bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of methylphenidate formulation on treatment patterns and hospitalizations: a retrospective analysis
Authors: Kemner Jason E , Lage Maureen J
Published: April 2006

Background

While stimulant therapy has been shown to be effective in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is less information concerning differences between alternative stimulant medications. The purpose of this study is to examine how different formulations of methylphenidate (MPH) affect treatment patterns and hospitalizations.

Methods

From a large claims database we retrospectively identified individuals age 6 or older who were diagnosed with ADHD and who received either once daily, extended-release oral system methylphenidate (OROS®MPH) (e.g., Concerta®) or three-times daily immediate-release generic methylphenidate (TID MPH). There were 5,939 individuals included in the analysis – 4,785 who initiated therapy with OROS MPH and 1,154 who initiated therapy with TID MPH. We used Analyses of Covariance (ANCOVAs) to examine differences in treatment patterns between individuals who initiated therapy on OROS MPH and those who initiated therapy on TID MPH. We used logistic and negative binomial multivariate regressions to examine the probability of being hospitalized and the hospital length of stay.

Results

Controlling for demographic characteristics, patient general health status, and comorbid diagnoses, significantly fewer individuals who initiated therapy with OROS MPH had a 15-day gap in therapy (85% vs. 97%, p < 0.0001 or a 30-day gap in therapy (77% vs. 95%, p < 0.0001) or switched to another ADHD medication (27% vs. 68%, p < 0.0001). Individuals who initiated therapy with OROS MPH stayed on therapy significantly longer (199 vs. 108 mean days, p < 0.0001) and more individuals received medication for 90% (24% vs. 5%, p < 0.0001), 80% (29% vs. 7%, p < 0.0001), or 75% (30% vs. 7%, p < 0.0001) of the days during the first year post initiation of therapy. Individuals who initiated therapy on OROS MPH were also significantly less likely to be hospitalized (odds ratio = 0.67, p = 0.0454) and stayed, on average, 0.69 fewer days in the hospital (p = 0.0035).

Conclusion

Results demonstrate that among individuals diagnosed with ADHD who receive either OROS MPH or TID MPH, the use of OROS MPH is associated with fewer gaps in medication, less switches in medication, and more days on intent-to-treat therapy. In addition, use of OROS MPH compared to TID MPH was associated with improved outcomes, as measured by the reduced use of hospitalizations.
Buoyancy studies in natural communities of square gas-vacuolate archaea in saltern crystallizer ponds
Authors: Oren Aharon , Pri-El Nuphar , Shapiro Orr , Siboni Nachshon
Published: April 2006

Background

Possession of gas vesicles is generally considered to be advantageous to halophilic archaea: the vesicles are assumed to enable the cells to float, and thus reach high oxygen concentrations at the surface of the brine.

Results

We studied the possible ecological advantage of gas vesicles in a dense community of flat square extremely halophilic archaea in the saltern crystallizer ponds of Eilat, Israel. We found that in this environment, the cells' content of gas vesicles was insufficient to provide positive buoyancy. Instead, sinking/floating velocities were too low to permit vertical redistribution.

Conclusion

The hypothesis that the gas vesicles enable the square archaea to float to the surface of the brines in which they live was not supported by experimental evidence. Presence of the vesicles, which are mainly located close to the cell periphery, may provide an advantage as they may aid the cells to position themselves parallel to the surface, thereby increasing the efficiency of light harvesting by the retinal pigments in the membrane.
Voluntary activation failure is detectable in some myositis patients with persisting quadriceps femoris weakness: an observational study
Authors: Molloy Catherine B , Al-Omar Ahmed O , Edge Kathryn T , Cooper Robert G
Published: April 2006

This cross-sectional, observational study was undertaken to examine whether voluntary activation failure could contribute to the persisting weakness observed in some patients with treated idiopathic inflammatory myositis. In 20 patients with myositis of more than six months' duration (5 males, 15 females; mean [± 1 SD] age 53 [11] years) and 102 normal subjects (44 males, 58 females; mean age 32 [8] years), isometric maximum voluntary contractions (MVCs) of the dominant quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects and patients were then normalised with respect to lean body mass (force per units of lean body mass), giving a result in Newtons per kilogram. Based on mass-normalised force data of normal subjects, patients were arbitrarily stratified into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch interpolation" technique was used to assess whether the QF voluntary activation of patients was complete. This technique relies on the fact that, because muscle activation is incomplete during submaximal voluntary contractions, electrical stimulation of the muscle can induce force increments superimposed on the submaximal voluntary force being generated. No between-gender differences were seen in the mass-normalised MVC results of healthy subjects, so the gender-combined results of 6.6 (1.5) N/kg were used for patient stratification. No between-gender difference was found for mass-normalised MVCs in patients: males 5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male patients were as great as those of normal subjects (p > 0.05), but mass-normalised MVCs of female patients were significantly smaller than those of the normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited interpolated twitches during electrical stimulation, but six of the 14 "weak" patients did, the biggest twitches being seen in the weakest patient. That interpolated twitches can be induced in some myositis patients with ongoing QF weakness during supposed MVCs clearly suggests that voluntary activation failure does contribute to QF weakness in those patients.
Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behçet's disease
Authors: Delunardo Federica , Conti Fabrizio , Margutti Paola , Alessandri Cristiano , Priori Roberta , Siracusano Alessandra , Riganò Rachele , Profumo Elisabetta , Valesini Guido , Sorice Maurizio , Ortona Elena
Published: April 2006

