bluuebunny/crossref_metadata_2025 huggingface dataset:
The Quality and Frequency of Mother–Toddler Conflict: Links With Attachment and Temperament
Authors: Laible Deborah , Panfile Tia , Makariev Drika
Published: March 2008

The goal of this study was to examine the links among attachment, child temperament, and the quality and frequency of mother–toddler conflict. Sixty‐four mothers and children took part in a series of laboratory tasks when the child was 30 months of age and an audiorecorded home observation when the child was 36 months of age. All episodes of conflict were identified from the videotapes/audiotapes, transcribed, and coded for conflict strategies, resolution, and themes. Mothers also completed measures of attachment security and child temperament. Concurrent attachment security was related to the quality of mother–toddler conflict (including resolution, justification, and compromise) at both periods but not to the frequency of conflict. In addition, aspects of child temperament (i.e., negative reactivity and activity level/impulsivity) were related to both the quality and the frequency of mother–toddler conflict.
Children’s Judgments of Disloyal and Immoral Peer Behavior: Subjective Group Dynamics in Minimal Intergroup Contexts
Authors: Abrams Dominic , Rutland Adam , Ferrell Jennifer M. , Pelletier Joseph
Published: March 2008

The developmental model of subjective group dynamics hypothesizes that peer exclusion during middle childhood involves inferences about group dynamics. To test the generality of this prediction, children judged, within minimal groups, peers whose behavior was loyal versus disloyal (Study 1: n = 46, mean age = 113 months) or morally acceptable versus unacceptable (Study 2: n = 121, mean age = 90 months). As hypothesized, in Study 1, children used their understanding of loyalty norms as a basis for evaluating peers. In both studies, higher commitment to the in‐group increased use of group‐based criteria for judging peers. In Study 2, children employed moral‐ and group‐based criteria independently for judging peers. Multiple classification skill was associated with lower intergroup bias and greater use of morality‐based judgment.
Testing an Individual Systems Model of Response Evaluation and Decision (RED) and Antisocial Behavior Across Adolescence
Authors: Fontaine Reid Griffith , Yang Chongming , Dodge Kenneth A. , Bates John E. , Pettit Gregory S.
Published: March 2008

This study examined the bidirectional development of aggressive response evaluation and decision (RED) and antisocial behavior across five time points in adolescence. Participants (n = 522) were asked to imagine themselves behaving aggressively while viewing videotaped ambiguous provocations and answered a set of RED questions following each aggressive retaliation (administered at Grades 8 and 11 [13 and 16 years, respectively]). Self‐ and mother reports of antisocial behavior were collected at Grades 7, 9/10, and 12 (12, 14/15, and 17 years, respectively). Using structural equation modeling, the study found a partial mediating effect at each hypothesized mediational path despite high stability of antisocial behavior across adolescence. Findings are consistent with an individual systems perspective by which adolescents’ antisocial conduct influences how they evaluate aggressive interpersonal behaviors, which affects their future antisocial conduct.
The Difficulties of Representing Continuous Extent in Infancy: Using Number Is Just Easier
Authors: Cordes Sara , Brannon Elizabeth M.
Published: March 2008

This study investigates the ability of 6‐month‐old infants to attend to the continuous properties of a set of discrete entities. Infants were habituated to dot arrays that were constant in cumulative surface area yet varied in number for small (< 4) or large (> 3) sets. Results revealed that infants detected a 4‐fold (but not 3‐fold) change in area, regardless of set size. These results are in marked contrast to demonstrations that infants of the same age successfully discriminate a 2‐ or 3‐fold change in number, providing strong counterevidence to the claim that infants use solely nonnumerical, continuous extent variables when discriminating sets. These findings also shed light on the processes involved in tracking continuous variables in infants.
Dragon Children: Identifying the Causal Effect of the First Child on Female Labour Supply with the Chinese Lunar Calendar*
Authors: Vere James P.
Published: March 2008

Instrumental variables (IV) estimates of the effect of fertility on female labour supply have only been able to identify the causal effect of second and higher parity children. This study uses exogenous variation in fertility caused by the Chinese lunar calendar to identify the effect of the first child. Additionally, weighting formulas are presented to interpret IV estimates as weighted average treatment effects in the case of multiple endogenous variables, which are useful when children vary in intensity by both number and age. The effect of the first child is found to be much greater than that of other children.
Causes of the first AIDS‐defining illness and subsequent survival before and after the advent of combined antiretroviral therapy*
Authors: Grabar S , Lanoy E , Allavena C , Mary‐Krause M , Bentata M , Fischer P , Mahamat A , Rabaud C , Costagliola D ,   on behalf of the Clinical Epidemiology Group of the French Hospital Database on HIV
Published: March 2008

Objectives

To analyse the impact of combined antiretroviral treatment (cART) on survival with AIDS, according to the nature of the first AIDS‐defining clinical illness (ADI); to examine trends in AIDS‐defining causes (ADC) and non‐AIDS‐defining causes (non‐ADC) of death.

Methods

From the French Hospital Database on HIV, we studied trends in the nature of the first ADI and subsequent survival in France during three calendar periods: the pre‐cART period (1993–1995; 8027 patients), the early cART period (1998–2000; 3504 patients) and the late cART period (2001–2003; 2936 patients).

