Feasibility and outcomes of combined transcatheter aortic valve replacement with other structural heart interventions in a single session: a matched cohort study

Background Concurrent cardiac diseases are frequent among elderly patients and invite simultaneous treatment to ensure an overall favourable patient outcome. Aim To investigate the feasibility of combined single-session percutaneous cardiac interventions in the era of transcatheter aortic valve implantation (TAVI). Methods This prospective, case–control study included 10 consecutive patients treated with TAVI, left atrial appendage occlusion and percutaneous coronary interventions. Some in addition had patent foramen ovale or atrial septal defect closure in the same session. The patients were matched in a 1:10 manner with TAVI-only cases treated within the same time period at the same institution regarding their baseline factors. The outcome was validated according to the Valve Academic Research Consortium (VARC) criteria. Results Procedural time (126±42 vs 83±40 min, p=0.0016), radiation time (34±8 vs 22±12 min, p=0.0001) and contrast dye (397±89 vs 250±105 mL, p<0.0001) were higher in the combined intervention group than in the TAVI-only group. Despite these drawbacks, no difference in the VARC endpoints was evident during the in-hospital period and after 30 days (VARC combined safety endpoint 32% for TAVI only and 20% for combined intervention, p=1.0). Conclusions Transcatheter treatment of combined cardiac diseases is feasible even in a single session in a high-volume centre with experienced operators.

Dynamics of Apis mellifera filamentous virus (AmFV) infections in honey bees and relationships with other parasites

Apis mellifera filamentous virus (AmFV) is a large double stranded DNA virus of honey bees, but its relationship with other parasites and prevalence are poorly known. We analyzed individual honey bees from three colonies at different times post emergence in order to monitor the dynamics of the AmFV gut colonization under natural conditions. Prevalence and loads of microsporidia and trypanosomes were also recorded, as well as five common honey bee RNA viruses. The results show that a high proportion of bees get infected with AmFV during the first week post-emergence (75%) and that AmFV DNA levels remained constant. A similar pattern was observed for microsporidia while trypanosomes seem to require more time to colonize the gut. No significant associations between these three infections were found, but significant positive correlations were observed between AmFV and RNA viruses. In parallel, the prevalence of AmFV in France and Sweden was assessed from pooled honey bee workers. The data indicate that AmFV is almost ubiquitous, and does not seem to follow seasonal patterns, although higher viral loads were significantly detected in spring. A high prevalence of AmFV was also found in winter bees, without obvious impact on overwintering of the colonies.

Cervical cancer screening in Hispanic women as compared with other ethnic groups on an urban campus

Although Pap screening has decreased morbidity and mortality from cervical cancer, reported statistics indicate that among ethnic groups, Hispanic women are one of the least likely to follow screening guidelines. Human papillomavirus (HPV), a major risk factor for cervical cancer, as well as pre-cancerous lesions, may be detected by early Pap screening. With a reported 43% prevalence of HPV infection in college women, regular Pap screening is important. The purpose of this descriptive, cross-sectional survey was to examine self-reported cervical cancer screening rates in a target population of primarily Mexican-American college women, and to discover if recognized correlates for screening behavior explained differences in screening rates between this and two other predominant groups on the University of Houston Downtown campus, non-Hispanic white and African-American. The sample size consisted of 613 women recruited from summer 2003 classes. A survey, adapted from an earlier El Paso study, and based on constructs of the Health Belief Model (HBM), was administered to women ages 18 and older. It was found that although screening rates were similar across ethnic groups, overall, the Hispanic group obtained screening less frequently, though this did not reach statistical significance. However, a significant difference in lower screening rates was found in Mexican American women ages <25. Additionally, of the predicted correlates, the construct of perceived barriers from the HBM was most significant for the Mexican American group for non-screening. For all groups, knowledge about cervical cancer was negatively correlated with ever obtaining Pap screening and screening within the past year. This implies that if health counseling is given at the time of women's screening visits, both adherence to appropriate screening intervals and risk factor avoidance may be more likely. Studies such as these are needed to address both screening behaviors and likelihood of follow-up for abnormal results in populations of multicultural, urban college women. ^

