The Effect of Systemic Racism and Homophobia on Police Enforcement and Sexual and Emotional Violence among Sex Workers in East London: Findings from a Cohort Study.

There is extensive qualitative evidence of violence and enforcement impacting sex workers who are ethnically or racially minoritized, and gender or sexual minority sex workers, but there is little quantitative evidence. Baseline and follow-up data were collected among 288 sex workers of diverse genders (cis/transgender women and men and non-binary people) in London (2018-2019). Interviewer-administered and self-completed questionnaires included reports of rape, emotional violence, and (un)lawful police encounters. We used generalized estimating equation models (Stata vs 16.1) to measure associations between (i) ethnic/racial identity (Black, Asian, mixed or multiple vs White) and recent (6 months) or past police enforcement and (ii) ethnic/racial and sexual identity (lesbian, gay or bisexual (LGB) vs. heterosexual) with recent rape and emotional violence (there was insufficient data to examine the association with transgender/non-binary identities). Ethnically/racially minoritized sex workers (26.4%) reported more police encounters partly due to increased representation in street settings (51.4% vs 30.7% off-street, p = 0.002). After accounting for street setting, ethnically/racially minoritized sex workers had higher odds of recent arrest (adjusted odds ratio 2.8, 95% CI 1.3-5.8), past imprisonment (aOR 2.3, 95% CI 1.1-5.0), police extortion (aOR 3.3, 95% CI 1.4-7.8), and rape (aOR 3.6, 95% CI 1.1-11.5). LGB-identifying sex workers (55.4%) were more vulnerable to rape (aOR 2.4, 95% CI 1.1-5.2) and emotional violence. Sex workers identifying as ethnically/racially minoritized (aOR 2.1, 95% CI 1.0-4.5), LGB (aOR 2.0, 95% CI 1.0-4.0), or who use drugs (aOR 2.0, 95% CI 1.1-3.8) were more likely to have experienced emotional violence than white-identifying, heterosexual or those who did not use drugs. Experience of any recent police enforcement was associated with increased odds of rape (aOR 3.6, 95% CI 1.3-8.4) and emotional violence (aOR 4.9, 95% CI 1.8-13.0). Findings show how police enforcement disproportionately targets ethnically/racially minoritized sex workers and contributes to increased risk of rape and emotional violence, which is elevated among sexual and ethnically/racially minoritized workers.

Gait risk factors for disease progression differ between non-traumatic and post-traumatic knee osteoarthritis.

OBJECTIVE: To examine if relationships between knee osteoarthritis (OA) progression with knee moments and muscle activation during gait vary between patients with non-traumatic and post-traumatic knee OA. DESIGN: This longitudinal study included participants with non-traumatic (n = 17) and post-traumatic (n = 18) knee OA; the latter group had a previous anterior cruciate ligament rupture. Motion capture cameras, force plates, and surface electromyography measured knee moments and lower extremity muscle activation during gait. Cartilage volume change were determined over 2 years using magnetic resonance imaging in four regions: medial and lateral plateau and condyle. Linear regression analysis examined relationships between cartilage change with gait metrics (moments, muscle activation), group, and their interaction. RESULTS: Measures from knee adduction and rotation moments were related to lateral condyle cartilage loss in both groups, and knee adduction moment to lateral plateau cartilage loss in the non-traumatic group only [ß = -1.336, 95% confidence intervals (CI) = -2.653 to -0.019]. Generally, lower levels of stance phase muscle activation were related to greater cartilage loss. The relationship between cartilage loss in some regions with muscle activation characteristics varied between non-traumatic and post-traumatic groups including for: lateral hamstring (lateral condyle ß = 0.128, 95%CI = 0.003 to 0.253; medial plateau ß = 0.199, 95%CI = 0.059 to 0.339), rectus femoris (medial condyle ß = -0.267, 95%CI = -0.460 to -0.073), and medial hamstrings (medial plateau; ß = -0.146, 95%CI = -0.244 to -0.048). CONCLUSION: Findings indicate that gait risk factors for OA progression may vary between patients with non-traumatic and post-traumatic knee OA. These OA subtypes should be considered in studies that investigate gait metrics as risk factors for OA progression.

