Prevalence and risk factors for polyomavirus reactivation in solid-organ transplantation

Background. Polyomavirus reactivation is common in solid-organ transplant recipients who are given immunosuppressive medications as standard treatment of care. Previous studies have shown that polyomavirus infection can lead to allograft failure in as many as 45% of the affected patients. Hypothesis. Ubiquitous polyomaviruses when reactivated by post-transplant immunosuppressive medications may lead to impaired renal function and possibly lower survival prospects. Study Overview. Secondary analysis of data was conducted on a prospective longitudinal study of subjects who were at least 18 years of age and were recipients of liver and/or kidney transplant at Mayo Clinic Scottsdale, Arizona. Methods. DNA extractions of blinded urine and blood specimens of transplant patients collected at Mayo Clinic during routine transplant patient visits were performed at Baylor College of Medicine using Qiagen kits. Virologic assays included testing DNA samples for specific polyomavirus sequences using QPCR technology. De-identified demographic and clinical patient data were merged with laboratory data and statistical analysis was performed using Stata10. Results. 76 patients enrolled in the study were followed for 3.9 years post transplantation. The prevalence of BK virus and JC virus urinary excretion was 30% and 28%. Significant association was observed between JC virus excretion and kidney as the transplanted organ (P = 0.039, Pearson Chi-square test). The median urinary JCV viral loads were two logs higher than those of BKV. Patients that excreted both BKV and JCV appeared to have the worst renal function with a mean creatinine clearance value of 71.6 millimeters per minute. A survival disadvantage was observed for dual shedders of BKV and JCV, log-rank statistics, p = 0.09; 2/5 dual-shedders expired during the study period. Liver transplant and male sex were determined to be potential risk factors for JC virus activation in renal and liver transplant recipients. All patients tested negative for SV40 and no association was observed between polyomavirus excretion and type of immunosuppressive medication (tacrolimus, mycophenolate mofetil, cyclosporine and sirolimus). Conclusions. Polyomavirus reactivation was common after solid-organ transplantation and may be associated with impaired renal function. Male sex and JCV infection may be potential risk factors for viral reactivation; findings should be confirmed in larger studies.^

The role of AKT-mediated phosphorylation in suppression of MAD1 and the development of new approach in protein complex detection

MAX dimerization protein 1 (MAD1) is a basic-helix-loop-helix transcription factors that recruits transcription repressor such as HDAC to suppress target genes transcription. It antagonizes to MYC because the promoter binding sites for MYC are usually also serve as the binding sites for MAD1 so they compete for it. However, the mechanism of the switch between MYC and MAD1 in turning on and off of genes' transcription is obscure. In this study, we demonstrated that AKT-mediated MAD1 phosphorylation inhibits MAD1 transcription repression function. The association between MAD1 and its target genes' promoter is reduced after been phosphorylated by AKT; therefore, consequently, allows MYC to occupy the binding site and activates transcription. Mutation of such phosphorylation site abrogates the inhibition from AKT. In addition, functional assays demonstrated that AKT suppressed MAD1-mediated transcription repression of its target genes hTERT and ODC. Cell cycle and cell growth were also been released from inhibition by MAD1 in the presents of AKT. Taken together, our study suggests that MAD1 is a novel substrate of AKT and AKT-mediated MAD1 phosphorylation inhibits MAD1function; therefore, activates MAD1 target genes expression. ^ Furthermore, analysis of protein-protein interaction is indispensable for current molecular biology research, but multiplex protein dynamics in cells is too complicated to be analyzed by using existing biochemical methods. To overcome the disadvantage, we have developed a single molecule level detection system with nanofluidic chip. Single molecule was analyzed based on their fluorescent profile and their profiles were plotted into 2 dimensional time co-incident photon burst diagram (2DTP). From this 2DTP, protein complexes were characterized. These results demonstrate that the nanochannel protein detection system is a promising tool for future molecular biology. ^

Impact of hormonal therapy on survival and racial disparities in a large community-based cohort of older men with local/regional prostate cancer

