Showing papers by "Georgetown University published in 1999"

Localization of Knowledge and the Mobility of Engineers in Regional Networks

Abstract: Knowledge, once generated, spills only imperfectly among firms and nations. We posit that since institutions and labor networks vary by region, there should be regional variations in the localization of spillovers. We investigate the relationship between the mobility of major patent holders and the localization of technological knowledge through the analysis of patent citations of important semiconductor innovations. We find that knowledge localization is specific to only certain regions (particularly Silicon Valley) and that the degree of localization varies across regions. By analyzing data on the interfirm mobility of patent holders, we empirically show that the interfirm mobility of engineers influences the local transfer of knowledge. The flow of knowledge is embedded in regional labor networks.

Carbon Nanotube Actuators

Abstract: Electromechanical actuators based on sheets of single-walled carbon nanotubes were shown to generate higher stresses than natural muscle and higher strains than high-modulus ferroelectrics. Like natural muscles, the macroscopic actuators are assemblies of billions of individual nanoscale actuators. The actuation mechanism (quantum chemical-based expansion due to electrochemical double-layer charging) does not require ion intercalation, which limits the life and rate of faradaic conducting polymer actuators. Unlike conventional ferroelectric actuators, low operating voltages of a few volts generate large actuator strains. Predictions based on measurements suggest that actuators using optimized nanotube sheets may eventually provide substantially higher work densities per cycle than any previously known technology.

Race, gender, and partnership in the patient-physician relationship.

Abstract: ContextMany studies have documented race and gender differences in health care received by patients. However, few studies have related differences in the quality of interpersonal care to patient and physician race and gender.ObjectiveTo describe how the race/ethnicity and gender of patients and physicians are associated with physicians' participatory decision-making (PDM) styles.Design, Setting, and ParticipantsTelephone survey conducted between November 1996 and June 1998 of 1816 adults aged 18 to 65 years (mean age, 41 years) who had recently attended 1 of 32 primary care practices associated with a large mixed-model managed care organization in an urban setting. Sixty-six percent of patients surveyed were female, 43% were white, and 45% were African American. The physician sample (n=64) was 63% male, with 56% white, and 25% African American.Main Outcome MeasurePatients' ratings of their physicians' PDM style on a 100-point scale.ResultsAfrican American patients rated their visits as significantly less participatory than whites in models adjusting for patient age, gender, education, marital status, health status, and length of the patient-physician relationship (mean [SE] PDM score, 58.0 [1.2] vs 60.6 [3.3]; P=.03). Ratings of minority and white physicians did not differ with respect to PDM style (adjusted mean [SE] PDM score for African Americans, 59.2 [1.7] vs whites, 61.7 [3.1]; P=.13). Patients in race-concordant relationships with their physicians rated their visits as significantly more participatory than patients in race-discordant relationships (difference [SE], 2.6 [1.1]; P=.02). Patients of female physicians had more participatory visits (adjusted mean [SE] PDM score for female, 62.4 [1.3] vs male, 59.5 [3.1]; P=.03), but gender concordance between physicians and patients was not significantly related to PDM score (unadjusted mean [SE] PDM score, 76.0 [1.0] for concordant vs 74.5 [0.9] for discordant; P=.12). Patient satisfaction was highly associated with PDM score within all race/ethnicity groups.ConclusionsOur data suggest that African American patients rate their visits with physicians as less participatory than whites. However, patients seeing physicians of their own race rate their physicians' decision-making styles as more participatory. Improving cross-cultural communication between primary care physicians and patients and providing patients with access to a diverse group of physicians may lead to more patient involvement in care, higher levels of patient satisfaction, and better health outcomes.

The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial

Abstract: ContextRaloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.ObjectiveTo determine whether women taking raloxifene have a lower risk of invasive breast cancer.Design and SettingThe Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.ParticipantsA total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.InterventionRaloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome MeasuresNew cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.ResultsThirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor–negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).ConclusionAmong postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.

