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Schools are facing many issues as a result of the recent pandemic, as well as societal pressures for all students to achieve. There have been unprecedented changes in the educational landscape with a growing concern for students' success and learning loss. Instructional leaders are expected to make innovative changes to meet the instructional needs of all students in K-12 public schools, whether brick-and-mortar or virtual platform. Principals are called to lead their schools and organize the initiatives needed to improve the constantly shifting and complex school environment. The authors will describe the effective efforts of two school leaders who supported innovative changes that resulted in two turnaround schools and addressed student learning loss. As instructional leaders and practitioners in the field, it is essential to support and sustain initiatives that promote student achievement and lessen learning loss. [ABSTRACT FROM AUTHOR]

Debate still exists regarding whether preventive surgical decompression should be offered to high-risk patients experiencing cerebellar stroke. This study aimed to predict neurologic decline based on risk factors, volumetric analysis, and imaging characteristics. This retrospective cohort study comprised patients ≥18 years who presented with acute cerebellar ischemic stroke (CIS) between January 2011 and December 2016. Diagnostic imaging was used to calculate metrics based on individual stroke, cerebellar, and posterior fossa volumes. Head computed tomography scans on presentation and day of peak swelling were used to tabulate a CIS score. The study included 86 patients; most were male and African American. Posterior inferior communicating artery stroke was most common (50%). On initial presentation imaging, 18.6% had documented hydrocephalus, 20.9% had brainstem compression, 22.1% had brainstem stroke, and 39.5% had stroke in another vascular territory. Cardioembolic stroke was the most common etiology, followed by cryptogenic stroke. Overall, patients who underwent surgical intervention had larger stroke volumes on presentation. Patients undergoing surgical intervention also experienced faster cerebellar swelling compared with patients without intervention. Total CIS scores were statistically significant and remained significant on the peak day of swelling. CIS score was independently associated with neurosurgical intervention; patients in this group with delayed interventions (median CIS score, 6; range, 4–8) later deteriorated and required emergent surgical decompression. Eleven patients without intervention had CIS score >6; 4 patients died of stroke complications. Volumetric studies and CIS score are objective measures that may help predict decline on imaging before clinical deterioration. [ABSTRACT FROM AUTHOR]

This essay examines Maya Angelou's 1980 memoir All God's Children Need Traveling Shoes. From 1962 to 1965, Angelou was part of a community of African American writers, artists, intellectuals, and activists who settled in Ghana as its first president, Kwame Nkrumah, seemed poised to usher in a new era of pan-African unity. Hoping to situate her identity within this dream of global pan-Africanism, Angelou narrates her relationship to Africa through the trope of diaspora-as-family. Her use of this metaphor, however, is complicated by her growing awareness of the involvement of Africans in the trans-Atlantic slave trade, as both victims and participants. While other scholarship on All God's Children focuses on Angelou's supposed inability to achieve a diasporan identity, I argue that Angelou is successfully able to come to terms with the trauma of the middle passage by listening to the "voices" of her enslaved ancestors (as they emerge within her own consciousness), and participating in an indigenous Ewe mourning ritual that she inadvertently precipitates. As a result of these experiences, Angelou comes to realize that while narration is important to the formation of both identity and community, African-descended people living in the Americas must first grapple with a historical trauma that exceeds the limits of narration. It is only when Angelou realizes this that she allows herself to be receptive to the spectral voices of her enslaved ancestors and the power of mourning to forge community across divides of time and place. [ABSTRACT FROM AUTHOR]

This article explores the aesthetic and political implications of the representations of the Black Radical Tradition and the CIA in the Marvel Entertainment movie, Black Panther. The article argues that by using the character, Killmonger, to misrepresent the Black Radical Tradition and by portraying the CIA as an ally of Wakanda, Black Panther distorts the history of colonization and resistance in Africa and aids the CIA in its current efforts to recruit agents of color. [ABSTRACT FROM AUTHOR]

Background: Body shape can be both a consequence and cause of a species’ evolution and ecology. There are many examples of phenotypes associated with specific ecological niches, likely as a result of specific selective regimes. A classic example of this is the phenotypic change associated with colonization of caves, including body and limb elongation. However, studies explicitly testing for differences in body shape between cave-dwelling and non-cave-dwelling lineages have been limited and so the role of the cave environment in determining morphological characteristics is still not completely understood. Here we examine variation in body shape among 405 individuals representing 20 species in the salamander genus Eurycea (Plethodontidae) and select outgroups exhibiting great diversity in morphology, ecological niche, and life history. Results: After analyzing morphometric data in a phylogenetic context using phylogenetic MANOVA and examination of the phylomorphospace, we found significant differences in body shape among cave-dwelling and non-cave-dwelling species and between aquatic and terrestrial species. Notably, limb elongation and reduced body and tail size characterized cave-dwelling species. Terrestrial species also exhibited elongation of the limbs and digits. We also observed differences in shape variance among paedomorphic and biphasic species. Our results suggest that the functional limitations imposed by habitat and life history played a key role in the evolution of body shape in this group in the context of their phylogenetic history. [ABSTRACT FROM AUTHOR]

The article presents the discussion on highlighting the important issue of chronic opioid use among patients with gastrointestinal disorders concerning about the high prevalence of opioid use among patients with gastrointestinal disorders.

Viable tumor cells actively release vesicles into the peripheral circulation and other biologic fluids, which exhibit proteins and RNAs characteristic of that cell. Our group demonstrated the presence of these extracellular vesicles of tumor origin within the peripheral circulation of cancer patients and proposed their utility for diagnosing the presence of tumors and monitoring their response to therapy in the 1970s. However, it has only been in the past 10 years that these vesicles have garnered interest based on the recognition that they serve as essential vehicles for intercellular communication, are key determinants of the immunosuppressive microenvironment observed in cancer and provide stability to tumor-derived components that can serve as diagnostic biomarkers. To date, the clinical utility of extracellular vesicles has been hampered by issues with nomenclature and methods of isolation. The term “exosomes” was introduced in 1981 to denote any nanometer-sized vesicles released outside the cell and to differentiate them from intracellular vesicles. Based on this original definition, we use “exosomes” as synonymous with “extracellular vesicles.” While our original studies used ultracentrifugation to isolate these vesicles, we immediately became aware of the significant impact of the isolation method on the number, type, content and integrity of the vesicles isolated. In this review, we discuss and compare the most commonly utilized methods for purifying exosomes for post-isolation analyses. The exosomes derived from these approaches have been assessed for quantity and quality of specific RNA populations and specific marker proteins. These results suggest that, while each method purifies exosomal material, there are pros and cons of each and there are critical issues linked with centrifugation-based methods, including co-isolation of non-exosomal materials, damage to the vesicle’s membrane structure and non-standardized parameters leading to qualitative and quantitative variability. The down-stream analyses of these resulting varying exosomes can yield misleading results and conclusions. [ABSTRACT FROM AUTHOR]

