bluuebunny/crossref_metadata_2025 huggingface dataset:
Second‐line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline*
Authors: Hosseinipour MC , Kumwenda JJ , Weigel R , Brown LB , Mzinganjira D , Mhango B , Eron JJ , Phiri S , Van Oosterhout JJ
Published: March 2010

Objectives

The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second‐line ART. We report outcomes for patients evaluated and initiated on second‐line treatment in Malawi.

Methods

Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV‐1 RNA copies/mL) and, if failure was confirmed, initiated on second‐line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months.

Results

Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second‐line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV‐related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV‐1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52).

Conclusions

Second‐line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.
Immigrant Suburban Settlement and the “Threat” to Middle Class Status and Identity: The Case of Farmers Branch, Texas
Authors: Brettell Caroline B. , Nibbs Faith G.
Published: March 2010

In the United States, the failure to achieve immigration reform at the national level has resulted in numerous responses in local communities that have been most impacted by the settlement of new immigrants. Some of these responses have emerged in suburban communities that have experienced a rapid rise in the foreign‐born population during the last twenty years. This essay offers an in‐depth analysis of one such community, Farmers Branch, Texas, covered nationally for a series of anti‐immigrant ordinances passed by its City Council. Following a description of the history of this community, the growth of its foreign‐born population, and the legal manoeuvres to control unauthorized immigration, the essay argues that anti‐immigrant legislation in local places like Farmers Branch is at its core a reflection of a debate about and anxiety over American identity ‐‐ how it is defined and how it is changing. In particular, these responses are about a perceived threat to middle class status and identity. This is discussed first in relationship to issues of home ownership and income and then, in relation to cultural dimensions of class, including matters of taste and the spatializations of middle class identity. Finally, the paper unpacks the concept of “rule of law”. By invoking the claim that Americans are law abiding while unauthorized immigrants have broken the law, lawfulness becomes an exclusionary tool and gives those who support anti‐immigrant ordinances a platform for legislating a certain quality of life, and de‐Americanizing those who do not fit their conceptualization of what it means to be American. Rule of law becomes a weapon in the fight for middle class status and the status quo.
Human midsagittal brain shape variation: patterns, allometry and integration
Authors: Bruner Emiliano , Martin‐Loeches Manuel , Colom Roberto
Published: March 2010

Midsagittal cerebral morphology provides a homologous geometrical reference for brain shape and cortical vs. subcortical spatial relationships. In this study, midsagittal brain shape variation is investigated in a sample of 102 humans, in order to describe and quantify the major patterns of correlation between morphological features, the effect of size and sex on general anatomy, and the degree of integration between different cortical and subcortical areas. The only evident pattern of covariation was associated with fronto‐parietal cortical bulging. The allometric component was weak for the cortical profile, but more robust for the posterior subcortical areas. Apparent sex differences were evidenced in size but not in brain shape. Cortical and subcortical elements displayed scarcely integrated changes, suggesting a modular separation between these two areas. However, a certain correlation was found between posterior subcortical and parietal cortical variations. These results should be directly integrated with information ranging from functional craniology to wiring organization, and with hypotheses linking brain shape and the mechanical properties of neurons during morphogenesis.
Collagen fibril morphology and mechanical properties of the Achilles tendon in two inbred mouse strains
Authors: Rigozzi S. , Müller R. , Snedeker J. G.
Published: March 2010

The relationship between collagen fibril morphology and the functional behavior of tendon tissue has been investigated in numerous experimental studies. Several of these studies suggest that larger fibril radius is a primary determinant of higher tendon stiffness and strength; others have shown that factors apart from fibril radius (such as fibril–fibril interactions) may be critical to improved tendon strength. In the present study, we investigate these factors in two inbred mouse strains that are widely used in skeletal structure–function research: C57BL/6J (B6) and C3H/HeJ (C3H). The aim was to establish a quantitative baseline that will allow one to assess how regulation of tendon extracellular matrix architecture affects tensile mechanical properties. We specifically focused on collagen fibril structure and glycosaminoglycan (GAG) content – the two primary constituents of tendon by dry weight – and their potential functional interactions. For this purpose, Achilles tendons from both groups were tested to failure in tension. Tendon collagen morphology was analyzed from transmission electron microscopy images of tendon sections perpendicular to the longitudinal axis. Our results showed that the two inbred strains are macroscopically similar, but C3H mice have a higher elastic modulus (P < 0.05). Structurally, C3H mice showed a larger collagen fibril radius compared to B6 mice (96 ± 7 nm and 80 ± 10 nm respectively). Tendons from C3H mice also showed smaller specific fibril surface (0.015 ± 0.001 nm nm−2 vs. 0.017 ± 0.003 nm nm−2 in the B6 tendons, P < 0.05), and accordingly a lower concentration of GAGs (0.60 ± 0.07 μg mg−1 vs. 0.83 ± 0.11 μg mg−1, P < 0.05). As in other studies of tendon structure and function, larger collagen fibril radius appears to be associated with stiffer tendon, but this functional difference could also be attributed to reduced potential surface area exchange between fibrils and the surrounding proteoglycan‐rich matrix, in which the hydrophilic GAG side chains may promote inter‐fibril sliding. This study provides an architectural and functional baseline for a comparative murine model that can be used to investigate the genetic regulation of tendon biomechanics.
Microglial peroxiredoxin V acts as an inducible anti‐inflammatory antioxidant through cooperation with redox signaling cascades
Authors: Sun Hu‐Nan , Kim Sun‐Uk , Huang Song Mei , Kim Jin‐Man , Park Young‐Ho , Kim Seok‐Ho , Yang Hee‐Young , Chung Kyoung‐Jin , Lee Tae‐Hoon , Choi Hoon Sung , Min Ju Sik , Park Moon‐Ki , Kim Sang‐Keun , Lee Sang‐Rae , Chang Kyu‐Tae , Lee Sang‐Ho , Yu Dae‐Yeul , Lee Dong‐Seok
Published: March 2010

