but minimal or no evidence of liver disease served as controls. Most kinetic indices, including the apparent oral clearance and area under the concentration‐time curves, were similar in patients and controls. Although the apparent terminal half‐life of methadone was longer (p= 0.04) in the patients with liver disease, the peak plasma methadone level was lower (p= 0.03). None of the patients had signs or symptoms of methadone overdosage or abstinence at the time of study. Six patients and one control had flattened plasma methadone concentration‐time curves. We hypothesize that, in severe liver disease, damage to hepatic drug‐metabolizing systems is offset by damage to the capacity of the liver to store and release unchanged methadone. The usual methadone maintenance dose may be continued in stable patients with severe alcoholic cirrhosis.
Chronic Alcoholism in Males: Cognitive Deficit as a Function of Age of Onset, Age, and Duration
Authors: Pishkin Vladimir , Lovallo William R. , Bourne Lyle E.
Published: February 2008

Performance on a cognitive rule‐teaming task was studied in detoxified alcohofics having earty/late onset and short‐/long‐tenn drinking histories, and in matched nonalcoholic controls. There were pronounced cognitive deficits in earty onset and long‐term alcoholics. Impairment was severest in the earty onset group, even though they were on the average 15 years younger than the tote onset group. Earty onset alcoholics were reiativety more impaired on both the abstract and the verbal Shipley measures. This group also manifested a relative deficit in ability to show positive transfer across problems. Chronicity of alcoholism also interfered with acquisition of an abstract relationship between concrete stimulus attributes. Age negatively influenced ability to perform abstractions, but not commonly tested verbal skills. The findings suggest that an earty onset of alcoholism, regardless of duration of problem drinking, is particularly predictive of cognitive impairment
Hepatic Safety of Once‐Monthly Injectable Extended‐Release Naltrexone Administered to Actively Drinking Alcoholics
Authors: Lucey Michael R. , Silverman Bernard L. , Illeperuma Ari , O’Brien Charles P.
Published: January 2008

Background:  Hepatoxicity has been reported with oral naltrexone. Hepatic safety data were examined from a 6‐month study evaluating the efficacy and safety of a now available extended‐release formulation of naltrexone (XR‐NTX) in patients with alcohol dependence.

Methods:  In all, 624 patients (68% male; median age of 44 years) were randomly assigned to XR‐NTX 380 mg (n = 205), XR‐NTX 190 mg (n = 210), or placebo (n = 209).

Results:  There were no significant differences in alanine aminotrasferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma‐glutamyltransferase in the XR‐NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic‐related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti‐inflammatory drugs, there was no increase in frequency of high LCTs or hepatic‐related adverse events in patients receiving XR‐NTX (either dose) compared with placebo.

Conclusion:  Extended‐release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol‐dependent patients.
Diffusion Tensor Measures of the Corpus Callosum in Adolescents With Adolescent Onset Alcohol Use Disorders
Authors: De Bellis Michael D. , Van Voorhees Elizabeth , Hooper Stephen R. , Gibler Nicole , Nelson Lauren , Hege Steve G. , Payne Martha E. , MacFall James
Published: January 2008

Background:  In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent‐onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders‐IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls.

Methods:  Adolescent subjects (25 males, 7 females) with an AUD (16.9 ± 1.2 years), who were recruited from substance abuse treatment programs and had co‐morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 ± 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan.

Results:  Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD.

Conclusions:  Lower MD and higher FA values in the AUD group suggest pre‐morbid vulnerability for accelerated prefrontal and temporo‐parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.
Association of the ε2 Allele of Apoe Gene to Hypertriglyceridemia and to Early‐Onset Alcoholic Cirrhosis
Authors: Hernández‐Nazará Zamira H. , Ruiz‐Madrigal Bertha , Martínez‐López Erika , Roman Sonia , Panduro Arturo
Published: January 2008

Background:  The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis.

Methods:  In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non‐hyperlipidemic (non‐H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR‐RFLP′s.

Results:  A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein‐cholesterol (HDL‐c) was detected in young‐aged patients (31.2 ± 6.2 years old vs. 46.3 ± 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non‐H group.