Disruption of p53 in human cancer cells alters the responses to therapeutic agents

Abstract: We have examined the effects of commonly used chemotherapeutic agents on human colon cancer cell lines in which the p53 pathway has been specifically disrupted by targeted homologous recombination. We found that p53 had profound effects on drug responses, and these effects varied dramatically depending on the drug. The p53-deficient cells were sensitized to the effects of DNA-damaging agents as a result of the failure to induce expression of the cyclin-dependent kinase inhibitor p21. In contrast, p53 disruption rendered cells strikingly resistant to the effects of the antimetabolite 5-fluorouracil (5-FU), the mainstay of adjuvant therapy for colorectal cancer. The effects on 5-FU sensitivity were observed both in vitro and in vivo, were independent of p21, and appeared to be the result of perturbations in RNA, rather than DNA, metabolism. These results have significant implications for future efforts to maximize therapeutic efficacy in patients with defined genetic alterations.

Shorter Survival in Advanced Human Immunodeficiency Virus Type 1 Infection Is More Closely Associated with T Lymphocyte Activation than with Plasma Virus Burden or Virus Chemokine Coreceptor Usage

Abstract: To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4+ T cells fell to

International Marketing Research

Abstract: About the Authors. Preface. 1. Marketing Research in a Global Environment. Introduction. Complexity of International Marketing. Importance of Research for International Marketing Decisions. Issues in International Marketing Research. Scope of the Book. 2. Designing International Marketing Research. Introduction. The International Marketing Research Plan. The International Marketing Research Process. Structuring the Unit of Analysis. Selecting Information Sources. Research Plan. Issues in Administering International Marketing Research. Summary. 3. Secondary Data Sources. Introduction. Locating the Appropriate Information. Information Sources. Information Requirements. Summary. 4. Uses of Secondary Data. Introduction. Market Entry. Demand Estimation. Assessing Market Interconnectedness. Summary. 5. Structuring Primary Data Collection. Introduction. Defining the Unit of Analysis. Selecting Units of Analysis. Structuring the Research Design. Cultural Bias in Research Design, Communication and Interpretation. Summary. 6. Establishing the Comparability of Multicountry Data. Introduction. Establishing Comparability: The Emic/Etic Dilemma. Establishing Data Equivalence. Determining Construct Validity. Establishing Construct Reliability. Summary. 7. Nonsurvey Data Collection Techniques. Introduction. Different Qualitative Techniques. Observational and Quasi-observational Data. Projective Techniques. In-depth Interviews. Summary. 8. Survey Instrument Design. Introduction. Questionnaire Design and Question Formulation. Type of Question. Use of Nonverbal Stimuli. Instrument Translation. Potential Sources of Bias Associated with the Research Instrument. Summary. 9. Sampling and Data Collection. Introduction. Sampling. Achieving Comparability in Sampling. Data Collection Procedures. Field Staff Organization and Training. Summary. 10. Multicountry Scales. Introduction. General Issues in Scale Development. Using Multi-item Scales in Cross-cultural Research. Developing Cross-cultural Scales. Summary. 11. Analysis of Multicountry Data. Introduction. Multicountry Data Analysis. Assessing the Differences in the Level of Variables between Countries. Summary. 12. Assessing Differences in the Structure of Variables. Introduction. Correlation Analysis. Means-End Hierarchies. Cluster Analysis. Multidimensional Scaling. Factor Analysis. Confirmatory Factor Analysis. Covariance Structure Models. Advances in Data Analysis. Summary. 13. The International Marketing Information System. Introduction. Information Components of the International Marketing System. Data Collection and Processing for the International Marketing Information System. Applying the Information System. Summary. 14. Challenges Facing International Marketing Research. Introduction. Coping with Change: Marketing Infrastructure and Technology. Contending with Complexity: Conducting Research in Emerging Markets. Confronting Competition: Marketing Research Services in a Global Environment. Conforming to Conscience: Ethics in International Marketing Research. Summary. 15. Future Directions in International Marketing Research. Introduction. Comparability and Equivalence Revisited. Developing the Research Design. Improving Analysis of Cross-cultural Data. The Growth of Internet Research. Conclusion. Subject Index. Author Index. Acknowledgements.

