bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem Cell Therapy in Bone Repair and Regeneration
Authors: ZAIDI NEEHA , NIXON ALAN J.
Published: December 2007

Abstract:  Stem cells of various origins, particularly endothelial progenitor cells (EPCs), have potential to enhance bone repair and regeneration. EPCs are resident in the bone marrow and home to ischemic sites to initiate vasculogenesis. Although it was previously believed that only local endothelial cells arrive at ischemic sites, new evidence suggests that EPCs are recruited from the periphery. This finding has a considerable array of therapeutic implications. For example, administered EPCs can localize to sites of osteogenesis where they increase blood vessel formation; this may be useful in enhancing fracture repair.
Proteasome Inhibitors Stimulate Both Bone Formation and Hair Growth by Similar Mechanisms
Authors: MUNDY GREGORY , GUTIERREZ GLORIA , GARRETT ROSS , GALLWITZ WOLFGANG , ROSSINI GIANNI , CHRISTIANSEN CLAUS , LANGENBERG ANDRIA
Published: December 2007

Abstract:  We propose that the remodeling process that occurs in localized areas on endosteal bone surfaces and in Haversian canals shares many features in common with the mammalian hair cycle. In both, there are phases of resorption or regeneration, a transition phase, and then a phase of growth, termed anagen in the hair follicle, and formation in the bone remodeling cycle. Furthermore, we suggest that these processes both use the same molecular mechanisms, and specifically the Hedgehog–BMP–Wnt signal transduction cascades. We have found that proteasome inhibitors, which enhance bone formation by effects on these cascades, also stimulate anagen induction and hair growth in the murine and human hair follicle, and propose they do so by effects on similar or identical molecular targets.
Bisphosphonates
Authors: RUSSELL R. GRAHAM G. , XIA ZHIDAO , DUNFORD JAMES E. , OPPERMANN UDO , KWAASI AARON , HULLEY PHILIPPA A. , KAVANAGH KATHRYN L. , TRIFFITT JAMES T. , LUNDY MARK W. , PHIPPS ROGER J. , BARNETT BOBBY L. , COXON FRASER P. , ROGERS MICHAEL J. , WATTS NELSON B. , EBETINO FRANK H.
Published: December 2007

Abstract:  The bisphosphonates (BPs) are well established as the treatments of choice for disorders of excessive bone resorption, including Paget's disease of bone, myeloma and bone metastases, and osteoporosis. There is considerable new knowledge about how BPs work. Their classical pharmacological effects appear to result from two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The inhibitory effects of the nitrogen‐containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch‐point enzyme in the mevalonate pathway. FPPS generates isoprenoid lipids used for the posttranslational modification of small GTP‐binding proteins essential for osteoclast function. Effects on other cellular pathways, such as preventing apoptosis in osteocytes, are emerging as other potentially important mechanisms of action. As a class, BPs share several common properties. However, as with other classes of drugs, there are obvious chemical, biochemical, and pharmacological differences among the various individual BPs. Each BP has a unique profile that may help to explain potential important clinical differences among the BPs, in terms of speed of onset of fracture reduction, antifracture efficacy at different skeletal sites, and the degree and duration of suppression of bone turnover. As we approach the 40th anniversary of the discovery of their biological effects, there remain further opportunities for using their properties for medical purposes.
Lipofuscin
Authors: JUNG TOBIAS , BADER NICOLLE , GRUNE TILMAN
Published: December 2007

Abstract:  One of the highlights of postmitotic aging is the intracellular accumulation of highly oxidized and cross‐linked proteins, known as lipofuscin. Lipofuscin is insoluble and not degradable by lysosomal enzymes or the proteasomal system, which is responsible for the recognition and degradation of misfolded and oxidatively damaged proteins. These aggregates have been found in various cell types, including heart, liver, kidney, neuronal tissue, and dermal tissue, and are associated with the life span of a single postmitotic cell and, consequently, of the whole organism. Lipofuscin formation appears to depend on the rate of oxidative damage to proteins, the functionality of mitochondrial repair systems, the proteasomal system, and the functionality and effectiveness of the lysosomes. This review highlights the current knowledge of the formation, distribution, and effects of lipofuscin in mammalian cells.
On the Recoverability of Choice Behaviors with Random Coefficients Choice Models in the Context of Limited Data and Unobserved Effects
Authors: Andrews Rick L. , Ainslie Andrew , Currim Imran S.
Published: December 2007