Given the lack of a serological test specific for Behçet's disease, its diagnosis rests upon clinical criteria. The clinical diagnosis is nevertheless difficult because the disease manifestations vary widely, especially at the onset of disease. The aim of this study was to identify molecules specifically recognized by serum autoantibodies in patients with Behçet's disease and to evaluate their diagnostic value. We screened a cDNA library from human microvascular endothelial cells with serum IgG from two patients with Behçet's disease and isolated a reactive clone specific to the carboxy-terminal subunit of Sip1 (Sip1 C-ter). Using ELISA, we measured IgG, IgM and IgA specific to Sip1 C-ter in patients with various autoimmune diseases characterized by the presence of serum anti-endothelial cell antibodies, such as Behçet's disease, systemic lupus erythematosus, systemic sclerosis and various forms of primary vasculitis, as well as in patients with diseases that share clinical features with Behçet's disease, such as inflammatory bowel disease and uveitis. IgM immunoreactivity to Sip1 C-ter was significantly higher in patients with Behçet's disease and in patients with primary vasculitis than in the other groups of patients and healthy subjects tested (P < 10-4 by Mann-Whitney test). ELISA detected IgG specific to Sip1 C-ter in sera from 11/56 (20%) patients with Behçet's disease, IgM in 23/56 (41%) and IgA in 9/54 (17%). No sera from patients with systemic lupus erythematosus, systemic sclerosis, inflammatory bowel disease, uveitis or healthy subjects but 45% of sera from patients with primary vasculitis contained IgM specific to Sip1 C-ter. Serum levels of soluble E-selectin, a marker of endothelial activation and inflammation, correlated with levels of serum IgM anti Sip-1 C-ter in patients with Behçet's disease (r = 0.36, P = 0.023). In conclusion, Sip1 C-ter is a novel autoantigen in Behçet's disease. IgM specific to Sip1 C-ter might be useful in clinical practice as an immunological marker of endothelial dysfunction in vasculitis.
Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Data from the Spanish registry BIOBADASER
Authors: Carmona Loreto , Gómez-Reino Juan J
Published: April 2006

The aim of the present work is to compare drug survival and safety of infliximab, etanercept, and adalimumab (tumor necrosis factor [TNF] antagonists) in spondylarthritis (SpA) with those of rheumatoid arthritis (RA). To this purpose, we analysed the data in BIOBADASER (2000–2005), a drug registry launched in 2000 for long-term follow-up of the safety of these biologics in rheumatic diseases. The rates of drug discontinuation and adverse events (AEs) in SpA (n = 1,524) were estimated and compared with those of RA (n = 4,006). Cox regression analyses were used to adjust for independent factors. Total exposure to TNF antagonists for SpA was 2,430 patient-years and 7,865 for RA. Drug survival in SpA was significantly greater than in RA at 1, 2, and 3 years. The hazard ratio (HR) for discontinuation in SpA compared with RA was 0.66 (95% confidence interval [CI], 0.57–0.76) after adjustment for age, gender, and use of infliximab. The difference remained after controlling for the individual medication and its place in the sequence of treatment. There were fewer SpA patients with AEs (17%) than RA patients (26%; p < 0.001). The HR for AEs in SpA was 0.80 (95% CI, 0.70–0.91) compared with RA after adjustment for age, disease duration, and use of infliximab. In conclusion, due in part to a better safety profile, survival of TNF antagonists in SpA is better than in RA. TNF antagonists are at present a safe and effective therapeutic option for long-term treatment of patients with SpA failing to respond to traditional drugs. Because chronic therapy is necessary, continual review of this issue is necessary.
Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay
Authors: Perreard Laurent , Fan Cheng , Quackenbush John F , Mullins Michael , Gauthier Nicholas P , Nelson Edward , Mone Mary , Hansen Heidi , Buys Saundra S , Rasmussen Karen , Orrico Alejandra Ruiz , Dreher Donna , Walters Rhonda , Parker Joel , Hu Zhiyuan , He Xiaping , Palazzo Juan P , Olopade Olufunmilayo I , Szabo Aniko , Perou Charles M , Bernard Philip S
Published: April 2006

Introduction

Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation.