The countryside or the city: Which environment is better for the honeybee?

For a number of years, the decline of honeybee (Apis mellifera) in North America and Europe has been the subject of much debate. Among the many factors proposed by hundreds of studies to explain this phenomenon is the hypothesis that agricultural activities using pesticides contribute to the weakness of bee colonies. Moreover, while urban beekeeping is presently booming in several cities, we do not know if this environment is more beneficial for bees than the typical, rural area. In the summer of 2018, we sampled honeybees (foragers and larvae) in rural (Laurentians) and urban (city of Montreal) areas and compared them using the following biomarkers: carotenoids, retinoids, α-tocopherol, metallothionein-like proteins (MTLPs), lipid peroxidation, triglycerides, acetylcholinesterase activity (AChE) and proteins. Pesticides, pharmaceuticals and personal care products (PPCPs) and metals were also quantified in honeybees' tissues. Our result revealed that, globally, urban foragers had higher levels of insecticides and PPCPs and that metals were in greater concentrations in urban larvae. Compared to rural foragers, urban foragers had higher concentrations of MTLPs, triglycerides, protein and AChE activity. The multifactorial analysis confirmed that insecticides, some metals and PPCPs were the most influential components in the contaminant‒biomarker relationships for both foragers and larvae.

Biological markers to establish a relationship between the health status of the St. Lawrence River yellow perch (Perca flavescens) with a gradient of anthropogenic disturbances.

Since the mid-1990s, the decline of the yellow perch population of Lake Saint-Pierre (hereinafter LSP) in Quebec, Canada has been the subject of several research programs. The combined effect of habitat deterioration, the presence of invasive species, and poor water quality negatively affected the yellow perch population in this lake. In 2013, we sampled yellow perch (larvae, juveniles and adults) at six sites along the St. Lawrence River representing a gradient of increasing human influences from upstream to downstream and measured several biomarkers including retinoid compounds (vitamin A). In the most contaminated sites (LSP, north and south shores), we found that retinoid stores were decreased in all three stages of development. To corroborate these results and to test other biomarkers, we once again sampled yellow perch (adults only) from the same sites. Results from our 2014 and 2015 samplings confirmed that LSP yellow perch appeared to be at a disadvantage compared to fish from upstream populations. Individuals from LSP have lower acetylcholinesterase (AChE) activity as well as lower retinoid levels in liver and plasma. These fish were also marked by lower levels of antioxidants such as lycopene and vitamin E. A discriminant analysis of this set of results confirmed that the yellow perch of the LSP could be easily discriminated from those of the other sites (2014 and 2015) on the basis of liver retinoid and, to a lesser extent, of the liver tocopherol and protein concentration of the muscle, as well as AChE activity and DROH (all-trans-3,4-dehydroretinol) measured in plasma.

Impact of the T2-weighted axial oblique MRI sequence in the assessment of peroneal tendons.

AIM: To define the role of the T2-weighted axial oblique sequence for the magnetic resonance imaging (MRI) assessment of peroneal tendon pathologies. MATERIALS AND METHODS: Two radiologists interpreted 180 ankle MRI examinations using standard sequences alone and then in combination with an axial oblique sequence. The readers indicated how likely a peroneal pathology was present using a five-level confidence scale. Diagnostic confidence, interobserver agreement, and clinical correlation were compared. Changes in diagnosis were recorded. RESULTS: For both readers, the diagnostic confidence was significantly higher using the axial oblique sequence for tendinosis and inframalleolar tenosynovitis for both tendons and for peroneus brevis partial and longitudinal split tears (p<0.001). For reader 1, the diagnostic confidence was also higher using the axial oblique sequence for peroneus longus partial tears (p=0.007). Changes in diagnosis were seen for tendinosis and tenosynovitis of both tendons and for peroneus brevis partial and longitudinal split tears in 0.6-10.8% of cases. Inter-rater reliability was significantly higher with the axial oblique sequence for the diagnosis of tendinosis, inframalleolar tenosynovitis, and partial tear for both tendons, and for peroneus brevis longitudinal split tear. Amongst 105 examinations with clinical information, peroneal pathologies were most frequently diagnosed as present in cases with lateral symptoms (17% versus 14%) and absent in cases without lateral symptoms (92% versus 86%) on the axial oblique sequence. CONCLUSION: The axial oblique sequence for the assessment of peroneal tendons allows for higher diagnostic confidence, inter-rater reliability, and clinical correlation and can lead to changes in diagnosis.