Objectives: Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle.Study Design: We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release.Results: Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants.Conclusions: LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness.Implications: This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants. [ABSTRACT FROM AUTHOR]

The melanocortin 3 receptor (MC3R) is involved in regulation of energy homeostasis. However, its transcript structure is not well understood. We therefore studied initiation and termination sites for hypothalamic murine Mc3r and human MC3R transcripts. Rapid Amplification of cDNA Ends (RACE) was performed for the 5′ and 3′ ends of murine and human hypothalamic RNA. 5′ RACE experiments using hypothalamic murine RNA indicated mouse hypothalamus expresses two major Mc3r transcription start sites: one with a 5′ UTR approximately 368 bases in length and another previously unknown transcript with a 5′ UTR approximately 440 bases in length. 5′ RACE experiments using human hypothalamic RNA identified a 5′ UTR beginning 533 bases upstream of the start codon with a 248 base splice. 3′ RACE experiments using hypothalamic murine RNA indicated the 3′ UTR terminates approximately 1286 bases after the translational stop codon, with a previously unknown 787 base splice between consensus splice donor and acceptor sites. 3′ RACE experiments using human MC3R transcript indicated the 3′ UTR terminates approximately 115–160 bases after the translational stop codon. These data provide insight into melanocortin 3 receptor transcript structure. [ABSTRACT FROM AUTHOR]

We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. [ABSTRACT FROM AUTHOR]

Population genetic differentiation will be influenced by the demographic history of populations, opportunities for migration among neighboring demes and founder effects associated with repeated extinction and recolonization. In natural populations, these factors are expected to interact with each other and their magnitudes will vary depending on the spatial distribution and age structure of local demes. Although each of these effects has been individually identified as important in structuring genetic variance, their relative magnitude is seldom estimated in nature. We conducted a population genetic analysis in a metapopulation of the angiosperm, Silene latifolia, from which we had more than 20 years of data on the spatial distribution, demographic history, and extinction and colonization of demes. We used hierarchical Bayesian methods to disentangle which features of the populations contributed to among population variation in allele frequencies, including the magnitude and direction of their effects. We show that population age, long-term size and degree of connectivity all combine to affect the distribution of genetic variance; small, recently-founded, isolated populations contributed most to increase FST in the metapopulation. However, the effects of population size and population age are best understood as being modulated through the effects of connectivity to other extant populations, i.e. FST diminishes as populations age, but at a rate that depends how isolated the population is. These spatial and temporal correlates of population structure give insight into how migration, founder effect and within-deme genetic drift have combined to enhance and restrict genetic divergence in a natural metapopulation. [ABSTRACT FROM AUTHOR]

The term ‘ubuntu’ defines how people and communities should interact, based on the aphorism that ‘a person is a person through other people’. Adopting a deontological perspective the paper reviews the work of many writers on ubuntu, and examines three possible interpretations of the ubuntu principle before deriving the principle that: ‘An action is right insofar as it promotes cohesion and reciprocal value amongst people. An action is wrong insofar as it damages relationships and devalues any individual or group.’ The various elements of this principle are discussed and some objections considered. A brief case study considers how the principle could be applied. [ABSTRACT FROM AUTHOR]

Abstract: Background: An oral dose of 0.75 mg levonorgestrel (LNG) taken shortly after sex was marketed as a routine, nonemergency contraceptive method until the 1990s. Because a hormonal method used only at the time of intercourse may be desirable for women who have infrequent sex, we conducted a study to reevaluate the potential of pericoital LNG as a primary means of contraception. Methods: We enrolled women aged 18–45 years in Brazil and the USA who expected to have sex 1–4 days per month for 6.5 months. Participants were instructed to take one tablet 0.75 mg LNG within 24 h before or after sex, with no more than one dose in any 24-h period. The primary efficacy measure was the Pearl Index among women aged 18–35 years. Results: The study was stopped after 72 of the planned 300 participants were enrolled due to slow recruitment and related feasibility considerations. In the primary analysis, three pregnancies occurred during 13.4 woman-years of follow-up, resulting in a Pearl Index of 22.4 (95% confidence interval, 4.6–65.4). No serious adverse events were reported, and vaginal bleeding patterns were generally acceptable. Conclusions: Our estimated Pearl Index was noticeably higher than expected from previous research of LNG for pericoital contraception. Although the regimen was safe and generally acceptable, the study was challenged by slow enrollment and curtailed person-years of follow-up, resulting in poor precision for the estimated treatment effect. Future research may inform whether our results are symptomatic of the regimen, study design or characteristics of the populations from which we recruited. Implications: Our study failed to confirm prior data suggesting that 0.75 mg LNG for pericoital contraception could be more effective than typical use of barrier methods among women having infrequent sex. Characterizing populations most likely to adhere to, and benefit from, pericoital regimens is essential to future research on these methods. [Copyright &y& Elsevier]

Abstract: Organisms that live in close association with other organisms make up a large part of the world’s diversity. One driver of this diversity is the evolution of host-species specificity, which can occur via reproductive isolation following a host-switch or, given the correct circumstances, via cospeciation. In this study, we explored the diversity and evolutionary history of Acrostichus nematodes that are associated with halictid bees in North America. First, we conducted surveys of bees in Virginia, and found six halictid species that host Acrostichus. To test the hypothesis of cospeciation, we constructed phylogenetic hypotheses of Acrostichus based on three genes. We found Acrostichus puri and Acrostichus halicti to be species complexes comprising cryptic, host-specific species. Although several nodes in the host and symbiont phylogenies were congruent and tests for cospeciation were significant, the host’s biogeography, the apparent patchiness of the association across the host’s phylogeny, and the amount of evolution in the nematode sequence suggested a mixture of cospeciation, host switching, and extinction events instead of strict cospeciation. Cospeciation can explain the relationships between Ac. puri and its augochlorine hosts, but colonization of Halictus hosts is more likely than cospeciation. The nematodes are vertically transmitted, but sexual transmission is also likely. Both of these transmission modes may explain host-species specificity and congruent bee and nematode phylogenies. Additionally, all halictid hosts come from eusocial or socially polymorphic lineages, suggesting that sociality may be a factor in the suitability of hosts for Acrostichus. [Copyright &y& Elsevier]