Random coefficients choice models are seeing widespread adoption in marketing research, partly because of their ability to generate household-level parameter estimates with limited data. However, the power of such models may tempt researchers to trust that they continue to produce reasonable estimates, when in fact either model misspecification or insufficient data limits the models' ability to recover household-level parameters successfully. If household-level choice behaviors are not recovered successfully, managerial decisions such as marketing-mix planning and targeting, direct marketing, segmentation, and forecasting may not produce the desired results. This study addresses the following questions. First, can random coefficients choice models correctly identify markets characterized by preference and response heterogeneity, state dependence, the use of alternative decision heuristics that result in reduced choice sets, and combinations of these effects? If so, how much data is required, and is this realistic given the size of data sets typically used in marketing analyses? Which model selection criteria should be used to identify these markets? When there is spurious market identification, which parameters contribute to the spurious result? An extensive simulation experiment is conducted wherein random coefficients logit models with varying specifications of parameter heterogeneity, state dependence effects, and choice set heterogeneity are applied to 128 experimental conditions. The results show which types of markets can be identified reliably and which cannot. Based on the results of the simulation, the authors develop a model selection heuristic that identifies the correct market in 81% of the experimental conditions. In contrast, strict application of the best model selection criterion alone results in correct market identification in at most 34% of experimental conditions. Interestingly, we find that the amount of data (number of households or number of purchases per household) does not affect our ability to identify the correct market type with this heuristic, so there is a good chance of identifying the correct market type even when little data is available.
Allocation Models and Heuristics for the Outsourcing of Repairs for a Dynamic Warranty Population
Authors: Ding Li , Glazebrook Kevin D. , Kirkbride Christopher
Published: December 2007

We consider a scenario in which a large equipment manufacturer wishes to outsource the work involved in repairing purchased goods while under warranty. Several external service vendors are available for this work. We develop models and analyses to support decisions concerning how responsibility for the warranty population should be divided between them. These also allow the manufacturer to resolve related questions concerning, for example, whether the service capacities of the contracted vendors are sufficient to deliver an effective post-sales service. Static allocation models yield information concerning the proportions of the warranty population for which the vendors should be responsible overall. Dynamic allocation models enable consideration of how such overall workloads might be delivered to the vendors over time in a way which avoids excessive variability in the repair burden. We apply dynamic programming policy improvement to develop an effective dynamic allocation heuristic. This is evaluated numerically and is also used as a yardstick to assess two simple allocation heuristics suggested by static models. A dynamic greedy allocation heuristic is found to perform well. Dividing the workload equally among vendors with different service capacities can lead to serious losses.
Ethical Perspectives on Political Excuses
Authors: Goodin Robert E.
Published: December 2007

Self-styled policy scientists pride themselves on their sensitivity to the ethical implications of social policies. However, the very nature of their enterprise focuses attention on certain aspects of political evaluation at the expense of others. For assessing social action-plans, the obvious bits of moral philosphy to borrow are those for appraising the behaviour of individual moral agents. Such instruments are well suited to praising or blaming policy-makers, individually and perhaps even collectively. But there is more to political evaluation than policy evaluation construed in this narrow way. Some moral goods, in politics as elsewhere, come as simple windfalls for which no one deserves credit; and there are some evils for which no one can be faulted. Thus, the virtue of the state, its balance of good over evil, is partially independent of anyone’s actions. Ethical equipment for levelling recriminations is totally inadequate for assessing these other dimensions of moral goodness.

These shortcomings are nowhere more apparent than with the familiar moral maxim, ‘ought implies can’, and its political analogue, ‘politics is the art of the possible’.
Considerations on the Social Background and Motivation of Councillors
Authors: Collins C.A.
Published: December 2007

The reorganization of British local government in 1974 brought ‘urban’ politics and an increase in partisanship to the shire countries. Formerly non-partisan areas have experienced the growth of party intervention and influence for the first time. Moreover, recent changes in the management structure of local government have increased the impact of party activity: thus the ‘one-pany’ policy committee; more ‘full-time’ members leading to a ‘backbench’ role for others; a vogue for the concept of mandate with officers seen as advisers to the majority party and other such developments are altering the political ground-rules. A much stronger political organization in many councils has underlined the distinctions between the leading members – the chairmen, group officers and others – who are often virtually full-time councillors, and those who are increasingly referred to as ‘back-benchers’. There have always been some whose influence has been high with other councillors, but it has never been so clear and formalized as it is now. The abolition of aldermen and the general increase in electoral volatility nationally and locally have added political uncertainty. These alternations have given impetus to the change of personnel caused by reorganized wards and council jurisdictions.
Contextual Bases of Responsiveness to Citizen Preferences and Group Demands
Authors: Getter Russell W , Schumaker Paul D
Published: December 2007

It is frequently asserted by democratic theorists that policymakers should be highly responsive to citizen inputs. Because of its importance in normative theory, the concept of responsiveness has been the subject of many empirical investigations seeking to describe and explain the degree of responsiveness of American state and local governments. However, broad generalizations regarding the degree of responsiveness of these governments and general explanations specifying the social and political conditions enhancing responsiveness have not been forthcoming. A major reason for the lack of cumulative knowledge in this area is that the concept of responsiveness to citizen inputs has been treated in a casual and often ambiguous fashion.