A comparison of muscle activation and knee mechanics during gait between patients with non-traumatic and post-traumatic knee osteoarthritis.

OBJECTIVE: The objective was to compare muscle activation and knee mechanics during gait between participants with non-traumatic knee osteoarthritis (OA), post-traumatic knee OA, and healthy adults. DESIGN: Participants with non-traumatic knee OA (n = 22), post-traumatic knee OA (n = 19), and healthy adults (n = 22) completed gait trials for this observational, cross-sectional study. Post-traumatic OA group had a history of traumatic anterior cruciate ligament (ACL) rupture. Surface electromyography (EMG) measured activation of seven lower extremity muscles. Motion capture cameras and force plates measured motion and force data. Principal component analysis (PCA) determined waveform characteristics (principal components) from EMG, knee angle, and knee external moment waveforms. Analysis of variance (ANOVA) examined group differences in principal component scores (PC-scores). Regression analyses examined if a variable that coded for OA group could predict PC-scores after accounting for disease severity, alignment, and lateral OA. RESULTS: There was lower gastrocnemius EMG amplitudes (P < 0.01; ANOVA) in the post-traumatic OA group compared to healthy group. Non-traumatic OA group had higher vastus lateralis, vastus medialis, and rectus femoris EMG compared to post-traumatic OA group (P = 0.01 to 0.04) in regression analyses. Also, non-traumatic OA group had higher and prolonged lateral hamstring EMG compared to healthy (P = 0.03; ANOVA) and post-traumatic OA (P = 0.04; regression) groups respectively. The non-traumatic OA group had lower knee extension (P < 0.05) and medial rotation (P < 0.05) moments than post-traumatic and healthy groups. CONCLUSIONS: Muscle activation and knee mechanics differed between participants with non-traumatic and post-traumatic knee OA and healthy adults. These OA subtypes had differences in disease characteristics that may impact disease progression.

Relationship between alignment and cartilage thickness in patients with non-traumatic and post-traumatic knee osteoarthritis.

OBJECTIVE: To compare cartilage thickness between patients with non-traumatic and post-traumatic knee osteoarthritis (OA) and healthy controls and to determine if disease severity and alignment impact these differences. DESIGN: Participants with non-traumatic (n = 22) and post-traumatic (n = 19) knee OA, and healthy controls (n = 22) were recruited for this cross-sectional study. Participants underwent 3T magnetic resonance imaging (T1-weighted, 3D sagittal gradient echo sequence) and cartilage thickness was determined in four regions: medial and lateral condyle, and medial and lateral plateau. Lower extremity alignment (mechanical axis angle) and disease severity (Kellgren-Lawrence scores) were measured from full length radiographs. Statistical analysis included one-way analysis of variance (ANOVA) and modified Bonferroni test adjusting for multiple pairwise comparisons. Linear regression analyses examined the relationship between cartilage thickness and knee OA group after controlling for disease severity, meniscal status, and alignment. RESULTS: In participants with predominantly medial compartment knee OA, compared to healthy controls, those with non-traumatic knee OA had diminished cartilage thickness in the medial plateau (p = 0.035) and those with post-traumatic knee OA had greater cartilage thickness in the lateral condyle (p = 0.044). In the lateral condyle, data revealed that alignment accounted for the variance in cartilage thickness (p = 0.035), in which a stronger relationship was found in the non-traumatic (r = -0.61) than the post-traumatic (r = -0.12) OA group. CONCLUSIONS: Emerging data demonstrated that participants with non-traumatic knee OA have a stronger relationship between alignment and cartilage thickness than those with post-traumatic knee OA. This indicates that factors involved in knee OA initiation and progression may differ between these OA subtypes.

