Studies On The Reproduction Of Indian Whiting Sill/160 5'/Ham/1 (Forskal) (Percoidei, Sillaginidae)

From the point of view of rational exploitation and proper management of the fishery resources as well as for the development of intensive aquaculture of fishes through selective breeding, brood stock development, domestication and genetic improvement, a sound knowledge of reproductive biology and physiology of the candidate species is of great importance. In recent times, a wealth of information on maturity, spawning habits, spawning periodicity, spawning season, size at maturity and fecundity of commercially important fishes has been generated. Gametogenesis involves the transformation of Primordial germ cells in the gonads into specialised cells or gametes, namely ova in the female and sperms in male, through a series of complex morphological and cytological events. The formation of male gamete is known as spermatogenesis. In the female, the primary growth phase involving the formation of primary oocyte from oogonia is known as oogenesis, which would be followed by the secondary growth phase, in which considerable increase in the size of the oocyte occurs, due mainly to accumulation of yolk. This process is known as vitellogenesis, which would be followed by final maturation and ovulation of the ova. In the present work, basic aspects of maturation and spawning, salient features of gametogenesis and associated biochemical changes occurring during these processes in an important cultivable fish, Sillago sihama belonging to the family Sillaginidae have been investigated.

Utilization of aquatic macrophyte Spirodela polyrhiza as phytotoxicological assessment and phytoremediation tool in selected polluted wetland sites in Ernakulam district

One of the objectives of the current investigation was to evaluate the effectiveness of Spirodela polyrhiza to remove heavy metals and other contaminants from the water samples collected from wetland sites of Eloor and Kannamaly under controlled conditions .The results obtained from the current study suggest that the test material S. polyrrhiza should be used in the biomonitoring and phytoremediation of municipal, agricultural and industrial effluents because of their simplicity, sensitivity and cost-effectiveness. The study throws light on the potential of this plant which can be used as an assessment tool in two diverse wetland in Ernakulum district. The results show the usefulness of combining physicochemical analysis with bioassays as such approach ensures better understanding of the toxicity of chemical pollutants and their influence on plant health. The results shows the suitability of Spirodela plant for surface water quality assessment as all selected parameters showed consistency with respect to water samples collected over a 3-monitoring periods. Similarly the relationship between the change in exposure period (2, 4 and 8 days) with the parameters were also studied in detail. Spirodela are consistent test material as they are homogeneous plant material; due to predominantly vegetative reproduction. New fronds are formed by clonal propagation thus, producing a population of genetically homogeneous plants. The result is small variability between treated individuals. It has been observed that phytoremediation of water samples collected from Eloor and Kannamaly using the floating plant system is a predominant method which is economic to construct, requires little maintenance and eco friendly.

Untersuchungen zu Controlled Traffic Farming und satellitenbasierten Lenksystemen