The Stability of a Unipolar World

Abstract: The collapse of the Soviet Union produced the greatest change in world power relationships since World War II. With Moscow’s headlong fall from superpower status, the bipolar structure that had shaped the security policies of the major powers for nearly half a century vanished, and the United States emerged as the sole surviving superpower. Commentators were quick to recognize that a new “unipolar moment” of unprecedented U.S. power had arrived.1 In 1992 the Pentagon drafted a new grand strategy designed to preserve unipolarity by preventing the emergence of a global rival.2 But the draft plan soon ran into controversy, as commentators at home and abroad argued that any effort to preserve unipolarity was quixotic and dangerous.3 Ofacials quickly backed away from the idea and now eschew the language of primacy or predominance, speaking instead of the United States as a “leader” or the “indispensable nation.”4 The rise and sudden demise of an ofacial strategy for preserving primacy lends credence to the widespread belief that unipolarity is dangerous and unstable. While scholars frequently discuss unipolarity, their focus is always on its demise. For neorealists, unipolarity is the least stable of all structures because any great concentration of power threatens other states and causes them to take action to restore a balance.5 Other scholars grant that a large

Universal Linker and Ligation Procedures for Construction of Genomic DNA Libraries Enriched for Microsatellites

Abstract: Microsatellite loci are highly informative genetic markers useful for population genetic studies, linkage mapping and parentage determination. Methods to identify novel microsatellite loci commonly use subtractive hybridization to enrich small-insert genomic libraries for repeat sequences. A critical step in enrichment is attachment of an oligonucleotide linker to genomic DNA fragments so that repeat-containing sequences can be recovered by PCR for cloning. Current linkers and ligation methods rely on single restriction enzymes to size-fraction genomic DNA and generate complementary ends. These restriction enzyme/linker combinations are often species-specific, give poor recovery of repeat-enriched DNA and yield library inserts that are not a broad sample of the genome. We have developed a blunt-end linker, named SNX for its restriction sites, that allows the use of combinations of restriction enzymes to digest the majority of genomic DNA into the 200-1000-bp range. SNX is attached to genomic DNA with a simultaneous ligation/restriction reaction that is highly efficient and improves recovery of sequences after subtractive hybridization. SNX can be used for microsatellite enrichment in any species, since ligation is independent of the restriction enzymes used to size-fraction genomic DNA. These methods improve current repeat-enrichment strategies, resulting in representative small-insert libraries with a very high proportion of positive clones.

Does Child Labor Displace Schooling? Evidence on Behavioral Responses to an Enrollment Subsidy

Abstract: Bangladesh's Food-for-Education program, offering a stipend considerably less than the mean child wage, was enough to ensure nearly full school attendance among participants. The enrollment subsidy also reduced the incidence of child labor, but that effect accounted for only a small proportion of the increase in school enrollment. Ravallion and Wodon try to determine whether children sent to work in rural Bangladesh are caught in a poverty trap, with the extra income to poor families from child labor coming at the expense of the children's longer-term prospects of escaping poverty through education. The poverty trap argument depends on children's work being substitutable for schooling. Casual observations and the descriptive statistics available from surveys seem to offer little support for the argument. To explore the question more deeply, Ravallion and Wodon use a targeted school stipend to identify how much child labor substitutes for schooling. They find that Bangladesh's Food-for-Education program is a strong incentive for school attendance. A stipend with a value considerably less than the mean child wage was enough to ensure nearly full school attendance among participants. The enrollment subsidy also reduced the incidence of child labor, an effect that accounted for only a small proportion of the increase in school enrollment. The reduction in the incidence of child labor among boys (girls) represents about one-quarter (one-eighth) of the increase in their school enrollment rate. Parents are clearly substituting other uses of their children's time to secure the current income gain from access to the program, with modest impact on earnings from their children's work. The authors' tests were limited. Work may well displace time for doing homework or attending after-school tutorials, for example. Ravallion and Quentin were unable to identify such effects from the data available. There may also be other welfare losses to children from work (such as exposure to an unsafe working environment) as well as welfare gains (such as skills learned from working that enhance returns to schooling). But their results do lead them to question the seemingly common view that child labor is a major factor perpetuating poverty in Bangladesh by keeping children from poor families out of school. This paper - a joint product of Poverty and Human Resources, Development Research Group, and Poverty Reduction and Economic Management Sector Unit, Latin America and the Caribbean Region - is part of a larger effort in the Bank to study behavioral responses to social programs. The authors may be contacted at mravallion@worldbank.org or qwodon@worldbank.org.

Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers

Abstract: Background The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

Autoregressive conditional skewness

Abstract: We present a new methodology for estimating time-varying conditional skewness. Our model allows for changing means and variances, uses a maximum likelihood framework with instruments, and assumes a non-central t distribution. We apply this method to daily, weekly, and monthly stock returns, and find that conditional skewness is important. In particular, we show that the evidence of asymmetric variance is consistent with conditional skewness. Inclusion of conditional skewness also impacts the persistence in conditional variance.

INPUT, INTERACTION, AND SECOND LANGUAGE DEVELOPMENT: An Empirical Study of Question Formation in ESL

Abstract: This study examines the relationship between different types of conversational interaction and SLA. Long's (1996) updated version of the interactionist hypothesis claims that implicit negative feedback, which can be obtained through negotiated interaction, facilitates SLA. Similar claims for the benefits of negotiation have been made by Pica (1994) and Gass (1997). Some support for the interaction hypothesis has been provided by studies that have explored the effects of interaction on production (Gass & Varonis, 1994), on lexical acquisition (Ellis, Tanaka, & Yamazaki, 1994), on the short-term outcomes of pushed output (see Swain, 1995), and for specific interactional features such as recasts (Long, Inagaki, & Ortega, 1998; Mackey & Philp, 1998). However, other studies have not found effects for interaction on grammatical development (Loschky, 1994). The central question addressed by the current study was: Can conversational interaction facilitate second language development? The study employed a pretest-posttest design. Adult ESL learners (N = 34) of varying L1 backgrounds were divided into four experimental groups and one control group. They took part in task-based interaction. Research questions focused on the developmental outcomes of taking part in various types of interaction. Active participation in interaction and the developmental level of the learner were considered. Results of this study support claims concerning a link between interaction and grammatical development and highlight the importance of active participation in the interaction.

Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys.

Abstract: Virus–specific antibodies protect individuals against a wide variety of viral infections1–7. To assess whether human immunodeficiency virus type 1 (HIV–1) envelope–specific antibodies confer resistance against primate lentivirus infections, we purified immunoglobulin (IgG) from chimpanzees infected with several different HIV–1 isolates, and used this for passive immunization of pig–tailed macaques. These monkeys were subsequently challenged intravenously with a chimeric simian–human immunodeficiency virus (SHIV) bearing an envelope glycoprotein derived form HIV–1DH12, a dual–tropic primary virus isolate. Here we show that anti–SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement for antibody–mediated protection in vivo. Using an assay that measures 100% neutralization, the titer in plasma for complete protection of the SHIV–challenged macaques was in the range of 1:5–1:8. The HIV–1–specific neutralizing antibodies studied are able to bind to native gp120 present on infectious virus particles. Administration of non–neutralizing anti–HIV IgG neither inhibited nor enhanced a subsequent SHIV infection.

Does Piped Water Reduce Diarrhea for Children in Rural India

Abstract: August 2001 Children's health improves on average as a result of policy interventions that expand access to piped water. However, the gains largely bypass children in poor and poorly educated families. The effects of public investments aimed at directly improving children's health are theoretically ambiguous, since the outcomes also depend on indirect effects through parental inputs. Jalan and Ravallion investigate the role of such inputs in influencing the incidence of child health gains from access to piped water in rural India. Using propensity score matching methods, they find that the prevalence and duration of diarrhea among children under five are significantly less on average for families with piped water than for families without it. But health gains largely bypass children in poor families, particularly when the mother is poorly educated. The authors' findings point to the importance of combining infrastructure investments with effective public action to promote health knowledge and income poverty reduction. This paper - a product of Poverty, Development Research Group - is part of a larger effort in the group to better measure and understand the welfare impacts of development projects. The study was funded by the Bank's Research Support Budget under the research project "Policies for Poor Areas" (RPO 681-39). The authors may be contacted at jjalan@worldbank.org or mravallion@worldbank.org.