Most scholars agree that responsiveness occurs when citizen concerns and activities, treated as input variables, are reflected in public policy, treated as output variables. A lack of responsiveness occurs when policymakers adopt and implement policies which are independent of, and contrary to, citizen concerns. However, the ambiguity of this definition is apparent if one considers the multiplicity of types of citizen inputs to which policymakers can potentially respond.
The Allocation of Federal Money in the United States: Aggregate Analysis by Correlation
Authors: Johnston R J
Published: December 2007

There is a considerable literature in the social sciences reporting analyses of variations between governments (almost invariably local governments) in their spending on various service areas. Much less attention has been paid to the spatial pattern of spending within the territory of a single government, largely because of a paucity of data. It is possible to analyse allocations of money to the states by the American federal government, however, and the present paper outlines some results of exploratory investigations into the influences on the spatial pattern of this spending.

Both economic and political variables have been used to account for patterns of inter-governmental spending. Economic variables cover the needs for different policies in different places, needs which vary because of spatial patterns of the target populations, and differences between places in the resources available to meet such needs. Political variables refer to the dispositions of different parties towards meeting certain perceived needs, and the abilities of representatives to obtain social and economic benefits for their constituents. As the analyses reported here are for aggregates – state populations – the measurement of needs is difficult and spatial variations in resources are of slight relevance only.
Social Service Studies and the Explanation of Policy Outcomes
Authors: Davies Bleddyn
Published: December 2007

At least two theoretical implications of studies of social services are not given their full weight in much political science writing. The first is that the influence on policy outcomes of factors external to the organiztion have their influence at a variety of levels and on a multeity of groups of actors. For instance, the operating environment is argued to affect provision through its effects on the characteristics of potential consumers and therefore on the demand they make of the organization, the professionals and others at the client interface, local teams, departments, and authorities. In particular, the literature has stressed the impact of demands made by consumers on the structures of outputs. In doing so, it has begun to integrate theories about the causes of variations in demand into the theory about causes of variations in provisions. This is reflected in the modelling literature which draws on the social service studies. The models focus at a level of explanation at which it is possible to look at a wide range of performance indicators and to draw on a great deal of detailed evidence, and face more squarely issues of causal priority in the determination of outcomes.
Degradation of polyethylene glycol and hemicellulose in the Vasa
Authors: Almkvist Gunnar , Persson Ingmar
Published: December 2007

Mass spectrometric analysis of aqueous wood extracts from the Swedish warship Vasa reveals a serious chemical condition in the depth of the wood. The surface is less affected. Polyethylene glycol, used as conservation agent, is affected and partly degraded, and low-molecular fragments from hemicellulose are found at sites with high iron content and low pH. These findings imply a catalytic oxidative process and acidic hydrolysis in the wood, which contributes to a new picture of the challenge of long-term preservation of the Vasa.
EphB Receptors Regulate Stem/Progenitor Cell Proliferation, Migration, and Polarity during Hippocampal Neurogenesis
Authors: Chumley Michael J. , Catchpole Timothy , Silvany Robert E. , Kernie Steven G. , Henkemeyer Mark
Published: December 2007

The adult brain maintains two regions of neurogenesis from which new neurons are born, migrate to their appropriate location, and become incorporated into the circuitry of the CNS. One of these, the subgranular zone of the hippocampal dentate gyrus, is of primary interest because of the role of this region in learning and memory. We show that mice lacking EphB1, and more profoundly EphB1 and EphB2, have significantly fewer neural progenitors in the hippocampus. Furthermore, other aspects of neurogenesis, such as polarity, cell positioning, and proliferation are disrupted in animals lacking the EphB1 receptor or its cognate ephrin-B3 ligand. Our data strongly suggest that EphB1 and ephrin-B3 cooperatively regulate the proliferation and migration of neural progenitors in the hippocampus and should be added to a short list of candidate target molecules for modulating the production and integration of new neurons as a treatment for neurodegenerative diseases or brain injury.
Fluorophore-Conjugated Iron Oxide Nanoparticle Labeling and Analysis of Engrafting Human Hematopoietic Stem Cells
Authors: Maxwell Dustin J. , Bonde Jesper , Hess David A. , Hohm Sarah A. , Lahey Ryan , Zhou Ping , Creer Michael H. , Piwnica-Worms David , Nolta Jan A.
Published: December 2007