Methods

Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and qRT-PCR data by hierarchical clustering. A proliferation signature was used as a single meta-gene (log2 average of 14 genes) to predict outcome within the context of estrogen receptor status and biological 'intrinsic' subtype.

Results

We found that the qRT-PCR assay could determine the intrinsic subtype (93% concordance with microarray-based assignments) and that the intrinsic subtypes were predictive of outcome. The proliferation meta-gene provided additional prognostic information for patients with the Luminal subtype (P = 0.0012), and for patients with estrogen receptor-positive tumors (P = 3.4 × 10-6). High proliferation in the Luminal subtype conferred a 19-fold relative risk of relapse (confidence interval = 95%) compared with Luminal tumors with low proliferation.

Conclusion

A real-time qRT-PCR assay can recapitulate microarray classifications of breast cancer and can risk-stratify patients using the intrinsic subtype and proliferation. The proliferation meta-gene offers an objective and quantitative measurement for grade and adds significant prognostic information to the biological subtypes.
Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients
Authors: Rhodes Andrew , Wort Stephen J , Thomas Helen , Collinson Paul , Bennett E David
Published: April 2006

Introduction

Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis.

Methods

Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human β-haemoglobin gene.

Results

Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65–362) ng/ml versus 74 (46–156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185–430) ng/ml versus 71 (46–113) ng/ml, P < 0.001) or in hospital (260 (151–380) ng/ml versus 68 (47–103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0–1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU.

Conclusion

Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.
Benchmarking ortholog identification methods using functional genomics data
Authors: Hulsen Tim , Huynen Martijn A , de Vlieg Jacob , Groenen Peter MA
Published: April 2006

Background

The transfer of functional annotations from model organism proteins to human proteins is one of the main applications of comparative genomics. Various methods are used to analyze cross-species orthologous relationships according to an operational definition of orthology. Often the definition of orthology is incorrectly interpreted as a prediction of proteins that are functionally equivalent across species, while in fact it only defines the existence of a common ancestor for a gene in different species. However, it has been demonstrated that orthologs often reveal significant functional similarity. Therefore, the quality of the orthology prediction is an important factor in the transfer of functional annotations (and other related information). To identify protein pairs with the highest possible functional similarity, it is important to qualify ortholog identification methods.

Results

To measure the similarity in function of proteins from different species we used functional genomics data, such as expression data and protein interaction data. We tested several of the most popular ortholog identification methods. In general, we observed a sensitivity/selectivity trade-off: the functional similarity scores per orthologous pair of sequences become higher when the number of proteins included in the ortholog groups decreases.

Conclusion

By combining the sensitivity and the selectivity into an overall score, we show that the InParanoid program is the best ortholog identification method in terms of identifying functionally equivalent proteins.
Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity
Authors: Goldman Devorah C. , Hackenmiller Renee , Nakayama Takuya , Sopory Shailaja , Wong Crispin , Kulessa Holger , Christian Jan L.
Published: April 2006

ProBMP4 is initially cleaved at a site adjacent to the mature ligand (the S1 site) allowing for subsequent cleavage at an upstream (S2) site. Mature BMP4 synthesized from a precursor in which the S2 site cannot be cleaved remains in a complex with the prodomain that is targeted for lysosomal degradation, and is thus less active when overexpressed in Xenopus. Here we report that mice carrying a point mutation that prevents S2 processing show severe loss of BMP4 activity in some tissues, such as testes and germ cells, whereas other tissues that are sensitive to Bmp4 dosage, such as the limb, dorsal vertebrae and kidney, develop normally. In a haploinsufficient background, inability to cleave the S2 site leads to embryonic and postnatal lethality due to defects in multiple organ systems including the allantois, placental vasculature, ventral body wall, eye and heart. These data demonstrate that cleavage of the S2 site is essential for normal development and, more importantly, suggest that this site might be selectively cleaved in a tissue-specific fashion. In addition, these studies provide the first genetic evidence that BMP4 is required for dorsal vertebral fusion and closure of the ventral body wall.
The TAGteam DNA motif controls the timing ofDrosophilapre-blastoderm transcription
Authors: Bosch John R. ten , Benavides Joseph A. , Cline Thomas W.
Published: April 2006