Conclusions:  This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process.
The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive Immunity
Authors: Waszkiewicz Napoleon , Szajda Sławomir Dariusz , Jankowska Anna , Zwierz Piotr , Czernikiewicz Andrzej , Szulc Agata , Zwierz Krzysztof
Published: January 2008

Background: Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems.

Methods: Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6‐hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva.

Results: At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002,p = 0.043, andp = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively).

Conclusion: Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.
Chronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic Cells
Authors: Ness Kristin J. , Fan Ji , Wilke Werner W. , Coleman Ruth A. , Cook Robert T. , Schlueter Annette J.
Published: January 2008

Background:  Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration.

Methods:  Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF‐α or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration.

Results:  Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non‐EtOH‐exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH‐fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application.

Conclusions:  Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.
Repeat Purchase amid Rapid Quality Improvement: Structural Estimation of Demand for Personal Computers
Authors: Prince Jeffrey T.
Published: January 2008

This paper estimates a structural model of demand for the personal computer (PC) by repeat purchasers. Taking advantage of a large data set on household‐level PC purchases, the econometric model uses variation in PC holdings among PC owners to identify households' marginal values of quality improvements. The analysis only requires data on a cross‐section of households along with observed PC offerings over time, and accounts for stock effects, forward‐looking behavior, and large amounts of household heterogeneity. The estimates allow us to measure sensitivity to long‐term and short‐term price and technology changes, as well as consumer welfare changes from technological improvements. The results show a large variation in marginal values for PC quality across households, and that failing to account for forward‐looking behavior results in biased estimates and a poorer fit to the data. Incorporating stock effects proves especially important because, for the data used here, the model's parameters are not only biased but also virtually impossible to pin down without them. The results also show that price elasticity is approximately 25% higher in the short term compared to the long term, and technology elasticity is approximately 35% higher in the short term compared to the long term. Furthermore, welfare measurements are significantly underestimated when using a model that does not account for forward‐looking behavior. Finally, the model is extended to include first‐time purchasers. The results show similar patterns, but should be interpreted with much caution owing to the likely presence of significant unobserved heterogeneity between new purchasers and repeat purchasers.
Are Frequent‐Flyer Programs a Cause of the “Hub Premium”?
Authors: Lederman Mara
Published: January 2008

This paper estimates the relationship between frequent‐flyer programs (FFPs) and fares at hub airports. I exploit the formation of partnerships that allowed members of one airline's FFP to earn that airline's points on flights operated by its partner. If FFPs allow an airline to charge higher fares on routes that depart from its hubs, these partnerships should allow an airline's partner to charge higher fares on routes that depart from these same airports. I find that offering the FFP points of the dominant carrier at an airport does, indeed, lead to higher fares. Combining these estimates with estimates of the “hub premium” suggests that FFPs may account for at least 25% of the “hub premium.”
Are Sunk Costs a Barrier to Entry?
Authors: Cabral Luís M. B. , Ross Thomas W.
Published: January 2008

The received wisdom is that sunk costs create a barrier to entry—if entry fails, then the entrant, unable to recover sunk costs, incurs greater losses. In a strategic context where an incumbent may prey on the entrant, sunk entry costs have a countervailing effect: they may effectively commit the entrant to stay in the market. By providing the entrant with commitment power, sunk investments may soften the reactions of incumbents. The net effect may imply that entry is more profitable when sunk costs are greater.
Designing Contracts for University Spin‐offs
Authors: Macho‐Stadler InÉs , Pérez‐Castrillo David , Veugelers Reinhilde
Published: January 2008

We provide a theoretical model about how to design academic spin‐off contracts between the university technology transfer office (TTO), the researcher, and the venture capitalist. The optimal contract entails the allocation of founder shares to the researcher to secure her participation in the venture. It may also require the researcher to be financially involved in the project to give her incentives to provide effort. We also show that when the TTO has better information than the other two participants concerning the likelihood of success of the spin‐off, it will end up owning both founder and financial shares in the venture.
Short Incomplete Sagittal Fractures of the Proximal Phalanx in Ten Horses Not Used for Racing
Authors: KUEMMERLE JAN M. , AUER JÖRG A. , RADEMACHER NATHALIE , LISCHER CHRISTOPH J. , BETTSCHART‐WOLFENSBERGER REGULA , FÜRST ANTON E.
Published: January 2008

Objective—To describe short incomplete sagittal fractures of the proximal phalanx (type Ia P1 fractures) in horses not used for racing and report outcome.