Cervicovaginal Human Papillomavirus Infection in Human Immunodeficiency Virus-1 (HIV)-Positive and High-Risk HIV-Negative Women

Abstract: Background: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIVnegative women participating in the Women’s Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. Methods: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. Results: Compared with HIV-negative women, HIV-positive women with a CD4 + cell count of less than 200/mm 3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32‐14.04), followed by women with a CD4 + count greater than 200/mm 3 and an HIV RNA load greater than 20 000 copies/mL (OR = 5.78; 95% CI = 4.17‐8.08) and women with a CD4 + count greater than 200/mm 3 and an HIV RNA load less than 20 000 copies/mL (OR = 3.12; 95% CI = 2.36‐4.12), after adjustment for other factors. Other risk factors among HIVpositive women included racial/ethnic background (AfricanAmerican versus Caucasian, OR = 1.64; 95% CI = 1.19‐ 2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20‐1.99), and younger age (age 40 years; OR = 1.75; 95% CI = 1.23‐2.49). Conclusions: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIVrelated disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well. [J Natl Cancer Inst 1999;91:226‐36]

Behavioral sampling methods for cetaceans: a review and critique

Abstract: Behavioral scientists have developed methods for sampling behavior in order to reduce observational biases and to facilitate comparisons between studies. A review of 74 cetacean behavioral field studies published from 1989 to 1995 in Marine Mammal Science and The Canadian Journal of Zoology suggests that cetacean researchers have not made optimal use of available methodology. The survey revealed that a large proportion of studies did not use reliable sampling methods. Ad libitum sampling was used most often (59%). When anecdotal studies were excluded, 45% of 53 behavioral studies used ad libitum as the predominant method. Other sampling methods were continuous, onezero, incident, point, sequence, or scan sampling. Recommendations for sampling methods are made, depending on identifiability of animals, group sizes, dive durations, and change in group membership.

Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association.

Abstract: ObjectiveTo establish, in a single resource, up-to-date recommendations for primary care physicians regarding prevention strategies for a first strokeParticipantsMembers of the National Stroke Association's (NSA's) Stroke Prevention Advisory Board and Cedars-Sinai Health System Department of Health Services Research convened on April 9, 1998, in an open meeting The conference attendees, selected to participate by the NSA, were recognized experts in neurology (9), cardiology (2), family practice (1), nursing (1), physician assistant practices (1), and health services research (2)EvidenceA literature review was carried out by the Department of Health Services Research, Cedars-Sinai Health System, Los Angeles, Calif, using the MEDLINE database search for 1990 through April 1998 and updated in November 1998 English-language guidelines, statements, meta-analyses, and overviews on prevention of a first stroke were reviewedConsensus ProcessAt the meeting, members of the advisory board identified 6 important stroke risk factors (hypertension, myocardial infarction [MI], atrial fibrillation, diabetes mellitus, blood lipids, asymptomatic carotid artery stenosis), and 4 lifestyle factors (cigarette smoking, alcohol use, physical activity, diet)ConclusionsSeveral interventions that modify well-documented and treatable cardiovascular and cerebrovascular risk factors can reduce the risk of a first stroke Good evidence for direct stroke reduction exists for hypertension treatment; using warfarin for patients after MI who have atrial fibrillation, decreased left ventricular ejection fraction, or left ventricular thrombus; using 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for patients after MI; using warfarin for patients with atrial fibrillation and specific risk factors; and performing carotid endarterectomy for patients with stenosis of at least 60% Observational studies support the role of modifying lifestyle-related risk factors (eg, smoking, alcohol use, physical activity, diet) in stroke prevention Measures to help patients improve adherence are an important component of a stroke prevention plan

Notch signalling pathway mediates hair cell development in mammalian cochlea.