The use of nanometer-sized iron oxide particles combined with molecular imaging techniques enables dynamic studies of homing and trafficking of human hematopoietic stem cells (HSC). Identifying clinically applicable strategies for loading nanoparticles into primitive HSC requires strictly defined culture conditions to maintain viability without inducing terminal differentiation. In the current study, fluorescent molecules were covalently linked to dextran-coated iron oxide nanoparticles (Feridex) to characterize human HSC labeling to monitor the engraftment process. Conjugating fluorophores to the dextran coat for fluorescence-activated cell sorting purification eliminated spurious signals from nonsequestered nanoparticle contaminants. A short-term defined incubation strategy was developed that allowed efficient labeling of both quiescent and cycling HSC, with no discernable toxicity in vitro or in vivo. Transplantation of purified primary human cord blood lineage-depleted and CD34+ cells into immunodeficient mice allowed detection of labeled human HSC in the recipient bones. Flow cytometry was used to precisely quantitate the cell populations that had sequestered the nanoparticles and to follow their fate post-transplantation. Flow cytometry endpoint analysis confirmed the presence of nanoparticle-labeled human stem cells in the marrow. The use of fluorophore-labeled iron oxide nanoparticles for fluorescence imaging in combination with flow cytometry allows evaluation of labeling efficiencies and homing capabilities of defined human HSC subsets.

Disclosure of potential conflicts of interest is found at the end of this article.
Distinct Effects of the Soluble Versus Membrane-Bound Forms of the Notch Ligand Delta-4 on Human CD34+CD38low Cell Expansion and Differentiation
Authors: Lahmar Medhi , Catelain Cyril , Poirault Sonia , Dorsch Marion , Villeval Jean-Luc , Vainchenker William , Albagli Olivier , Lauret Evelyne
Published: December 2007

Although Notch ligands are considered to activate signaling through direct cell-cell contact, the existence of soluble forms has been demonstrated. However, their roles remain controversial: soluble forms have been reported to mimic the biological activity of membrane-bound form, whereas other studies rather suggested an antagonistic activity toward their full-length counterparts. We previously observed that membrane-bound Delta4-expressing S17 stroma (mbD4/S17) reduced human CD34+CD38low cell proliferation and favored self-renewal. Here, we assessed the effects of a soluble form of Delta4 (solD4) by exposing CD34+CD38low cells to S17 feeders engineered to express solD4 (solD4/S17). In contrast to mbD4/S17, (a) solD4/S17 increased 10-fold cell production after 2 weeks, through enhanced cell proliferation, and (b) it did not preserve colony-forming cell and long-term culture-initiating cell potential of output CD34+ cells. mbD4 and solD4 appeared to also differ in their signaling. Indeed, mbD4, but not solD4, strongly activated both CSL (the nuclear mediator of Notch signaling) in Hela cells overexpressing Notch1 and transcription of some classic Notch target genes in CD34+CD38low cells. Furthermore, both biological effects and CSL activation elicited by mbD4 were strictly dependent upon the γ-secretase complex, whereas solD4 enhanced cell expansion in a partially γ-secretase-independent manner. Altogether, these results suggest that part of solD4 activity did not rely upon canonical Notch pathway.

Disclosure of potential conflicts of interest is found at the end of this article.
Connexin Expression and Functional Analysis of Gap Junctional Communication in Mouse Embryonic Stem Cells
Authors: Wörsdörfer Philipp , Maxeiner Stephan , Markopoulos Christian , Kirfel Gregor , Wulf Volker , Auth Tanja , Urschel Stephanie , von Maltzahn Julia , Willecke Klaus
Published: December 2007

Gap junctional intercellular communication (GJIC) has been suggested to be necessary for cellular proliferation and differentiation. We wanted to investigate the function of GJIC in mouse embryonic stem (ES) cells using pharmacological inhibitors or a genetic approach to inhibit the expression of connexins, that is, the subunit proteins of gap junction channels. For this purpose, we have analyzed all known connexin genes in mouse ES cells but found only three of them, Cx31, Cx43, and Cx45, to be expressed as proteins. We have demonstrated by coimmunoprecipitation that Cx31 and Cx43, as well as Cx43 and Cx45, probably form heteromeric gap junction channels, whereas Cx31 and Cx45 do not. The pharmacological inhibitors reduced GJIC between ES cells to approximately 3% and initiated apoptosis, suggesting an antiapoptotic effect of GJIC. In contrast to these results, reduction of GJIC to approximately 5% by decreased expression of Cx31 or Cx45 via RNA interference in homozygous Cx43-deficient ES cells did not lead to apoptosis. Additional studies suggested that apoptotic death of ES cells and adult stem cells reported in the literature is likely due to a cytotoxic side effect of the inhibitors and not due to a decrease of GJIC. Using the connexin expression pattern in mouse ES cells, as determined in this study, multiple connexin-deficient ES cells can now be genetically engineered in which the level of GJIC is further decreased, to clarify whether the differentiation of ES cells is qualitatively or quantitatively compromised.