Study Design—Retrospective study.

Animals—Horses (n=10) with type Ia P1 fractures.

Methods—Retrieved data of horses with type Ia P1 fractures were signalment, history and results of orthopedic examination. Radiographs were re‐evaluated for position and length of the fracture line, presence of osteoarthritis or subchondral cystic lesions (SCL), periosteal new bone formation and subchondral sclerosis. Conservative treatment (n=4) included box confinement for 2 months followed by 1 month of hand walking. Surgical therapy (n=6) consisted of internal fixation by screws inserted in lag fashion in 5 horses. Concurrent SCL were debrided by curettage via a transcortical drilling approach. In 1 horse, only SCL curettage but not internal fixation was performed. Outcome was assessed on a clinical and radiographic follow‐up examination in all horses.

Results—Mean follow‐up time was 27 months (median, 13.5 months; range, 9 months to 9 years). All horses treated with internal fixation were sound at follow‐up and had radiographic fracture healing. Of the 4 horses managed conservatively, 3 remained lame and only 1 horse had radiographic evidence of fracture healing. Catastrophic fracture propagation occurred in 2 horses not treated by internal fixation, 20 and 30 months after diagnosis, respectively.

Conclusions—Horses with a type Ia P1 fracture treated surgically had a better outcome than those managed conservatively and lack of fracture healing seemingly increases the risk of later catastrophic fracture.

Clinical Relevance—Surgical repair of type Ia P1 fractures should be considered to optimize healing and return to athletic use.
A Method for Intervertebral Space Distraction Before Stabilization Combined with Complete Ventral Slot for Treatment of Disc‐Associated Wobbler Syndrome in Dogs
Authors: SHAMIR MERAV H. , CHAI ORIT , LOEB EMMANUEL
Published: January 2008

Objective—To evaluate the use of a modified K‐wire spacer for maintaining intervertebral distraction after ventral decompression and during stabilization as a treatment for disc‐associated wobbler syndrome in large breed dogs.

Study Design—A retrospective study.

Animals—Dogs (n=7) with disc‐associated wobbler syndrome.

Methods—Medical records (2003–2006) of dogs treated by a modified surgical method were evaluated. Data retrieved were signalment, onset and duration of clinical signs, neurologic abnormalities, diagnostic methods, surgical procedure, immediate, and long‐term (≥1 year) postoperative clinical and radiographic outcome.

Results—Mean duration of clinical signs was 4.8 months. Neurologic signs included ataxia (2), ambulatory tetraparesis (2), and non‐ambulatory tetraparesis (3). Three dogs had disc protrusion in 2 sites, 2 dogs had the procedure in 1 location and stabilization of both affected sites. All dogs improved dramatically and remained for 1–3 years. One dog had recurrence of cervical discomfort 13 months later.

Conclusions—Despite the limited number of dogs, overall initial successful outcome with only 1 dog having mild recurrence 13 months later supports further use and evaluation of this technique.

Clinical Relevance—Distraction using a K‐wire spacer after ventral decompression followed by stabilization should be considered in dogs with disc‐associated wobbler syndrome to prevent collapse of the intervertebral space.
Tibial Osteotomies for Cranial Cruciate Ligament Insufficiency in Dogs
Authors: KIM STANLEY E. , POZZI ANTONIO , KOWALESKI MICHAEL P. , LEWIS DANIEL D.
Published: January 2008

Objective— To review the biomechanical considerations, experimental investigations, and clinical data pertaining to tibial osteotomy procedures for treatment of cranial cruciate ligament (CrCL) insufficiency in dogs.

Study Design— Literature review.

Methods— Literature search through Pub Med, Veterinary Information Network, Commonwealth Agricultural Bureau Abstracts, and conference proceedings abstracts (November 1977 to March 2007).

Results— Reported tibial osteotomy procedures attempt to eliminate sagittal instability (cranial tibial thrust) in CrCL‐deficient stifles by altering the conformation of the proximal tibia. Functional stability can be achieved by decreasing the tibial plateau slope (cranial tibial closing wedge osteotomy [CTWO], tibial plateau leveling osteotomy [TPLO], combined TPLO and CTWO, proximal intraarticular osteotomy, chevron wedge osteotomy), altering the alignment of the patellar tendon (tibial tuberosity advancement), or both (triple tibial osteotomy). Clinical reports assessing the efficacy of these procedures frequently use subjective outcome measures, and the periods of follow‐up evaluation are highly variable. Satisfactory results have been reported in most (>75%) dogs irrespective of the type of tibial osteotomy procedure.