Objective: The aim of this study was to examine how calibration uncertainty affects the overall uncertainty of a mathematical model and to evaluate potential drivers of calibration uncertainty. Methods: A lifetime Markov model of the natural history of human papillomavirus (HPV) infection and cervical disease was developed to assess the cost effectiveness of a hypothetical HPV vaccine. Published data on cervical cancer incidence and mortality and prevalence of pre-cursor lesions were used as endpoints to calibrate the age- and HPV-type-specific transition probabilities between health states using the Nelder-Mead simplex method of calibration. A conventional probabilistic sensitivity analysis (PSA) was performed to assess uncertainty in vaccine efficacy, cost and utility estimates. To quantify the uncertainty around calibrated transition probabilities, a second PSA (calibration PSA) was performed using 25 distinct combinations of objective functions and starting simplexes. Results: The initial calibration produced an incremental cost-effectiveness ratio (ICER) of $US4300 per QALY for vaccination compared with no vaccination, and the conventional PSA gave a 95% credible interval of dominant to $US9800 around this estimate (2005 values). The 95% credible interval for the ICERs in the calibration PSA ranged from $US1000 to $US37 700. Conclusions: Compared with a conventional PSA, the calibration PSA results reveal a greater level of uncertainty in cost-effectiveness results. Sensitivity analyses around model calibration should be performed to account for uncertainty arising from the calibration process. [ABSTRACT FROM AUTHOR]

Power transformers can experience large inrush currents upon energization, the severity of which depends on the source strength, the leakage impedance and residual flux of the transformer, and the angle of the applied voltage at energization. A novel inrush current reduction strategy has been implemented which involves setting a single-phase transformer's residual flux to a known polarity after the transformer has been de-energized, a process called “prefluxing,” and controlling the instant of transformer energization based on the flux polarity, seeking not to eliminate inrush current but to substantially reduce it. Unlike a popular suggested solution, this strategy does not require prior knowledge of the transformer's flux. The device used for prefluxing is simple in construction and operates at substantially lower voltage levels when compared to the transformer's rated voltage. The presented strategy has been successfully implemented on an 18-kVA laboratory transformer with inrush current levels reduced below the rated current of the transformer even when accounting for typical breaker deviations. This paper describes the operation of the reduction strategy, including theory, device sizing, and implementation, and presents the successful laboratory results, all of which provide the basis for implementing inrush current reduction in three-phase transformers using a three-pole circuit breaker. [ABSTRACT FROM PUBLISHER]

Cancer cells, both in vivo and in vitro, have been demonstrated to release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and nucleic acids. While only recently have the roles of these vesicular components in intercellular communication become elucidated, significant evidence has demonstrated that tumor exosomes can exert a broad array of detrimental effects on the immune system-ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells and T regulatory cells. Immunosuppressive exosomes of tumor origin can be found within neoplastic lesions and in biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and genetic intercellular exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. By understanding the nature of these tumor-derived exosomes/microvesicles and their roles in mediating cancer progression and modulating the host immune response will significantly impact therapeutic approaches targeting exosomes. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess the impact of simulating temporal changes in health-care practice patterns when calibrating longitudinal models to cross-sectional data. Methods: A Markov model of cervical cancer was calibrated to recent age-specific US data on the prevalence of cervical abnormalities, cervical cancer incidence, and related mortality. The impact of failing to account for temporal changes in screening practices was assessed by comparing results from 1) a conventional calibration that incorrectly assumed that all women had been exposed to current screening practices in the past and 2) an historically accurate calibration that reflected the fact that US women 65 years of age and older had not received currently available screening practices at younger ages. Results: The parameter set derived from conventional calibration produced a cervical cancer incidence rate of 13.4 per 100,000 among women aged 65 years and older, which is equal to the target end point. However, when this parameter set was used in the model to simulate the effects of historically correct screening, cervical incidence and related mortality in the 65 years and older age group were overestimated by 18% and 47%, respectively. Finally, when the parameter set was correctly calibrated by assuming historical changes in screening in the calibration process, excellent calibration to both incidence and mortality was obtained. Conclusions: Calibrating longitudinal models to cross-sectional data without accounting for temporal changes in clinical practice may result in a parameter set that is not as optimized as it appears and may lead to bias in evaluating the effectiveness of interventions. [Copyright &y& Elsevier]

Background: Mathematical models are commonly used to predict future benefits of new therapies or interventions in the healthcare setting. The reliability of model results is greatly dependent on accuracy of model inputs but on occasion, data sources may not provide all the required inputs. Therefore, calibration of model inputs to epidemiological endpoints informed by existing data can be a useful tool to ensure credibility of the results. Objective: To compare different computational methods of calibrating a Markov model to US data. Methods: We developed a Markov model that simulates the natural history of human papillomavirus (HPV) infection and subsequent cervical disease in the US. Because the model consists of numerous transition probabilities that cannot be directly estimated from data, calibration to multiple disease endpoints was required to ensure its predictive validity. Goodness of fit was measured as the mean percentage deviation of model-predicted endpoints from target estimates. During the calibration process we used the manual, random and Nelder-Mead calibration methods. Results: The Nelder-Mead and manual calibration methods achieved the best fit, with mean deviations of 7% and 10%, respectively. Nelder-Mead accomplished this result with substantially less analyst time than the manual method, but required more intensive computing capability. The random search method achieved a mean deviation of 39%, which we considered unacceptable despite the ease of implementation of that method. Conclusions: The Nelder-Mead and manual techniques may be preferable calibration methods based on both performance and efficiency, provided that sufficient resources are available. [ABSTRACT FROM AUTHOR]

The article reports on a study that demonstrates the impact of receptive anal intercourse on the measured effectiveness of the topical product vaginal microbicides in the U.S. For assessing effectiveness and power as a function of microbicide efficacy, a mathematical model has been proposed in the study. The study revealed that heterosexual anal sex has the potential in significantly reducing the power of a vaginal microbicide trial.