Prostate cancer (CaP) is the most diagnosed non-cutaneous malignancy and the second leading cause of cancer mortality among United States males. Major racial disparities in incidence, survival, as well as treatment persist. The mortality is three times higher among African Americans (AAs) compared with Caucasians. Androgen carcinogenesis has been persistently implicated but results are inconsistent; and hormone manipulation has been the main stay of treatment for metastatic disease, supportive of the androgen carcinogenesis. The survival disadvantage of AAs has been attributed to the differences in socioeconomic factors (SES), tumor stage, and treatment. We hypostasized that HT prolongs survival in CaP and that the racial disparities in survival is influenced by variation in HT and primary therapies as well as SES. To address these overall hypothesis, we first utilized a random-effect meta-analytic design to examine evidence from randomized trials on the efficacy of androgen deprivation therapy in localized and metastatic disease, and assessed, using Cox proportional hazards models, the effectiveness of HT in prolonging survival in a large community-based cohort of older males diagnosed with local/regional CaP. Further we examined the role of HT and primary therapies on the racial disparities in CaP survival. The results indicated that adjuvant HT compared with standard care alone is efficacious in improving overall survival, whereas HT has no significant benefit in the real world experience in increasing the overall survival of older males in the community treated for local/regional disease. Further, racial differences in survival persist and were explained to some extent by the differences in the primary therapies (radical prostatectomy, radiation and watchful waiting) and largely by SES. Therefore, given the increased used of hormonal therapy and the cost-effectiveness today, more RCTs are needed to assess whether or not survival prolongation translates to improved quality of life, and to answer the research question on whether or not the decreased use of radical prostatectomy by AAs is driven by the Clinicians bias or AAs's preference of conservative therapy and to encourage AAs to seek curative therapies, thus narrowing to some degree the persistent mortality disparities between AAs and Caucasians. ^

Environmental influences on self-reported leisure-time physical activity in the Austin/Travis County STEPS survey 2005--2009

This study was an examination of environmental and social correlates of physical inactivity in a socio-economically disadvantaged community. This study was a secondary analysis of data collected by the Austin/Travis County Department of Health and Human Services. The study included an analysis of perceived environmental influences (e.g. access to physical support features like sidewalks and streetlights). This study also investigated several features of the social environment (e.g. perceived neighborhood crime and social influence). Participants’ beliefs and attitudes about the neighborhood were investigated. Results included estimates of the association between neighborhood factors and physical inactivity controlling for age, gender and education. This study found significant associations for social and environmental variables with physical inactivity. The goal of this work was to identify factors that contribute to inactivity and address a number of environmental and neighborhood risk factors that contribute to sedentary behaviors in a population of relative social and economic disadvantage.^

REPRODUCTIVE PERFORMANCE IN THE DES-EXPOSED DAUGHTERS

This research examined the relation between prenatal exposure to diethylstilbestrol (DES) and subsequent reproductive performance in females. Although previous studies have agreed that unfavorable pregnancy outcomes (spontaneous abortions, stillbirths, ectopic pregnancies, and premature births) occur with greater frequency in the exposed as compared to unexposed women, the role of exposure to DES in-utero on subsequent fertility (pregnancy achievement) remains controversial. Also, the possibility that the reproductive dysfunction reported in exposed women might be due to familial predisposition to reproductive dysfunction rather than to DES exposure has not been examined heretofore.^ The purposes of the research were to: (1) measure the overall differences in rates of live births between exposed and unexposed women; (2) determine if infertility or early unrecognized spontaneous miscarriages (as opposed to recognized fetal death) contributes to poor reproductive performance in the exposed; and (3) determine if constitutional predisposition contributes to poor reproductive performance in exposed daughters.^ The study population comprised those participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project who were identified through review of prenatal records. Birth interval curves (survival analyses) were used to compare the reproductive performance of exposed daughters and unexposed women. Birth interval curves were also constructed for unexposed siblings (of exposed participants) and unexposed nonsiblings to determine the role of constitutional predisposition in the reproductive performance of exposed daughters.^ The DES-daughters, as compared to unexposed women, were found to be at a reproductive disadvantage when the overall differences in rates of live births were compared.^ When the differences in rates of live births due specifically to infertility or early unrecognized spontaneous miscarriages (as opposed to recognized fetal death) were examined, the exposed maintained the reproductive disadvantage. This analysis was suggestive but not statistically significant for the first-birth-interval and was neither suggestive nor significant in the second-birth-interval. (Abstract shortened with permission of author.) ^

A health disparities perspective on developing emerging infectious disease preparedness