Conclusions— Currently available data does not allow accurate comparisons between different tibial osteotomy procedures, or with traditional methods of stabilizing the CrCL‐deficient stifle. Carefully designed long‐term clinical studies and further biomechanical analyses are required to determine the optimal osteotomy technique, and whether these procedures are superior to other stabilization methods.

Clinical Relevance— Limb function in dogs with CrCL insufficiency can be improved using the currently described tibial osteotomy techniques.
Osteophytosis, Subchondral Bone Sclerosis, Joint Effusion and Soft Tissue Thickening in Canine Experimental Stifle Osteoarthritis: Comparison Between 1.5 T Magnetic Resonance Imaging and Computed Radiography
Authors: D'ANJOU MARC‐ANDRÉ , MOREAU MAXIM , TRONCY ÉRIC , MARTEL‐PELLETIER JOHANNE , ABRAM FRANÇOIS , RAYNAULD JEAN‐PIERRE , PELLETIER JEAN‐PIERRE
Published: January 2008

Objective— To compare use of 1.5 T magnetic resonance imaging (MRI) and computed radiography (CR) for morphologic and temporal evaluation of osteophytosis, subchondral sclerosis, joint effusion, and synovial thickening in experimentally induced canine stifle osteoarthritis (OA).

Study Design— Prospective study.

Animals— Dogs (n=8).

Methods— CR (mediolateral and caudocranial projections) and MRI (dorsal 3D T1‐weighted gradient echo, sagittal 3D SPGR and T2‐weighted fast spin echo with fat saturation) were performed at baseline (n=8) and at week 4 (n=5), week 8 (n=8), and week 26 (n=5) after cranial cruciate ligament transection. Osteophytosis, subchondral bone sclerosis, and joint effusion were scored on CR and MRI, and synovial thickening on MRI.

Results— MRI was more sensitive than CR for detection of osteophytosis and could better discriminate joint effusion from soft tissue thickening, although scores for these variables strongly correlated between modalities (ρ=0.94 [osteophytosis] and 0.80 [effusion]; P<.001). Scores for subchondral bone sclerosis also correlated (ρ=0.54, P<.004), although this variable may have been over interpreted on CR. Joint effusion and synovial thickening peaked at week 8, before partially regressing at week 26. Conversely, osteophytosis and sclerosis progressed semi‐linearly over 26 weeks.

Conclusion— MRI is more sensitive than radiography in assessing onset and progression of osteophytosis in canine experimental stifle OA and provides enhanced discrimination between joint effusion and synovial thickening.

Clinical Relevance— MRI is as a more powerful imaging modality that should be increasingly used in animals to assess the joint related effects of disease‐modifying OA drugs.
Creating University Spin‐Offs: A Science‐Based Design Perspective*
Authors: Van Burg Elco , Romme A. Georges L. , Gilsing Victor A. , Reymen Isabelle M. M. J.
Published: January 2008

Academic entrepreneurship by means of university spin‐offs commercializes technological breakthroughs, which may otherwise remain unexploited. However, many universities face difficulties in creating spin‐offs. This article adopts a science‐based design approach to connect scholarly research with the pragmatics of effectively creating university spin‐offs. This approach serves to link the practice of university spin‐off creation, via design principles, to the scholarly knowledge in this area. As such, science‐based design promotes the interplay between emergent and deliberate design processes. This framework is used to develop a set of design principles that are practice based as well as grounded in the existing body of research on university spin‐offs. A case‐study of spin‐off creation at a Dutch university illustrates the interplay between initial processes characterized by emergent design and the subsequent process that was more deliberate in nature. This case study also suggests there are two fundamentally different phases in building capacity for university spin‐off creation. First, an infrastructure for spin‐off creation (including a collaborative network of investors, managers and advisors) is developed that then enables support activities to individual spin‐off ventures. This study concludes that to build and increase capacity for creating spin‐offs, universities should do the following: (1) create university‐wide awareness of entrepreneurship opportunities, stimulate the development of entrepreneurial ideas, and subsequently screen entrepreneurs and ideas by programs targeted at students and academic staff; (2) support start‐up teams in composing and learning the right mix of venturing skills and knowledge by providing access to advice, coaching, and training; (3) help starters in obtaining access to resources and developing their social capital by creating a collaborative network organization of investors, managers, and advisors; (4) set clear and supportive rules and procedures that regulate the university spin‐off process, enhance fair treatment of involved parties, and separate spin‐off processes from academic research and teaching; and (5) shape a university culture that reinforces academic entrepreneurship by creating norms and exemplars that motivate entrepreneurial behavior. These and other results of this study illustrate how science‐based design can connect scholarly research to the pragmatics of actually creating spin‐offs in academic institutions.
Design‐Inspired Innovation by James Utterback, Bengt Arne Vedin, Eduardo Alvarez, Sten Ekman, Susan Walsh Sanderson, Bruce Tether, and Roberto Verganti
Authors: Feldman Laurence P.
Published: January 2008