J. Neurochem. (2010) 114, 39–50.

Reactive oxygen species (ROS) actively participate in microglia‐mediated pathogenesis as pro‐inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up‐regulated by lipopolysaccharide (LPS) through activation of the ROS‐sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS‐stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS‐mediated Prx V up‐regulation in BV‐2 microglial cells and is closely associated with the activation of the c‐jun N‐terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS‐mediated Prx V induction. Furthermore, NO induces Prx V up‐regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS‐stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK‐dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.
Methylglyoxal‐mediated anxiolysis involves increased protein modification and elevated expression of glyoxalase 1 in the brain
Authors: Hambsch Boris , Chen Bud‐Gen , Brenndörfer Julia , Meyer Melanie , Avrabos Charilaos , Maccarrone Giuseppina , Liu Ray H. , Eder Matthias , Turck Christoph W. , Landgraf Rainer
Published: March 2010

J. Neurochem. (2010) 113, 1240–1251.

Methylglyoxal (MG) is a highly reactive metabolite that forms adducts with basic amino acid side chains in proteins. MG is degraded by glyoxalase1 (GLO1), an enzyme shown to be differentially expressed in several mouse models of anxiety‐related behavior. As yet, molecular mechanisms by which altered GLO1 expression influences emotionality have not been elucidated. Here we report that both MG concentration and protein modification are altered in brain tissue of a mouse model for trait anxiety, with elevated levels in low anxiety‐related behavior relative to high anxiety‐related behavior animals. Accordingly, repeated intracerebroventricular injections of MG mediated anxiolysis in inbred high anxiety‐related behavior and outbred CD1 mice. We found that anxiolytic‐like properties of MG were independent of GLO1 expression. In contrast, antidepressant‐like properties of intracerebroventricular MG were suppressed in CD1 mice carrying extra copies of the GLO1 gene. Moreover, MG treatment increased expression of GLO1 only in CD1 mice that did not have extra copies of GLO1. Taken together, these results suggest that the MG levels in brain are negatively correlated with anxiety. Thereby, we identified a novel molecular mechanism for anxiety‐related behavior in mice that may help to elucidate genesis of psychiatric disorders in humans.
Evaluation of acute congestive heart failure in dogs and cats: 145 cases (2007–2008)
Authors: Goutal Caroline M. , Keir Iain , Kenney Shale , Rush John E. , Freeman Lisa M.
Published: March 2010

Objective –To characterize the clinical presentation, management, and in‐hospital outcomes of dogs and cats diagnosed with acute congestive heart failure (CHF).

Design –Retrospective study of animals seen between January 2007 and May 2008.

Setting –Emergency service at a university teaching hospital.

Animals –Ninety dogs and 55 cats with CHF.

Measurements and Main Results –Patient characteristics, including age, clinical signs, clinicopathologic abnormalities, diagnostic testing, and outcome were recorded. Forty‐eight of the animals already were receiving cardiac medications at the time of presentation. The most common diseases represented were chronic valvular disease and cardiomyopathies. Cats had significantly lower median body temperature at admission compared with dogs (P<0.001). The most common abnormalities were elevated lactate (64%), elevated BUN (52%), hypochloremia (31%), hyperglycemia (27%), and elevated liver enzymes (26%). Many of these became even more prevalent during hospitalization. One hundred and sixteen animals were discharged from the hospital, for a survival rate of 80%. There was no survival difference between dogs and cats (P=0.39). Dogs that developed hypokalemia during hospital stay (P=0.04) were more likely to survive compared with those without hypokalemia and initial body temperature was lower for those cats that did not survive (P=0.02). Of those that did not survive, the majority were euthanized (n=25), while 4 dogs died.

Conclusions –Dogs and cats presented to the emergency service with CHF had a high survival rate. In cats, initial body temperature was lower for those cats that did not survive. Although clinicopathologic abnormalities were common in both species, only dogs with hypokalemia had improved survival to hospital discharge.
Depositional environments and chronology of Late Weichselian glaciation and deglaciation in the central North Sea
Authors: GRAHAM ALASTAIR G. C. , LONERGAN LIDIA , STOKER MARTYN S.
Published: March 2010

Graham, A.G.C., Lonergan, L. & Stoker, M.S. 2010: Depositional environments and chronology of Late Weichselian glaciation and deglaciation in the central North Sea. Boreas, Vol. 39, pp. 471–491. 10.1111/j.1502‐3885.2010.00144.x. ISSN 0300‐9483.