Equilibria with Local Governments and Commuting: Income Sorting vs. Income Mixing

Tiebout's (1956) model of fiscal competition suggests income sorting between jurisdictions while the Alonso (1964), Mills (167) and Muth (1969) model of the monocentric city suggests income sorting over space. However, strict income sorting is not empirically observed. We add fiscal competition to the spatial model by considering a circular inner city surrounded by a suburb. The fiscal difference between the jurisdictions and the commuting advantage of locations closer to the city center are capitalized into house prices. In addition to the traditional equilibrium with income sorting, there are equilibria with income mixing - both across jurisdictions and across space.

Myanmar's Economic Relations with China: Can China Support the Myanmar Economy?

Against the background of closer diplomatic, political and security ties between Myanmar and China since 1988, their economic relations have also grown stronger throughout the 1990s and up to 2005. China is now a major supplier of consumer and capital goods to Myanmar, in particular through border trade. China also provides a large amount of economic cooperation in the areas of infrastructure, energy and state-owned economic enterprises. Nevertheless, Myanmar’s trade with China has failed to have a substantial impact on its broad-based economic and industrial development. China’s economic cooperation apparently supports the present regime, but its effects on the whole economy will be limited with an unfavorable macroeconomic environment and distorted incentives structure. As a conclusion, strengthened economic ties with China will be instrumental in regime survival, but will not be a powerful force affecting the process of economic development in Myanmar.

Does high speed rail compete fairly with other transportation modes? Madrid-Barcelona case study

Transportation modes produce many external costs such as congestion, accidents, and environmental impacts (pollution, noise and so on). From the microeconomic theory it is well known that in order to maximize social welfare, transportation modes should internalize the marginal costs they produce. Allocative efficiency is achieved when all transportation modes are priced at their social marginal cost. The objective of this research is to evaluate to what extent different passenger transport modes internalize their social marginal costs. This analysis is important since it affects the competitiveness of the different transport modes for a given OD pair. The case study analyzed is the corridor Madrid-Barcelona in Spain and the different transport modes have been considered (cars, buses, high-speed train and air). The research calculates the marginal social cost per user for each transportation mode, and it compares it with the average fare—allowing for the effect of discriminatory taxes—currently paid by the users. The external costs are calculated according to the guidelines established by the European Union. The gap between the marginal social cost and the price paid by users will provide the extra cost per passenger that each transport mode should have to pay for internalizing the external cost it produces. The research shows that external costs already produced by road and air transport modes are much higher than those produced by rail. However, the results show that road transport already internalizes every external costs it produces because users pay high fuel taxes. In other words, although rail transportation produces lower external costs, road transportation pays more than it should on the basis of the social marginal costs. The results of this work might be of help for Europ ean policy actions to be undertaken in the future.

Localization and Recycling of gp27 (hp24γ3): Complex Formation with Other p24 Family Members

We report here the characterization of gp27 (hp24γ3), a glycoprotein of the p24 family of small and abundant transmembrane proteins of the secretory pathway. Immunoelectron and confocal scanning microscopy show that at steady state, gp27 localizes to the cis side of the Golgi apparatus. In addition, some gp27 was detected in COPI- and COPII-coated structures throughout the cytoplasm. This indicated cycling that was confirmed in three ways. First, 15°C temperature treatment resulted in accumulation of gp27 in pre-Golgi structures colocalizing with anterograde cargo. Second, treatment with brefeldin A caused gp27 to relocate into peripheral structures positive for both KDEL receptor and COPII. Third, microinjection of a dominant negative mutant of Sar1p trapped gp27 in the endoplasmic reticulum (ER) by blocking ER export. Together, this shows that gp27 cycles extensively in the early secretory pathway. Immunoprecipitation and coexpression studies further revealed that a significant fraction of gp27 existed in a hetero-oligomeric complex. Three members of the p24 family, GMP25 (hp24α2), p24 (hp24β1), and p23 (hp24δ1), coprecipitated in what appeared to be stochiometric amounts. This heterocomplex was specific. Immunoprecipitation of p26 (hp24γ4) failed to coprecipitate GMP25, p24, or p23. Also, very little p26 was found coprecipitating with gp27. A functional requirement for complex formation was suggested at the level of ER export. Transiently expressed gp27 failed to leave the ER unless other p24 family proteins were coexpressed. Comparison of attached oligosaccharides showed that gp27 and GMP25 recycled differentially. Only a very minor portion of GMP25 displayed complex oligosaccharides. In contrast, all of gp27 showed modifications by medial and trans enzymes at steady state. We conclude from these data that a portion of gp27 exists as hetero-oligomeric complexes with GMP25, p24, and p23 and that these complexes are in dynamic equilibrium with individual p24 proteins to allow for differential recycling and distributions.