Abstract: The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic.

Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant

Abstract: Background The intraocular ganciclovir implant is effective for local treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS), but it does not treat or prevent other systemic manifestations of cytomegalovirus infection. Methods Three hundred seventy-seven patients with AIDS and unilateral cytomegalovirus retinitis were randomly assigned to one of three treatments: a ganciclovir implant plus oral ganciclovir (4.5 g daily), a ganciclovir implant plus oral placebo, or intravenous ganciclovir alone. The primary outcome measure was the development of new cytomegalovirus disease, either contralateral retinitis or biopsy-proved extraocular disease. Results The incidence of new cytomegalovirus disease at six months was 44.3 percent in the group assigned to the ganciclovir implant plus placebo, as compared with 24.3 percent in the group assigned to the ganciclovir implant plus oral ganciclovir (P=0.002) and 19.6 percent in the group assigned to intravenous ganciclovir ...

ULTIMATE ATTAINMENT IN L2 PHONOLOGY: The Critical Factors of Age, Motivation, and Instruction

Abstract: Within both first and second language acquisition research, a critical or sensitive period for complete attainment has largely been substantiated in phonological studies, although it is questionable whether age should be examined in isolation from sociopsychological influences and the extent of exposure to the second language. This study sets out to challenge the Critical Period Hypothesis (CPH) by examining phonological performance among highly motivated subjects who use German daily as graduate student instructors and who have been immersed in the language through in-country residence, augmented by years of instruction in both language- and content-based courses. The methodology developed seeks to expand the realm of factors that are potentially conflated with age, such as instruction, motivation, suprasegmental training, and self-perception of productive accuracy, and other factors that have not been addressed in previous studies on ultimate attainment. Production tasks target sounds difficult for nonnative speakers (NNSs) according to contrastive analysis, and task types range in complexity from isolated words to sentences, paragraphs, and free speech. A mean rating was computed for each speaker, including native speaker controls, according to native speaker judgments. When averaged across all tasks, nonnative speaker performance did not overlap with native performance. However, several variables correlated significantly with outcome, including suprasegmental training, which indicated performance closer to native level.

Thermoacoustic computed tomography--technical considerations.

Abstract: We have constructed a thermoacoustic computed tomography scanner for imaging soft tissue in the human body. Thermoacoustic signals are induced in soft tissue by irradiation with 434 MHz rf energy. The thermoacoustic signals are detected by an array of transducers mounted on a hemispherical bowl. A three-dimensional, filtered backprojection algorithm is used to reconstruct rf absorption patterns within soft tissue. We have demonstrated soft tissue differentiation sufficient to delineate the normal internal structures of an excised lamb kidney using safe levels of rf radiation.

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation.

Abstract: Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism

Abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson’s disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units from NAD to nuclear proteins after DNA damage, are dramatically spared from MPTP neurotoxicity. MPTP potently activates PARP exclusively in vulnerable dopamine containing neurons of the substantia nigra. MPTP elicits a novel pattern of poly(ADP-ribosyl)ation of nuclear proteins that completely depends on neuronally derived nitric oxide. Thus, NO, DNA damage, and PARP activation play a critical role in MPTP-induced parkinsonism and suggest that inhibitors of PARP may have protective benefit in the treatment of Parkinson’s disease.

Explicitness, intake, and the issue of awareness: another piece to the puzzle

Abstract: The conditions (implicit or explicit) under which exposure to L2 input takes place and the level of awareness raised while processing input may be strongly related to the learning process. This study investigates how intake was affected both by awareness and by the conditions under which a problem-solving task was performed. Spanish conditional sentences were presented to learners through five different degrees of explicitness, which were the result of combining the factors [±formal instruction] and [±directions to search for rules]. Intake was measured through a multiple-choice recognition test administered immediately after the experimental task. Level of awareness was assessed by means of think-aloud protocols collected during input processing. Results indicate that (a) the degrees of explicitness had a differential effect on intake, (b) the higher the level of awareness demonstrated, the stronger the effect on intake, and (c) the conditions under which the task was administered influenced the way information was processed.