Geological constraints on ice‐sheet deglaciation are essential for improving the modelling of ice masses and understanding their potential for future change. Here, we present a detailed interpretation of depositional environments from a new 30‐m‐long borehole in the central North Sea, with the aim of improving constraints on the history of the marine Late Pleistocene British–Fennoscandian Ice Sheet. Seven units characterize a sequence of compacted and distorted glaciomarine diamictons, which are overlain by interbedded glaciomarine diamictons and soft, bedded to homogeneous marine muds. Through correlation of borehole and 2D/3D seismic observations, we identify three palaeoregimes. These are: a period of advance and ice‐sheet overriding; a phase of deglaciation; and a phase of postglacial glaciomarine‐to‐marine sedimentation. Deformed subglacial sediments correlate with a buried suite of streamlined subglacial bedforms, and indicate overriding by the SE–NW‐flowing Witch Ground ice stream. AMS 14C dating confirms ice‐stream activity and extensive glaciation of the North Sea during the Last Glacial Maximum, between c. 30 and 16.2 14C ka BP. Sediments overlying the ice‐compacted deposits have been reworked, but can be used to constrain initial deglaciation to no later than 16.2 14C ka BP. A re‐advance of British ice during the last deglaciation, dated at 13.9 14C ka BP, delivered ice‐proximal deposits to the core site and deposited glaciomarine sediments rapidly during the subsequent retreat. A transition to more temperate marine conditions is clear in lithostratigraphic and seismic records, marked by a regionally pervasive iceberg‐ploughmarked erosion surface. The iceberg discharges that formed this horizon are dated to between 13.9 and 12 14C ka BP, and may correspond to oscillating ice‐sheet margins during final, dynamic ice‐sheet decay.
Sedimentary evidence for a major glacial oscillation and proglacial lake formation in the Solway Lowlands (Cumbria, UK) during Late Devensian deglaciation
Authors: LIVINGSTONE STEPHEN J. , Ó COFAIGH COLM , EVANS DAVID J.A. , PALMER ADRIAN
Published: March 2010

Livingstone, S. J., Ó Cofaigh, C., Evans, D. J. A. & Palmer, A. 2010: Sedimentary evidence for a major glacial oscillation and proglacial lake formation in the Solway Lowlands (Cumbria, UK) during Late Devensian deglaciation. Boreas, Vol. 39, pp. 505–527. 10.1111/j.1502‐3885.2010.00149.x. ISSN 0300‐9483.

This paper is a sedimentological investigation of Late Devensian glacial deposits from the Solway Lowlands, northwest England, in the central sector of the last British–Irish Ice Sheet. In this region, laminated glaciolacustrine sediments occur, sandwiched between diamictons interpreted as subglacial tills. At one location the laminated sediments are interpreted as varves, and indicate the former presence of a proglacial lake. Correlation of these varves with other laminated sediments indicates that the glacial lake was at least 140 km2 in area and probably much larger. Extensive beds of sand, silt and gravel throughout the Solway Basin associated with the lake demonstrate ice‐free conditions over a large area. Based on the number of varves, the lake was in existence for at least 261 years. The stratigraphic sequence of varves bracketed by tills implies a major glacial oscillation prior to the Scottish Re‐advance (16.8 cal. ka BP). This oscillation is tentatively correlated with the Gosforth oscillation at c.19.5 cal. ka BP. Subsequent overriding of these glaciolacustrine sediments during a westward‐moving re‐advance demonstrates rapid ice loss and then gain within the Solway Lowlands from ice‐dispersal centres in the Lake District, Pennines and Southern Uplands. It is speculated that the existence of this and other lakes along the northeastern edge of the Irish Sea Basin would have influenced ice‐sheet dynamics.
Postglacial changes in the Asian summer monsoon system: a pollen record from the eastern margin of the Tibetan Plateau
Authors: ZHOU WEIJIAN , YU SHI‐YONG , BURR GEORGE S. , KUKLA GEORGE J. , JULL A. J. T. , XIAN FENG , XIAO JIAYI , COLMAN STEVEN M. , YU HUAGUI , LIU ZHAO , KONG XIANGHUI
Published: March 2010

Zhou, W., Yu, S.‐Y., Burr, G. S., Kukla, G. J., Jull, A. J. T., Xian, F., Xiao, J., Colman, S. M., Yu, H., Liu, Z. & Kong, X. 2010: Postglacial changes in the Asian summer monsoon system: a pollen record from the eastern margin of the Tibetan Plateau. Boreas, Vol. 39, pp. 528–539. 10.1111/j.1502‐3885.2010.00150.x. ISSN 0300‐9483.