Diese Arbeit behandelt Controlled Traffic Farming (CTF) Anbausysteme, bei denen für alle Arbeitsgänge satellitengesteuert immer dieselben Fahrspuren benutzt werden. Lässt sich mit CTF die Belastung des Bodens verringern und die Effizienz von Direktsaat-Anbausystemen steigern? Neben agronomischen und bodenphysikalischen Parametern wurden Auswirkungen von Lenksystemen und Umsetzungsmöglichkeiten von CTF in die Praxis untersucht. Die Analyse einer CTF-Umsetzung unter europäischen Bedingungen mit der Verwendung von Standardmaschinen zeigte, dass sich CTF-Anbausysteme mit den heute zur Verfügung stehenden Maschinen für Dauergrünland, Mähdruschfrüchte und Mais auf kleiner und grösser strukturierten Flächen relativ einfach mechanisieren lassen. Bei Zuckerrüben und Kartoffeln können Kompromisse notwendig sein. Generell erfordern CTF-Anbausysteme eine sorgfältige Planung und Umsetzung in die Praxis. Im dreijährigen Feldversuch (Winterweizen, Wintergerste, Kunstwiese mit Kleegrasmischung) auf einem Lehmboden wurde CTF-Direktsaat mit konventionell zufällig befahrenen Direktsaat- und Pflugverfahren verglichen. Unter CTF zeigte sich eine Differenzierung der nicht, gering und intensiv befahrenen Varianten. Auf dem vorliegenden kompakten Boden mit 1150 mm Jahresniederschlag waren die Unterschiede zwischen den nicht befahrenen Flächen und den mit niedrigem Kontaktflächendruck befahrenen Flächen eher gering. In den nicht befahrenen Flächen entwickelten Eindringwiderstand und Kohlendioxidgehalt der Bodenluft nach drei Jahren signifikant bessere Werte. Bodendichte und Porosität zeigten hingegen keinen eindeutig interpretierbaren Trend. Aufgrund teils suboptimaler Feldaufgänge liess sich keine generelle agronomische Tendenz ableiten. Die intensive Befahrung der Pflegefahrgassen zeigte allerdings klar negative bodenkundliche und planzenbauliche Auswirkungen. Es bietet sich daher an, vor allem für Pflegearbeiten permanent dieselben Fahrspuren zu nutzen. In der Untersuchung zu den Auswirkungen von Lenksystemen zeigten sich signifikante Vorteile von Lenksystemen in einer Verminderung der Fahrerbelastung und einer höheren Lenkgenauigkeit vor allem bei grossen Arbeitsbreiten ohne Spuranreisser. Die meisten anderen Messparameter waren mit Lenksystem leicht vorteilhafter als ohne, unterschieden sich aber nicht signifikant voneinander. Fahrer und naturräumliche Gegebenheiten wie die Schlagform hatten einen wesentlich grösseren Einfluss. Gesamthaft betrachtet erweitert CTF in Kombination mit weiteren Bodenschutzmass-nahmen die Möglichkeiten, Bodenverdichtungen zu vermeiden, den Bedarf an energieintensiver Bodenlocke-rung zu reduzieren und die Entwicklung einer stabileren Bodenstruktur mit höherer Tragfähigkeit zu fördern. Zusammen mit einer an Kultur und Anbausystem angepassten Saatbettbereitung und den in geraden Reihen einfacher durchführbaren mechanischen Pflegemassnahmen ergeben sich gute Voraussetzungen für die Gestaltung agronomisch leistungsfähiger und ökologisch nachhaltiger Anbausysteme.

Status and Potential of Smallholder Livestock Production Systems in Xishuangbanna, southern P.R. China