Results

The three most frequent initial ADIs were Pneumocystis carinii (jirovecii) pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's sarcoma (13.9%) in the pre‐cART period. In the late cART period, the most frequent ADIs were tuberculosis (22.7%), PCP (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first ADI fell significantly after the arrival of cART. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma and Mycobacterium avium complex infection. After an ADI, the 3‐year risk of death from an ADC fell fivefold between the pre‐cART and late cART periods (39%vs. 8%), and fell twofold for non‐ADCs (17%vs. 9%).

Conclusions

The relative frequencies of initial ADI have changed since the advent of cART. Tuberculosis is now the most frequent initial ADI in France; this is probably the result of the increasing proportion of migrants from sub‐Saharan Africa. After a first ADI, cART has a major impact on ADCs and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar.
Atazanavir and lopinavir with ritonavir alone or in combination: analysis of pharmacokinetic interaction and predictors of drug exposure
Authors: Di Giambenedetto S , De Luca A , Villani P , Bacarelli A , Ragazzoni E , Regazzi M , Cauda R , Navarra P
Published: March 2008

Objectives

Studies on the pharmacokinetic interaction between atazanavir and lopinavir with ritonavir (lopinavir/ritonavir) report contradictory results. We aimed to establish the in vivo interaction between these two protease inhibitors as well as the variables influencing drug exposure.

Methods

Pharmacokinetic parameters were investigated in HIV‐infected patients treated with atazanavir 300 mg with ritonavir 100 mg q24h (group A) or lopinavir/ritonavir 400/100 mg q12h (group B) or atazanavir 300 mg q24h with lopinavir/ritonavir 400/100 mg q12h (group C). Patients receiving other concomitant protease inhibitors or non‐nucleoside reverse transcriptase inhibitors were excluded.

Results

In group A (n=10), mean ± standard deviation atazanavir Cmin was 390 ± 460 ng/mL, Cmax 3051 ± 1996 ng/mL and AUC24 29 913 ± 17 686 ng/mL/h. In group B (n=9), lopinavir Cmin was 7562 ± 4292 ng/mL, Cmax 12 944 ± 4838 ng/mL and AUC0–12 122 313 ± 38 225 ng/mL/h. In group C (n=7), atazanavir Cmin was 876 ± 460 ng/mL (P=0.039 vs. group A), Cmax 3421 ± 3399 ng/mL and AUC0–24 65 055 ± 49 843 ng/mL/h (two‐sided P>0.05 for each comparison with group A), lopinavir Cmin was 7471 ± 3745 ng/mL, Cmax 10 143 ± 5217 ng/mL and AUC0–12 104 501 ± 43 565 ng/mL/h (P>0.05 for each comparison with group B). When analysing all the groups, including controls from routine clinical practice, higher body mass index was associated with lower atazanavir Cmin and with lower lopinavir Cmax. Atazanavir Cmin showed a correlation with total bilirubin levels.

Conclusions

Combination with lopinavir/ritonavir provides higher atazanavir Cmin than combination with ritonavir alone, possibly because of an effect of the additional ritonavir dose. Low BMI may be associated with higher drug exposure.
Exhumation of a Variscan orogenic complex: insights into the composite granulitic–amphibolitic metamorphic basement of south‐east Corsica (France)
Authors: GIACOMINI F. , DALLAI L. , CARMINATI E. , TIEPOLO M. , GHEZZO C.
Published: March 2008

A structural, petrological and geochronological (U‐Th‐Pb of zircon and monazite) study reveals that the lower crust sequences of the Variscan high‐grade basement cropping out between Solenzara and Porto Vecchio, south‐east Corsica (France) have been tectonically juxtaposed along with middle crustal rocks during the extrusion of the orogenic root of the Variscan chain. We propose that a system of high‐temperature, orogen‐parallel shear zones that developed under a transpressive dextral tectonic regime caused the exhumation of the entire sequence. This tectonic complex is thus made up of rocks having undergone different P–T conditions (eclogite‐?, high‐pressure granulite facies and amphibolite facies) at different times, reflecting the progressive foreland migration of the orogenic front. The Solenzara granulites were derived from burial of continental crust to high‐pressure (1.8–1.4 GPa) and high‐ to ultrahigh‐temperature conditions (900–1000 °C) during the Variscan convergence: U–Pb ELA‐ICPMS zircon dating constrained the timing of this metamorphism at c. 360 Ma. The gneisses cropping out at Porto Vecchio are middle crustal‐level rocks that reached their peak temperature conditions (700–750 °C at <1.0 GPa) at c. 340 Ma. The diachronism of the metamorphic events, the foliation patterns and their geometry suggest that the granulites were exhumed to middle crustal levels through channel flow tectonics under continuous compression. The amphibolite facies gneisses of Porto Vecchio and the granulites of Solenzara were accreted through the development of a major dextral mylonitic zone forming under amphibolite facies conditions: in situ monazite isotope dating (ELA‐ICPMS) revealed that this deformation occurred at c. 320 Ma and was accompanied by the emplacement of syntectonic high‐K melts. A final HTLP static overprint, constrained at 312–308 Ma by monazite U‐Th‐Pb isotope dating, is related to the emplacement of the igneous products of the Sardinia‐Corsica batholith and marks the transition from the Variscan orogenic event to the Permian extension.
What Drives Morally Committed Citizens? A Study of the Antecedents of Public Service Motivation
Authors: Perry James L. , Brudney Jeffrey L. , Coursey David , Littlepage Laura
Published: March 2008