A new pollen record constrained by 32 AMS radiocarbon dates from the Hongyuan peatland in the Zoige Basin reveals the long‐term dynamics of an alpine wetland ecosystem on the eastern margin of the Tibetan Plateau over the last 13 500 years. Changes in pollen assemblages and influxes suggest that local vegetation has experienced three distinct stages, from alpine coniferous forest–meadow (13 500–11 500 cal. a BP), through alpine coniferous forest (11 500–3000 cal. a BP), back to alpine coniferous forest–meadow (3000 cal. a BP–present). This record reflects an ecosystem response along a transition zone where the South Asian and East Asian monsoon systems may have had different palaeoclimatic influences. A comparison of this record with other pollen records across the Tibetan Plateau shows common features with regard to large‐scale Holocene climatic changes, but highlights a pattern of regional temporal and spatial variability that depends on the topography and position relative to the South Asian and East Asian monsoon fronts.
The Variability of IPO Initial Returns
Authors: LOWRY MICHELLE , OFFICER MICAH S. , SCHWERT G. WILLIAM
Published: March 2010

The monthly volatility of IPO initial returns is substantial, fluctuates dramatically over time, and is considerably larger during “hot” IPO markets. Consistent with IPO theory, the volatility of initial returns is higher for firms that are more difficult to value because of higher information asymmetry. Our findings highlight underwriters’ difficulty in valuing companies characterized by high uncertainty, and raise serious questions about the efficacy of the traditional firm‐commitment IPO process. One implication of our results is that alternate mechanisms, such as auctions, could be beneficial for firms that value price discovery over the auxiliary services provided by underwriters.
The New Game in Town: Competitive Effects of IPOs
Authors: HSU HUNG‐CHIA , REED ADAM V. , ROCHOLL JÖRG
Published: March 2010

We analyze the effect of initial public offerings (IPOs) on industry competitors and provide evidence that companies experience negative stock price reactions to completed IPOs in their industry and positive stock price reactions to their withdrawal. Following a successful IPO in their industry, they show significant deterioration in their operating performance. These results are consistent with the existence of IPO‐related competitive advantages through the loosening of financial constraints, financial intermediary certification, and the presence of knowledge capital. These aspects of competitiveness are significant in explaining the cross‐section of underperformance as well as survival probabilities for competing firms.
Financial Structure, Acquisition Opportunities, and Firm Locations
Authors: ALMAZAN ANDRES , DE MOTTA ADOLFO , TITMAN SHERIDAN , UYSAL VAHAP
Published: March 2010

This paper investigates the relation between firms' locations and their corporate finance decisions. We develop a model where being located within an industry cluster increases opportunities to make acquisitions, and to facilitate those acquisitions, firms within clusters maintain more financial slack. Consistent with our model we find that firms located within industry clusters make more acquisitions, and have lower debt ratios and larger cash balances than their industry peers located outside clusters. We also document that firms in high‐tech cities and growing cities maintain more financial slack. Overall, the evidence suggests that growth opportunities influence firms' financial decisions.
Taxes on Tax‐Exempt Bonds
Authors: ANG ANDREW , BHANSALI VINEER , XING YUHANG
Published: March 2010

Implicit tax rates priced in the cross section of municipal bonds are approximately two to three times as high as statutory income tax rates, with implicit tax rates close to 100% using retail trades and above 70% for interdealer trades. These implied tax rates can be identified because a portion of secondary market municipal bond trades involves income taxes. After valuing the tax payments, market discount bonds, which carry income tax liabilities, trade at yields around 25 basis points higher than comparable municipal bonds not subject to any taxes. The high sensitivities of municipal bond prices to tax rates can be traced to individual retail traders dominating dealers and other institutions.
Do Bonds Span Volatility Risk in the U.S. Treasury Market? A Specification Test for Affine Term Structure Models
Authors: ANDERSEN TORBEN G. , BENZONI LUCA
Published: March 2010

We propose using model‐free yield quadratic variation measures computed from intraday data as a tool for specification testing and selection of dynamic term structure models. We find that the yield curve fails to span realized yield volatility in the U.S. Treasury market, as the systematic volatility factors are largely unrelated to the cross‐section of yields. We conclude that a broad class of affine diffusive, quadratic Gaussian, and affine jump‐diffusive models cannot accommodate the observed yield volatility dynamics. Hence, the Treasury market per se is incomplete, as yield volatility risk cannot be hedged solely through Treasury securities.
Corporate Political Contributions and Stock Returns
Authors: COOPER MICHAEL J. , GULEN HUSEYIN , OVTCHINNIKOV ALEXEI V.
Published: March 2010

We develop a new and comprehensive database of firm‐level contributions to U.S. political campaigns from 1979 to 2004. We construct variables that measure the extent of firm support for candidates. We find that these measures are positively and significantly correlated with the cross‐section of future returns. The effect is strongest for firms that support a greater number of candidates that hold office in the same state that the firm is based. In addition, there are stronger effects for firms whose contributions are slanted toward House candidates and Democrats.
Advancing Firm Growth Research: A Focus on Growth Mode Instead of Growth Rate
Authors: McKelvie Alexander , Wiklund Johan
Published: March 2010