With Chinas rapid economic development during the last decades, the national demand for livestock products has quadrupled within the last 20 years. Most of that increase in demand has been answered by subsidized industrialized production systems, while million of smallholders, which still provide the larger share of livestock products in the country, have been neglected. Fostering those systems would help China to lower its strong urban migration streams, enhance the livelihood of poorer rural population and provide environmentally save livestock products which have a good chance to satisfy customers demand for ecological food. Despite their importance, China’s smallholder livestock keepers have not yet gained appropriate attention from governmental authorities and researchers. However, profound analysis of those systems is required so that adequate support can lead to a better resource utilization and productivity in the sector. To this aim, this pilot study analyzes smallholder livestock production systems in Xishuangbanna, located in southern China. The area is bordered by Lao and Myanmar and geographically counts as tropical region. Its climate is characterized by dry and temperate winters and hot summers with monsoon rains from May to October. While the regionis plain, at about 500 m asl above sea level in the south, outliers of the Himalaya mountains reach out into the north of Xishuangbanna, where the highest peak reaches 2400 m asl. Except of one larger city, Jinghong, Xishuangbanna mainly is covered by tropical rainforest, areas under agricultural cultivation and villages. The major income is generated through inner-Chinese tourism and agricultural production. Intensive rubber plantations are distinctive for the lowland plains while small-scaled traditional farms are scattered in the mountane regions. In order to determine the current state and possible future chances of smallholder livestock production in that region, this study analyzed the current status of the smallholder livestock sector in the Naban River National Nature Reserve (NRNNR), an area which is largely representative for the whole prefecture. It covers an area of about 50square kilometer and reaches from 470 up to 2400 m asl. About 5500 habitants of different ethnic origin are situated in 24 villages. All data have been collected between October 2007 and May 2010. Three major objectives have been addressed in the study: 1. Classifying existing pig production systems and exploring respective pathways for development 2. Quantifying the performance of pig breeding systemsto identify bottlenecks for production 3. Analyzing past and current buffalo utilization to determine the chances and opportunities of buffalo keeping in the future In order to classify the different pig production s ystems, a baseline survey (n=204, stratified cluster sampling) was carried out to gain data about livestock species, numbers, management practices, cultivated plant species and field sizes as well associo-economic characteristics. Sampling included two clusters at village level (altitude, ethnic affiliation), resulting in 13 clusters of which 13-17 farms were interviewed respectively. Categorical Principal Component Analysis (CatPCA) and a two-step clustering algorithm have been applied to identify determining farm characteristics and assort recorded households into classes of livestock production types. The variables keep_sow_yes/no, TLU_pig, TLU_buffalo, size_of_corn_fields, altitude_class, size_of_tea_plantationand size_of_rubber_fieldhave been found to be major determinants for the characterization of the recorded farms. All farms have extensive or semi-intensive livestock production, pigs and buffaloes are predominant livestock species while chicken and aquaculture are available but play subordinate roles for livelihoods. All pig raisers rely on a single local breed, which is known as Small Ear Pig (SMEP) in the region. Three major production systemshave been identified: Livestock-corn based LB; 41%), rubber based (RB; 39%) and pig based (PB;20%) systems. RB farms earn high income from rubber and fatten 1.9 ±1.80 pigs per household (HH), often using purchased pig feed at markets. PB farms own similar sized rubber plantations and raise 4.7 ±2.77 pigs per HH, with fodder mainly being cultivated and collected in theforest. LB farms grow corn, rice and tea and keep 4.6 ±3.32 pigs per HH, also fed with collected and cultivated fodder. Only 29% of all pigs were marketed (LB: 20%; RB: 42%; PB: 25%), average annual mortality was 4.0 ±4.52 pigs per farm (LB: 4.6 ±3.68; RB: 1.9 ±2.14; PB: 7.1 ±10.82). Pig feed mainly consists of banana pseudo stem, corn and rice hives and is prepared in batches about two to three times per week. Such fodder might be sufficient in energy content but lacks appropriate content of protein. Pigs therefore suffer from malnutrition, which becomes most critical in the time before harvest season around October. Farmers reported high occurrences of gastrointestinal parasites in carcasses and often pig stables were wet and filled with manure. Deficits in nutritional and hygienic management are major limits for development and should be the first issues addressed to improve productivity. SME pork was found to be known and referred by local customers in town and by richer lowland farmers. However, high prices and lacking availability of SME pork at local wet-markets were the reasons which limited purchase. If major management constraints are overcome, pig breeders (PB and LB farms) could increase the share of marketed pigs for town markets and provide fatteners to richer RB farmers. RB farmers are interested in fattening pigs for home consumption but do not show any motivation for commercial pig raising. To determine the productivity of input factors in