A systematic review of the literature yielded 10 articles that explored the interaction between race/ethnicity, citizenship, socioeconomic status, and health literacy domains with respect to preparedness agenda development. Current emerging infectious disease (EID) preparedness plans do not adequately address the needs of vulnerable populations for the events before, during, and after an epidemic. Central to the disadvantage of most vulnerable populations are various health disparity domains that persist as barriers for individuals and communities alike to engage in preparedness efforts. Seven out of the ten articles discussed the importance of including health disparity domains in preparedness policy. Two proposed frameworks for an emerging infectious disease framework that considers health disparities are presented in this study. ^ Framework 1 is beneficial for the evaluation phase after a disaster has struck and preparedness efforts have been initiated. It considers several existing disparities and remediation strategies at the individual, community, and system levels to reach adequate restructuring of preparedness aims. Framework 2 serves as a "how to" carry out preparedness during a disaster event. It is a revision of a framework proposed by Blumenshine et al. (2008) and explores those characteristics central to pandemic preparedness plan development/deployment. Although two frameworks were devised, no one framework will adequately address the needs of vulnerable populations during an epidemic. However, the two frameworks propose to demonstrate the inclusion of important health disparity domains in preparedness plan development. ^ The National Consensus Panel for Emergency Preparedness and Cultural Diversity has released guidelines that are considered the leading strategies necessary to reorient preparedness infrastructure. In order for vulnerable populations to benefit from ample protection during a disaster, inclusion of health disparity domains in the development phases of preparedness must occur prior to full deployment in communities. Although "promising practices" and other methods at the frontier of exploring these multidimensional constraints has entered the research arena, new studies on adequate preparedness merit further investigation and support.^

Understanding mental illness in Nigeria: Bringing culture and traditional medicine into mental health policy

One of the major challenges in treating mental illness in Nigeria is that the health care facilities and mental health care professionals are not enough in number or well equipped to handle the burden of mental illness. There are several barriers to treatment for individual Nigerians which include the following: such as the lack of understanding of the root causes of mental illness, lack of financial support to get mental treatment, lack of social support (family, friends, neighbors), the fear of stigmatization concerning being labeled as mentally ill or being in association with the mentally ill, and the consultation of traditional native healers who may be unknowingly prolonging illness, rather than addressing and treating them due to lack of formal education and standardization of their treatments. Another barrier is the non-health nature of the mental health services in Nigeria. Traditional healers are essentially the mental health system. The elderly, women, and children are the most vulnerable groups in times of strife and hardships. Their mental well-being must be taken into account as well as their special needs in times of personal or societal crisis. ^ Nigerian mental health policy is geared toward forming a mental health system, but in actuality only a mental illness care system is the observed result of the policy. The government of Nigeria has drafted a mental health policy, yet its actual implementation into the Nigerian health infrastructure and society waits to be materialized. The limited health legislation or policy implementations tend to favor those who have access to these urban areas and the facilities' health services. Nigerians living in rural areas are at a disadvantage; many of them may not even be aware of services available to help them understand and treat mental illness. Perhaps, government driven health interventions geared toward mental illness in rural areas would reach an underserved Nigerians and Africans in general. Issues with political instability and limited infrastructure often hinder crucial financial resources and legislation from reaching the people that are truly in need of governmental leadership in regards to mental health policy.^ Traditional healers are a severely untapped resource in the treatment of mental illness within the Nigerian population. They are abundant within Nigerian communities and are meeting a real need for the mentally ill. However, much can be done to remove the barriers that prevent the integration of traditional healers within the mental health system and improve the quality of care they administer within the population. Mental illness is almost exclusively coped with through traditional medicine practices. Mobilization and education from each strata of Nigerian society and government as well as input from the medical community can improve how traditional medicine is utilized as a treatment for clinical illness and help alleviate the heavy burden of mental illness in Nigeria. Currently, there is no existing policy making structure for a working mental health system in Nigeria, and traditional healers are not taken into account in any formulation of mental health policy. Advocacy for mental illness is severely inadequate due to fear of stigmatization, with no formally recognized national of regional mental health association.^

Family Structure and Obesity Among U.S. Children

Child obesity in the U.S. is a significant public health issue, particularly among children from disadvantaged backgrounds. Thus, the roles of parents’ human and financial capital and racial and ethnic background have become important topics of social science and public health research on child obesity. Less often discussed, however, is the role of family structure, which is an important predictor of child well-being and indicator of family socioeconomic status. The goal of this study, therefore, is to investigate how preschool aged children’s risk of obesity varies across a diverse set of family structures and whether these differences in obesity are moderated by family poverty status and the mothers’ education. Using a large nationally representative sample of children from the Early Childhood Longitudinal Study – Birth Cohort, we find that preschoolers raised by two biological cohabiting parents or a relative caregiver (generally the grandparent) have greater odds of being obese than children raised by married biological parents. Also, poor children in married biological parent households and non-poor children in married step parent households have greater obesity risks, while poor children in father only, unmarried step, and married step parent families actually have lower odds of obesity than children in non-poor intact households. The implications of these findings for policy and future research linking family structure to children’s weight status are discussed.

