Monitoring trends in HIV prevalence among young people, aged 15 to 24 years, in Manicaland, Zimbabwe

BACKGROUND: In June 2001, the United Nations General Assembly Special Session (UNGASS) set a target of reducing HIV prevalence among young women and men, aged 15 to 24 years, by 25% in the worst-affected countries by 2005, and by 25% globally by 2010. We assessed progress toward this target in Manicaland, Zimbabwe, using repeated household-based population serosurvey data. We also validated the representativeness of surveillance data from young pregnant women, aged 15 to 24 years, attending antenatal care (ANC) clinics, which UNAIDS recommends for monitoring population HIV prevalence trends in this age group. Changes in socio-demographic characteristics and reported sexual behaviour are investigated. METHODS: Progress towards the UNGASS target was measured by calculating the proportional change in HIV prevalence among youth and young ANC attendees over three survey periods (round 1: 1998-2000; round 2: 2001-2003; and round 3: 2003-2005). The Z-score test was used to compare differences in trends between the two data sources. Characteristics of participants and trends in sexual risk behaviour were analyzed using Student's and two-tailed Z-score tests. RESULTS: HIV prevalence among youth in the general population declined by 50.7% (from 12.2% to 6.0%) from round 1 to 3. Intermediary trends showed a large decline from round 1 to 2 of 60.9% (from 12.2% to 4.8%), offset by an increase from round 2 to 3 of 26.0% (from 4.8% to 6.0%). Among young ANC attendees, the proportional decline in prevalence of 43.5% (from 17.9% to 10.1%) was similar to that in the population (test for differences in trend: p value = 0.488) although ANC data significantly underestimated the population prevalence decline from round 1 to 2 (test for difference in trend: p value = 0.003) and underestimated the increase from round 2 to 3 (test for difference in trend: p value = 0.012). Reductions in risk behaviour between rounds 1 and 2 may have been responsible for general population prevalence declines. CONCLUSIONS: In Manicaland, Zimbabwe, the 2005 UNGASS target to reduce HIV prevalence by 25% was achieved. However, most prevention gains occurred before 2003. ANC surveillance trends overall were an adequate indicator of trends in the population, although lags were observed. Behaviour data and socio-demographic characteristics of participants are needed to interpret ANC trends

Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using singlemolecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

‘Nedoceratops’: An Example of a Transitional Morphology

Background: The holotype and only specimen of the chasmosaurine ceratopsid dinosaur ‘Nedoceratops hatcheri ’ has been the source of considerable taxonomic debate since its initial description. At times it has been referred to its own genus while at others it has been considered synonymous with the contemporaneous chasmosaurine Triceratops. Most recently, the debate has focused on whether the specimen represents an intermediate ontogenetic stage between typical young adult Triceratops and the proposed mature morphology, which was previously considered to represent a distinct genus, ‘Torosaurus’. Methodology/Principal Findings: The only specimen of ‘Nedoceratops hatcheri ’ was examined and the proposed diagnostic features of this taxon were compared with other chasmosaurine ceratopsids. Every suggested autapomorphy of ‘Nedoceratops ’ is found in specimens of Triceratops. In this study, Triceratops includes the adult ‘Torosaurus ’ morphology. The small parietal fenestra and elongate squamosals of Nedoceratops are consistent with a transition from a short, solid parietalsquamosal frill to an expanded, fenestrated condition. Objections to this hypothesis regarding the number of epiossifications of the frill and alternations of bone surface texture were explored through a combination of comparative osteology and osteohistology. The synonymy of the three taxa was further supported by these investigations. Conclusions/Significance: The Triceratops, ‘Torosaurus’, and ‘Nedoceratops ’ morphologies represent ontogenetic variatio

Torosaurus Is Not Triceratops: Ontogeny in Chasmosaurine Ceratopsids as a Case Study in Dinosaur Taxonomy

Background: In horned dinosaurs, taxonomy is complicated by the fact that the cranial ornament that distinguishes species changes with age. Based on this observation, it has been proposed that the genera Triceratops and Torosaurus are in fact synonymous, with specimens identified as Torosaurus representing the adult form of Triceratops. The hypothesis of synonymy makes three testable predictions: 1) the species in question should have similar geographic and stratigraphic distributions, 2) specimens assigned to Torosaurus should be more mature than those assigned to Triceratops, and 3) intermediates should exist that combine features of Triceratops and Torosaurus. The first condition appears to be met, but it remains unclear whether the other predictions are borne out by the fossil evidence. Methodology/Principal Findings: We assessed the relative maturity of Torosaurus and Triceratops specimens by coding skulls for characters that vary with maturity, and then using a clustering analysis to arrange them into a growth series. We found that a well-defined sequence of changes exists in horned dinosaurs: development of cranial ornament occurs in juveniles, followed by fusion of the skull roof in subadults, and finally, the epoccipitals, epijugals, and rostral fuse to the skull in adults. Using this scheme, we identified mature and immature individuals of both Torosaurus and Triceratops. Furthermore, we describe the ventral depressions on the frill of Triceratops, and show that they differ in shape and position from the parietal fenestrae of Torosaurus. Thus, we conclude that these structures are not intermediates between the soli