pig production, eproductive performance, feed quality and quantity as well as weight development of pigs under current management were recorded. The data collection included a progeny history survey covering 184 sows and 437 farrows, bi-weekly weighing of 114 pigs during a 16-months time-span on 21 farms (10 LB and 11 PB) as well as the daily recording of feed quality and quantity given to a defined number of pigs on the same 21 farms. Feed samples of all recorded ingredients were analyzed for their respective nutrient content. Since no literature values on thedigestibility of banana pseudo stem – which is a major ingredient of traditional pig feed in NRNNR – were found, a cross-sectional digestibility trial with 2x4 pigs has been conducted on a station in the research area. With the aid of PRY Herd Life Model, all data have been utilized to determine thesystems’ current (Status Quo = SQ) output and the productivity of the input factor “feed” in terms of saleable life weight per kg DM feed intake and monetary value of output per kg DM feed intake.Two improvement scenarios were simulated, assuming 1) that farmers adopt a culling managementthat generates the highest output per unit input (Scenario 1; SC I) and 2) that through improved feeding, selected parameters of reproduction are improved by 30% (SC II). Daily weight gain averaged 55 ± 56 g per day between day 200 and 600. The average feed energy content of traditional feed mix was 14.92 MJ ME. Age at first farrowing averaged 14.5 ± 4.34 months, subsequent inter-farrowing interval was 11.4 ± 2.73 months. Littersize was 5.8 piglets and weaning age was 4.3 ± 0.99 months. 18% of piglets died before weaning. Simulating pig production at actualstatus, it has been show that monetary returns on inputs (ROI) is negative (1:0.67), but improved (1:1.2) when culling management was optimized so that highest output is gained per unit feed input. If in addition better feeding, controlled mating and better resale prices at fixed dates were simulated, ROI further increased to 1:2.45, 1:2.69, 1:2.7 and 1:3.15 for four respective grower groups. Those findings show the potential of pork production, if basic measures of improvement are applied. Futureexploration of the environment, including climate, market-season and culture is required before implementing the recommended measures to ensure a sustainable development of a more effective and resource conserving pork production in the future. The two studies have shown that the production of local SME pigs plays an important role in traditional farms in NRNNR but basic constraints are limiting their productivity. However, relatively easy approaches are sufficient for reaching a notable improvement. Also there is a demand for more SME pork on local markets and, if basic constraints have been overcome, pig farmers could turn into more commercial producers and provide pork to local markets. By that, environmentally safe meat can be offered to sensitive consumers while farmers increase their income and lower the risk of external shocks through a more diverse income generating strategy. Buffaloes have been found to be the second important livestock species on NRNNR farms. While they have been a core resource of mixed smallholderfarms in the past, the expansion of rubber tree plantations and agricultural mechanization are reasons for decreased swamp buffalo numbers today. The third study seeks to predict future utilization of buffaloes on different farm types in NRNNR by analyzing the dynamics of its buffalo population and land use changes over time and calculating labor which is required for keeping buffaloes in view of the traction power which can be utilized for field preparation. The use of buffaloes for field work and the recent development of the egional buffalo population were analyzed through interviews with 184 farmers in 2007/2008 and discussions with 62 buffalo keepers in 2009. While pig based farms (PB; n=37) have abandoned buffalo keeping, 11% of the rubber based farms (RB; n=71) and 100% of the livestock-corn based farms (LB; n=76) kept buffaloes in 2008. Herd size was 2.5 ±1.80 (n=84) buffaloes in early 2008 and 2.2 ±1.69 (n=62) in 2009. Field work on own land was the main reason forkeeping buffaloes (87.3%), but lending work buffaloes to neighbors (79.0%) was also important. Other purposes were transport of goods (16.1%), buffalo trade (11.3%) and meat consumption(6.4%). Buffalo care required 6.2 ±3.00 working hours daily, while annual working time of abuffalo was 294 ±216.6 hours. The area ploughed with buffaloes remained constant during the past 10 years despite an expansion of land cropped per farm. Further rapid replacement of buffaloes by tractors is expected in the near future. While the work economy is drastically improved by the use of tractors, buffaloes still can provide cheap work force and serve as buffer for economic shocks on poorer farms. Especially poor farms, which lack alternative assets that could quickly be liquidizedin times of urgent need for cash, should not abandon buffalo keeping. Livestock has been found to be a major part of small mixed farms in NRNNR. The general productivity was low in both analyzed species, buffaloes and pigs. Productivity of pigs can be improved through basic adjustments in feeding, reproductive and hygienic management, and with external support pig production could further be commercialized to provide pork and weaners to local markets and fattening farms. Buffalo production is relatively time intensive, and only will be of importance in the future to very poor farms and such farms that cultivate very small terraces on steep slopes. These should be encouraged to further keep buffaloes. With such measures, livestock production in NRNNR has good chances to stay competitive in the future.