The Drosophila sex-determination switch gene Sex-lethal(Sxl) and the X-chromosome signal element genes (XSEs) that induce the female-specific expression of Sxl are transcribed extremely early in development when most of the genome of this organism is still silent. The DNA sequence CAGGTAG had been implicated in this pre-cellular blastoderm activation of sex-determination genes. A genome-wide computational search,reported here, suggested that CAGGTAG is not specific to early sex-determination genes, since it is over-represented upstream of most genes that are transcribed pre-cellular blastoderm, not just those involved in sex determination. The same search identified similarly over-represented,one-base-pair degenerate sequences as possible functional synonyms of CAGGTAG. We call these heptamers collectively, the TAGteam. Relevance of the TAGteam sequences to pre-cellular blastoderm transcription was established through analysis of TAGteam changes in Sxl, scute (an XSE), and the `ventral repression element' of the pattern-formation gene zerknüllt.Decreasing the number of TAGteam sites retarded the onset of pre-blastoderm transcription, whereas increasing their number correlated with an advanced onset. Titration of repressors was thought to be the rate-limiting step determining the onset of such early transcription, but this TAGteam dose effect shows that activators must also play an important role in the timing of pre-blastoderm gene expression.
Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube
Authors: Liu Shasha , Liu Fangyu , Schneider Amanda E. , St. Amand Tara , Epstein Jonathan A. , Gutstein David E.
Published: April 2006

Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior studies suggest a vital role for CNC expression of Cx43 in heart development. Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT phenotype, although coronary vasculature was abnormal in this mutant line. A broader CKO mediated by P3pro (Pax3)-Cre,involving both ventral and dorsal aspects of the thoracic neural tube and CNC,resulted in infundibular bulging and coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre-mediated loss of Cx43 in the neural tube was characterized by a late phase of cellular delamination from the dorsal and lateral neural tube, a markedly increased abundance of neuroepithelium-derived cells outside of the neural tube and an excess of such cells infiltrating the heart and infundibulum. Thus, expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43 is not required in the CNC for normal OFT morphogenesis. Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development.
Editorial: Save Research—Abandon the Case Method of Teaching
Authors: Shugan Steven M.
Published: April 2006

The case method of teaching and the corresponding Socratic Method predate the discovery of the scientific method for advancing knowledge and problem solving. The case method applies known principles (e.g., laws) to specific situations while the scientific method focuses on discovering principles. Although the case method might be effective at teaching leadership and persuasion skills, it can lack the spirit of inquiry and the worship of the truth associated with the scientific method. Moreover, unlike legal cases, business cases lack precedent (i.e., stare decisis), the foundation of written law, and rigorous adjudication. More importantly, the traditional case method of teaching often ignores important research findings. Consequently, it helps destroy the link between academic research and classroom learning. Students lose the benefit of important research findings while leaving the classroom with false confidence about what they know. Researchers lose an incentive to do research relevant to their students. Eventually, there is less research worth teaching, and fewer students value the knowledge learned through painstaking research. Although we might covet the skill of persuasion, time might gradually elevate previously less persuasive managers who have better skills with analysis and collecting relevant information. Great teaching requires great content, in addition to active learning.
Proportional Representation, ‘Party Hopping’ and the Limits of Electoral Regulation: A Cautionary Tale from New Zealand
Authors: Geddis Andrew
Published: April 2006

The ‘proper’ role for an elected representative is a long debated question, one which has been made even more complicated by the domination of the electoral process by mass membership political parties. In the wake of New Zealand's adoption of the mixed member proportional voting system, that country has chosen to prescribe through legislation a ‘party team mandate’ role for Members of Parliament (MPs). This ‘party hopping law’ requires any MP who leaves the party for which he or she was elected also to leave his or her seat in Parliament. However, the use of legal regulation to impose a fixed representative ideal upon MPs has led to a number of negative consequences for New Zealand's political processes. This article examines the theory behind the party hopping law, outlines the reasons why it was enacted, traces the concrete consequences of its adoption, and draws some broader lessons as to the limits of legal regulation in the electoral arena.
Criminal Networks, Illegal Immigration and the Threat to Border Security
Authors: James Adrian
Published: April 2006

This paper considers some of the challenges posed to law enforcement agencies in post-modernity by the emergence of transnational criminal networks. Law enforcement, once very much local in character, must now reshape its structures and processes to meet the new and emerging risks presented. Though the paper uses the topic of illegal immigration to reveal something of the nature of such networks and the threat they pose, it also observes that fundamentally, transnational criminal networks are profit-driven and that, perhaps, it is misguided to think of these groups either as commodity-specific or process-specific. The paper concludes that law enforcement agencies need to meet the challenge that such networks present by managing their business with equal flexibility and resourcefulness. Though mechanisms to support that business are being developed, law enforcement agencies must not lose sight of the fact that it is successful outcomes, in the form of the dismantling and disruption of transnational criminal networks, rather than the new processes themselves (that simply underpin law enforcement's efforts) that are important.
Police Perceptions of Their Working Environment: Surveying the Small Department
Authors: Sims Barbara , Ruiz Jim , Weaver Ginger , Harvey William L.
Published: April 2006