Disclosure of potential conflicts of interest is found at the end of this article.
Downregulation of Multiple Stress Defense Mechanisms During Differentiation of Human Embryonic Stem Cells
Authors: Saretzki Gabriele , Walter Theresia , Atkinson Stuart , Passos Jõao F. , Bareth Bettina , Keith W. Nicol , Stewart Rebecca , Hoare Stacey , Stojkovic Miodrag , Armstrong Lyle , von Zglinicki Thomas , Lako Majlinda
Published: December 2007

Evolutionary theory predicts that cellular maintenance, stress defense, and DNA repair mechanisms should be most active in germ line cells, including embryonic stem cells that can differentiate into germ line cells, whereas it would be energetically unfavorable to keep these up in mortal somatic cells. We tested this hypothesis by examining telomere maintenance, oxidative stress generation, and genes involved in antioxidant defense and DNA repair during spontaneous differentiation of two human embryonic stem cell lines. Telomerase activity was quickly downregulated during differentiation, probably due to deacetylation of histones H3 and H4 at the hTERT promoter and deacetylation of histone H3 at hTR promoter. Telomere length decreased accordingly. Mitochondrial superoxide production and cellular levels of reactive oxygen species increased as result of increased mitochondrial biogenesis. The expression of major antioxidant genes was downregulated despite this increased oxidative stress. DNA damage levels increased during differentiation, whereas expression of genes involved in different types of DNA repair decreased. These results confirm earlier data obtained during mouse embryonic stem cell differentiation and are in accordance with evolutionary predictions.

Disclosure of potential conflicts of interest is found at the end of this article.
Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves
Authors: Kerr Carolyn L. , Windeyer Claire , Bouré Ludovic P. , Mirakhur Kuldip K. , McDonell Wayne
Published: December 2007

Objective—To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery.

Animals—13 male calves 2 to 26 days of age.

Procedures—In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction.

Results—The quality of induction was excellent in all calves. The XGK requirements were 0.57 ± 0.18 mL/kg and 2.70 ± 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant.

Conclusions and Clinical Relevance—Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.
Evaluation of a bench-top coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and fibrinogen concentrations in healthy dogs
Authors: Mineo Heather K. , Garabed Rebecca B.
Published: December 2007

Objective—To evaluate a bench-top coagulation analyzer for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in healthy dogs.

Animals—55 healthy adult dogs.

Procedures—PT, APTT, and fibrinogen concentration were determined by use of the coagulation analyzer. Values were compared with results obtained independently by a conventional laboratory.

Results—Correlations (with 95% confidence intervals) between the coagulation analyzer and conventional laboratory values were 0.760 (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT, APTT, and fibrinogen concentration, respectively. Using linear regression, comparison of data from the coagulation analyzer and the conventional laboratory provided equations relating the coagulation analyzer values with values from the conventional laboratory and suggested that APTT and fibrinogen values from the coagulation analyzer and conventional laboratory were approximately the same within expected random variation. Prothrombin time values for the coagulation analyzer were significantly offset from the PT values for the conventional laboratory but still were correlated reasonably well with the conventional laboratory values.

Conclusions and Clinical Relevance—By use of the mechanical method of analysis, fibrinogen concentrations obtained with a bench-top coagulation analyzer correlated well with results for a conventional laboratory, indicating that the coagulation analyzer is a reliable instrument for determination of this coagulation variable. Coagulation analyzer results for PT and APTT correlated less strongly with those for the conventional laboratory, but they would still be considered clinically reliable.
Epidemiologic characteristics of catastrophic musculoskeletal injuries in Thoroughbred racehorses
Authors: Cruz Antonio M. , Poljak Zvonimir , Filejski Catherine , Lowerison Mark L. , Goldie Kyle , Martin S. Wayne , Hurtig Mark B.
Published: December 2007

Objective—To determine characteristics, incidence rate, and possible associations with selected demographic characteristics of catastrophic musculoskeletal injuries (CMIs) in Thoroughbred racehorses.

Animals—76 Thoroughbreds with CMIs.

Procedures—Incidence rates of CMIs during racing or training were calculated with number of CMIs as the numerator and overall numbers of races or training events during 2004 and 2005 as the denominators. Exact 95% confidence intervals were calculated. Associations between incidence and dichotomous exposure factors, nominal factors, and ordinal factors were determined. Only univariable associations were examined.

Results—76 horses were euthanized because of CMI and represented 2.36 and 1.69 deaths/1,000 racing starts in 2004 and 2005, respectively. Of these, 57 were euthanized within 60 days before or after a race, which yielded a point incidence of 1.05/1,000 racing starts and 0.39/1,000 training starts.

