Immunotherapeutic strategies for bladder cancer.

Bladder cancer is a common urologic malignancy with rising incidence in the elderly population. In most cases, bladder cancer is non-muscle-invasive at diagnosis and shows dramatically high recurrence rates, although current treatments often reduce the risk of disease progression. Immunotherapy using intravesical instillation of Bacillus Calmette-Guérin (BCG) remains the most effective therapy for patients with high risk tumors. However, BCG-therapy has important limitations including substantial adverse events and frequent treatment failure. Thus, it appears crucial to either improve or replace current therapy using new immunotherapeutic strategies. Here, we discuss the clinical trials that assessed therapeutic vaccination of bladder cancer patients using tumor associated antigens and we also argue for novel approaches arising from murine models. Vaccination routes to induce appropriate T-cell homing in the tumor site as well as the use of local immunostimulation to enhance recruitment of vaccine-induced T cells are discussed to highlight what we believe is a promising therapeutic vaccination strategy for patients with non-muscle-invasive bladder cancer.

Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages.

The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent.

Nitrogen and Potassium in Narrow-Row Cotton

ABSTRACT Information on fertilizer management for cotton in narrow-row cropping system is scarce; therefore, studies are needed to improve nutrient stewardship for such systems. The aim of this study was to evaluate the effects of nitrogen and potassium application on yield and fiber quality of cotton under a narrow-row system. A field trial was carried out for three years, where the treatments were set up in an incomplete factorial arrangement [(4 × 4) + 1] under a randomized block design, with four N rates (20, 40, 60, and 80 kg ha-1), four K2O rates (0, 40, 80, and 120 kg ha-1), and one control (no N or K2O), for a total of 17 treatments, with four replicates. Urea and potassium chloride were applied on the soil surface 20 days after crop emergence. Varieties used were FMT 701 (2009/2010 and 2010/2011) and FMT 709 (2011/2012). Cotton yield and fiber quality parameters were measured. In the narrow-row cropping system, cotton lint yield was positively affected by N and K application. Cotton yield in relation to K applications was not dependent on N rates. Potassium application increased the micronaire index and fiber resistance, whereas high N rates reduced fiber resistance.

Mixed mating in androdioecious Mercurialis annua inferred using progeny arrays and diploid-acting microsatellite loci in a hexaploid background.

Background and Aims The frequency at which males can be maintained with hermaphrodites in androdioecious populations is predicted to depend on the selfing rate, because self-fertilization by hermaphrodites reduces prospective siring opportunities for males. In particular, high selfing rates by hermaphrodites are expected to exclude males from a population. Here, the first estimates are provided of the mating system from two wild hexaploid populations of the androdioecious European wind-pollinated plant M. annua with contrasting male frequencies.Methods Four diploid microsatellite loci were used to genotype 19-20 progeny arrays from two populations of M. annua, one with males and one without. Mating-system parameters were estimated using the program MLTR.Key Results Both populations had similar, intermediate outcrossing rates (t(m) = 0.64 and 0.52 for the population with and without males, respectively). The population without males showed a lower level of correlated paternity and biparental inbreeding and higher allelic richness and gene diversity than the population with males.Conclusions The results demonstrate the utility of new diploid microsatellite loci for mating system analysis in a hexaploid plant. It would appear that androdioecious M. annua has a mixed-mating system in the wild, an uncommon finding for wind-pollinated species. This study sets a foundation for future research to assess the relative importance of the sexual system, plant-density variation and stochastic processes for the regulation of male frequencies in M. annua over space and time.

The effect of innovation and sex-specific migration on neutral cultural differentiation

Studies of behaviour are increasingly focusing on acquisition of traits through cultural inheritance. Comparison of patterns of spatial population structure (FST) between neutral genetic loci and behavioural or cultural traits can been used to test hypotheses about demography, life history, and the mechanisms of inheritance/transmission of these traits in humans, chimpanzees and other animals. Here, we develop analytical expectations to show how FST in cultural traits can differ strongly from that measured at neutral genetic markers if migration is largely restricted to one sex but social learning is predominantly modelled on the other (e.g. males migrate, females serve as models for cultural traits), if one individual is the learning model for many, or if rates of innovation (individual learning) are high or rates of social learning are low. We discuss how comparisons of FST between genetic loci and behavioural traits can be applied to evaluate the importance of innovation in shaping patterns of cultural differentiation, as even low rates of innovation can considerably reduce FST, relative to observed structure at neutral genetic loci. Our results also suggest that differentiation in neutral cultural traits should occur over much smaller scales in species with male migration and female enculturation (or the reverse).