This paper reports the findings of an exploratory study designed to provide a local police chief and other key stakeholders with perceptions of police officers related to policing a small town in south central Pennsylvania. Following a brief review of the literature that examines many of the issues addressed in the present study, the methodology and major findings from the study are reported and discussed. The paper concludes with recommendations for possible interventions that could be undertaken, by not only the department in question, but by small police departments in other locations as well.
Service Culture for the Implementation of Community Policing: A Case Study of the Malaysian Police
Authors: Cheurprakobkit Sutham , Puthpongsiriporn Sarit
Published: April 2006

Although a police service function is a key component of community policing, very few studies on service culture have been conducted, especially in the Royal Malaysian Police which has adopted and practised the concept of community policing since 1979. This study surveyed 297 Kuala Lumpur Metropolitan police officers regarding their attitudes toward the concept of service culture in their police force and the impact service culture has on community policing. Overall, the study's results show that Malaysian police support community policing and believe service culture is part of their police organisation. However, only two of the seven cultural values (internal communication and service orientation) were positively and significantly correlated with commitment to practising community policing. The study recommends proper training on community policing (particularly for police administrators and new recruits) and creation of relevant service culture conducive to the implementation of community policing.
Health Performance and Age Restriction Policies in Policing
Authors: Pascarella Joseph E.
Published: April 2006

Age restriction policies in policing and law enforcement are discriminatory age restriction policies that have been permitted because of the physical abilities necessary for effective policing and law enforcement. However, there are few empirical studies that validate the necessity of age restriction policies based upon variations of health performance of a large group of police or law enforcement officers over the course of their entire careers. This article is a cohort analysis of 3,012 police officers hired in 1985 and follows their careers for a 19-year period through the end of 2003. A logistic regression equation was constructed to determine if there are any variations in health performance between younger and older police officers as measured by disability pensions. Although there is some evidence that older police officers were more likely to receive heart disability pensions, age restriction policies should be agency-based and determined by a totality of circumstances such as the detriment to public safety, protection of individual rights, efficiency of the agency, and financial costs.
Electronic Curfew Orders and Juvenile Offenders
Authors: Sanger Janine
Published: April 2006

In the last two decades government sentencing policy has increasingly looked at ways of dealing with offenders within the community. As with many criminal justice strategies the government turned to America for inspiration in penal policy. One of the more controversial strategies to be adopted was the use of electronic tagging for young offenders at a time when Home Office statistics show this group has increased its reoffending rate. This article discusses the findings of research, undertaken in the Southampton area of the UK, which considered its effectiveness as an overall deterrent to crime and anti-social behaviour. Its conclusion questions the viability of tagging as a deterrence.
Police Officer Discretion and Race in an American Midwestern City: Predicting Arrests, Citations, and Warnings: A Multivariate Examination
Authors: Leinfelt Fredrik H.
Published: April 2006

In the recent past, there has been a significant policy space and political salience for issues pertaining to racial profiling and alleged discriminatory police practices. The notion of race as an influencing criterion for police decision making is particularly problematic as it challenges the fundamental assumption that the legal system is impartial and just. Biased policing practices will lead to allegations of constitutional rights violations, allegations of civil rights violations, create citizen distrust in law enforcement, and undermine legitimate law enforcement efforts. The present study analysed 13,566 traffic stops collected over a 24-month period in a midwestern American city with a population of roughly 33,000. The dataset contained a total of 66 predictors, including interaction terms and dummy variable coding. Multivariate regression findings do not lend conclusive support to the notion that police officers use race as a pretext for making arrests, issuing traffic citations, and/or giving warnings to motorists in the examined jurisdiction. Policy implications and future research directions are discussed.
APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer
Authors: Groskopf Jack , Aubin Sheila MJ , Deras Ina Lim , Blase Amy , Bodrug Sharon , Clark Craig , Brentano Steven , Mathis Jeannette , Pham Jimmykim , Meyer Troels , Cass Michelle , Hodge Petrea , Macairan Maria Luz , Marks Leonard S , Rittenhouse Harry
Published: April 2006

Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine.

Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated.

Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles.

Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.
Ultrasensitive Monitoring of HIV-1 Viral Load by a Low-Cost Real-Time Reverse Transcription-PCR Assay with Internal Control for the 5′ Long Terminal Repeat Domain
Authors: Drosten Christian , Panning Marcus , Drexler Jan Felix , Hänsel Florian , Pedroso Celia , Yeats Jane , de Souza Luna Luciano Kleber , Samuel Matthew , Liedigk Britta , Lippert Ute , Stürmer Martin , Doerr Hans Wilhelm , Brites Carlos , Preiser Wolfgang
Published: April 2006

Background: Current HIV-1 viral-load assays are too expensive for resource-limited settings. In some countries, monitoring of antiretroviral therapy is now more expensive than treatment itself. In addition, some commercial assays have shown shortcomings in quantifying rare genotypes.

Methods: We evaluated real-time reverse transcription-PCR with internal control targeting the conserved long terminal repeat (LTR) domain of HIV-1 on reference panels and patient samples from Brazil (n = 1186), South Africa (n = 130), India (n = 44), and Germany (n = 127).

Results: The detection limit was 31.9 IU of HIV-1 RNA/mL of plasma (>95% probability of detection, Probit analysis). The internal control showed inhibition in 3.7% of samples (95% confidence interval, 2.32%–5.9%; n = 454; 40 different runs). Comparative qualitative testing yielded the following: Roche Amplicor vs LTR assay (n = 431 samples), 51.7% vs 65% positives; Amplicor Ultrasensitive vs LTR (n = 133), 81.2% vs 82.7%; BioMerieux NucliSens HIV-1 QT (n = 453), 60.5% vs 65.1%; Bayer Versant 3.0 (n = 433), 57.7% vs 55.4%; total (n = 1450), 59.0% vs 63.8% positives. Intra-/interassay variability at medium and near-negative concentrations was 18%–51%. The quantification range was 50–10 000 000 IU/mL. Viral loads for subtypes A–D, F–J, AE, and AG yielded mean differences of 0.31 log10 compared with Amplicor in the 103–104 IU/mL range. HIV-1 N and O were not detected by Amplicor, but yielded up to 180 180.00 IU/mL in the LTR assay. Viral loads in stored samples from all countries, compared with Amplicor, NucliSens, or Versant, yielded regression line slopes (SD) of 0.9 (0.13) (P <0.001 for all).

Conclusions: This method offers all features of commercial assays and covers all relevant genotypes. It could allow general monitoring of antiretroviral therapy in resource-limited settings.
Segregating Variation in the Transcriptome:CisRegulation and Additivity of Effects
Authors: Hughes Kimberly A , Ayroles Julien F , Reedy Melissa M , Drnevich Jenny M , Rowe Kevin C , Ruedi Elizabeth A , Cáceres Carla E , Paige Ken N
Published: April 2006

Properties of genes underlying variation in complex traits are largely unknown, especially for variation that segregates within populations. Here, we evaluate allelic effects, cis and trans regulation, and dominance patterns of transcripts that are genetically variable in a natural population of Drosophila melanogaster. Our results indicate that genetic variation due to the third chromosome causes mainly additive and nearly additive effects on gene expression, that cis and trans effects on gene expression are numerically about equal, and that cis effects account for more genetic variation than do trans effects. We also evaluated patterns of variation in different functional categories and determined that genes involved in metabolic processes are overrepresented among variable transcripts, but those involved in development, transcription regulation, and signal transduction are underrepresented. However, transcripts for proteins known to be involved in protein–protein interactions are proportionally represented among variable transcripts.
A Genetic Test of the Role of the Maternal Pronucleus in Wolbachia-Induced Cytoplasmic Incompatibility in Drosophila melanogaster
Authors: Ferree Patrick M , Sullivan William
Published: April 2006

Cytoplasmic incompatibility (CI) is a reproductive sterility found in arthropods that is caused by the endoparasitic bacteria Wolbachia. In CI, host progeny fail to develop during early embryogenesis if Wolbachia-infected males fertilize uninfected females. It is widely accepted that this lethality is caused by some unknown Wolbachia-induced modification of the paternal nuclear material in the host testes. However, the direct means by which this modification leads to early embryonic death are currently unresolved. Results from previous studies suggested that CI lethality occurs as a result of asynchrony in cell cycle timing between the paternal and maternal pronuclei. This hypothesis can be tested experimentally by the prediction that the Wolbachia-modified paternal pronucleus should support androgenetic development (i.e., from the paternal pronucleus only). Using specific mutations in Drosophila melanogaster that produce androgenetic progeny, we demonstrate that the Wolbachia-induced modification inhibits this type of development. This result suggests that CI occurs independently of the maternal pronucleus and argues against pronuclear asynchrony as the primary cause of CI lethality. We propose that CI occurs instead as the result of either a developmentally incompetent paternal pronucleus or asynchrony between the paternal pronucleus and the cell cycle of the egg cytoplasm.
Mapping Novel Traits by Array-Assisted Bulk Segregant Analysis in Saccharomyces cerevisiae
Authors: Brauer Matthew J , Christianson Cheryl M , Pai Dave A , Dunham Maitreya J
Published: April 2006