This study examines the relationship between public service motivation and antecedents believed to be important determinants of moral commitment. Research conducted during the past decade indicates that public service motivation is a valid construct that is useful for predicting outcomes that are important to public organizations and to society. The sample for the empirical study consists of winners of the Daily Point of Light Award and the President’s Community Volunteer Award. Antecedents studied are volunteer experience, religious activity, and parental socialization. Quantitative and qualitative analyses are used to identify key determinants of public sector motivation. Religious activity is positively related to formal and informal volunteering. Interviews strongly support the quantitative findings, especially the importance of religion, but also highlight the role of life‐changing events.
The Importance of Trust in Government for Public Administration: The Case of Zoning
Authors: Cooper Christopher A. , Knotts H. Gibbs , Brennan Kathleen M.
Published: March 2008

Many scholars argue that citizens with higher levels of political trust are more likely to grant bureaucratic discretion to public administrators than citizens with lower levels of trust. Trust, therefore, can relieve the tension between managerial flexibility and political accountability in the modern administrative state. Unfortunately, there is little empirical evidence showing that trust is actually associated with citizens’ willingness to cede policy‐making power to government. This article tests theories about political trust and citizen competence using the case of zoning. Trust in local government is found to be an important predictor of support for zoning, but trust in state government and trust in national government have no effect. These findings suggest that trust affects policy choice and helps determine how much power citizens grant to local administrators.
Jump‐Starting Collaboration: The ABCD Initiative and the Provision of Child Development Services through Medicaid and Collaborators
Authors: Berry Carolyn , Krutz Glen S. , Langner Barbara E. , Budetti Peter
Published: March 2008

Many policy problems require governmental leaders to forge vast networks beyond their own hierarchical institutions. This essay explores the challenges of implementation in a networked institutional setting and incentives to induce coordination between agencies and promote quality implementation. It describes the national evaluation of the Assuring Better Child Health and Development program, a state‐based program intended to increase and enhance the delivery of child development services for low‐income children through the health care sector, using Medicaid as its primary vehicle. Using qualitative evaluation methods, the authors found that all states implemented programs that addressed their stated goals and made changes in Medicaid policies, regulations, or reimbursement mechanisms. The program catalyzed interagency cooperation and coordination. The authors conclude that even a modest level of external support and technical assistance can stimulate significant programmatic change and interorganizational linkages within public agencies to enhance provision of child development services.
Reemployment Services in the Netherlands: A Comparative Study of Bureaucratic, Market, and Network Forms of Organization
Authors: Svensson Jörgen , Trommel Willem , Lantink Tineke
Published: March 2008

Progress in New Public Management research requires careful comparison of different organizational approaches to public tasks, preferably within a single political and institutional setting. This paper presents a study of three approaches to reemployment services, a recent development in the Netherlands. How do bureaucratic, networked, and market‐based forms of organization function with regard to the new public aim of second‐tier reemployment in the Netherlands? It appears that there is no simple dependence between performance and instrumental or organizational features. Even in the setting of a single welfare state, intricate interactions exist between performance, stakeholder interests, and institutional conditions. Given the importance of these interactions, New Public Management research would benefit by shifting focus away from organizational performance toward a “politics of institutional structuring.”
A Crisis of Authority? A Conversation with Alasdair Roberts about the Bush Years
Authors: Moynihan Donald
Published: March 2008

Alasdair Roberts’s recent book The Collapse of Fortress Bush: The Crisis of Authority in American Government is an appraisal of the George W. Bush administration’s response to the 9/11 attacks and its management of the global war on terrorism. This war, Roberts argues, is a neoliberal war designed to accommodate assumptions about the boundaries of governmental action that became prevalent after Ronald Reagan’s election to the presidency in 1980. Concerns about the renaissance of the “imperial presidency” are simplistic and misplaced, Roberts proposes, because they largely ignore how executive authority in the United States has been weakened by political, economic, and institutional forces. President Bush’s actions after 9/11 reflect the limitations of his power. His White House was unable to impose significant burdens on citizens or the economy, felt forced to expand power surreptitiously, and chose to act militarily because the armed services enjoyed a level of legitimacy that was absent from the rest of government.
Citizens and Resource Allocation: Improving Decision Making with Interactive Web‐Based Citizen Participation
Authors: Robbins Mark D , Simonsen Bill , Feldman Barry
Published: March 2008

Collective consumption and benefit characterize many government services. Moreover, government services are mostly paid for collectively through taxes—there is little or no relationship between the taxes paid by a household and its use of a particular service. Public sector decision makers face complex budget problems with difficult solutions. Involving citizens meaningfully in these decisions has long been a conundrum. The authors teamed up with the town of West Hartford, Connecticut, to develop a Web‐based survey to overcome some of these participation problems and help decision makers better understand citizen preferences. The Web survey allowed for real‐time interactivity and was tailored to present respondents with trade‐offs between service levels and taxes.
Local Dysfunction and Asymmetrical Deformation of Mitral Annular Geometry in Ischemic Mitral Regurgitation: A Novel Computerized 3D Echocardiographic Analysis
Authors: Daimon Masao , Saracino Giuseppe , Gillinov A. Marc , Koyama Yasushi , Fukuda Shota , Kwan Jun , Song Jong‐Min , Kongsaerepong Vorachai , Agler Deborah A. , Thomas James D. , Shiota Takahiro
Published: March 2008