Since plant mitochondrial genomes exhibit some of the slowest known synonymous substitution rates, it is generally believed that they experience exceptionally low mutation rates. However, the use of synonymous substitution rates to infer mutation rates depends on the implicit assumption that synonymous sites are evolving neutrally (or nearly so). To assess the validity of this assumption in plant mitochondrial genomes, we examined coding sequence for footprints of selection acting at synonymous sites. We found that synonymous sites exhibit an AT rich and pyrimidine skewed nucleotide composition compared to both non-synonymous sites and non-coding regions. We also found some evidence for selection associated with both biased codon usage and conservation of regulatory sequences involved in mRNA processing, although some of these findings are subject to alternative non-adaptive interpretations. Regardless, the inferred strength of selection appears too weak to account for the variation in substitution rates between the mitochondrial genomes of plants and other multicellular eukaryotes. Therefore, these results are consistent with the interpretation that plant mitochondrial genomes experience a substantially lower mutation rate rather than increased functional constraints acting on synonymous sites. Nevertheless, there are important nucleotide composition patterns (particularly the differences between synonymous sites and non-coding DNA) that remain largely unexplained. [ABSTRACT FROM AUTHOR]

Laser tweezers Raman spectroscopy (LTRS) was used to characterize the Raman fingerprints of the metabolic states of Escherichia coii (E. coii) cells and to determine the spectral changes associated with cellular response to the antibiotic Cefazolin. The Raman spectra of E. coil cells sampled at different time points in the bacterial growth curve exhibited several spectral features that enabled direct identification of the growth phase of the bacteria. Four groups of Raman peaks were identified based on similarities in the time-dependent behavior of their intensities over the course of the growth curve. These groupings were also consistent with the different biochemical species represented by the Raman peaks. Raman peaks associated with DNA and RNA displayed a decrease in intensity overtime, while protein-specific Raman vibrations increased at different rates. The adenine ring-breathing mode at 729 and the 1245 cm-1 vibration peaked in intensity within the first 10 h and decreased afterward. Application of principal component analysis (PCA) to the Raman spectra enabled accurate identification of the different metabolic states of the bacterial cells. The Raman spectra of cells exposed to Cefazolin at the end of log phase exhibited a different behavior. The 729 and 1245 cm-1 Raman peaks showed a slight decrease in intensity from 4 to 10 h after inoculation. Moreover, a shift in the spectral position of the adenine ringbreathing mode from 724 to 729 cm-1, which was observed during normal bacterial growth, was inhibited during antibiotic drug treatment. These results suggest that potential Raman markers exist that can be used to identify E. coli cell response to antibiotic drug treatment. [ABSTRACT FROM AUTHOR]

Presents literary criticism of the books "Another Country" by James Baldwin, "The Black Boy Looks at the White Boy" by Norman Mailer and "Soul On Ice" by Eldridge Cleaver. It explores race and masculinity during the post-World War II era. It states that the vision of racial reconciliation that Cleaver presents is teleological and predicated on cultural hybridity rather than social justice while Baldwin's work is said to be far more skeptical of its white characters' attempts to seek social and cultural interaction with African Americans.

Abstract: Objectives: Current antigen-based diagnostic assays for ovarian cancers rely on intravasation of specific aberrantly expressed proteins and their achieving detectable steady-state concentrations, resulting in their inability to truly detect small early lesions. In contrast, tumor antigen immunorecognition is observed following initial transformation events. Our objective was to characterize humoral antitumor responses in terms of IgG subclasses generated and tumor antigens recognized. Methods: For patients with benign and malignant ovarian disease, tumor-reactive IgG subclasses were characterized by Western immunoblotting. Antigen recognition patterns were analyzed by 2-dimensional electrophoresis and proteins exhibiting shared or stage-specific recognition were defined by mass spectrometry (MS) sequencing. Results: Sera from ovarian cancer patients exhibited significantly greater immunoreactivities than either controls or women with benign disease. While late-stage patients recognized more proteins at greater intensity, stage-specific differential recognition patterns were observed in the IgG subclasses, with the greatest recognition appearing in IgG2 subclasses. Immunoreactivity in IgG2 and IgG3 from stage I and II patients appears to be most intense with nuclear antigens >40 kDa, while, in stage III patients, additional immunoreactivity was present in the <40 kDa components. Stage III patients also exhibited similar reaction with membrane antigens <40 kDa. Two-dimensional electrophoresis revealed 32 stage-linked antigenic differences with 11 in early-stage and 21 in late-stage ovarian cancer. Conclusions: Owing to the timing and stability of humoral responses, quantitation of IgG subclasses recognizing specific tumor antigens provides superior biomarkers for early cancer identification and allows for differentiation of benign versus malignant ovarian masses and early- and late-stage cancers. [Copyright &y& Elsevier]