Nonlocal Coherent Denoising of RF Data for Ultrasound Elastography.

Ultrasound elastography infers mechanical properties of living tissues from ultrasound radiofrequency (RF) data recorded while the tissues are undergoing deformation. A challenging yet critical step in ultrasound elastography is to estimate the tissue displacement (or, equivalently the time delay estimate) fields from pairs of RF data. The RF data are often corrupted with noise, which causes the displacement estimator to fail in many in vivo experiments. To address this problem, we present a nonlocal, coherent denoising approach based on Bayesian estimation to reduce the impact of noise. Despite incoherent denoising algorithms that smooth the B-mode images, the proposed denoising algorithm is used to suppress noise while maintaining useful information such as speckle patterns. We refer to the proposed approach as COherent Denoising for Elastography (CODE) and evaluate its performance when CODE is used in conjunction with the two state-of-art elastography algorithms, namely: (i) GLobal Ultrasound Elastography (GLUE) and (ii) Dynamic Programming Analytic Minimization elastography (DPAM). Our results show that CODE substantially improves the strain result of both GLUE and DPAM.

A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data.

Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts.

Assortative mixing as a source of bias in epidemiological studies of sexually transmitted infections: the case of smoking and human papillomavirus.

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects' individual-level characteristics. Two conditions that can result in confounding by the subjects' partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking-HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1-C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects' individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R 0), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias.

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India.

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.

Differences between seven measures of self-reported numbers of clients of female sex workers in southern India: implications for individual- and population-level analysis.

Quantifying sexual activity of sub-populations with high-risk sexual behaviour is important in understanding HIV epidemiology. This study examined inconsistency of seven outcomes measuring self-reported clients per month (CPM) of female sex workers (FSWs) in southern India and implications for individual/population-level analysis. Multivariate negative binomial regression was used to compare key social/environmental factors associated with each outcome. A transmission dynamics model was used to assess the impact of differences between outcomes on population-level FSW/client HIV prevalence. Outcomes based on 'clients per last working day' produced lower estimates than those based on 'clients per typical day'. Although the outcomes were strongly correlated, their averages differed by approximately two-fold (range 39.0-79.1 CPM). The CPM measure chosen did not greatly influence standard epidemiological 'risk factor' analysis. Differences across outcomes influenced HIV prevalence predictions. Due to this uncertainty, we recommend basing population-based estimates on the range of outcomes, particularly when assessing the impact of interventions.

Men who have sex with men and women in Bangalore, South India, and potential impact on the HIV epidemic.

OBJECTIVE: The aim of this study was to quantify differences in patterns of sexual behaviour among men who have sex with men and women (MSMW) compared with men who have sex with men only (MSMO), and to examine the extent to which bisexual behaviour may act as a bridge for introducing HIV infection into the general population. METHODS: A cross-sectional survey in Bangalore city in 2006, which sampled men seeking sex with men in public places and hammams (bath houses where transgender individuals sell sex to men). RESULTS: Among a sample of 357 men reporting same-sex behaviour; 41% also reported sex with a woman in the past year and 14% were currently married to a woman, only two of whom had informed their wives about having sex with men. Condom use was very inconsistent with all male partners, while 98% reported unprotected vaginal sex with their wives. MSMW reported lower rates of risky behaviour with other men than MSMO: fewer reported selling sex (17% vs 58%), or receptive anal sex with known (28% vs 70%) or unknown (30% vs 59%) non-commercial partners. CONCLUSION: Bisexual behaviour was common among men seeking sex with men sampled in this survey. Although MSMW reported lower rates of risky sexual behaviour with male partners than MSMO, inconsistent condom use with both male and female partners indicates a potential means of HIV transmission into the general population. HIV prevention programmes and services should reach bisexual men who potentially expose their male and female partners to HIV.

Incremental role of male circumcision on a generalised HIV epidemic through its protective effect against other sexually transmitted infections: from efficacy to effectiveness to population-level impact.