Ecological-economic optimization of biodiversity conservation under climate change

Substantial investment in climate change research has led to dire predictions of the impacts and risks to biodiversity. The Intergovernmental Panel on Climate Change fourth assessment report(1) cites 28,586 studies demonstrating significant biological changes in terrestrial systems(2). Already high extinction rates, driven primarily by habitat loss, are predicted to increase under climate change(3-6). Yet there is little specific advice or precedent in the literature to guide climate adaptation investment for conserving biodiversity within realistic economic constraints(7). Here we present a systematic ecological and economic analysis of a climate adaptation problem in one of the world's most species-rich and threatened ecosystems: the South African fynbos. We discover a counterintuitive optimal investment strategy that switches twice between options as the available adaptation budget increases. We demonstrate that optimal investment is nonlinearly dependent on available resources, making the choice of how much to invest as important as determining where to invest and what actions to take. Our study emphasizes the importance of a sound analytical framework for prioritizing adaptation investments(4). Integrating ecological predictions in an economic decision framework will help support complex choices between adaptation options under severe uncertainty. Our prioritization method can be applied at any scale to minimize species loss and to evaluate the robustness of decisions to uncertainty about key assumptions.

Using register data to assess the impact of response enhancement methods on the risk of nonresponse bias and survey costs

The pursuit of high response rates to minimise the threat of nonresponse bias continues to dominate decisions about resource allocation in survey research. Yet a growing body of research has begun to question this practice. In this study, we use previously unavailable data from a new sampling frame based on population registers to assess the value of different methods designed to increase response rates on the European Social Survey in Switzerland. Using sampling data provides information about both respondents and nonrespondents, making it possible to examine how changes in response rates resulting from the use of different fieldwork methods relate to changes in the composition and representativeness of the responding sample. We compute an R-indicator to assess representativity with respect to the sampling register variables, and find little improvement in the sample composition as response rates increase. We then examine the impact of response rate increases on the risk of nonresponse bias based on Maximal Absolute Bias (MAB), and coefficients of variation between subgroup response rates, alongside the associated costs of different types of fieldwork effort. The results show that increases in response rate help to reduce MAB, while only small but important improvements to sample representativity are gained by varying the type of effort. These findings lend further support to research that has called into question the value of extensive investment in procedures aimed at reaching response rate targets and the need for more tailored fieldwork strategies aimed both at reducing survey costs and minimising the risk of bias.

Recruiting and Retaining Women and Minorities in Public Sector Engineering Positions, HR-348, 1995

The objective of phase one of this research was to assess the degree to which currently employed Iowa Department of Transportation (DOT) employees would be affected by a more aggressive policy to recruit and retain women and minority engineers. The DOT's "Future Agenda" was used as a baseline to focus on efforts to update and implement a recruitment plan that would target underrepresented classes. The primary question that emerged out of phase one was how could the Iowa DOT strengthen its ties with Iowa State University (ISU) to produce increased numbers of in-state applicants for engineering positions. This introduced the objective of phase two, which was to identify problem areas resulting in unacceptably high attrition rates for women, minorities, and to a lesser degree, Caucasian men in the College of Engineering at ISU, particularly Civil and Construction Engineering (CCE). Past research has focused on (1) projected shortages of qualified civil engineers, (2) the obstacles confronting women in a traditionally male-oriented profession, and (3) minorities who are often unprepared to succeed in the rigors of an engineering curriculum because of a lack of academic preparedness. The researchers in this study, in contrast, chose to emphasize institutional reasons why women, minorities, and some Caucasian men often feel a sense of isolation in the engineering program. It was found that one of the key obstacles to student retention is the lack of visibility of the civil engineering profession. The visibility problem led to the hypothesis that many engineering students do not have a clear conception of what the practice of civil engineering entails. It was found that this may be a better predictor of attrition than the stereotypical assumption that a majority of students leave their engineering programs because they are not academically able to compete. Recommendations are offered to strengthen the ties between ISU's Department of CCE and the Iowa DOT in order to counter the visibility issue. It was concluded that this is a vital step because over the next 5-15 years 40% of DOT engineers currently employed will be phasing into retirement. If the DOT expects to draw sufficient numbers of engineers from within the state of Iowa and if increasing numbers of them are to be women and minorities, a university connection will help to produce the qualified applicants to fulfill this need.