We demonstrate a new method, microarray-assisted bulk segregant analysis, for mapping traits in yeast by genotyping pooled segregants. We apply a probabilistic model to the progeny of a single cross and as little as two microarray hybridizations to reliably map an auxotrophic marker, a Mendelian trait, and a major-effect quantitative trait locus.
Does the Acid Hydrolysis–Incubation Method Measure Meaningful Soil Organic Carbon Pools?
Authors: Paul Eldor A. , Morris Sherri J. , Conant Richard T. , Plante Alain F.
Published: April 2006

The literature was reviewed and analyzed to determine the feasibility of using a combination of acid hydrolysis and CO2–C release during long‐term incubation to determine soil organic carbon (SOC) pool sizes and mean residence times (MRTs). Analysis of 1100 data points showed the SOC remaining after hydrolysis with 6MHCl ranged from 30 to 80% of the total SOC depending on soil type, depth, texture, and management. Nonhydrolyzable carbon (NHC) in conventional till soils represented 48% of SOC; no‐till averaged 56%, forest 55%, and grassland 56%. Carbon dates showed an average of 1200 yr greater MRT for the NHC fraction than total SOC. Long‐term incubation, involving measurement of CO2evolution and curve fitting, measured active and slow pools. Active‐pool C comprised 2 to 8% of the SOC with MRTs of days to months; the slow pool comprised 45 to 65% of the SOC and had MRTs of 10 to 80 yr. Comparison of field14C and13C data with hydrolysis–incubation data showed a high correlation between independent techniques across soil types and experiments. There were large differences in MRTs depending on the length of the experiment. Insertion of hydrolysis–incubation derived estimates of active (Ca), slow (Cs), and resistant pools (Cr) into the DAYCENT model provided estimates of daily field CO2evolution rates. These were well correlated with field CO2measurements. Although not without some interpretation problems, acid hydrolysis–laboratory incubation is useful for determining SOC pools and fluxes especially when used in combination with associated measurements.
Overview of the Symposium Proceedings, “Meaningful Pools in Determining Soil Carbon and Nitrogen Dynamics”
Authors: Olk Daniel C. , Gregorich Edward G.
Published: April 2006

Extraction of soil organic matter (SOM) fractions has been a long‐standing approach to elucidating the pivotal roles of SOM in soil processes. Several types of extraction procedures are commonly used, and all provide partial information on SOM function. This report and accompanying papers summarize the information regarding SOM functions in real‐world issues that has been gained through physical or chemical fractionations. Each procedure has its strengths and weaknesses; each is capable to some degree of distinguishing labile SOM fractions from nonlabile fractions for studying soil processes, such as the cycling of a specific soil nutrient or anthropogenic compound, and each is based on an agent for SOM stabilization. Physical fractionations capture the effects on SOM dynamics of the spatial arrangement of primary and secondary organomineral particles in soil, but they do not consider chemical agents for SOM stabilization. They appear better suited for C cycling than N cycling. Chemical fractionations cannot consider the spatial arrangement, but their purely organic fractions are suitable for advanced chemical characterization and can be used to elucidate molecular‐level interactions between SOM and nutrients or other organic compounds. During all fractionations, the potential exists for sample alteration or mixing of material among fractions. We call for better coordination of research efforts by (i) developing integrated fractionation procedures that include physical, chemical, and/or biological components, and (ii) categorizing fractionations by their most suitable applications, defined by the nutrient, compound, or soil process in question, land use or crop type, crop management strategies, soil type, and possibly other factors. Selecting the most suitable fractionation procedure for a given research application would enable more precise approximation of the functional SOM pool.
Hydrochloric Fractions in Hedley Fractionation May Contain Inorganic and Organic Phosphates
Authors: He Zhongqi , Fortuna Ann-Marie , Senwo Zachary N. , Tazisong Irenus A. , Honeycutt C. Wayne , Griffin Timothy S.
Published: April 2006