BACKGROUND: Male circumcision (MC) can reduce HIV acquisition. However, a better understanding of the indirect protective effect of MC on sexually transmitted infections (STIs) is required. OBJECTIVE: To assess the incremental benefits conferred by MC on HIV infection at the individual level in circumcision trials (no herd immunity effect) and at the population level (with herd immunity effect) owing to its protective effect against other STIs. METHODS: A dynamic stochastic model of HIV and STI infections in a Kenyan population was used to simulate the impact of MC offered to a few trial participants or to a large proportion of men in order to study the protective role of MC on HIV infection at the individual and population levels. RESULTS: Fewer than 20% of the HIV infections prevented in the circumcised arm of the circumcision trials (individual level) could be attributable to the efficacy of MC against STIs rather than against HIV. At the population level, MC can significantly reduce the prevalence of HIV, especially among men and women in the longer term. However, even at the population level, the long-term incremental impact of MC on HIV due to the protection against STI is modest (even if MC efficacy against the STI and STI prevalence was high). CONCLUSIONS: The protection of MC against STI contributes little to the overall effect of MC on HIV. Additional work is needed to determine whether, and under what conditions, the protective effect of MC efficacy against STIs can have a significant incremental benefit on the HIV epidemic.

Sexual identity and its contribution to MSM risk behavior in Bangaluru (Bangalore), India: the results of a two-stage cluster sampling survey.

In India, there are categories of MSM (hijras, kothis, double-deckers, panthis and bisexuals), which are generally associated with different HIV-risk behaviors. Our objective was to quantify differences across MSM identities (n = 357) and assess the extent they conform to typecasts that prevail in policy-orientated discourse. More feminine kothis (26%) and hijras (13%) mostly reported receptive sex, and masculine panthis (15%) and bisexuals (23%) insertive anal sex. However, behavior did not always conform to expectation, with 25% and 16% of the sample reporting both insertive and receptive anal intercourse with known and unknown noncommercial partners, respectively (p < 0.000). Although behavior often complied with stereotyped role and identity, male-with-male sexual practices were fluid. Reification of these categories in an intervention context may hinder our understanding of the differential HIV risk among MSM.

Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach.

BACKGROUND: There is an urgent need to evaluate HIV prevention interventions, thereby improving our understanding of what works, under what circumstances and what is cost effective. OBJECTIVES: To describe an integrated mathematical evaluation framework designed to assess the population-level impact of large-scale HIV interventions and applied in the context of Avahan, the Indian AIDS Initiative, in southern India. The Avahan Initiative is a large-scale HIV prevention intervention, funded by the Bill & Melinda Gates Foundation, which targets high-risk groups in selected districts of the six states most affected by the HIV/AIDS epidemic (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Nagaland and Manipur) and along the national highways. METHODS: One important component of the monitoring and evaluation of Avahan relies on an integrated mathematical framework that combines empirical biological and behavioural data from different subpopulations in the intervention areas, with the use of tailor-made transmission dynamics models embedded within a Bayesian framework. RESULTS: An overview of the Avahan Initiative and the objectives of the monitoring and evaluation of the intervention is given. The rationale for choosing this evaluation design compared with other possible designs is presented, and the different components of the evaluation framework are described and its advantages and challenges are discussed, with illustrated examples. CONCLUSIONS: This is the first time such an approach has been applied on such a large scale. Lessons learnt from the CHARME project could help in the design of future evaluations of large-scale interventions in other settings, whereas the results of the evaluation will be of programmatic and public health relevance.

Impacts of agriculture on the parasite communities of northern leopard frogs (Rana pipiens) in southern Quebec, Canada.