Background: A recent study found fewer hospitalizations for congestive heart failure (CHF) patients receiving high-dose versus low-dose statin therapy. Objective: To examine the cost effectiveness of high-dose versus low-dose statin therapy in CHF patients. Methods: Two scenarios (literature-based [base-case scenario] vs trial-based post-event mortality [alternative scenario]) assessed the cost effectiveness of atorvastatin 80mg/day (A80) versus atorvastatin 10 mg/day (A10) in patients with both CHF and coronary heart disease (CHD) [CHF/CHD], using a lifetime Markov model. The model predicts treatment-specific probabilities of major and minor cardiovascular events and death, based on clinical trial data. The quality of life and costs were literature based. Measures included costs per life-year saved (LYS) and QALY gained. Health consequences and costs were discounted at 3.0% annually. Analyses were conducted from the payer perspective and valued in $US, year 2006-7 values. Results: Literature-based mortality estimates (base case) increased life-years and QALYs for A80 compared with A10 (incremental cost-effectiveness ratios [ICERs]: $US9600 per LYS; $US13 600 per QALY). At a willingness to pay of $US100 000 per QALY, A80 was cost effective in 80% of simulations. A10 dominated A80 when using trial-based mortality estimates (alternative scenario). At a willingness to pay of $US100 000 per QALY, A80 was cost effective in 48% of simulations. Conclusions: Intensive A80 treatment may be cost effective versus A10 in cardiovascular prevention in CHF/CHD patients in the US, due to projected gains in life expectancy and health-related quality of life. However, the results are highly sensitive to assumptions about the mortality rate in the model. When using the mortality rate observed in the trial, A10 dominates A80. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Most ovarian cancers are diagnosed at advanced stage (67%) and prospects for significant improvement in survival reside in early diagnosis. Our objective was to validate our array assay for the identification of ovarian cancer based on quantitation of tumor-reactive IgG. Methods: The diagnostic array utilizes specific exosome-derived antigens to detect reactive IgG in patients'' sera. Specific protein targets were isolated by immunoaffinity from exosomes derived from ovarian tumor cell lines. Sera were obtained from age-matched female volunteers, women with benign ovarian disease and with ovarian cancer. Immunoreactivity was also compared between exosomal proteins and their recombinant counterparts. Results: Sera from ovarian cancer patients exhibited significantly greater immunoreactivities than either normal controls or women with benign disease (both considered negative to all antigens tested). Reactivities with nucleophosmin, cathepsin D, p53, and SSX common antigen for patients with all stages of ovarian cancer were significantly higher than for controls and women with benign ovarian disease. Reactivity with placental type alkaline phosphatase, TAG 72, survivin, NY-ESO-1, GRP78, and Muc16 (CA125) allowed the differentiation between Stage III/IV and early stage ovarian cancer. Conclusions: The quantitation of circulating tumor-reactive IgG can be used to identify the presence of ovarian cancer. The analyses of IgG recognition of specific exosomal antigens allows for the differentiation of women with benign ovarian masses from ovarian cancer, as well as distinguishing early and late stage ovarian cancers. Thus, the quantitative assessment of IgG reactive with specific tumor-derived exosomal proteins can be used as diagnostic markers for ovarian cancer. [Copyright &y& Elsevier]

Abstract: Background: Male condom functionality studies are typically crossover trials in which enrolled couples use both experimental and latex control condoms for sexual intercourse. Noninferiority of the experimental type is assessed using confidence intervals for differences in breakage and slippage probabilities. Seemingly straightforward, the design, analysis and interpretation of functionality studies are complicated by the choice of noninferiority criterion, study population and the potential for learning effects. Methods: Power calculations, secondary data analyses and simulations were used to illustrate concerns and make recommendations. Results: The probability of failure can be too low to draw meaningful conclusions in certain population subgroups. Learning effects among inexperienced users can exaggerate differences in performance and undermine power. A product which is, on average, inferior to latex may still be a viable prophylactic for a large percentage of couples. Conclusions: Heterogeneity of failure probabilities, combined with small acceptable differences in performance, requires care when selecting study participants. Pilot data, adequate training on condom use and reasonable expectations regarding performance of a new condom type are essential to maximizing the chance of identifying a noninferior product. [Copyright &y& Elsevier]

While written during Malcolm X's Muslim years, the narrative standpoint of The Autobiography of Malcolm X (As Told to Alex Haley) often mirrors the "cool pose" he adopted as a hustler in the black ghettoes of Harlem and Roxbury. By focusing on the way that cool pose gets enacted through "showdowns," a symbolic transaction Malcolm and the other street hustlers in The Autobiography use to bolster their "masculinity," this essay supplements the performative model of gender with a consideration of the ways that "masculinity" also involves exchanges of gender power. [ABSTRACT FROM AUTHOR]

Problem This study addressed the ability of genistein to reverse the loss of T-cell signaling components, induced by estrogen deficiency associated with aging. Method of study Using Jurkat 6.1 T cells, genistein regulation of CD3ζ, JAK3, and NFκB was analysed by Western immunoblotting at 4 or 40 pg/mL (post- and pre-menopausal levels, respectively) estradiol (E2). Corresponding gene expressions were quantified by real-time polymerase chain reaction (RT-PCR). For functionality, levels of IL-2 were correlated with its transcription by RT-PCR. Results At 4 pg/mL E2, signaling proteins were decreased compared with 40 pg/mL: CD3ζ, 1.58-fold; JAK3, 1.75-fold; and NFκB, 1.73-fold ( P < 0.001). Genistein, at 0.5 and 5.0 μm, added to 4 pg/mL E2 induced their expression to 40 pg/mL levels. While significantly diminished IL-2 mRNA levels were observed at 4 pg/mL E2, genistein induced IL-2 mRNA to 40 pg/mL levels. Conclusion Genistein restores CD3ζ, NFκB and JAK3 proteins and mRNAs at post-meonopausal estrogen levels, in vitro, with no significant effect at pre-menopausal estrogen levels. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the budgetary impact of varenicline in the United Kingdom (UK) in the first 5 years after its introduction to the smoking-cessation aid market, from the National Health Service (NHS) pharmacy perspective. Methods: The economic impact of varenicline to the national health budget is estimated in a population of current, former, and new smokers. The analyses are based on data from a variety of secondary sources including national health data, clinical trials, and meta-analyses of smoking-cessation aids. The number of patients seeking aid and the treatment patterns are estimated using 2004 national health surveys, costs for medications from national prescription drug pricing tariffs, and efficacy of the various smoking-cessation aids from clinical trial data. Sensitivity analyses were performed to evaluate the impact of varying the patient parameters and costs. Results: Model estimates suggest that the budgetary impact of varenicline would be £3.6 million in the second year after its introduction, with a 95% confidence interval of £0.63 to £7.2 million, and a resultant increase of 0.05% to the total NHS pharmacy budget. The model predicts that the addition of varenicline to the market would result in an additional 162,000 successful smoking-cessation attempts and 103,000 fewer smokers over 5 years, when compared to the world without varenicline. Conclusion: The introduction of varenicline is likely to result in greater numbers of individuals succeeding at smoking cessation, with an approximately £3.6 million (0.05%) increase in the NHS pharmacy budget. [ABSTRACT FROM AUTHOR]