Books reviewed in this issue:

Design‐Inspired Innovation

Designing Interactions

The Elegant Solution: Toyota's Formula for Mastering Innovation

Rainbows & Ratholes: Best Practices for Managing Successful Projects
Body Mass Index and Effectiveness of Reperfusion Strategies: Implications for the Management of Patients with ST‐Elevation Myocardial Infarction
Authors: MEHTA RAJENDRA H. , GITT ANSELM K. , JÜNGER CLAUS , ZEYMER UWE , SCHIELE RUDOLF , ZAHN RALF , SENGES JOCHEN ,   ON BEHALF OF THE MITRA‐PLUS REGISTRY
Published: January 2008

Background:

Fibrinolytic therapy has maximum dose limit in patients with ST‐elevation myocardial infarction (STEMI). Consequently, obese patients receive lower dose of fibrinolytic per kg body weight compared to lower weight patients. Whether the relatively lower dose results in lower effectiveness of fibrinolytic agents versus primary percutaneous coronary interventions (PCI) in patients with higher body mass index (BMI) is not known.

Methods:

We analyzed 7,630 STEMI patients receiving primary PCI (46%) or fibrinolysis (54%) <24 hours of symptom onset from the MITRA PLUS registry. The relative effectiveness of the 2 reperfusion strategies on in‐hospital death (adjusted with propensity scores) and bleeding were studied in 3 BMI groups: I‐BMI 20–24.9 kg/m2 (n = 2,277), II‐BMI 25–29.9 kg/m2 (n = 3,763), and III‐BMI ≥30 kg/m2 (n = 1,590).

Results:

BMI was inversely related to death, shock, stroke, and bleeding in patients treated with either reperfusion strategy. However, compared with primary PCI, fibrinolysis was associated with higher adjusted death with similar relative adjusted difference in all 3 groups (group I OR 1.69, 95% CI 1.19–2.44; group II OR 1.89, 95% CI 1.39–2.56; group III OR 1.85, 95% CI 1.08–3.22).

Conclusions:

Compared with primary PCI, fibrinolysis was associated with relatively similar higher risk of death in all 3 BMI groups. Whether the differences in death between fibrinolysis and primary PCI in the high‐BMI categories can be reduced by higher fibrinolytic doses without increasing bleeding risks needs evaluation in future studies.
Short‐Term Effects of Biocorrodible Iron Stents in Porcine Coronary Arteries
Authors: WAKSMAN RON , PAKALA RAJBABU , BAFFOUR RICHARD , SEABRON RUFUS , HELLINGA DAVID , TIO FERMIN O.
Published: January 2008

Background: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries.

Methods: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry.

Results: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas.