Anatomy and Taxonomic Status of the Chasmosaurine Ceratopsid Nedoceratops hatcheri from the Upper Cretaceous Lance Formation of Wyoming, U.S.A

Background: The validity of Nedoceratops hatcheri, a chasmosaurine ceratopsid dinosaur known from a single skull recovered in the Lance Formation of eastern Wyoming, U.S.A., has been debated for over a century. Some have argued that the taxon is an aberrant Triceratops, and most recently it was proposed that N. hatcheri represents an intermediate ontogenetic stage between ‘‘young adult’ ’ and ‘‘old adult’ ’ forms of a single taxon previously split into Triceratops and Torosaurus. Methodology/Principal Findings: The holotype skull of Nedoceratops hatcheri was reexamined in order to map reconstructed areas and compare the specimen with other ceratopsids. Although squamosal fenestrae are almost certainly not of taxonomic significance, some other features are unique to N. hatcheri. These include a nasal lacking a recognizable horn, nearly vertical postorbital horncores, and relatively small parietal fenestrae. Thus, N. hatcheri is tentatively considered valid, and closely related to Triceratops spp. The holotype of N. hatcheri probably represents an ‘‘old adult,’ ’ based upon bone surface texture and the shape of the horns and epiossifications on the frill. In this study, Torosaurus is maintained as a genus distinct from Triceratops and Nedoceratops. Synonymy of the three genera as ontogenetic stages of a single taxon would require cranial changes otherwise unknown in ceratopsids, including additions of ossifications to the frill and repeated alternation of bone surface texture between juvenile and adult morphotypes

HLA Immunogenotype Determines Persistent Human Papillomavirus Virus Infection in HIV-Infected Patients Receiving Antiretroviral Treatment

A proportion of human immunodeficiency virus (HIV)–infected patients develop persistent, stigmatizing human papillomavirus (HPV)–related cutaneous and genital warts and anogenital (pre)cancer. This is the first study to investigate immunogenetic variations that might account for HPV susceptibility and the largest to date to categorize the HPV types associated with cutaneous warts in HIV-positive patients. The HLA class I and II allele distribution was analyzed in 49 antiretroviral (ART)–treated HIV-positive patients with persistent warts, 42 noninfected controls, and 46 HIV-positive controls. The allele HLA-B*44 was more frequently identified in HIV-positive patients with warts (P = .004); a susceptible haplotype (HLA-B*44, HLA-C*05; P = .001) and protective genes (HLA-DQB1*06; P = .03) may also contribute. Cutaneous wart biopsy specimens from HIV-positive patients harbored common wart types HPV27/57, the unusual wart type HPV7, and an excess of Betapapillomavirus types (P = .002), compared with wart specimens from noninfected controls. These findings suggest that HLA testing might assist in stratifying those patients in whom vaccination should be recommended

Personal epistemologies and disciplinarity in the workplace: implications for international students in higher education

Workplace experiences for international students undertaking higher education programs are important aspects of their university experience. This is because many of the programs in which they are enrolled are directed towards particular occupations. Nevertheless, these workplace experiences can be both engaging and daunting for all, but perhaps no more so than for international students, who may be unfamiliar with Australian workplace mores and practices, and therefore less able to understand and negotiate with them than their domestic counterparts. Not only do international students have to become familiar with the requirements of their selected profession but also need to understand and negotiate unfamiliar cultural environments. These students often have to engage in complex and demanding learning processes when engaging in work placements, perhaps more so than their domestic peers. Because of these discipline-based and workplace environmental challenges, it is necessary for these students and their mentors or supervisors to try and effectively mediate their participation and learning in the work placements. If all of those involved in work placements are aware of these factors, then the experiences and outcomes should potentially be more beneficial for all parties (i.e., students, supervisors, university staff, and workplaces). These issues are explored in this chapter through the notions of disciplinarity, which attends to the epistemological nuances of particular study or knowledge areas and how students develop skills as disciplinary professionals. With a focus on international students, the elaborations of these issues are explored through consideration of interculturalisation and how both the experiences and experiencing of international students impacts upon the success of their work placements. Using these concepts as explanatory bases stands to permit the illumination and elaboration of the complexity of factors and processes occurring as these students learn about, and participate in, their selected professional discipline and the cultural environment of its practice

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

BACKGROUND: Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a "second hit" mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. METHODS: We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. RESULTS: First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. CONCLUSION: These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

T-REX: software for the processing and analysis of T-RFLP data

Softwar