Enhancing the Dexterity of a Robot Hand Using Controlled Slip

Humans can effortlessly manipulate objects in their hands, dexterously sliding and twisting them within their grasp. Robots, however, have none of these capabilities, they simply grasp objects rigidly in their end effectors. To investigate this common form of human manipulation, an analysis of controlled slipping of a grasped object within a robot hand was performed. The Salisbury robot hand demonstrated many of these controlled slipping techniques, illustrating many results of this analysis. First, the possible slipping motions were found as a function of the location, orientation, and types of contact between the hand and object. Second, for a given grasp, the contact types were determined as a function of the grasping force and the external forces on the object. Finally, by changing the grasping force, the robot modified the constraints on the object and affect controlled slipping slipping motions.

Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.

Apatite-Polymer Composite Particles for Controlled Delivery of BMP-2: In Vitro Release and Cellular Response

Bone morphogenetic protein-2 (BMP-2) has the ability to induce osteoblast differentiation of undifferentiated cells, resulting in the healing of skeletal defects when delivered with a suitable carrier. We have applied a versatile delivery platform comprising a novel composite of two biomaterials with proven track records – apatite and poly(lactic-co-glycolic acid) (PLGA) – to the delivery of BMP-2. Sustained release of this growth factor was tuned with variables that affect polymer degradation and/or apatite dissolution, such as polymer molecular weight, polymer composition, apatite loading, and apatite particle size. The effect of released BMP-2 on C3H10T1/2 murine pluripotent mesenchymal cells was assessed by tracking the expression of osteoblastic makers, alkaline phosphatase (ALP) and osteocalcin. Release media collected over 100 days induced elevated ALP activity in C3H10T1/2 cells. The expression of osteocalcin was also upregulated significantly. These results demonstrated the potential of apatite-PLGA composite particles for releasing protein in bioactive form over extended periods of time.

Subcutaneous study on the controlled release of Etanidazole and Taxol for the treatment of Glioma

BALB/c nude mice 6 weeks old were inoculated with glioma C6 cell-line and the efficacy of the different amount of Etanidazole-discs and Taxol-microspheres was investigated. Poly (D,L-lactic-co-glycolic acid) (PLGA) was used as the main encapsulating polymer and polyethylene glycol was added to increase the porosity. The 1% drug loading microspheres of each drug were produced by spray drying and the discs were obtained by compressing the Etanidazole-microspheres. Intra-tumoral injection followed by irradiation resulted in high systemic dosage and thus systemic toxicity. Tumors grown for 6 days, 9 days and 16 days were implanted with 0.5 mg or 1.0 mg or 1.5 mg of the drug. A radiation dosage of 2 Gy each time for a number of times was given for animals implanted with Etanidazole and no irradiation was given for animals implanted with Taxol. Increasing the number of doses clearly decreased the rate of tumor growth. The increase in the amount of drug on smaller sized tumors controlled the tumor better and there was agglomeration of the microspheres resulting in deviation of release profile of the drug as compared to the in vitro studies. It was observed that 1.0 mg of Taxol given to a tumor grown for 6 days was able to suppress the tumor for a total period of approximately two months and no tumor resurrection was observed during the second month.

Fabrication of Controlled Release Devices Using Supercritical Antisolvent Method

In this study, the supercritical antisolvent with enhanced mass transfer method (SASEM) is used to fabricate micro and nanoparticles of biocompatible and biodegradable polymer PLGA (poly DL lactide co glycolic acid). This process may be extended to the encapsulation of drugs in these micro and nanoparticles for controlled release purposes. Conventional supercritical antisolvent (SAS) process involves spraying a solution (organic solvent + dissolved polymer) into supercritical fluid (CO[subscript 2]), which acts as an antisolvent. The high rate of mass transfer between organic solvent and supercritical CO[subscript 2] results in supersaturation of the polymer in the spray droplet and precipitation of the polymer as micro or nanoparticles occurs. In the SASEM method, ultrasonic vibration is used to atomize the solution entering the high pressure with supercritical CO[subscript 2]. At the same time, the ultrasonic vibration generated turbulence in the high pressure vessel, leading to better mass transfer between the organic solvent and the supercritical CO₂. In this study, two organic solvents, acetone and dichloromethane (DCM) were used in the SASEM process. Phase Doppler Particle Analyzer (PDPA) was used to study the ultrasonic atomization of liquid using the ultrasonic probe for the SASEM process. Scanning Electron Microscopy (SEM) was used to study the size and morphology of the polymer particles collected at the end of the process.

CAC controlled services sharing a link with connectionless data services in an ATM network: a performance evaluation study

In the B-ISDN there is a provision for four classes of services, all of them supported by a single transport network (the ATM network). Three of these services, the connected oriented (CO) ones, permit connection access control (CAC) but the fourth, the connectionless oriented (CLO) one, does not. Therefore, when CLO service and CO services have to share the same ATM link, a conflict may arise. This is because a bandwidth allocation to obtain maximum statistical gain can damage the contracted ATM quality of service (QOS); and vice versa, in order to guarantee the contracted QOS, the statistical gain have to be sacrificed. The paper presents a performance evaluation study of the influence of the CLO service on a CO service (a circuit emulation service or a variable bit-rate service) when sharing the same link

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Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.