Conclusion: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.
Genetic Diversity of Parasitic Dinoflagellates in the Genus Amoebophrya and Its Relationship to Parasite Biology and Biogeography
Authors: KIM SUNJU , PARK MYUNG GIL , KIM KEUN‐YONG , KIM CHANG‐HOON , YIH WONHO , PARK JONG SOO , COATS D. WAYNE
Published: January 2008

ABSTRACT. We determined 18S rRNA gene sequences of Amoebophrya strains infecting the thecate dinoflagellates Alexandrium affine and Gonyaulax polygramma from Korean coastal waters and compared those data with previously reported sequences of Amoebophrya from cultures, infected cells concentrated from field samples, and environmental 18S rRNA gene sequences obtained from a variety of marine environments. Further, we used these data to examine genetic diversity in Amoebophrya strains relative to geographic origin, host phylogeny, site of infection, and host specificity. In our analyses of known dinoflagellate taxa, the 13 available Amoebophrya sequences clustered together within the dinoflagellates as three groups forming a monophyletic group with high bootstrap support (maximum likelihood, ML: 100%) or a posterior probability (PP) of 1. When the Amoebophrya sequences were analyzed along with environmental sequences associated with Marine Alveolate Group II, nine subgroups formed a monophyletic group with high bootstrap support (ML: 100%) and PP of 1. Sequences known to be from Amoebophrya spp. infecting dinoflagellate hosts were distributed in seven of those subgroups. Despite differences in host species and geographic origin (Korea, United States, and Europe), Amoebophrya strains (Group II) from Gymnodinium instriatum, A. affine, Ceratium tripos (AY208892), Prorocentrum micans, and Ceratium lineatum grouped together by all of our tree construction methods, even after adding the environmental sequences. By contrast, strains within Groups I and III divided into several lineages following inclusion of environmental sequences. While Amoebophrya strains within Group II mostly developed within the host cytoplasm, strains in Groups I and III formed infections inside the host nucleus, a trait that appeared across several of the subgroups. Host specificity varied from moderately to extremely species‐specific within groups, including Group II. Taken together, our results imply that genetic diversity in Amoebophrya strains does not always reflect parasite biology or biogeography.
Phylogenetic and Primary Sequence Characterization of Cathepsin B Cysteine Proteases from the Oxymonad Flagellate Monocercomonoides
Authors: DACKS JOEL B. , KURU TEKLU , LIAPOUNOVA NATALIA A. , GEDAMU LASHITEW
Published: January 2008

ABSTRACT. Cysteine proteases are crucial for general lysosomal function and for the pathogenic mechanisms of many protistan parasites. Cathepsin B cysteine proteases are currently defined by the presence of the “occluding loop” motif and have been best characterized from humans and their parasites. Though related to a variety of pathogenic excavate flagellates, oxymonads are themselves commensals. While studying this cell biologically aberrant protist lineage, we identified 11 different cathepsin B homologues. These were found to be expressed, at comparable levels to common house‐keeping genes, such as elongation factor 1‐α, α‐tubulin, β‐tubulin, and glyceraldehyde phosphate dehydrogenase. Primary structure examination of the cathepsin B homologues identified putative signal peptide sequences, and the pre‐, pro‐, and mature domains of the protein. However, the occluding loop motif was either partially or entirely absent. Comparative genomics, sequence alignment, and phylogenetics of cathepsin sequences from across the diversity of eukaryotes demonstrated that absence of the occluding loop is not a feature exclusive to oxymonads, but is relatively common, suggesting that the “occluding loop” should no longer be used as the defining feature of the cathepsin B subfamily. Overall, this report identifies an abundant protein family in oxymonads, and provides insight both into the evolution and classification of cathepsin B cysteine proteases.
Using Inhibitors to Investigate the Involvement of Cell Signaling in Predation by Marine Phagotrophic Protists
Authors: HARTZ AARON J. , SHERR BARRY F. , SHERR EVELYN B.
Published: January 2008

ABSTRACT. Phagotrophic protists are major consumers of microbial biomass in aquatic ecosystems. However, biochemical mechanisms underlying prey recognition and phagocytosis by protists are not well understood. We investigated the potential roles of cell signaling mechanisms in chemosensory response to prey, and in capture of prey cells, by a marine ciliate (Uronema sp.) and a heterotrophic dinoflagellate (Oxyrrhis marina). Inhibition of protein kinase signal transduction biomolecules caused a decrease in both chemosensory response and predation. Inhibition of G‐protein coupled receptor signaling pathways significantly decreased chemosensory response but had no effect on prey ingestion. Inhibitor compounds did not appear to affect general cell health, but had a targeted effect. These results support the idea that cell signaling pathways known in other eukaryotic organisms are involved in feeding behavior of free‐living protists.
Responses of the Ciliates Tetrahymena and Paramecium to Vertebrate Odorants and Tastants
Authors: RODGERS LINDSAY F. , MARKLE KAREN L. , HENNESSEY TODD M.
Published: January 2008