The development of firm growth research has been notably slow. In this paper, we argue that a major reason for this lack of development is the impatience of researchers to prematurely address the question of “how much?” before adequately providing answers to the question “how?” On the basis of an extensive review of the literature, we suggest how growth research can advance by changing focus to growth mode (organic, acquisition, hybrid). Toward this end, we provide a research agenda that helps establish the types of questions that growth researchers can ask within this new focus.
Dialysis in the poisoned patient
Authors: BAYLISS George
Published: March 2010

Patients who ingest toxic substances may require extracorporeal removal of the poisons or their toxic metabolites if native renal clearance is not sufficient because of acute kidney injury, acuity of symptoms, or burden of toxin. Here, a case is presented, and the literature on renal replacement therapy in the event of acute intoxication is reviewed. Extracorporeal therapy efficacy is examined in terms of the characteristics of the toxin (molecular size, charge, protein, or lipid binding); the patient (body habitus and volume of distribution); and the process (membrane effects on extraction ratios and sieving, role of blood, and dialysate flow rates). The choice of extracorporeal therapy and hemodialysis prescriptions for specific poisonings are discussed.
Rate‐Dependent Indentation Response of Structural Ceramics
Authors: Klecka Michael A. , Subhash Ghatu
Published: March 2010

Static and dynamic (high‐rate) indentation hardness values are determined for ZrO2, SiC, and Si3N4 ceramics. While the static hardness is determined using a conventional Vickers tester, the dynamic hardness is determined using a custom‐designed tester that can produce a single indent within a 100‐μs duration. The results indicated that the dynamic hardness is 7%–10% greater than the static hardness, depending on the type of ceramic material. Indentation‐induced crack length is also appreciably smaller under dynamic indentation compared with static indentation. However, when the influence of increased hardness (i.e., reduced indentation size) under dynamic indentation is factored into the crack length measurements, the difference in crack length between static and dynamic indents disappears for SiC and Si3N4. In the ZrO2 ceramic, the difference in crack lengths continues to persist, indicating that ductile behavior (transformation toughening) may be a factor for rate‐dependent fracture characteristics in ceramics in this strain rate regime.
Effect of Exposure to an American Indian Mascot on the Tendency to Stereotype a Different Minority Group
Authors: Kim‐Prieto Chu , Goldstein Lizabeth A. , Okazaki Sumie , Kirschner Blake
Published: March 2010

Numerous findings have documented the adverse effects of stereotypes on those negatively portrayed by the stereotypes. Less is known about the ramifications of stereotype exposure on those who are not the objects of the stereotypic depictions. Two studies examined the effect of exposure to an American Indian sports mascot on the stereotype endorsement of a different minority group. Study 1 used an unobtrusive prime, while Study 2 used a more engaged prime. Study 2 also investigated the effect among those unfamiliar with the controversy regarding American Indian sports mascots. Results from both studies show that participants primed with an American Indian sports mascot increased their stereotyping of a different ethnic minority group.
Simultaneous use of serum IgG and IgM for risk scoring of suspected early Lyme borreliosis: graphical and bivariate analyses
Authors: DESSAU RAM B. , EJLERTSEN TOVE , HILDEN JØRGEN
Published: March 2010

Dessau RB, Ejlertsen T, Hilden J. Simultaneous use of serum IgG and IgM for risk scoring of suspected early Lyme borreliosis: graphical and bivariate analyses. APMIS 2010; 118: 313–23.

The laboratory diagnosis of early disseminated Lyme borreliosis (LB) rests on IgM and IgG antibodies in serum. The purpose of this study was to refine the statistical interpretation of IgM and IgG by combining the diagnostic evidence provided by the two immunoglobulins and exploiting the whole range of the quantitative variation in test values. ELISA assays based on purified flagella antigen were performed on sera from 815 healthy Danish blood donors as negative controls and 117 consecutive patients with confirmed neuroborreliosis (NB). A logistic regression model combining the standardized units of the IgM and IgG ELISA assays was constructed and the resulting disease risks graphically evaluated by receiver operating characteristic and ‘predictiveness’ curves. The combined model improves the discrimination between NB patients and blood donors. Hence, it is possible to report a predicted risk of disease graded for each individual patient, as is theoretically preferable. The predictiveness curve, when adapted to the local pretest probability of LB, allows high‐risk and low‐risk thresholds to be defined instead of cut‐offs based on the laboratory characteristics only, and it allows the extent of under‐ and over‐treatment to be assessed. It is shown that an example patient with low ELISA results in IgM and IgG, considered negative by the conventional cut‐off, has a relatively high risk of belonging to the truly diseased population and a low risk of being false positive. Using a 20% high‐risk threshold for advising the clinician to consider treatment, the sensitivity of the assay is increased from 76% to 85%, while the specificity is maintained at around 95%.
Multiple human papilloma virus types in cervical infections: competition or synergy?
Authors: MEJLHEDE NINA , PEDERSEN BO V. , FRISCH MORTEN , FOMSGAARD ANDERS
Published: March 2010

Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A. Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010; 118: 346–52.

Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR‐based commercial microarray assay for mucosal types. Of the HPV‐positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV‐16 infection had 0.4 times the odds of having HPV‐51 compared with women not infected with HPV‐16. HPV‐16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type‐specific protection, depending on whether the types vaccinated against compete with other HPV types or not.
Peri‐implant soft tissue and bone crest alterations at fixed dental prostheses: a 3‐year prospective study
Authors: Chang Moontaek , Wennström Jan L.
Published: March 2010

Objectives: The aim of this 3‐year prospective study involving patients receiving implant‐supported fixed dental prostheses (FDPs) was to longitudinally evaluate soft and hard tissue alterations from the time of implant placement.

Material and methods: Sixteen subjects with 18 implant‐supported FDPs on 43 implants were included in the study. Peri‐implant soft and hard tissue assessments were performed at implant placement, 2, 6, 12, 24 and 36 months. Variables describing the peri‐implant soft tissue conditions and topography were assessed by clinical, photographic and study model assessments. Variables of implant position and bone topography were measured in radiographs taken at each examination interval. Multilevel regression models were formulated to identify factors of significance for proximal bone crest alterations and proximal soft tissue height.

Results: During the first 6 months after the one‐stage implant placement surgery, the soft tissue margin receded about 0.6 mm at facial implant sites, while a mean increase was observed at tooth‐facing proximal sites (1.1 mm) and no change at inter‐implant sites. Loss in proximal bone crest height was more pronounced at inter‐implant than tooth–implant units at 6 months (0.6 vs. 0.1 mm). Between 6 and 36 months, no further significant soft or hard tissue changes were observed. Multilevel regression analysis revealed that the proximal bone crest level significantly influenced the proximal soft tissue height assessed from the implant/abutment level. Significant predictors for loss in proximal bone crest level over the 3 years were horizontal inter‐unit distance, type of proximal unit (tooth/implant or inter‐implant) and peri‐implant bone‐level change.

Conclusions: Soft and hard tissue changes around implant‐supported FDPs took place primarily during the first 6 months after the one‐stage implant installation surgery. The pattern of tissue alterations during the follow‐up differed between tooth–implant and inter‐implant proximal sites.

To cite this article:
 Chang M, Wennström JL. Peri‐implant soft tissue and bone crest alterations at fixed dental prostheses: a 3‐year prospective study. Clin. Oral Impl. Res. 21, 2010; 527–534. doi: 10.1111/j.1600‐0501.2009.01874.x
Factors influencing resonance frequency analysis assessed by Osstell™mentor during implant tissue integration: I. Instrument positioning, bone structure, implant length
Authors: Sim Christina P. C. , Lang Niklaus P.
Published: March 2010

Aim: To monitor longitudinally the development of implant stability of SLA Straumann® tissue‐level implants using resonance frequency analysis (RFA) and to determine the influence of instrument positioning, bone structure and implant length on the assessment of RFA.

Material and methods: Thirty‐two healthy adult patients received either 8 mm, ∅4.1 mm Straumann® Standard Plus tissue‐level implants (n=16: Group A) or 10 mm, ∅4.1 mm Straumann® Standard Plus tissue‐level implants (n=16: Group B). During healing, RFA was performed on Weeks 0,1, 2, 3, 4, 5, 6, 8 and 12. The implants were restored after 10 weeks (impression taking) and 12 weeks. In addition, probing depth, presence of plaque and bleeding on probing were assessed. Implant stability quotient (ISQ) values of Groups A and B were compared using unpaired t‐tests and longitudinally applying paired t‐tests between Week 0 and the subsequent time points.

Results: Positioning of the Osstell™mentor device did not affect the ISQ values. Generally, ISQ values increased continuously during healing from a mean of 65.1 (SD 16.97) to 74.7 (SD 5.17) (significantly from Week 0 to Weeks 6, 8 and 12). Lower bone density (Type III or IV) resulted in significantly lower ISQ values up to Week 8. Implant length affected the increase in ISQ values over time. While no significant increase was observed with 10 mm implants, ISQ values of 8 mm implants increased significantly from Week 0 to Weeks 6, 8 and 12.

Conclusions: Using Osstell™mentor, ISQ values are reproducible irrespective of instrument positioning. ISQ values are affected by the bone structure and implant length. Hence, no predictive values can be attributed to implant stability.

To cite this article:
 Sim CPC, Lang NP. Factors influencing resonance frequency analysis assessed by Osstell™mentor during implant tissue integration: I. Instrument positioning, bone structure, implant length. Clin. Oral Impl. Res. 21, 2010; 598–604. doi: 10.1111/j.1600‐0501.2009.01878.x
Cement thickness at implant‐supported single‐tooth Lava assemblies: a scanning electron microscopic investigation
Authors: Apicella D. , Veltri M. , Chieffi N. , Balleri P. , Ferrari M.
Published: March 2010

Objectives: The fit of implant‐supported single‐tooth Lava zirconia assemblies was investigated in this study. The implant–abutment interface, the interface between the metallic and the zirconia portion of the abutment and the interface between Lava abutments and copings were evaluated. The adaptation of titanium abutments to implants and Lava copings was investigated as a control.