Conclusions and Clinical Relevance—Incidence rate of CMIs at 2 Ontario racetracks was similar to that at other North American racetracks. A cumulative death rate of 1 to 2 deaths/wkshould be considered typical when designing prevention strategies and offers a baseline value for measuring improvement.
Telomere length in normal and neoplastic canine tissues
Authors: Cadile Casey D. , Kitchell Barbara E. , Newman Rebecca G. , Biller Barbara J. , Hetler Elizabeth R.
Published: December 2007

Objective—To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues.

Sample Population—57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs.

Procedures—Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois.

Results—Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length.

Conclusions and Clinical Relevance—Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human antitelomerase strategies.
Comparison of the effects of caffeine and doxapram on respiratory and cardiovascular function in foals with induced respiratory acidosis
Authors: Giguère Steeve , Sanchez L. Chris , Shih Andre , Szabo Nancy J. , Womble Ariel Y. , Robertson Sheilah A.
Published: December 2007

Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.

Animals—6 clinically normal foals (1 to 3 days old).

Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).

Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO2 increased from baseline values after administration of saline solution or caffeine. The PaCO2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.

Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.
Fetal protection against continual exposure to bovine viral diarrhea virus following administration of a vaccine containing an inactivated bovine viral diarrhea virus fraction to cattle
Authors: Grooms Daniel L. , Bolin Steven R. , Coe Paul H. , Borges Rafael J. , Coutu Christopher E.
Published: December 2007

Objective—To evaluate the efficacy of a commercially available killed bovine viral diarrhea virus (BVDV) vaccine to protect against fetal infection in pregnant cattle continually exposed to cattle persistently infected with the BVDV.

Animals—60 crossbred beef heifers and 4 cows persistently infected with BVDV.

Procedures—Beef heifers were allocated to 2 groups. One group was vaccinated twice (21-day interval between the initial and booster vaccinations) with a commercially available vaccine against BVDV, and the other group served as nonvaccinated control cattle. Estrus was induced, and the heifers were bred. Pregnancy was confirmed by transrectal palpation. Four cows persistently infected with BVDV were housed with 30 pregnant heifers (15 each from the vaccinated and nonvaccinated groups) from day 52 to 150 of gestation. Fetuses were then harvested by cesarean section and tested for evidence of BVDV infection.

Results—1 control heifer aborted after introduction of the persistently infected cows. Bovine viral diarrhea virus was isolated from 14 of 14 fetuses obtained via cesarean section from control heifers but from only 4 of 15 fetuses obtained via cesarean section from vaccinated heifers; these proportions differed significantly.

Conclusions and Clinical Relevance—A commercially available multivalent vaccine containing an inactivated BVDV fraction significantly reduced the risk of fetal infection with BVDV in heifers continually exposed to cattle persistently infected with BVDV. However, not all vaccinated cattle were protected, which emphasizes the need for biosecurity measures and elimination of cattle persistently infected with BVDV in addition to vaccination within a herd.
Calcitonin Secretion by Human Placental Tissue
Authors: Balabanova S. , Kruse B. , Wolf A. S.
Published: December 2007

We have investigated the synthesis in vitro of calcitonin (CT) by human placenta at. term. Separate placental tissue samples were incubated in culture medium with various Ca concentrations for 6 h. The CT concentrations in the medium were determined by radio‐immunoassay. In addition the effect of DB‐cAMP on the synthesis was also studied. We could demonstrate CT secretion in all experiments. The CT concentrations were determined by two different antibodies. Both antibodies registered the CT secretion. Addition of DB‐cAMP to the culture medium stimulates the synthesis.
Female Urinary Stress Incontinence Treated with Teflon Injections
Authors: Osther Palle J. , Røhl Hardy
Published: December 2007

Twenty‐six women with urinary stress incontinence underwent transperineal or transurethral Teflon injections. The results were classified into three grades (good, moderate, and poor). Good or moderate results were obtained in 50%. No major immediate complications or long‐term sideeffects were observed. This intervention is associated with a minimum of discomfort for the patient and hospitalization can be limited to 48‐72 h. The procedure can be carried out with good effect on women previously classically operated on without success and it does not prevent subsequent surgical intervention for urinary incontinence should this prove necessary.
Routine Hospital Care Does Not Improve Prognosis in Twin Gestation
Authors: Rydhström Håkan , Nordensköld Fredrik , Grennert Lars , Ohrlander Sten , Aberg Ånders
Published: December 2007