Accurately characterizing phosphorus (P) forms is a prerequisite to developing effective remediation strategies to minimize the adverse environmental impact of agricultural expansion. Modified or unmodified Hedley sequential fractionation procedures have been widely used for characterizing P forms in soil, animal manure, and biosolids. Hydrochloric acid (HCl) fractions in these procedures have often been assumed to contain no organic P. As a result, many researchers for the last two decades have measured concentrations of inorganic P in HCl fractions without measuring organic P. In this study, we measured colorimetrically concentrations of inorganic P in untreated (control) HCl fractions after 3‐phytase incubation or oxidative autoclaving of these fractions. Phosphorus concentrations in some samples were also determined by inductively coupled plasma optical emission spectroscopy. The increases in measured P concentrations, compared with the controls, were attributed to organic P in these fractions. Data for 15 soil and eight manure samples indicated that, although HCl fractions of some samples contained negligible amounts of organic P, others contained significant amounts of organic P. The concentrations of organic P were greater than inorganic P in one soil sample and two manure samples. We recommend that organic P in HCl fractions be measured experimentally to determine whether the HCl fraction contains inorganic and organic P. Identification of possible organic P species contained in HCl fractions of the Hedley sequential fractionation schemes would provide more accurate and comprehensive knowledge of the fates and interchanges of P forms in soil and animal manure under various environmental conditions.
Fate of Nitrogen‐15 in a Perennial Ryegrass Seed Field and Herbaceous Riparian Area
Authors: Davis J. H. , Griffith S. M. , Horwath W. R. , Steiner J. J. , Myrold D. D.
Published: April 2006

Intensive management of grass seed fields in the poorly drained soils of the Willamette Valley, Oregon, has prompted concern in the capacity of these landscapes and their associated minimally managed riparian areas to process and retain fertilizer N. Our goal was to determine the extent of N losses and effectiveness of a riparian area and an adjacent perennial ryegrass seed field to retain N. The fate of fertilizer 15NH4 and 15NO3 was determined with a 15N tracer experiment. During the second year of the study, 15N recovery in the plant and soil (0–30 cm) from the cropping system was 51% for 15NH4 and 43% for 15NO3 whereas recovery in the riparian area was only 20% of 15NH4 and 31% of 15NO3 Greater cropping system retention of 15N resulted from both greater uptake by the crop and greater retention of 15N in the soil. Low recovery of 15N in the riparian area was possibly the result of two significant spring flood events saturating the surface soil of the riparian area but not the cropping system. The prolonged seasonal saturated conditions significantly reduced riparian plant biomass production and N uptake and increased the potential of N loss through overland flow and denitrification. Results indicate that the cropping system had larger available N pools and a larger potential to retain fertilizer N than the riparian zone. However, both areas were prone to substantial loss of applied N.
The Ladies in Skelton's 'Garland, of Laurel'
Authors: Tucker M. J.
Published: April 2006

The mystery of John Skelton's Howard connection has never been satisfactorily explained. Indeed, one usually thinks of the Tudor poet (1460?-1529) as a court poet and tutor to Henry VIII rather than as the protégé of the Howard Countess of Surrey who directed her daughters and gentlewomen to honor him with a laurel crown. Of course, the recitation of this apparently biographical incident in which eleven gentlewomen joyfully decked Skelton's brow with laurel, became the basis for Skelton's most autobiographical poem, The Garland of Laurel.

Published October 3, 1523, the usual assumption is that the Countess of Surrey is none other than Elizabeth Howard, née Stafford (d. 1558), the wife of Thomas Howard, Earl of Surrey and in due course third Duke of Norfolk (d. 1554).
The Political and Ideological Context of Innocent Gentillet's Anti-Machiavel
Authors: D'Andrea Antonio
Published: April 2006

Machiavelli's controversial reputation secured an easy, though ambiguous, success to the Discours … Contre Nicolas Machiavel Florentin. While the author, the Huguenot jurisconsult Innocent Gentillet, remained virtually unknown outside of Geneva and the Dauphiné even to his contemporaries, his work, first published anonymously in 1576, was for a long time widely read and discussed in the light of the controversy stirred up by Machiavelli's doctrines. As early as 1580, Montaigne very likely alludes to Gentillet's work and puts it alongside Machiavelli's Discourses on Livy.
Two Notes on Imprese in Elizabethan Literature: Daniel's Additions to The Worthy Tract of Paulus Iovius*; Sidney's Arcadia and theTournament Scene in The Unfortunate Traveller
Authors: von Koppenfels Werner
Published: April 2006

The list of examples appended by Daniel to his translation of Paolo Giovio's Imprese has proved rather a puzzle to his commentators. Joan Rees, author of the standard monograph on Daniel, gives what seems to be the generally accepted view on the subject: ‘Daniel at this time was himself a good Italian scholar…. Perhaps Florio helped Daniel to collect material for the original part of his work since all the examples in his own [i.e., Daniel's] collection of devices are Italian and it is not easy to find the sources. It is unlikely that Daniel had gathered them himself on the spot…'; and she adds in a footnote: ‘Giovio's book had been translated into French in 1561 but there is no evidence that Daniel based his translation on the French version rather than the Italian original.’