ABSTRACT. The ciliates Tetrahymena and Paramecium respond to strong depolarizing stimuli with Ca2+‐based action potentials, ciliary reversals, and consequent bouts of backward and forward swimming called “avoidance reactions” (ARs). We found that several representative tastants and odorants cause repetitive ARs in Tetrahymena and Paramecium at low (nM to μM) concentrations. Tetrahymena responded well to capsaicin, quinine, quinacrine, denatonium benzoate, eugenol, piperine, chloroquine, carvacrol, allyl isothiocyanate (AITC), and menthol. Chemosensory adaptation was seen with carvacrol, eugenol, quinacrine, and capsaicin. Cross‐adaptation was seen between some of these compounds, suggesting possible similarities in their chemosensory transduction or adaptation pathways. Paramecium only responded well to AITC, quinacrine, piperine, and eugenol (with the effective concentration for 50% response [EC50] values in the μM range) while chemosensory adaptation was only seen to eugenol in Paramecium, suggesting possible species differences. Tetrahymena and Paramecium may have primitive receptors that can recognize these and other compounds or some of these compounds can act independently of specific receptors.
Ingestion and Inactivation of Bacteriophages by Tetrahymena
Authors: HENNEMUTH WENDY , RHOADS LAURA S. , EICHELBERGER HENRY , WATANABE MIKI , VAN BELL KEVIN M. , KE LEI , KIM HYESUK , NGUYEN GIANG , JONAS JEREMY D. , VEITH DEREK , VAN BELL CRAIG T.
Published: January 2008

ABSTRACT. Abiotic factors are thought to be primarily responsible for the loss of bacteriophages from the environment, but ingestion of phages by heterotrophs may also play a role in their elimination. Tetrahymena thermophila has been shown to ingest and inactivate bacteriophage T4 in co‐incubation experiments. In this study, other Tetrahymena species were co‐incubated with T4 with similar results. In addition, T. thermophila was shown to inactivate phages T5 and λ in co‐incubations. Several approaches, including direct visualization by electron microscopy, demonstrated that ingestion is required for T4 inactivation. Mucocysts were shown to have no role in the ingestion of T4. When 35S‐labeled T4 were fed to T. thermophila in a pulse‐chase experiment, the degradation of two putative capsid proteins, gp23* and hoc, was observed. In addition, a polypeptide with the apparent molecular mass of 52 kDa was synthesized. This suggests that Tetrahymena can use phages as a minor nutrient source in the absence of bacteria.
Continuous Culture of Perkinsus mediterraneus, a Parasite of the European Flat Oyster Ostrea edulis, and Characterization of Its Morphology, Propagation, and Extracellular Proteins in Vitro
Authors: CASAS SANDRA M. , REECE KIMBERLY S. , LI YANLI , MOSS JESSICA A. , VILLALBA ANTONIO , LA PEYRE JEROME F.
Published: January 2008

ABSTRACT. Continuous in vitro cultures of Perkinsus mediterraneus were established from tissues of infected European flat oysters, Ostrea edulis. The parasite proliferated in protein‐free medium and divided by schizogony in vitro. Cell morphology was similar to that observed for P. mediterraneus in tissues of naturally infected O. edulis and for other Perkinsus spp. cultured in vitro. Parasite cells enlarged approximately 8‐fold when placed in alternative Ray's fluid thioglycollate medium, and stained black with Lugol's iodine solution, a response characteristic of Perkinsus spp. DNA sequences matched those determined previously for P. mediterraneus, and phylogenetic analyses on three different data sets indicated that this was a Perkinsus species with a close relationship to another recently described species, Perkinsus honshuensis. Parasite viability was high (>90%) in vitro, but the proliferation rate was low, with densities generally increasing 2‐to‐6‐fold between subcultures at 6‐wk intervals. Enzyme analysis of cell‐free culture supernatants revealed protease‐, esterase‐, glycosidase‐, lipase‐, and phosphatase‐like activities. Incubation with class‐specific protease inhibitors showed that P. mediterraneus produced serine proteases, and eight proteolytic bands with molecular weights ranging from 34 to 79 kDa were detected in the supernatants by gelatin sodium dodecylsulfate‐polyacrylamide gel electrophoresis.
Differentially Expressed Genes During Fruiting Body Development in the Aggregative Ciliate Sorogena stoianovitchae (Ciliophora: Colpodea)
Authors: SUGIMOTO HIROKI , ENDOH HIROSHI
Published: January 2008