The effects of routine hospital care in twin gestation were evaluated by comparing the gestational outcome in two neighbouring university departments in southern Sweden. In Malmö, 79% (175/223) of all women with a twin pregnancy were given routine hospital care between the 26‐28th and 35th gestational week, whereas in Lund only 4% (16/409) received such treatment. Hospitalization averaged 9 weeks in Malmö, versus 2 weeks in Lund. We found no significant differences between the two areas regarding gestational length, birth weight, or perinatal mortality. This study indicates that routine hospital care does not improve the prognosis in twin gestation.
Postpartum Anuria Caused by Silent Bilateral Nephrolithiasis
Authors: Jakobson J. , Norman M. , Ulmsten U. , Westgren M.
Published: December 2007

A case of remarkable silent anuria caused by bilateral nephrolithiasis in the post‐partum period is reported. The anuria was not associated with any kind of pain and the diagnosis was not revealed until three days postpartum when an intravenous pyelography was carried out. Differential diagnosis and management of nephrolithiasis are discussed. Ultrasound scanning is recommended as a routine procedure for all patients with signs and symptoms of renal dysfunction during pregnancy.
Chylothorax as A Complication After Delivery
Authors: Tornling Göran , Axelsson Goran , Peterffy Arpad
Published: December 2007

A 23‐year old female who developed a chylothorax as a probable complication after delivery is described and a possible mechanism is proposed. Conservative treatment was unsuccessful and the surgical management was complicated by an anatomical variation with the thoracic duct presenting as a plexiform system instead of a single duct.
Don't Think Twice, It's Alright: SPD-Left Party/PDS Coalitions in the Eastern German Länder
Authors: Olsen Jonathan , Hough Dan
Published: December 2007

This article analyses the development of Left Party/PDS-SPD coalitions in the eastern German Länder. It develops an explanatory framework based on attempts to understand how red-green coalitions came into being in the 1990s. The article concludes that red-red coalitions emerge when four basic criteria are fulfilled: the SPD has few other viable potential coalition options and believes it can gain in strategic terms; the ideological distance between the Left Party/PDS and SPD is small; and the personal relationships between Land-level leaders are good. The paper also argues that the heterogeneity of the Left Party/PDS is likely to ensure that Land-specific solutions to Land-specific coalition dilemmas are very likely to remain of significance in the future.
"The Whole World Is In Uproar": Discourses of Fear, Instability, and Global Change in West German Media, 1977-1980
Authors: Stehle Maria
Published: December 2007

After presenting a brief summary of the events leading up to the German Autumn, this article offers a close analysis of media responses in major German newspapers and magazines in the months following these violent and confusing political developments. It compares these responses to reports in January 1980, where the events of the late 1970s serve as a catalyst for fears of global change. Media articulate these fears about the stability and identity of the West German nation state in increasingly vague and generalized terms and relate them to a global situation that is "out of control." The discussions in this article suggest that these expressed fears reveal tensions, interruptions, and gaps in the conservative fantasy of the secure and prosperous Western nation state.
Clinical Reasoning of a Generative Artificial Intelligence Model Compared With Physicians
Authors: Cabral Stephanie , Restrepo Daniel , Kanjee Zahir , Wilson Philip , Crowe Byron , Abdulnour Raja-Elie , Rodman Adam
Published: April 2024

This cross-sectional study assesses the ability of a large language model to process medical data and display clinical reasoning compared with the ability of attending physicians and residents.
Petitions for Extreme Risk Protection Orders and Second Amendment Sanctuary Status in Colorado
Authors: Knoepke Christopher E. , Barnard Leslie M. , Batta Nisha , McCarthy Megan , Thies Kimberly , Olivencia Christian , Robinson Caitlin , Kettering Shalyn , Huss Sheila , Betz Marian E.
Published: April 2024

Importance

Extreme risk protection orders (ERPOs) temporarily bar individuals adjudicated as being at risk of violence (including suicide) from buying or possessing firearms. In protest, many US jurisdictions have declared themselves “Second Amendment sanctuaries” (2A sanctuaries). Many 2A sanctuaries continue to use ERPOs in low numbers, suggesting a poorly defined risk threshold at which they are acceptable.

Objective

To characterize circumstances under which ERPOs are used in 2A sanctuaries, highlighting their most broadly acceptable applications.

Design, Setting, and Participants

This cross-sectional study of civil court documents analyzed petitions for ERPOs filed in Colorado from January 2020 to December 2022. All petitions during the study period were included following de-duplication. These include petitions filed by law enforcement and family members against adults allegedly at risk of firearm violence across the state. Data were analyzed on a rolling basis between January 2020 and June 2023.

Exposure

ERPO petition filed in Colorado.

Main Outcomes and Measures

Seventy-seven data elements defined a priori were abstracted from all petitions and case files, including respondent demographics, petitioner types (family or law enforcement), types of threats (self, other, mass violence, combination), violence risk factors, and case outcomes (granted, denied).