Nitrogen fertilization impact on agronomic traits of maize hybrids released at different decades

Genetic selection of maize hybrids is often conducted using high N rates during the breeding cycle. This procedure may either lead to the release of genotypes that present nitrogen luxury consumption or require a stronger N input to accomplish their yield potential. This work was carried out to evaluate the effects of N rates on grain yield and N use efficiency of hybrids cultivated in different decades in Southern Brazil. The trial was performed in Lages, Santa Catarina State. A split plot design was used. Hybrids Ag 12, Ag 28, Ag 303 and Ag 9012, released during the 60's, 70's, 80's and 90's, respectively, were evaluated in the main plots. Nitrogen rates equivalent to 0, 50, 100 and 200 kg ha-1 were side-dressed in the split-plots when each hybrid had six fully expanded leaves. Modern-day hybrid Ag 9012 had higher grain yield than hybrids of earlier eras, regardless of N rates. Under high doses of N, the older hybrids Ag 12 and Ag 28 took up more N and presented higher values of shoot dry matter at flowering than Ag 9012. Nonetheless, they set less grains per ear which contributed to decrease their grain yield and N use efficiency.

Laparoscopic Gastric Banding Outcomes Do Not Depend on Device or Technique. Long-Term Results of a Prospective Randomized Study Comparing the Lapband® and the SAGB®.

BACKGROUND: Gastric banding still represents one of the most widely used bariatric procedures. It provides acceptable weight loss in many patients, but has frequent long-term complications. Because different types of bands may lead to different results, we designed a randomized study to compare the Lapband® with the SAGB®. We hereby report on the long-term results. METHODS: Between December 1998 and June 2002, 180 morbidly obese patients were randomized between Lapband® or SAGB®. Weight loss, long-term morbidity, and need for reoperation were evaluated. RESULTS: Long-term weight loss did not differ between the two bands. Patients who maintained their band had an acceptable long-term weight loss of between 50 and 60 % EBMIL. In both groups, about half the patients developed long-term complications, with about 50 % requiring major redo surgery. There was no difference in the overall rates of long-term complications or failures between the two groups, but patients who had a Lapband® were significantly more prone to develop band slippage/pouch dilatation (13.3 versus 0 %, p < 0,001). CONCLUSIONS: Although in the absence of complication, gastric banding leads to acceptable weight loss; the long-term complication and major reoperation rates are very high independently from the type of band used or on the operative technique. Gastric banding leads to relatively poor overall long-term results and therefore should not be considered the procedure of choice for the treatment of morbid obesity. Patients should be informed of the limited overall weight loss and the very high complication rates.

Prévention du sida chez les toxicomanes en Suisse: une évolution encourageante. [Prevention of AIDS in drug addicts in Switzerland: an encouraging development].

Switzerland has adopted a prevention strategy including the promotion of non-sharing injection material and use of condoms. The access to sterile equipment has been made easier, but regional differences still exist. Studies conducted between 1989 and 1992 among drug users in different Swiss regions are reviewed in order to examine if progress in prevention occurred. Syringe sharing diminished everywhere, but rather high sharing rates persist where sterile material is less accessible. Condom use increased, but the situation is still unsatisfactory considering the high HIV prevalence among i.v. drug users. Where several surveys have been conducted consecutively, a stabilization of HIV prevalence was observed. This suggests a slowing down of the progression of the epidemic among drug users. These results, obtained in few years, are encouraging in the light of the pessimism which prevailed at the beginning of the epidemic about the ability of drug users to adopt preventive behaviour.

Salvage treatment for venous aneurysm complicating vascular access arteriovenous fistula: use of an exoprosthesis to reinforce the vein after aneurysmorrhaphy.

OBJECTIVES: We report a new salvage technique for treating venous aneurysms (VAs) complicating vascular access arteriovenous fistula (AVF) using externally reinforced venous aneurysmorrhaphy. DESIGN: A retrospective study over a 20-month period from a single centre. PATIENTS: Patients presenting to the vascular surgery department, Bordeaux University Hospital for revision of a vascular access AVF were included. METHODS: Reinforced venous aneurysmorrhaphy consisted in removal of redundant vessel wall followed by reinforcement using an external prosthetic graft. Patency, diameter and flow were assessed by duplex ultrasound at 1, 6 and 12 months after salvage. RESULTS: Thirty-eight eligible patients were identified. Five were excluded because VA was associated with central vein stenosis; the remaining 33 underwent salvage. Indications were rapidly expanding or painful VA in seven cases; VA with frequent bleeding or damaged overlying skin in eight; VA in close relation to a stenosis in two; and VA associated with high-flow rate in 16. Cannulation was attempted after 30 days. Mean follow-up time was 12 S.D. 5 months (range: 4-22). Two repaired AVFs failed. Primary 1-year patency was 93%. No aneurysm or infection occurred. Reduction of high flow was successful in 12 of 16 patients. The remaining four required re-operation. CONCLUSIONS: Reinforced venous aneurysmorrhaphy is effective in controlling venous dilation and achieving patency. Reduction of high-flow rates was not always achieved. Further study is needed to evaluate long-term efficacy of this treatment.