Material and methods: Twenty implants were randomly assigned and connected to Lava abutments (group 1) or titanium abutments (group 2). All specimens were subjected to scanning electron microscopy (SEM) analysis of the fixture/abutment fit. Afterwards, specimens were luted to Lava copings and subjected to a SEM evaluation of the marginal external adaptation of the abutments with the copings. Finally, the samples were embedded in resin, sectioned and subjected to SEM analysis of the following interfaces; group 1: titanium/zirconia interface (between the constitutive components of the Lava abutment) and the zirconia/zirconia interface (between the Lava abutment and the coping); group 2: the titanium/zirconia interface (between the titanium abutment and the Lava coping). Non‐parametric analysis of variance and a post hoc test were used for statistical analysis.

Results: Significant differences emerged in the cement thickness between titanium and zirconia components of the Lava abutments as compared with the thickness measured at the interface between Lava copings and the abutments investigated. No differences were found in cement thickness between Lava copings and the two different abutments.

Conclusions: When Lava abutments are used, the most critical cement thickness is the internal interface between its titanium and zirconia components. Lava coping adaptation for both Lava and titanium abutments is within the clinical acceptable range.

To cite this article:
 Apicella D, Veltri M, Chieffi N, Balleri P, Ferrari M. Cement thickness at implant‐supported single‐tooth Lava assemblies: a scanning electron microscopic investigation. Clin. Oral Impl. Res. 21, 2010; 747–750. doi: 10.1111/j.1600‐0501.2009.01882.x
Long‐term response of osteogenic cells on micron and submicron‐scale‐structured hydrophilic titanium surfaces: sequence of cell proliferation and cell differentiation
Authors: Klein Marcus Oliver , Bijelic Ana , Toyoshima Takeshi , Götz Hermann , Von Koppenfels Roxana Laura , Al‐Nawas Bilal , Duschner Heinz
Published: March 2010

Objective: Modifications of surface topography and surface chemistry are key factors for guiding target cells during dental implant healing. Recent in vitro studies confirmed promotion of early osteogenic cell differentiation on submicron scaled surfaces in particular when hydrophilized. However, no long‐term observations on both osteogenic cell proliferation as well as on cell maturation have been reported for respectively modified surfaces. Aim of this study was to monitor osteogenic cell proliferation and expression of specific osteogenic cell differentiation markers on a protein level over an extended period of 3 weeks with respect to surface modifications.

Material and methods: Modified titanium (Ti) disks were obtained from Institute Straumann, representing the following surfaces: smooth pretreatment (PT), sandblasted/acid etched (SLA), and hydrophilized (modSLA). Surface topography was analyzed by scanning electron microscopy, surface elemental composition was assessed by X‐Ray Photoelectronic Spectroscopy (XPS). Tissue culture polystyrene (TCPS) served as a control substrate. Human osteogenic cells (HOB‐c) were cultivated on the respective substrates. After 24 hrs, 48 hrs, 72 hrs, 7 d, 14 d and 21 d, cell count was assessed as well as osteogenic cell differentiation utilizing cellular Quantitative Immuno‐Cytochemistry (QIC) assay for collagen type I (COL), alkaline phosphatase (AP), osteopontin (OPN) and osteocalcin (OC). Data were normalized with respect to internal controls.

Results: In contrast to the other modified Ti disks, modSLA stands out due to low surface carbon contamination. TCPS and PT surfaces preserved a rather immature, mitotic active osteogenic phenotype (high proliferation rates, no increase of OC production), SLA and especially modSLA surfaces promoted the maturation of osteogenic precursors into post‐mitotic osteoblasts. In detail, modSLA resulted in lowest cell proliferation rates, but exhibited highest expression rates of OC.

Discussion: Our results, which confirm previous studies, reveal long‐term promotion of osteogenic cell maturation by topography (micron and submicron scale roughness) and surface hydrophilicity.

To cite this article:
 Klein MO, Bijelic A, Toyoshima T, Götz H, von Koppenfels RL, Al‐Nawas B, Duschner H. Long‐term response of osteogenic cells on micron and submicron‐scale‐structured hydrophilic titanium surfaces: sequence of cell proliferation and cell differentiation.  Clin. Oral Impl. Res. 21, 2010; 642–649. doi: 10.1111/j.1600‐0501.2009.01883.x
Biological width following immediate implant placement in the dog: flap vs. flapless surgery
Authors: Blanco Juan , Alves Célia Coutinho , Nuñez Vanesa , Aracil Luis , Muñoz Fernando , Ramos Isabel
Published: March 2010

Objective: To assess the marginal soft tissue healing process after flap or flapless surgery in immediate implant placement in a dog model.

Material and methods: This study was carried out on five Beagle dogs. Four implants were placed in the lower jaw in each dog immediately after tooth extraction. Flap surgery was performed before the extraction on one side (control) and flapless on the other (test). After 3 months of healing, the dogs were sacrificed and prepared for histological analysis.