Introduced species often exhibit changes in genetic variation, population structure, selection regime and phenotypic traits as they colonize and expand into new ranges. For these reasons, species invasions are increasingly recognized as promising systems for studying adaptive evolution over contemporary time scales. However, changes in phenotypic traits during invasion occur under non-equilibrium demographic conditions and may reflect the influences of prior evolutionary history and chance events, as well as selection. We briefly review the evidence for phenotypic evolution and the role of selection during invasion. While there is ample evidence for evolutionary change, it is less clear if selection is the primary mechanism. We then discuss the likelihood that stochastic events shift phenotypic distributions during invasion, and argue that hypotheses of adaptation should be tested against appropriate null models. We suggest two experimental frameworks for separating stochastic evolution from adaptation: statistically accounting for phenotypic variation among putative invasion sources identified by using phylogenetic or assignment methods and by comparing estimates of differentiation within and among ranges for both traits and neutral markers ( QST vs. FST). Designs that incorporate a null expectation can reveal the role of history and chance in the evolutionary process, and provide greater insights into evolution during species invasions. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Most ovarian cancer patients are diagnosed at an advanced stage (67%) and prospects for significant improvement in survival reside in early diagnosis. While expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin, microRNA profiling has been limited to tissue specimens. Tumors actively release exosomes into the peripheral circulation and we now demonstrate the association of microRNAs with circulating tumor-derived exosomes. Methods: Circulating tumor exosomes were isolated using a modified MACS procedure with anti-EpCAM. Initially, microRNA profiles of ovarian tumors were compared to those of tumor exosomes isolated from the same patients. Levels of 8 microRNAs (miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205 and miR-214) previously demonstrated as diagnostic, were compared in exosomes isolated from sera specimens of women with benign disease and various stages of ovarian cancer. Results: MicroRNA from ovarian tumor cells and exosomes from the same patients were positive for 218 of 467 mature microRNAs analyzed. The levels of the 8 specific microRNAs were similar between cellular and exosomal microRNAs (exhibiting correlations from 0.71 to 0.90). While EpCAM-positive exosomes were detectable in both patients with benign ovarian disease and ovarian cancer, exosomal microRNA from ovarian cancer patients exhibited similar profiles, which were significantly distinct from profiles observed in benign disease. Exosomal microRNA could not be detected in normal controls. Conclusions: These results suggest that microRNA profiling of circulating tumor exosomes could potentially be used as surrogate diagnostic markers for biopsy profiling, extending its utility to screening asymptomatic populations. [Copyright &y& Elsevier]

Currently, a combination of technologies is typically required to assess the malignancy of cancer cells. These methods often lack the specificity and sensitivity necessary for early, accurate diagnosis. Here we demonstrate using clinical samples the application of laser trapping Raman spectroscopy as a novel approach that provides intrinsic biochemical markers for the noninvasive detection of individual cancer cells. The Raman spectra of live, hematopoietic cells provide reliable molecular fingerprints that reflect their biochemical composition and biology. Populations of normal T and B lymphocytes from four healthy individuals and cells from three leukemia patients were analyzed, and multiple intrinsic Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for cancer cell identification. A combination of two multivariate statistical methods, principal component analysis (PCA) and linear discriminant analysis (LDA), was used to confirm the significance of these markers for identifying cancer cells and classifying the data. The results indicate that, on average, 95% of the normal cells and 90% of the patient cells were accurately classified into their respective cell types. We also provide evidence that these markers are unique to cancer cells and not purely a function of differences in their cellular activation. [ABSTRACT FROM AUTHOR]

The authors present their views on the effectiveness trials of HIV prevention agents during pregnancy. They say that strategies designed to address the substantial challenge of managing many issues related to pregnancy will have implications for other trial features such as recruitment, retention, cost and organization. They discuss the optimal way to allay safety concerns and to ensure analytic validity of HIV prevention trials through minimizing the number of pregnancies.

Objectives: Data from the Intergroup Exemestane Study (IES) suggest that switching to the aromatase inhibitor, exemestane, after 2 to 3 years of tamoxifen therapy prolongs disease-free survival versus continuing on tamoxifen therapy. We sought to evaluate the cost-effectiveness of this management strategy. Methods: A Markov model was developed to predict patients' transitions across various health states based on treatment strategy (continuing tamoxifen vs. switching to exemestane), breast cancer status (no recurrence, local or distant recurrence, contralateral breast cancer), and other related health events (osteoporosis, endometrial cancer, death). Rates of disease-related events (recurrence and contralateral breast cancer) were estimated using data from the IES. Survival and lifetime medical-care costs by type of disease-related event were estimated using SEER-Medicare data. The model was used to estimate direct costs (in 2004 USdollars), life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. Results: Switching to exemestane versus continuing tamoxifen therapy was associated with increased disease-free survival (181 vs. 172 months), QALYs (12.21 vs. 11.89), and net discounted lifetime costs of cancer care ($12,124 vs. $7724 per patient). The incremental cost-effectiveness ratio of exemestane was $20,100 per QALY gained (95% confidence interval: $12,100, $59,000). Sensitivity analyses showed that results were robust to plausible variations in recurrence rates, costs, and utilities. Conclusions: Switching postmenopausal early-stage breast cancer patients to exemestane after 2 to 3 years of tamoxifen appears to be a cost-effective treatment strategy versus completing a 5-year course of tamoxifen. [ABSTRACT FROM AUTHOR]

Speed profile models can be used as a diagnostic tool by highway engineers. Previous work has investigated relationships between operating speed and geometric roadway elements for permanent roadway conditions on predominantly two-lane rural roads. However, little research of this type has been directed specifically toward construction work zones. In this study, a speed profile model for construction work zones on high speed highways was developed using artificial neural networks and made available for use by practitioners through a MS EXCEL interface. The model inputs include horizontal and vertical alignment variables, cross section dimensions and traffic control features. A linear reference system is used for model input and output. Three categories of vehicles—cars, trucks, and all vehicles—were used in this study. Models for the 15th percentile speed, mean speed, and 85th percentile speed were developed. [ABSTRACT FROM AUTHOR]