Objective: Most studies of the pathogenesis of functional mitral regurgitation (MR) have focused on alterations in ventricular function and geometry. We used a novel 3D echocardiographic method to assess abnormalities in mitral annular (MA) geometry and motion in patients with ischemic MR (IMR) and compared these data to those obtained from normal subjects and from patients with MR caused by dilated cardiomyopathy (DMR). Methods: Real time 3D echo was performed in 12 normal subjects, 25 with IMR, and 14 with DMR. Eight points along the saddle‐shaped MA were identified using our software at systole and diastole. From these eight points, four annular diameters at each cardiac phase were determined. Annular motion was assessed by measuring local displacement (LD) of a given point between systole and diastole. Results: Annular motion was different between groups: IMR had smaller LD in posterior MA segments than did normals (2.6 ± 1.1 vs 4.8 ± 1.9 mm, P < 0.01), while DMR had globally reduced LD. In IMR systolic MA dilatation was striking in the anterior–posterior (diameter; IMR vs controls, 28.3 ± 3.5 vs 22.5 ± 2.2 mm, P< 0.05) and anterolateral–posteromedial (31.7 ± 3.5 vs 25.1 ± 2.2 mm, P < 0.05) directions; in IMR, systolic MA diameters in these two directions correlated with MR severity
(P = 0.02)
. MA dilatation occurred globally in DMR. Conclusion: This novel 3D echo method demonstrated that MA motion and dilatation were asymmetric in IMR and symmetric in DMR. These differences in MA geometry and motion may aid in the development of distinct new therapies for IMR and DMR.
Myocardial Performance Index Correlates with Right Ventricular Ejection Fraction Measured by Nuclear Ventriculography
Authors: Karnati Pavan K. , El‐Hajjar Mohammad , Torosoff Mikhail , Fein Steven A.
Published: March 2008

Background: Assessment of right ventricular (RV) ejection fraction (EF) by two‐dimensional echocardiography (2D ECHO) is practical but limited because of complex geometry of the RV. Techniques used for accurate measurement of RV EF are invasive or costly. However, derivation of 2D ECHO Doppler parameters to estimate RV function could be useful and inexpensive. Methods: RV EF measured by nuclear ventriculography was compared with 2D ECHO estimates of myocardial performance index (MPI) and peak tricuspid annular systolic velocity (PTASV). Linear regression analysis and sensitivity analysis were used to analyze the data. Results: RV EF measured by nuclear ventriculography correlated with MPI significantly (r =–0.55, P = 0.005) but not with PTASV (r = 0.09, P = 0.69). Using abnormal RV EF <45% measured by nuclear ventriculography, the sensitivity and specificity for MPI > 0.50 were 45.4% and 100%, respectively. The sensitivity and specificity of PTASV ≤ 17.25 cm/sec in detecting abnormal RV EF were 100% and 35.4%. Conclusion: MPI greater than 0.50 indicates that RV function is abnormal and a value of PTASV > 17.25 cm/sec indicates normal RV function.
Partial Anomalous Pulmonary Venous Connection Associated with Lutembacher's Syndrome
Authors: Anwar Ashraf M. , Nosir Youssef F. M. , Ajam Aref , Galal Ahmed N , Ashmeg Abdullah , Chamsi‐Pasha Hassan
Published: March 2008

Lutembacher's syndrome is a rare combination of congenital atrial septal defect and mitral stenosis (almost always rheumatic). The hemodynamic effect of this combination makes the clinical diagnosis difficult due to a wide variation of clinical presentation. Echocardiography and cardiac catheterization are useful tools for proper diagnosis and planning of the therapeutic strategy. We present a 28‐year‐old female with Lutembacher's syndrome associated with partial anomalous pulmonary venous connection (PAPVC), which was surgically corrected. To our knowledge, this combination has never been reported in the literature.
Assessment of the Tei Index by Tissue Doppler Imaging in Patients with Acromegaly: Serum Growth Hormone Level Is Associated with the Tei Index
Authors: Baykan Merih , Erem Cihangir , Gedikli Ömer , Hacıhasanoğlu Arif , Erdoğan Turan , Koçak Mustafa , Kaplan Şahin , Kırış Abdülkadir , Çelik Şükrü
Published: March 2008