Studies on the role of the hydrophobic domain of Ost4p in interactions with other subunits of yeast oligosaccharyl transferase

In the yeast, Saccharomyces cerevisiae, oligosaccharyl transferase (OT), which catalyzes the transfer of dolichol-linked oligosaccharide chains to nascent polypeptides in the endoplasmic reticulum, consists of nine nonidentical membrane protein subunits. Genetic and biochemical evidence indicated these nine proteins exist in three subcomplexes. Three of the OT subunits (Ost4p, Ost3p, and Stt3p) have been proposed to exist in one subcomplex. To investigate the interaction of these three membrane proteins, initially we carried out a mutational analysis of Ost4p, which is an extraordinarily small membrane protein containing only 36 amino acid residues. This analysis indicated that when single amino acid residues in a region close to the luminal face of the putative transmembrane domain of Ost4p were changed into an ionizable amino acid such as Lys or Asp, growth at 37°C and OT activity measured in vitro were impaired. In addition, using immunoprecipitation techniques and Western blot analysis, we found that with these mutations the interaction between Ost4p, Ost3p, and Stt3p was disrupted. Introduction of Lys or Asp residues at other positions in the putative transmembrane domain or at the N or C terminus of Ost4p had no effect on disrupting subunit interactions or impairing the activity of OT. These findings suggest that a localized region of the putative transmembrane domain of Ost4p mediates in stabilization of the interaction with the two other OT subunits (Ost3p and Stt3p) in a subcomplex in the endoplasmic reticulum membrane.

Involvement of the amygdala in memory storage: Interaction with other brain systems

There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving the amygdala. In rats, lesions of the amygdala and the stria terminalis block the effects of posttraining administration of epinephrine and glucocorticoids on memory. Furthermore, memory is enhanced by posttraining intra-amygdala infusions of drugs that activate β-adrenergic and glucocorticoid receptors. Additionally, infusion of β-adrenergic blockers into the amygdala blocks the memory-modulating effects of epinephrine and glucocorticoids, as well as those of drugs affecting opiate and GABAergic systems. Second, an intact amygdala is not required for expression of retention. Inactivation of the amygdala prior to retention testing (by posttraining lesions or drug infusions) does not block retention performance. Third, findings of studies using human subjects are consistent with those of animal experiments. β-Blockers and amygdala lesions attenuate the effects of emotional arousal on memory. Additionally, 3-week recall of emotional material is highly correlated with positron-emission tomography activation (cerebral glucose metabolism) of the right amygdala during encoding. These findings provide strong evidence supporting the hypothesis that the amygdala is involved in modulating long-term memory storage.

DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines.

Vaccination of two chimpanzees against hepatitis B virus (HBV) by intramuscular injection of plasmid DNA encoding the major and middle HBV envelope proteins induced group-, subtype- and preS2-specific antibodies. These were initially of IgM isotype, and then they were of IgG (predominantly IgGl) isotype. The chimpanzee injected with 2 mg of DNA attained >100 milli-international units/ml of anti-HBs antibody after one injection and 14,000 milli-international units/ml after four injections. A smaller dose (400 microg) induced lower and transient titers, but a strong anamnestic response occurred 1 year later. Comparison with responses in 23 chimpanzees receiving various antigen-based HBV vaccines suggests that the DNA approach is promising for prophylactic immunization against HBV.

Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors.

Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription. To investigate protein-protein interactions involved in TFIID assembly and in TAF-mediated activator functions, we have cloned and expressed cDNAs encoding human TAFII80 and TAFII31. Coimmunoprecipitation assays showed that TAFII80 interacted with TAFII250, TAFII31, TAFII20, and TBP, but not with TAFII55. Similar assays showed that TAFII80 interacted with TFIIE alpha and with TFIIF alpha (RAP74) but not with TFIIB, TFIIE beta, or TFIIF beta (RAP30). Further studies with TAFII80 mutations revealed three distinct interaction domains which fall within regions conserved in human TAFII80, Drosophila TAFII60, and yeast TAFII60. The N terminus of TAFII80 (residues 1-100) interacts with both TAFII31 and TAFII20, while two C-terminal regions are involved, respectively, in interactions with TAFII250 and TFIIF alpha (RAP74) (residues 203-276) and with TBP and TFIIE alpha (residues 377-505). The interactions between TAFII80 and general factors TFIIE alpha and TFIIF alpha (RAP74) could be important for recruitment of GTFs during activator-dependent transcription. Because TAFs 80, 31, and 20 show sequence similarities to histones H4, H3, and H2B, as well as some parallel interactions, this subset of TAFs may form a related core structure within TFIID.

Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives).

Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors of HIV-1 replication in cell culture and HIV-1 reverse transcriptase activity. These compounds were markedly active against a series of mutant HIV-1 strains, containing the Leu-100-->Ile, Val-106-->Ala, Glu-138-->Lys, or Tyr-181-->Cys mutations in their reverse transcriptase. However, the thiocarboxanilide derivatives selected for mutations at amino acid positions 100 (Leu-->Ile), 101 (Lys-->Ile/Glu), 103 (Lys-->Thr/Asp) and 141 (Gly-->Glu) in the HIV-1 reverse transcriptase. The compounds completely suppressed HIV-1 replication and prevented the emergence of resistant virus strains when used at 1.3-6.6 microM--that is, 10- to 25-fold lower than the concentration required for nevirapine and bis(heteroaryl)piperazine (BHAP) U90152 to do so. If UC42 was combined with the [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)]-beta-D-pentofuranosyl (TSAO) derivative of N3-methylthymine (TSAO-m3T), virus breakthrough could be prevented for a much longer time, and at much lower concentrations, than if the compounds were used individually. Virus breakthrough could be suppressed for even longer, and at lower drug concentrations, if BHAP was added to the combination of UC42 with TSAO-m3T, which points to the feasibility of two- or three-drug combinations in preventing virus breakthrough and resistance development.

Gender and health inequalities: intersections with other relevant axes of oppression

The risk of disease, disability, and mortality as well as access to health services are unfairly distributed among the population, with certain groups bearing an unequally larger burden of ill health and poorer access to care due to gender, sexual identity/orientation, ethnic background, or class. According to the WHO Commission on Social Determinants of Health (CSDH), these health inequalities emanate from socioeconomic and political factors (governance, cultural values, macroeconomic policies), which generate a set of socioeconomic positions in society according to which populations are stratified based on gender, ethnicity, education, income, or other factors. These societal inequalities influence people’s material and psychosocial circumstances as well as behavioral and biological factors, which in turn impact on health inequalities. Tackling gender, race/ethnic, and socioeconomic inequalities in society is thus recognized as the most powerful action to cope with unequal health risks distribution, and social innovations focusing on these ‘root causes’ are needed in order to prevent and stop endemic social inequalities and social exclusion in health within low-income as well as high-income countries. Increasing existing knowledge and making visible the health status of the most vulnerable and invisible groups are critical in order to contribute to this imperative challenge.

Manuscript on United States relations with England and France,

Untitled and undated manuscript written by Tudor offering his opinions on political and commercial relations between the United States, England, and France, and the causes of American animosity toward those countries. Topics and events referenced include the slave trade, Napoleon, and the Little Belt Affair. Introduction and parts one through three.