Lazos sociales y estrategias: ¿una opción para las familias hortícolas empobrecidas?

La problemática central de este artículo es mostrar las particularidades que asumen los lazos sociales de algunos sectores de la población rururbana platense, particularmente en aquellos grupos familiares vinculados a la producción hortícola en situaciones de empobrecimiento y/o desventaja social. En este sentido es dable destacar que este estudio se enmarca en los procesos de cambio socio-económicos que, en las últimas décadas del siglo XX, implicaron una multiplicidad de transformaciones sociales en nuestro país; por tanto, el presente análisis se ubica en una realidad compleja de cambios sociales y desigualdades que, durante la década del '90, configuraron un escenario que repercutió en las condiciones de vida y de reproducción social de los sujetos a los que se hace referencia. Se presentarán las aproximaciones logradas en torno a los cambios o permanencias de los vínculos que estas familias despliegan (como colectivo o individualmente); de las estrategias que se elaboran cuando transitan situaciones económico-sociales críticas; de cómo repercuten estas situaciones en la organización familiar, en sus condiciones de vida y por ende en su reproducción social. Pero teniendo presente que el foco del análisis está en los lazos sociales y las formas de sociabilidad de estos grupos sociales. En este marco, se presentará un conjunto de interrogantes y problematizaciones que me permitieron profundizar en estas cuestiones; por tanto, no es mi pretensión mostrar resultados concluyentes, sino explicitar el abordaje de dicha problemática a partir de algunas reflexiones teóricas y de los datos obtenidos durante el trabajo de campo.

Lazos sociales y estrategias: ¿una opción para las familias hortícolas empobrecidas?

La problemática central de este artículo es mostrar las particularidades que asumen los lazos sociales de algunos sectores de la población rururbana platense, particularmente en aquellos grupos familiares vinculados a la producción hortícola en situaciones de empobrecimiento y/o desventaja social. En este sentido es dable destacar que este estudio se enmarca en los procesos de cambio socio-económicos que, en las últimas décadas del siglo XX, implicaron una multiplicidad de transformaciones sociales en nuestro país; por tanto, el presente análisis se ubica en una realidad compleja de cambios sociales y desigualdades que, durante la década del '90, configuraron un escenario que repercutió en las condiciones de vida y de reproducción social de los sujetos a los que se hace referencia. Se presentarán las aproximaciones logradas en torno a los cambios o permanencias de los vínculos que estas familias despliegan (como colectivo o individualmente); de las estrategias que se elaboran cuando transitan situaciones económico-sociales críticas; de cómo repercuten estas situaciones en la organización familiar, en sus condiciones de vida y por ende en su reproducción social. Pero teniendo presente que el foco del análisis está en los lazos sociales y las formas de sociabilidad de estos grupos sociales. En este marco, se presentará un conjunto de interrogantes y problematizaciones que me permitieron profundizar en estas cuestiones; por tanto, no es mi pretensión mostrar resultados concluyentes, sino explicitar el abordaje de dicha problemática a partir de algunas reflexiones teóricas y de los datos obtenidos durante el trabajo de campo.

Lazos sociales y estrategias: ¿una opción para las familias hortícolas empobrecidas?

La problemática central de este artículo es mostrar las particularidades que asumen los lazos sociales de algunos sectores de la población rururbana platense, particularmente en aquellos grupos familiares vinculados a la producción hortícola en situaciones de empobrecimiento y/o desventaja social. En este sentido es dable destacar que este estudio se enmarca en los procesos de cambio socio-económicos que, en las últimas décadas del siglo XX, implicaron una multiplicidad de transformaciones sociales en nuestro país; por tanto, el presente análisis se ubica en una realidad compleja de cambios sociales y desigualdades que, durante la década del '90, configuraron un escenario que repercutió en las condiciones de vida y de reproducción social de los sujetos a los que se hace referencia. Se presentarán las aproximaciones logradas en torno a los cambios o permanencias de los vínculos que estas familias despliegan (como colectivo o individualmente); de las estrategias que se elaboran cuando transitan situaciones económico-sociales críticas; de cómo repercuten estas situaciones en la organización familiar, en sus condiciones de vida y por ende en su reproducción social. Pero teniendo presente que el foco del análisis está en los lazos sociales y las formas de sociabilidad de estos grupos sociales. En este marco, se presentará un conjunto de interrogantes y problematizaciones que me permitieron profundizar en estas cuestiones; por tanto, no es mi pretensión mostrar resultados concluyentes, sino explicitar el abordaje de dicha problemática a partir de algunas reflexiones teóricas y de los datos obtenidos durante el trabajo de campo.