For a species rapidly expanding its geographic range, such as during biological invasion, most alleles in the introduced range will have their evolutionary origins in the native range. Yet, the way in which historical processes occurring over evolutionary time in the native range contribute to the diversity sampled during contemporary invasion is largely unknown. We used chloroplast DNA (cpDNA) gene genealogies and coalescent methods to study two congeneric plants, Silene latifolia and S. vulgaris. We examined how phylogenetic diversity was shaped by demographic growth and historical range expansions in the native European range, and how this history affected the diversity sampled during their recent invasion of North America. Genealogies from both species depart from neutrality, likely as a result of demographic expansion in the ancestral range, the timing of which corresponds to shortly after each species originated. However, the species differ in the spatial distribution of cpDNA lineages across the native range. Silene latifolia shows a highly significant phylogeographic structure that most likely reflects different avenues of the postglacial expansion into northern Europe from Mediterranean refugia. By contrast, cpDNA lineages in S. vulgaris have been widely scattered across Europe during, or since, the most recent post-glacial expansion. These different evolutionary histories resulted in dramatic differences in how phylogenetic diversity was sampled during invasion of North America. In S. latifolia, relatively few, discrete invasion events from a structured native range resulted in a rather severe genetic bottleneck, but also opportunities for admixture among previously isolated lineages. In S. vulgaris, lack of genetic structure was accompanied by more representative sampling of phylogenetic diversity during invasion, and reduced potential for admixture. Our results provide clear insights into how historical processes may feed forward to influence the phylogenetic diversity of species invading new geographic ranges. [ABSTRACT FROM AUTHOR]

Abstract: Treatment failures result from resistance to chemotherapy in ovarian cancer. The effect of cisplatin and paclitaxel treatments on chemosensitivity was studied in ovarian cancer cells developed from a patient with stage IIIC disease. Cells (UL-3A, UL-3B) that recovered from cisplatin (Cis) and paclitaxel (Tax) treatments showed higher levels of p53, mdr-1 and chemoresistance than untreated controls. EC50 values of Cis and Tax for UL-3A clones were 7.2–34.6, average 20.9μg/ml, while UL-3B clones ranged from 11.8–252.0μg/ml, with a mean value of 73.2μg/ml for Cis, and 260.0–4400.0nM (mean 2555.0nM) for Tax. Selection pressures during treatment may contribute to drug resistance. [Copyright &y& Elsevier]

Abstract: Evidence suggests that maternal cell-mediated immunity is suppressed during pregnancy and that failure to suppress immune responses can result in partial or total rejection of the fetus. The molecular events associated with suppression of maternal T-cell activation mediated by circulating pregnancy-associated 14kDa zeta inhibitor protein (ZIP) were defined in women with and without histories of recurrent pregnancy loss (RPL). Using cDNA microarray analysis, ZIP modulations of specific genes associated with T-cell activation signaling were defined. Alterations of defined components were confirmed at the protein level using chromatographically purified ZIP from normal pregnancies versus analogous material from women experiencing RPL. Based on microarray analyses, ZIP from normal pregnancies induced an increase (≥2-fold) in the expression of 19 genes and a decrease (≥2-fold) in 15 genes, when incubated with cultured T-cells. In contrast, when T-cells were incubated with analogous material from RPL or non-pregnant controls, no significant differences were observed in the expression of these genes. At the protein level, ZIP from normal pregnancies induced decreases in CD3-zeta (2.36-fold), JAK3 (2.41-fold), STAT5 (1.85-fold), and NF-κB (4.24-fold) and a 2.05-fold increase in SOCS2 (all at p <0.001 compared to RPL and non-pregnant controls). The suppressive effects of Zip can lead to the failure of T-cell production of Th1 cytokines, such as IL-2. The 14kDa circulating ZIP from normal pregnancies suppressed components within the JAK/STAT pathway and induced suppressors of cytokine stimulation, SOCS2. [Copyright &y& Elsevier]

Chloroplast and nuclear DNA sequence variation among populations and species was used to examine the phylogenetic history and hybridization of the North American Houstonia lineage. The ancestral species in the lineage do not show evidence of hybridization; however, the more recently derived species in eastern North America contain a wide degree of morphological and genetic variation both within and among species. Furthermore, there is a clear association between hybridization and polyploidy in the Houstonia lineage, with all potential hybrids occurring among species that contain polyploid populations. This suggests that polyploidy may break down species barriers and allow hybridization among lineages. These results indirectly support speciation models that involve genetic incompatibilities among species arising from gene silencing or genomic reorganization. [ABSTRACT FROM AUTHOR]

Clinical evidence suggests that cell-mediated immunity is altered during pregnancy and that failure to suppress the maternal immune response can lead to placentation failure, resulting in partial or total rejection of the fetus. In contrast to women experiencing recurrent spontaneous abortions (RSA), normal uncomplicated pregnancies are associated decreased T-cell proliferation and production of Th1 cytokines and increased T-cell apoptosis. This study addresses a circulating factor in normal pregnancy that may mediate these events. Sera were obtained from three groups: pregnant women who have uncomplicated term deliveries (Group 1, n = 8), pregnant women with a history of RSA, who subsequently abort (Group 2, n = 10), and age-matched non-pregnant female controls (Group 3, n = 8). Pregnancy sera were obtained between 10 and 12 weeks of gestation. Using chromatography, a CD3-zeta inhibitory factor (or analogous fraction) was isolated from each patient within each group and incubated with cultured T-cells, Jurkat and HUT-78 cells. Apoptosis was assayed by a cell-death ELISA and IL-2 production by cytokine-specific ELISA. Apoptosis regulatory proteins and signaling molecules were analyzed by western immunoblotting. Group 1 material induced a significant increase in apoptosis versus Groups 2 and 3. No significant apoptosis was observed between Groups 2 and 3. Material from Group 1 resulted in an increase in the bax expression compared to Groups 2 and 3 (P < 0.001), while no significant differences were observed in the expression of bcl-2. IL-2 secretion was inhibited 2.8-fold by material from Group 1 compared to Groups 2 and 3. Group 1 material decreased the expression of CD3-zeta, JAK3 and STAT5 compared to Groups 2 and 3 (as defined by densitometric units).Circulating materials from normal pregnancies are associated with increased lymphoid apoptosis, possibly through increased bax, and diminished production of the Th1 cytokine, IL-2. Our findings indicate that women experiencing RSA fail to suppress CD3-zeta and JAK3, suggesting a deficiency in this circulating factor that induces their suppression in normal pregnancy. [Copyright &y& Elsevier]