Background: The Tei index reflects both systolic and diastolic ventricular function. The aim of this study was to assess the Tei index by tissue Doppler imaging (TDI) and also to evaluate the correlation with growth hormone (GH) and the Tei index and left ventricular (LV) function assessed by TDI in patients with acromegaly.Methods: We prospectively evaluated 25 patients with acromegaly and 27 control subjects. LV systolic and diastolic function was assessed by conventional echocardiography and TDI. Results: Peak E velocity and E/A ratio were lower in those with acromegaly than in those without (P = 0.01; P = 0.002, respectively). Deceleration time of the mitral E‐wave (P = 0.01) and isovolumic relaxation time (IVRT) (P = 0.01) were higher in acromegalic patients than those in controls (P = 0.006, P = 0.002). Em (P = 0.01) and Em/Am (P = 0.001) were lower in patients with acromegaly than in controls. In patients with acromegaly, the Tei index was significantly higher than that in controls (0.49 ± 13.4 vs 0.39 ± 5.2, P = 0.005). GH was positively correlated with the Tei index (r = 0.65, P = 0.041), Em/Am (r = 0.63, P = 0.021), and interventricular septum (IVS) thickness (r = 0.65, P = 0.008) only in patients with acromegaly. LV diastolic dysfunction was detected 36% by conventional echocardiography and 48% by the Tei index derived from TDI in acromegalic patients. Conclusion: TDI analysis of mitral annular velocities is useful to assess LV diastolic dysfunction in patients with acromegaly. GH was positively correlated with the Tei index and LV diastolic dysfunction. The Tei index may be superior to conventional mitral Doppler indices for identification of LV diastolic dysfunction in patients with acromegaly.
Ratio of Left Atrial to Left Ventricular Size: An Anatomical Marker of the Diastolic Left Ventricular Pressure‐Volume Relationship
Authors: Spevack Daniel M. , Blum Liran , Malhotra Divya , Nazari Reza , Ostfeld Robert J. , Doddamani Sanjay , Bello Ricardo , Cohen Hillel W. , Sonnenblick Edmund H.
Published: March 2008

Background: Classification of diastolic heart function is best defined by the degree of leftward and upward shift of the diastolic pressure‐volume relationship (DPVR). Direct measurement of DPVR, however, requires invasive techniques. Increased left atrial (LA) size is a marker of left ventricular (LV) diastolic hypertension, and so, the LA/LV diameter ratio has the potential to mark the degree of upward and leftward shift in the LV‐DPVR. We thus investigated the association of this novel marker with exposures known to induce diastolic dysfunction and with clinical evidence of diastolic dysfunction. Methods and Results: Reports from 7,803 patients undergoing maximal exercise stress echocardiography were reviewed. Increased LA/LV diameter ratio predicted diminished exercise capacity (P < 0.001) in a multivariate regression analysis. Increased LA and decreased LV diameters were each independently associated with exercise capacity (P < 0.001, both). Increased LA/LV diameter ratio was associated with hypertension (P = 0.001), diabetes (P = 0.03) and with increased severity of LV hypertrophy (P< 0.001). Those with LA/LV diameter ratio > 1.0 were more likely to use loop diuretics, odds ratio = 2.5 [95% CI, 1.4, 4.5], compared to those with lower ratio values.
Conclusions: Increased LA/LV diameter ratio was observed in subjects with hypertension, diabetes and LV hypertrophy. Increased ratio predicted worse exercise capacity and was associated with more frequent loop diuretic use. These data are consistent with the hypothesis that this ratio is a noninvasive marker of the LV‐DPVR.
ROC‐Based Utility Function Maximization for Feature Selection and Classification with Applications to High‐Dimensional Protease Data
Authors: Liu Zhenqiu , Tan Ming
Published: March 2008

Summary In medical diagnosis, the diseased and nondiseased classes are usually unbalanced and one class may be more important than the other depending on the diagnosis purpose. Most standard classification methods, however, are designed to maximize the overall accuracy and cannot incorporate different costs to different classes explicitly. In this article, we propose a novel nonparametric method to directly maximize the weighted specificity and sensitivity of the receiver operating characteristic curve. Combining advances in machine learning, optimization theory, and statistics, the proposed method has excellent generalization property and assigns different error costs to different classes explicitly. We present experiments that compare the proposed algorithms with support vector machines and regularized logistic regression using data from a study on HIV‐1 protease as well as six public available datasets. Our main conclusion is that the performance of proposed algorithm is significantly better in most cases than the other classifiers tested. Software package in MATLAB is available upon request.
Discriminant Analysis for Longitudinal Data with Multiple Continuous Responses and Possibly Missing Data
Authors: Marshall Guillermo , De la Cruz‐Mesía Rolando , Quintana Fernando A. , Barón Anna E.
Published: March 2008

SummaryMultiple outcomes are often used to properly characterize an effect of interest. This article discusses model‐based statistical methods for the classification of units into one of two or more groups where, for each unit, repeated measurements over time are obtained on each outcome. We relate the observed outcomes using multivariate nonlinear mixed‐effects models to describe evolutions in different groups. Due to its flexibility, the random‐effects approach for the joint modeling of multiple outcomes can be used to estimate population parameters for a discriminant model that classifies units into distinct predefined groups or populations. Parameter estimation is done via the expectation‐maximization algorithm with a linear approximation step. We conduct a simulation study that sheds light on the effect that the linear approximation has on classification results. We present an example using data from a study in 161 pregnant women in Santiago, Chile, where the main interest is to predict normal versus abnormal pregnancy outcomes.
Adaptive Weighted Learning for Unbalanced Multicategory Classification
Authors: Qiao Xingye , Liu Yufeng
Published: March 2008

Summary In multicategory classification, standard techniques typically treat all classes equally. This treatment can be problematic when the dataset is unbalanced in the sense that certain classes have very small class proportions compared to others. The minority classes may be ignored or discounted during the classification process due to their small proportions. This can be a serious problem if those minority classes are important. In this article, we study the problem of unbalanced classification and propose new criteria to measure classification accuracy. Moreover, we propose three different weighted learning procedures, two one‐step weighted procedures, as well as one adaptive weighted procedure. We demonstrate the advantages of the new procedures, using multicategory support vector machines, through simulated and real datasets. Our results indicate that the proposed methodology can handle unbalanced classification problems effectively.
An Epidemic of Illicit Fentanyl Deaths in Cook County, Illinois: September 2005 through April 2007
Authors: Denton J. Scott , Donoghue Edmund R. , McReynolds Jennifer , Kalelkar Mitra B.
Published: March 2008