Feeding of nauplii, copepodites and adults of Calanipeda aquaedulcis (Calanoida) in Mediterranean salt marshes

Feeding of the different developmental stages of Calanipeda aquaedulcis on natural particles (bacterio-, phyto- and microzooplankton) was measured in a Mediterranean salt marsh (Empordà wetlands, NE Iberian Peninsula). Bottle incubations were performed in the field both in autumn and spring. The results showed differences in the diet of the different developmental stages due to both prey type and size. In general, the size of the ingested prey increased with increasing size of the C. aquaedulcis stage. While C. aquaedulcis adults had high ingestion rates and selection coefficients for large prey (micro- and nanoplankton), nauplii preferentially consumed smaller prey items (picoplankton). Copepodites showed the widest prey size range, including pico-, nano- and microplankton. Nevertheless, the lower size limit for particle capture was similar for all stages, i.e. between 1.7 and 2.1 μm. Omnivory was observed in all stages of C. aquaedulcis. Heterotrophic prey (picoplankton, dinoflagellates and ciliates) were the most ingested items. The ability to partition the available food among the different developmental stages could represent an advantage in times of ood scarcity because it may reduce intraspecific competition. This may explain how C. aquaedulcis is able to predominate in the zooplankton community for several weeks during spring and summer ven in situations of low food availability

Assessment of Asphalt Interlayer Designed on Jointed Concrete, InTrans Project 13-475, 2014

Reflective cracking in hot mix asphalt (HMA) overlays has been a common cause of poor pavement performance in Iowa for many years. Reflective cracks commonly occur in HMA overlays when deteriorated portland cement concrete is paved over with HMA. This results in HMA pavement surfaces with poor ride quality and increased transportation maintenance costs. To delay the formation of cracks in HMA overlays, the Iowa Department of Transportation (Iowa DOT) has begun to implement a crack-relief interlayer mix design specification. The crack-relief interlayer is an asphalt-rich, highly flexible HMA that can resist cracking in high strain loading conditions. In this project, the field performance of an HMA overlay using a one inch interlayer was compared to a conventional HMA overlay without an interlayer. Both test sections were constructed on US 169 in Adel, Iowa as part of an Iowa DOT overlay project. The laboratory performance of the interlayer mix design was assessed for resistance to cracking from repeated strains by using the four-point bending beam apparatus. An HMA using a highly polymer modified binder was designed and shown to meet the laboratory performance test criteria. The field performance of the overlay with the interlayer exceeded the performance of the conventional overlay that did not have the interlayer. After one winter season, 29 percent less reflective cracking was measured in the pavement section with the interlayer than the pavement section without the interlayer. The level of cracking severity was also reduced by using the interlayer in the overlay.

Road Safety Audit for US 151 from Amana to US 30 in Cedar Rapids in Benton, Iowa and Linn Counties, Iowa, 2010

US 151 was originally constructed as IA 149 in 1931-1934 and has been rehabilitated several times. The most recent major improvements, which were completed in 2005-2006, consisted of hot mix asphalt resurfacing and partial shoulder paving. Major widening and resurfacing improvements were also completed in 2007 between Fairfax and US 30 in Cedar Rapids. According to a preliminary 2009 estimate, traffic volumes range from about 5,900 vehicles per day (vpd) north of Amana to about 14,400 vpd at the US 30 interchange in Cedar Rapids. In response to high crash densities and medium to medium-high crash rates along the route, the Iowa Department of Transportation (Iowa DOT) requested a road safety audit to examine the roadway and suggest possible mitigation. Representatives from the Iowa DOT, Federal Highway Administration, Institute for Transportation, local law enforcement, and state government met to review crash data and discuss potential safety improvements to this segment of US 151. This report outlines the findings and recommendations of the road safety audit team for addressing the safety concerns on this roadway.