Objective. In women with advanced ovarian cancer, levels of CD3-zeta on peripheral blood lymphocytes have previously been demonstrated to correlate with responsiveness to interleukin (IL)-2 therapy. The aims of this study were to identify the circulating component that modulated zeta expression and to define whether this suppressive activity could serve as a marker of biotherapy responsiveness.Methods. Sera were obtained from 17 patients with advanced ovarian cancer treated with intraperitoneal IL-2 in a phase I trial between 1987 and 1990. Nine of these patients exhibited a clinical response, while eight did not respond. Six additional sera from age-matched, noncancer-bearing women were used as controls. Jurkat E6-1 cells were used to assay modulation of CD3-zeta by sera and serum-derived components. Jurkat cells were exposed to serum or chromatographically fractionated serum components for 4 days and zeta expression was analyzed by Western immunoblots and quantitated by densitometry.Results. The effect of sera on zeta expression was compared between responders and nonresponders. Incubation of Jurkat cells with sera from responders suppressed CD3-zeta expression by 36.7% (vs. control treated), while treatment with sera from nonresponders produced an 83.7% reduction in zeta expression (difference between groups, P < 0.001). When sera from nonresponders were chromatographically fractionated, a <20 kDa component was identified that correlated with decreased zeta chain expression. This component was diminished in the sera of responders and absence in controls.Conclusions. Thus, in patients with advanced ovarian cancer, a circulating component, which decreases zeta expression, can be identified as a marker for responsiveness to IL-2 therapy. [Copyright &y& Elsevier]

Background. Previous research investi-gating the relationship between the time of admission and mortality rates has yielded inconsistent results and has not been conducted in the pediatric intensive care unit (PICU) patient population. Objective. To determine whether an association be-tween the time of admission (weekday versus weekend and daytime versus evening) and the risk of death exists among pediatric patients included in a cohort of children admitted to a national sample of PICUs. Design/Methods. We analyzed retrospectively a co-hort of consecutive admissions to 15 PICUs included in the Pediatric Intensive Care Unit Evaluations database. The odds of death were analyzed by using mixed-effects, multivariate, logistic regression, with clustering at the hospital level. The primary independent variables were admission to the PICU on a weekend and admission to the PICU during evening hours. The severity of illness was adjusted by using the Pediatric Risk of Mortality III probability of death score. Patients. All 20 547 emergency PICU admissions made between May 1995 and December 2001 were in-cluded in the analyses. Main Outcome Measures. The primary outcome was death within 48 hours after admission to the PICU. Results. Pediatric patients admitted to the PICU dur-ing evening hours had higher odds of death (odds ratio [OR]: 1.28; 95% confidence interval [CI]: 1.00-1.62) than did those admitted during daytime hours. Subgroup analyses revealed higher odds of death among patients admitted with shock (OR: 4.09; 95% CI: 1.65--10.1), with congenital cardiovascular disease (OR: 3.90; 95% CI: 1.37-- 11.1), or after cardiac arrest (OR: 1.80; 95% CI: 1.04 --3.13). There was no association between mortality rates and the day of admission (weekend admissions versus weekday admissions). Conclusions. An increased risk of death exists for some pediatric patients admitted to the PICU during evening hours. It remains necessary to determine... [ABSTRACT FROM AUTHOR]

A Galerkin descretization of the electric field integral equation for perfectly conducting surfaces using RaoWilton-Glisson basis functions requires the numerical evaluation of integrals with singular kernels over triangular regions. These singularities have been traditionally handled by utilizing a "singularity extraction" procedure to produce a regular integral and an analytic function to replace the original singular integral. A new approach is presented here in which the four-dimensional (4-D) weakly singular integrals unique to the Galerkin Rao-WiltonGlisson electric field integral equation solution for perfectly conducting surfaces are transformed into integrals with regular integrands. The transformations allow some of the integrations to be performed analytically, in some cases reducing the original 4-D integral into a 1-D numerical integration. The accuracy and convergence properties of the new method are demonstrated by evaluating the scalar potential function over a unit triangle. [ABSTRACT FROM AUTHOR]

Salamanders in the genus Desmognathus (Caudata: Plethodontidae) are distributed along an aquatic to terrestrial habitat gradient in the southern Appalachian Mountains. The spatial distribution of species is believed to have formed as aquatic ancestors displaced lineages by competition and predatory interactions into less optimal terrestrial habitats. Aquatic and terrestrial species may also display different patterns of genetic diversity due to the differing likelihood of gene flow via aquatic corridors. To determine whether phylogenetic patterns were consistent with these hypotheses, we sequenced portions of the cytochrome oxidase I and 12S rRNA genes of the mitochondrial genome from 96 individuals belonging to 10 species in the genus Desmognathus. In addition, we combined our dataset with an earlier published dataset for the 12S rRNA genes. The order of species divergence is consistent with aquatic ancestors having displaced taxa into more terrestrial habitats, but the major lineages within the genus Desmognathus arose suddenly, and therefore, the specific sequence of events is not well resolved. The phylogenetic analyses among species suggest that direct-development and a terrestrial lifestyle are ancestral in the genus Desmognathus, but the degree of adult terrestriallity is labile, with some species having re-invaded terrestrial habitats. We present evidence of a clade of Desmognathus quadramaculatus from North Carolina that is distinct from the D. quadramaculatus/Desmognathus marmoratus clade. Within species, estimates of Tajima’s D and Fu and Li’s statistics suggest the species experienced population expansions at different times in the past. Current levels of sequence diversity in northern populations, therefore, reflect different arrival times, and hence, differences in the opportunity for among population divergence. The recent arrival of most species over large portions of their geographic ranges suggests that most extant communities have been assembled, a posteriori, by the recent assortment of species along the aquatic to terrestrial gradient according to their ecologies. [Copyright &y& Elsevier]

Presents a study that explored the joint effects of migration and population subdivision on speciation in a spatially explicit context. Background on models of speciation; Spatial pattern of genetic incompatibilities for a representative run of a stepping-stone model with ten demes; Effect of migration and population subdivision on the accumulation of reproductive isolation in structured populations.

Presents genealogical evidence of selfish gene epidemics where some genetic elements spread infectiously in populations by increasing the rate of genetic transmission at the expense of other genes in the genome. Cytoplasmic male sterility; Sequence variation at cytoplasmic loci; Reduction in sequence diversity of chloroplast genome of Silene vulgaris.