Abstract:  Between September 2005 and April 2007, 350 fentanyl intoxication deaths were investigated and certified by the Cook County Medical Examiners Office. Investigations revealed that the majority of these fatalities were by intravenous injection of a white powder followed by a rapid collapse. The fentanyl was clandestinely produced in a lab in Toluca, Mexico and sold by the Mickey Cobra street gang. The term “Drop Dead” was coined for this “tainted heroin.” Postmortem samples were screened by ELISA and confirmed by standard GC‐MS methods. Fentanyl fatalities peaked at 47 per month in May and June 2006. Fifty‐two percent were single fentanyl intoxications, with the remainder accompanied by either cocaine, morphine from heroin, or alcohol. This epidemic stressed the limited resources of the toxicology laboratory and autopsy service of the Medical Examiners Office. The clandestine lab was terminated, distributing gang members and leaders arrested, and the epidemic ceased in April 2007.
Can APB 2000 Be Used to Discern Sincerity of Effort in Unimpaired Subjects from Maximal Performance in Subjects with Shoulder Pain?
Authors: Lohman Everett B. , Thorpe Donna L. , Prior Marilyn , George James , Kim Jimmy P.
Published: March 2008

Abstract:  The automated pegboard (APB 2000), which has been found to objectively quantify motor performance, was used to differentiate maximal motor performance among subjects with shoulder pain, healthy unimpaired subjects performing normally and also while feigning shoulder pain. Six participants with shoulder pain and 15 healthy unimpaired individuals participated. Individuals with shoulder pain were tested on the APB 2000 using their affected upper extremity. Unimpaired participants were instructed to perform normally on the test with randomly selected upper extremity and to feign shoulder pain with the other upper extremity. The two tests for the unimpaired participants were conducted 1 week apart. There were significant differences in mean performance time for normal, patient, and feigned performance, with 80, 111, and 149 sec for the three groups respectively (p < 0.0005). There was also considerable overlap in the three distributions of performance times. These preliminary findings suggest that the APB 2000 is able to distinguish performance time between these three groups. Whether it can be used to distinguish between maximal performance and submaximal performance in individuals suspected of submaximal performance requires further study.
Recovery and STR Amplification of DNA from RFLP Membranes*
Authors: Steadman Shelly A. , McDonald J. David , Andrews John S. , Watson Nigel D.
Published: March 2008

Abstract:  Restriction fragment length polymorphism (RFLP) techniques were utilized in the forensic DNA community until the mid 1990s when less labor‐intensive polymerase chain reaction short tandem repeat (PCR STR) techniques became available. During the transition from RFLP technology to PCR‐based STR platforms, a method for comparing RFLP profiles to STR profiles was not developed. While the preferred approach for applying new technology to old cases would be to analyze the original biological stain, this is not always possible. For unsolved cases that previously underwent RFLP analysis, the only DNA remaining may be restriction cut and bound to nylon membranes. These studies investigate several methods for obtaining STR profiles from membrane bound DNA, including removal of bound DNA with bases, acids, detergents, various chemicals, and conventional cell extraction solutions. Direct multiplex STR amplification of template in the membrane‐bound state was also explored. A partial STR profile was obtained from DNA that was recovered from an archived membrane using conventional extraction buffer components, indicating promise for recovering useful STR information from RFLP membranes that have been maintained in long‐term frozen storage.
Using Ninhydrin to Detect Gravesoil*
Authors: Carter David O. , Yellowlees David , Tibbett Mark
Published: March 2008

Abstract:  Some death scene investigations commence without knowledge of the location of the body and/or decomposition site. In these cases, it is necessary to locate the remains or the site where the body decomposed prior to movement. We hypothesized that the burial of a mammalian cadaver will result in the release of ninhydrin reactive nitrogen (NRN) into associated soil and that this reaction might have potential as a tool for the identification of clandestine graves. Juvenile rat (Rattus rattus) cadavers were buried in three contrasting soil types in Australian tropical savanna ecosystems and allowed to decompose over a period of 28 days. Soils were sequentially harvested and analyzed for NRN. Cadaver burial resulted in an approximate doubling (mean = 1.7 ± 0.1) in the concentration of soil NRN. This reaction has great potential to be used as a presumptive test for gravesoil and this use might be greatly enhanced following more detailed research.
Yet Another Method for Marking Incisal Edges of Teeth for Bitemark Analysis
Authors: Metcalf Roger D.
Published: March 2008

Abstract:  Over the years many methods have been proposed and presented for marking or “highlighting” the incisal edges of anterior teeth on a dental stone model—one of the critical steps in production of transparent overlays for bitemark analysis. A method is presented here that is an extension and refinement of the “paint the edges” method shown at least as early as 1966 by Gustafson. This method uses “invisible ink” and ultraviolet illumination to produce a very high contrast image of the incisal edges of the teeth on the model. The advantages of this new method are that it is nondestructive, it does not leave visible marks on the models, operator subjectivity in selecting the portions of anterior teeth to be highlighted is reduced, and the author submits that this technique lends itself to easy construction of overlays using computer image‐processing software such as Adobe Photoshop® and ImageJ.
Allele Frequencies of 15 STR Loci in the Population of the City of Quito, Ecuador
Authors: Gómez María Atilia , Peñaherrera María Serena , Aguirre‐Tello Víctor , Vela‐Cavinato Margarita , Giovambattista Guillermo
Published: March 2008