Given that numerous amphibians are suffering population declines, it is becoming increasingly important to examine the relationship between disease and environmental disturbance. Indeed, while many studies relate anthropogenic activity to changes in the parasitism of snails and fishes, little is known of the impact on the parasites of amphibians, particularly from agriculture. For 2 years, the parasite communities of metamorphic northern leopard frogs from 7 agricultural wetlands were compared with those from 2 reference wetlands to study differences in parasite community diversity and abundance of various species under pristine conditions and 3 categories of disturbance: only agricultural landscape, only pesticides, and agricultural landscape with pesticides. Agricultural (and urban) area was negatively related to species richness, and associated with the near absence of adult parasites and species that infect birds or mammals. We suggest that agriculture and urbanization may hinder parasite transmission to frogs by limiting access of other vertebrate hosts of their parasites to wetlands. The only parasite found at all localities was an unidentified echinostome infecting the kidneys. This parasite dominated communities in localities surrounded by the most agricultural land, suggesting generalist parasites may persist in disrupted habitats. Community composition was associated with dissolved organic carbon and conductivity, but few links were found with pesticides. Pollution effects may be masked by a strong impact of land use on parasite transmission.

What is the achievable effectiveness of the India AIDS Initiative intervention among female sex workers under target coverage? Model projections from southern India.

BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk groups such as female and male sex workers and their clients, to limit HIV transmission in the general population. OBJECTIVES: To assess the potential effectiveness of the Avahan intervention at the level of coverage targeted, in different epidemiological settings in India. METHODS: A deterministic compartmental model of the transmission dynamics of HIV and two sexually transmitted infections, and sensitivity analysis techniques, were used, in combination with available behavioural and epidemiological data from Mysore and Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic sexually transmitted infection (STI) management (STI treatment), periodic presumptive treatment of STI (PPT), and condom components of the Avahan intervention targeted to female sex workers (FSW). RESULTS: If all components of the intervention reach target coverage (that is, PPT, STI treatment and condom use), the intervention is expected to prevent 22-35% of all new HIV infections in FSW and in the total population over 5 years in a low transmission setting like Mysore, and to be half as effective in high transmission settings such as Bagalkot. The results were sensitive to small variations in intervention coverage. The condom component alone is expected to prevent around 20% of all new HIV infections over 5 years in Mysore and around 6% for the STI component alone; compared with 7%-14% for the PPT component alone. Multivariate sensitivity analyses suggested that interventions may be more effective in settings with low FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The Avahan intervention is expected to be effective. However, to be able to demonstrate effectiveness empirically in the different settings, it is important to achieve target coverage or higher, which in the case of PPT could take a number of years to achieve. These preliminary model predictions need to be validated with more detailed mathematical models, as better data on sexual behaviour, condom use, STI and HIV trends over time, and intervention coverage data accumulate over the course of the programme.

PD-0200347, an alpha2delta ligand of the voltage gated calcium channel, inhibits in vivo activation of the Erk1/2 pathway in osteoarthritic chondrocytes: a PKCalpha dependent effect.

OBJECTIVE: To explore the in vivo effects of PD-0200347, an alpha(2)delta ligand of voltage gated Ca(2+) channels, on cell signalling in osteoarthritic (OA) chondrocytes from an experimental dog model, and examine the effect of PD-0200347 on the major signalling pathways involved in OA cartilage degradation. METHODS: OA was surgically induced in dogs by sectioning the anterior cruciate ligament. OA dogs were divided into three groups and treated orally with (a) placebo; (b) 15 mg/kg/day PD-0200347, or (c) 90 mg/kg/day PD-0200347. The animals were killed 12 weeks after surgery. Cartilage specimens from femoral condyles and tibial plateaus were processed for immunohistochemistry. Specific antibodies against the phosphorylated form of PKCalpha, Ras, c-Raf, the MAP kinases Erk1/2, p38, JNK, and the transcription factors, CREB and Elk-1, were used. RESULTS: Levels of all the tested signalling mediators were increased in the placebo treated (OA) group compared with the normal group. PD-0200347 treatment significantly reduced the levels of the active forms of PKCalpha, c-Raf, Erk1/2, and Elk-1; however, the levels of the active forms of Ras, p38, JNK, and CREB were not affected by the PD-0200347 treatment. CONCLUSION: The action of PD-0200347 on OA chondrocytes is probably mediated through the inhibition of Erk1/2 activation via a Ras independent mechanism. This effect is associated with reduction of the activation of transcription factors such as Elk-1, which leads to the inhibition of the induction of the major catabolic factors involved in the degradation process of OA cartilage.