Results: Ten implants were placed in each group. Two failed (one of each group). The length of the junctional epithelium in the flapless group was 2.54 mm (buccal) and 2.11 mm (lingual). In the flap group, the results were very similar: 2.59 mm (buccal) and 2.07 mm (lingual), with no significant differences observed between the groups. The length of the connective tissue in the flapless group was 0.68 mm (buccal) and 0.54 mm (lingual), and 1.09 mm at the buccal and 0.91 mm at the lingual aspect in the flap group, with no significant differences between groups. The difference between the mean distance from the peri‐implant mucosa margin to the first bone–implant contact at the buccal aspect was significant between both groups (3.02 mm‐flapless and 3.69 mm flap group). However, this difference was mostly due to the Pm3 group (flapless: 2.95/flap: 3.76) because no difference could be detected in the Pm4 group. Both groups showed minimal recession, with no significant differences between groups (flapless group – 0.6 mm buccal and 0.42 mm lingual; flap group – 0.67 and 0.13 mm).

Conclusion: The clinical evaluation of immediate implant placement after 3 months of healing indicated that buccal soft tissue retraction was lower in the flapless group than in the flap group, without significant differences. The mean values of the biological width longitudinal dimension at the buccal aspect were higher in the flap group than in the flapless group, this difference being mostly due to the Pm3, probably because of a thinner biotype in this region.

To cite this article:
 Blanco J, Alves CC, Nuñez V, Aracil L, Muñoz F, Ramos I. Biological width following immediate implant placement in the dog: flap vs. flapless surgery. Clin. Oral Impl. Res. 21, 2010; 624–631. doi: 10.1111/j.1600‐0501.2009.01885.x
Multiple myeloma: chemotherapy or transplantation in the era of new drugs
Authors: Palumbo Antonio , Rajkumar S. Vincent
Published: March 2010

Objective: To review the current results of studies incorporating novel agents in multiple myeloma (MM) and discuss the role of autologous stem‐cell transplantation (ASCT) in the era of new active drugs for the treatment of this disease. The outlook for patients with symptomatic MM is changing with the introduction of bortezomib, thalidomide, and lenalidomide into the repertoire of available chemotherapeutic agents. Compared with standard chemotherapy, a survival benefit has been reported for the first time in 30 yrs. Methods: Articles published in English between 1969 and 2008 were identified by searching PubMed for ‘myeloma’, ‘diagnosis’, ‘thalidomide’, ‘bortezomib’, ‘lenalidomide’, ‘dexamethasone’, ‘prednisone’, ‘doxorubicin’, ‘cyclophosphamide’, ‘melphalan’, ‘combination chemotherapy’, and ‘autologous transplantation’. Results: In randomized studies, bortezomib, thalidomide, and lenalidomide have each been combined with dexamethasone, alkylating agents, or doxorubicin, and such combinations resulted in significant improvement in progression‐free survival. Conclusions: The incorporation of new drugs as induction therapy along with ASCT appears to produce very good partial response rates, slightly superior to those achieved by conventional chemotherapy with new drugs. How to best optimize induction, consolidation, and maintenance therapy and how to best select and prepare patients for ASCT are still to be determined. Randomized trials are needed to directly compare the current best chemotherapeutic approach with best ASCT strategies and to guide clinical practice for patients with MM.
Cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration
Authors: Elliott Michelle A. , Letendre Louis , Gastineau Dennis A. , Winters Jeffrey L. , Pruthi Rajiv K. , Heit John A.
Published: March 2010

Background:  Early initiation of plasma exchange (PE) allows more than 80% of patients with idiopathic thrombotic thrombocytopenic purpura (TTP), most commonly because of severe ADAMTS13 deficiency, to achieve remission and mandates urgency in diagnosis and therapy. Metastatic cancer may present with a microangiopathic hemolytic anemia with thrombocytopenia that is clinically similar to TTP but does not respond to PE. ADAMTS13 activity can be diagnostic but usually not immediately available. Recognition of cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia (CA‐MHA) is paramount to avoid inappropriate PE therapy and delays in cancer‐specific chemotherapy.

Objective:  To identify distinguishing characteristics of CA‐MHA and TTP to facilitate early recognition of CA‐MHA.

Methods:  In a retrospective cohort study, baseline clinical and laboratory data of consecutive adult patients with CA‐MHA (n = 7) or autoimmune TTP (n = 7) from a registry of patients with clinically suspected acute TTP referred for PE were compared.

Results:  The frequencies of bone pain and respiratory symptoms were significantly greater among patients with CA‐MHA compared to patients with TTP; other baseline clinical and laboratory characteristics did not differ significantly between the two groups. Response to PE and mortality at day 30 were significantly worse for CA‐MHA (14% and 71%, respectively) compared to patients with TTP (86% and 14%, respectively).

Conclusions:  Baseline clinical and laboratory characteristics largely do not distinguish acute CA‐MHA from autoimmune acute TTP. While all suspected acute patients TTP should receive urgent PE, bone pain, respiratory symptoms, or inadequate PE response should prompt an early search for CA‐MHA.