Population:

Quito City Population (Ecuador, South America, n = 116–207).
Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV irradiation
Authors: Yamaguchi Yuji , Coelho Sergio G. , Zmudzka Barbara Z. , Takahashi Kaoruko , Beer Janusz Z. , Hearing Vincent J. , Miller Sharon A.
Published: March 2008

Abstract:  Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II–III skin were irradiated at 100–600 J/m2 every 2–7 days over a 4‐ to 5‐week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m2) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana–Masson staining, melanocyte function by expression of melanocyte‐specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46‐phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53‐positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV‐induced DNA damage but not as effectively as constitutive pigmentation.
Selective feeding in a generalist invertivore, age‐0 striped bass
Authors: Howe D. V. , Jordan R. C. , Juanes F.
Published: March 2008

Abstract –  Age‐0 striped bass (Morone saxatilis) and potential benthic and epibenthic invertebrate prey were collected at three sites in the mid‐estuarine region of the Hudson River, New York, USA. Diet was related to prey availability to investigate the role of selectivity in feeding behaviour. The effects of prey availability and selectivity on stomach fullness were also examined. Gammarid amphipods and chironomid larvae were most numerous as stomach contents; and chironomid larvae, polychaetes, and isopods were the most numerous invertebrates captured. When selective feeding occurred, gammarid amphipods, Crangon spp. shrimp, and chironomid larvae were most commonly the preferred prey. Selective feeding correlated with higher stomach fullness. Fullness was also higher when the preferred prey was categorized as epibenthic versus benthic. Interaction between prey availability and environmental conditions appears to be an important determinant of age‐0 striped bass feeding behaviour.
Satisfied Worms
Authors: Foley John F.
Published: March 2008

The rise in the incidence of obesity has stimulated interest in determining the mechanisms that are involved in controlling appetite and thus preventing overeating. Discovering the signals responsible for making a person feel satisfied (or satiated) after eating might help in the development of therapies to prevent obesity. You
et al
. used the worm
Caenorhabditis
elegans
as a model system to study the factors that control appetite.
C
.
elegans
normally feed and move constantly when food is available, but the authors found that worms exposed to a high-quality (high nutritional value) food source gradually decreased their rates of food intake and movement, compared with those of worms exposed to low-quality food. The former worms entered a state of quiescence that resembled the resting state of satiated mice. Mutant
C. elegans
that had a defect in nutrient absorption from the intestine were less quiescent than their wild-type counterparts. Mutant
C. elegans
that were singly deficient in the worm homologs of insulin, transforming growth factor-β (TGF-β), or either of the receptors for TGF-β exhibited much shorter periods of quiescence compared with those of wild-type worms.
C
.
elegans
with a loss-of-function mutation in the cGMP-dependent protein kinase (PKG) homolog EGL-4 (which is downstream of insulin and TGF-β) are known to be larger and more migratory than wild-type
C
.
elegans
. The authors found that
egl-4
loss-of-function mutants never entered a state of quiescence during feeding, whereas
egl-4
gain-of-function mutants showed a longer duration of quiescence than did wild-type worms. Finally, worms deficient in the enzyme that synthesizes cGMP had a shorter duration of quiescence than did wild-type worms. This study suggests that insulin- and TGF-β-mediated signals through PKG may serve as targets of therapies against obesity.

Y.-j. You, J. Kim, D. M. Raizen, L. Avery, Insulin, cGMP, and TGF-β signals regulate food intake and quiescence in
C
.
elegans
: A model for satiety.
Cell
Metab
.
7
, 249-257 (2008).
[PubMed]
Mitochondrial Proteases Required for Survival
Authors: Gough Nancy R.
Published: March 2008

The mitochondria are key players in mediating cell death or survival. The release of mitochondrial proteases contributes to cell death during apoptosis. However, knockout of genes encoding the mitochondrial proteases HtrA2 or Parl results in increased susceptibility to apoptosis of lymphocytes and neurons; thus, the function of these enzymes in cell death and survival is complex. Chao
et al
. screened for genes that suppressed apoptosis of fetal liver cells null for Janus kinase 2 and identified the gene
Hax1
, which encodes an antiapoptotic protein that is localized to the mitochondrial intermembrane space through a C-terminal transmembrane domain and that has BH1- and BH2-like domains, which make it related to Bcl-2 proteins. When the gene was disrupted in mice, the phenotype, loss of lymphocytes and neurodegeneration in the striatum and cerebellar cortex, was similar to the phenotype of mice lacking functional HtrA2 or Parl. Thus, the authors investigated whether these three proteins have a functional interaction that is important for setting the threshold for apoptosis. Hax1 and HtrA2 had been previously reported to interact in a yeast two-hybrid screen. HtrA2 is synthesized as an inactive precursor that is cleaved within the mitochondria to produce the active form. Chao
et al
. found that the abundance of processed HtrA2 was decreased in Hax1-null mouse tissues. Furthermore, when COS-7 cells were transfected with both HtrA2 and Hax1 or with HtrA2 and Parl, the abundance of processed HtrA2 was increased compared with that in cells only transfected with HtrA2. In addition, coimmunoprecipitation experiments with endogenous proteins or those from transfected cells showed that Hax1 interacted with both HtrA2 and Parl. Thus, the authors suggest that Hax1 aids in the presentation of HtrA2 to Parl for processing and activation. How this affects apoptosis was the next question. Although knockout of
Bax
,
Bak
, or
Bim
(genes encoding proapoptotic Bcl-2 proteins) did not alleviate the neurodegeneration found in the Hax1-deficient animals, knockout of
Bax
or
Bim
did rescue Hax1-deficient lymphocytes from cell death induced by cytokine withdrawal. Activated T cells that were deficient in Hax1 or that had a mutated HtrA2 with disrupted protease activity showed faster kinetics for the appearance of the activated form of Bax, an event associated with apoptosis. Thus, the proteins of the intermembrane space appear to contribute to regulation of apoptosis before mitochondrial membrane permeabilization.