Results

Of a total 338 ERPOs filed in Colorado, 126 (37.3%) occurred in 2A sanctuaries. Sixty-one of these 2A petitions were granted emergency orders, and 40 were full 1-year ERPOs after a hearing. Forty ERPOs (31.7%) were petitioned for by law enforcement. Petitions in non-2A counties were more likely to have been filed by law enforcement (138 of 227 [64.9%] vs 40 of 126 [31.7%]; P < .001) and to have had an emergency order granted (177 of 227 [78.0%] vs 61 of 126 [48.4%]; P < .001) than in 2A sanctuaries. Qualitative analysis of cases in 2A sanctuaries revealed common aggravating risk characteristics, including respondents experiencing hallucinations, histories of police interaction, and substance misuse. ERPOs have been granted in 2A sanctuaries against individuals threatening all forms of violence we abstracted for (themselves, others, and mass violence).

Conclusions and Relevance

In this examination of ERPO petitions across Colorado, more than a third of filings occurred in 2A sanctuaries. Nonetheless, law enforcement represent proportionately fewer petitions in these areas, and petitions are less likely to be granted. Serious mental illness, substance misuse, and prior interactions with law enforcement featured prominently in 2A sanctuary petitions. These case circumstances highlight dangerous situations in which ERPOs are an acceptable risk-prevention tool, even in areas politically predisposed to opposing them.
Unraveling Surface Reconstruction During Oxygen Evolution Reaction on the Defined Spinel Oxide Surface
Authors: Yeom Kyungbeen , Jo Jinwoung , Shin Heejong , Ji Hyunsoo , Moon Sungjin , Park Ji Eun , Lee Seongbeom , Shim Jaehyuk , Mok Dong Hyeon , Bootharaju Megalamane S. , Back Seoin , Hyeon Taeghwan , Sung Yung‐Eun
Published: April 2024

The reconstructed surface structure of Co‐based spinel oxides serves as the active site for oxygen evolution reaction (OER). However, the structural complexity of spinel oxides and surface dynamics during the OER hinder the understanding of the reconstruction mechanism and electronic structure of the active site. In this study, spinel Co3O4@(CoFeV)3O4 nanocube (CoFeV) is reported, a (001) facet‐defined spinel oxide comprising Co, Fe, and V deposited on the Co3O4 nanocube template to exclude facet‐dependent factors. Introducing highly dissoluble V cations accelerates the reconstruction process to enhance the electrocatalytic activity. CoFeV exhibited enhanced electrocatalytic activity (266 mV at 10 mA cm−2 in 1 M KOH) and durability (maintained stable electrocatalytic activity during a 200 h chronopotentiometry (CP) test at 100 mA cm−2) with significantly enlarged electrochemically active surface area (ECSA). The experimental and theoretical results demonstrated that V dissolution during catalysis induced oxygen vacancies, accelerating the surface reconstruction to highly active oxyhydroxide. Consequently, the anion exchange membrane water electrolyzer (AEMWE) of CoFeV as the anode exhibited a remarkable performance of 6.19 A cm−2 at 2.0 Vcell in 1 M KOH and robust durability for 96 h at a constant current density of 500 mA cm−2.
Skin‐Inspired All‐Natural Biogel for Bioadhesive Interface
Authors: Lan Lingyi , Ping Jianfeng , Li Huiyan , Wang Chengjun , Li Guang , Song Jizhou , Ying Yibin
Published: April 2024

Natural material‐based hydrogels are considered ideal candidates for constructing robust bio‐interfaces due to their environmentally sustainable nature and biocompatibility. However, these hydrogels often encounter limitations such as weak mechanical strength, low water resistance, and poor ionic conductivity. Here, inspired by the role of natural moisturizing factor (NMF) in skin, a straightforward yet versatile strategy is proposed for fabricating all‐natural ionic biogels that exhibit high resilience, ionic conductivity, resistance to dehydration, and complete degradability, without necessitating any chemical modification. A well‐balanced combination of gelatin and sodium pyrrolidone carboxylic acid (an NMF compound) gives rise to a significant enhancement in the mechanical strength, ionic conductivity, and water retention capacity of the biogel compared to pure gelatin hydrogel. The biogel manifests temperature‐controlled reversible fluid‐gel transition properties attributed to the triple‐helix junctions of gelatin, which enables in situ gelation on diverse substrates, thereby ensuring conformal contact and dynamic compliance with curved surfaces. Due to its salutary properties, the biogel can serve as an effective and biocompatible interface for high‐quality and long‐term electrophysiological signal recording. These findings provide a general and scalable approach for designing natural material‐based hydrogels with tailored functionalities to meet diverse application needs.