ABSTRACT. Sorogena stoianovitchae is the only ciliate that undergoes fruiting body development. Previously, we demonstrated that the developmental process is divided into five distinct stages: aggregation, compact aggregation, secretion of a mucous matrix, stalk elongation, and completion of the fruiting body. When S. stoianovitchae is mildly starved, several hundreds of cells aggregate beneath the water surface, and the aggregate develops into an aerial fruiting body. Essential requirements for fruiting body development are high‐cell density, a light–dark cycle, and a dark period of more than 8 consecutive hours. In addition, the initial aggregation begins during the night, and light stimulation at sunrise triggers subsequent development. To elucidate the genes involved in fruiting body development, we carried out a reverse transcription‐polymerase chain reaction (RT‐PCR) in cells before and after such development. Thirty‐six sequences with stage‐specific expression patterns were cloned and partially sequenced. BLASTX search revealed that sequences with high identity for extracellular proteins (mucin, proteophosphoglycan) or membrane proteins (surface protein, TM9SF) are likely candidates for aggregation material, mucous matrix, and stalk material. Other sequences showed similarities to proteins, such as the casein kinase related to exocytosis in Paramecium, suggesting that they are involved in exocytosis signaling pathways for fruiting body development.
The right to work: Linking human rights and employment policy
Authors: MUNDLAK Guy
Published: January 2008

This article outlines various explanations for singling out the right to work from the roster of human rights, and emphasizes the dilemmas associated with regulating the labour market as a barrier to the development of the right. It compares two frameworks that address these concerns from the contrasted perspectives of human rights and employment policy — namely, the General Comment of the Committee on Economic, Social and Cultural Rights, and the European Employment Strategy. While these approaches are not natural allies, they can complement each other and construct an institutional system guided by the right to work as a superordinate norm.
Informality, the State and the social contract in Latin America: A preliminary exploration
Authors: SAAVEDRA Jaime , TOMMASI Mariano
Published: January 2008

This article sees informality in Latin America as a reflection of dysfunctional interactions between individuals and the State and of the latter's inability to perform adequately in regard to redistribution and the provision of public goods and services. This translates into low rates of social security contribution and coverage; pervasive evasion of tax, labour and business regulations; and low levels of tax collection, law enforcement and trust in the State. The challenge for these countries, the authors argue, is to build more inclusive social contracts underpinned by realistic domestic consensus, taking account of country‐specific institutional backgrounds and prevailing social norms.
Thymic epithelial cells of human patients affected by myasthenia gravis overexpress IGF‐I immunoreactivity
Authors: MARINOVA TSVETANA T. , KUERTEN STEFANIE , PETROV DANAIL B. , ANGELOV DOYCHIN N.
Published: January 2008

Accumulating evidence shows that several kinds of thymic cells express insulin‐like growth factor‐I (IGF‐I), which is known to play an important role in T cell ontogeny under both physiological and pathological conditions. Still, little is known about the mechanisms of IGF‐I involvement in the pathological transformation of the thymocyte microenvironment. The present study focuses on a comparative analysis of the IGF‐I immunoreactivity of thymic epithelial cells (EC) from human patients with hyperplasia‐associated myasthenia gravis (MG) versus physiological thymic tissue from healthy controls using immunohistochemistry and immunoelectron microscopy. We show that myasthenic EC overexpress IGF‐I in comparison to EC from control subjects. The IGF‐I immunoreactivity in the medullary and cortical EC from MG patients was stronger than in the normal gland. The increased expression of IGF‐I and more frequent distribution of IGF‐I and IGF‐I‐receptor (IGF‐IR) immunopositive EC correlated with modulation in the immunoreactivity of double (IGF‐I/IGF‐IR) positive EC. Our data provide new immunocytochemial evidence for alterations of IGF‐I and IGF‐IR immunoreactivity in EC from pathological thymi. The persisting expression of IGF‐I and IGF‐IR most likely indicates that the myasthenic thymus is still capable of governing IGF‐I signaling pathways, which are involved in the local regulation of T cell development and plasticity.