J.-R. Chao, E. Parganas, K. Boyd, C. Y. Hong, J. T. Opferman, J. N. Ihle, Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons.
Nature
452
, 98-102 (2008).
[PubMed]
Toward a Designer GAS Vaccine
Authors: Ash Caroline
Published: March 2008

M proteins are antigenically variable cell-surface virulence factors of group A
Streptococcus
(GAS). This organism is an important cause of human illness and notably provokes the autoimmune disease rheumatic fever. McNamara
et al.
examined a fragment of M1 that binds to host fibrinogen and promotes inflammation. The M1 protein consists of α-helical coiled coils bearing distinctive structural features that impart irregularity and instability to the coiled coil. These features mimic muscle myosin and tropomyosin, which may explain postinfection autoimmune responses. Mice immunized with a mutant, stabilized M protein exhibited reduced harmful inflammation without compromising protective immune responses.

C. McNamara, A. S. Zinkernagel, P. Macheboeuf, M. W. Cunningham, V. Nizet, P. Ghosh, Coiled-coil irregularities and instabilities in group A
Streptococcus
M1 are required for virulence.
Science
319
, 1405-1408 (2008).
[Abstract]
[Full Text]
Yorkie’s Elusive Partner
Authors: Foley John F.
Published: March 2008

The Hippo (Hpo) kinase cascade plays a critical role, conserved from
Drosophila
to mammals, in the control of cell proliferation and organ size. As a consequence of Hpo activation in
Drosophila
, the transcriptional coactivator Yorkie (Yki) is phosphorylated and sequestered in the cytoplasm. The exclusion of Yki from the nucleus results in the reduced expression of
cyclin E
, which stimulates cell proliferation, and
diap1
, which is an antiapoptotic gene. Two aspects of Hpo signaling that have thus far remained elusive are the identity of the transcription factor that pairs with Yki to stimulate cell growth and whether Yki directly activates the genes whose expression is antagonized by Hpo. Two groups, Zhang
et
al
. and Wu
et
al
., performed very similar studies that identified the transcription factor Scalloped (Sd), a homolog of mammalian TEF proteins, as the binding partner of Yki. Reporter assays in a
Drosophila
cell line showed that the Sd-Yki complex formed a transcriptional unit whose activity was inhibited by Hpo. In
Drosophila
, outgrowth of cells in the eye caused by the overexpression of Yki was blocked when Sd was depleted by RNA interference, as was Yki-mediated expression of Hpo-target genes. Binding of Sd to Yki was necessary for both the nuclear translocation of Yki and the recruitment of Yki to the
diap1
enhancer, the first evidence of the direct activation of an Hpo-target gene by Yki. Considering that the mammalian Yki homolog YAP is implicated in organ outgrowth and certain cancers (see Bandura and Edgar), these studies suggest that TEF-YAP complexes, the mammalian homologs of Sd-Yki, may serve as targets for therapies against tumorigenesis.

L. Zhang, F. Ren, Q. Zhang, Y. Chen, B. Wang, J. Jiang, The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.
Dev
.
Cell
14
, 377-387 (2008).
[PubMed]

S. Wu, Y. Liu, Y. Zheng, J. Dong, D. Pan, The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway.
Dev
.
Cell
14
, 388-398 (2008).
[PubMed]

J. L. Bandura, B. A. Edgar, Yorkie and Scalloped: Partners in growth activation.
Dev
.
Cell
14
, 315-316 (2008).
[PubMed]
Synthetic Biology in Action
Authors: Ray L. Bryan
Published: March 2008

One goal of synthetic biology is to remodel intracellular processes at will. Bashor
et al.

(see the Perspective by Pryciak) wanted to engineer new regulatory properties into the well-studied mitogen-activated protein kinase pathway in yeast that mediates the response to mating pheromones. By creating proteins with customized protein interaction domains, which altered the association of signaling proteins with a key scaffold protein that assembles proteins that participate in the signaling pathway, the authors changed complex regulatory properties of the signaling pathway. A gradual dose response could be modified into a switchlike all-or-none response, the time course of system response could be varied, or adaptation (a process in which output diminishes even in the presence of continued stimulus) could be added.

C. J. Bashor, N. C. Helman, S. Yan, W. A. Lim, Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics.
Science
319
, 1539-1543 (2008).
[Abstract]
[Full Text]

P. M. Pryciak, Customized signaling circuits.
Science
319
, 1489-1490 (2008).
[Summary]
[Full Text]