Daily MODIS composites of thin-ice thickness and ice-surface temperatures for the Southern Weddell Sea

Based upon high-resolution thermal-infrared Moderate-Resolution Imaging Spectroradiometer (MODIS) satellite imagery in combination with ERA-Interim atmospheric reanalysis data, we derived long-term polynya parameters such as polynya area, thin-ice thickness distribution and ice-production rates from daily cloud-cover corrected thin-ice thickness composites. Our study is based on a thirteen year investigation period (2002-2014) for the austral winter (1 April to 30 September) in the Antarctic Southern Weddell Sea. The focus lies on coastal polynyas which are important hot spots for new-ice formation, bottom-water formation and heat/moisture release into the atmosphere. MODIS has the capability to resolve even very narrow coastal polynyas. Its major disadvantage is the sensor limitation due to cloud cover. We make use of a newly developed and adapted spatial feature reconstruction scheme to account for cloud-covered areas. We find the sea-ice areas in front of Ronne and Brunt Ice Shelf to be the most active with an annual average polynya area of 3018 ± 1298 and 3516 ± 1420 km2 as well as an accumulated volume ice production of 31 ± 13 and 31 ± 12 km**3, respectively. For the remaining four regions, estimates amount to 421 ± 294 km**2 and 4 ± 3 km**3 (Antarctic Peninsula), 1148 ± 432 km**2 and 12 ± 5 km**3 (Iceberg A23A), 901 ± 703 km**2 and 10 ± 8 km**3 (Filchner Ice Shelf) as well as 499 ± 277 km**2 and 5 ± 2 km**3 (Coats Land). Our findings are discussed in comparison to recent studies based on coupled sea-ice/ocean models and passive-microwave satellite imagery, each investigating different parts of the Southern Weddell Sea.

Disciplining Investment Incentives: A Lost Cause?

An E15 Initiative think piece: Investment incentives rank among the most important policy instruments governments employ to influence the locational decisions of multinational firms. In the wake of the recent increase in locational competition and the growing impact of investment incentives and support measures for state-owned enterprises (SOEs), the need for enhanced disciplines on investment incentives has gained political and academic salience. This think piece explores the evolution of investment incentives from a development and rule-making perspective. It summarises the existing literature and examines current practices and recent trends in FDI flows and the use of various investment incentives. This is followed by a discussion of the reasons for the observed stalemate in attempts at disciplinary rule-making. The paper concludes by putting forth recommendations for data gathering and transparency that could further the move toward improved global governance founded on the increasing complementarities of trade, investment, and competition law and policy as the core pillars of a more open, inclusive, and just world economy.

Growth of the Firm and Economic Backwardness: A Case Study and Analysis of China's Mobile Handset Industry

Economic backwardness often influences the growth of firms in developing countries. In this paper, we investigate the growth conditions and paths available for latecomers competing with first movers. Employing the concepts of boundaries of the firm and the disadvantage of backwardness, we present a case study of China's mobile handset industry and proceed to develop a simple model. We find that although significant disadvantage does not allow latecomers to grow, there are possibilities for changing the conditions of growth if latecomers can utilize outside resources and/or indigenous advantages.

Intra-regional trade between China, Japan, and Korea : before and after the financial crisis

East Asian economies have been heavily dependent on the U.S. and EU markets, especially for the export of final goods. Therefore, once the financial crisis hit Western economies hard, the East Asian economies lost their major markets.Their production networks then worked to the region's disadvantage and stifled industrial development.This reflects the vulnerability of the East Asian economies which have adopted an export-led growth strategy. Such vulnerability needs to be addressed to prevent future economic crises, as well as to sustain economic growth. This paper examines the trade structure of the three countries-China, Japan, and Korea-before and after the Lehman Shock, and discusses how the three countries should cooperate in addressing imbalances in the trade structure.