DNA-m6A calling and integrated long-read epigenetic and genetic analysis with fibertools.

Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule and single-nucleotide resolution. Long-read epigenetic studies encompass both the direct identification of native cytosine methylation as well as the identification of exogenously placed DNA N6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using single-molecule sequencing, as well as coprocessing single-molecule genetic and epigenetic architectures, is limited by computational demands and a lack of supporting tools. Here, we introduce fibertools, a state-of-the-art toolkit that features a semisupervised convolutional neural network for fast and accurate identification of m6A-marked bases using PacBio single-molecule long-read sequencing, as well as the coprocessing of long-read genetic and epigenetic data produced using either PacBio or Oxford Nanopore sequencing platforms. We demonstrate accurate DNA-m6A identification (>90% precision and recall) along >20 kilobase long DNA molecules with a ~1,000-fold improvement in speed. In addition, we demonstrate that fibertools can readily integrate genetic and epigenetic data at single-molecule resolution, including the seamless conversion between molecular and reference coordinate systems, allowing for accurate genetic and epigenetic analyses of long-read data within structurally and somatically variable genomic regions.

Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Combining revealed and stated preference models for artificial reef siting: A study in the Florida Keys.

This paper investigates divers' preferences for artificial reef diving and willingness to pay (WTP) for large ship, artificial reef site attributes in the Florida Keys. We investigate diver demand for existing decommissioned ships that have been sunk off the Florida Keys as well as demand for four new vessels that are available for disposal from the U.S. Department of Transportation Maritime Administration inventory. Using survey data from divers, we compare revealed preference (RP) site choices, stated preference (SP) choices from a discrete choice experiment, and joint RP/SP choices. Our analysis also incorporates stated attribute non-attendance (ANA) at the choice-task level. Our results indicate that the joint RP/SP models with stated ANA are preferred, leading to decreases in marginal WTP as well as decreases in the variability of marginal WTP estimates in the 95% confidence intervals. Results provide a framework for directing more efficient future decision making regarding sinkings at locations that will enhance welfare for divers.

FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment.

PURPOSE: We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma. METHODS: We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation. RESULTS: Thirty-one consecutive patients, median age 60 years (range, 30-78), were identified from 2016 to 2018. The median number of combination-ICI cycles to the first post-FDG-PET/CT response assessment was 3 (interquartile range (IQR), 2-4). The best-overall responses were complete metabolic response (CMR) in 25 (80%), partial metabolic response (PMR) in 3 (10%), and progressive metabolic disease (PMD) in 3 (10%) patients. Patients with PMD had significantly higher pre-treatment wbMTV (p = 0.009). At a median follow-up of 21.5 months, 26 (84%) patients were alive with median progression-free and overall survival not reached. Secondary progression occurred in 9/31 (29%) patients at a median of 8.2 months (IQR, 6.9-15.5), of those majority (78%) was detected by FDG-PET/CT. Of 36 findings on post-FDG-PET/CT suggestive of irAE, 29 (80%) had clinical confirmation. In 3 (7%), the FDG-PET/CT findings preceded clinical presentation. The most common FDG-PET/CT detectable irAEs were endocrinopathies (36%) and enterocolitis (35%). CONCLUSION: FDG-PET/CT response evaluation predicts the long-term outcome of patients treated with first-line combination-ICIs. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.

Altruistic and Private Values For Saving Lives With an Oyster Consumption Safety Program.

We use data from an Internet-based survey and estimate the benefits of an oyster consumption safety policy with the contingent valuation method. In addition to providing a context-specific estimate of willingness-to-pay for oyster safety, we consider an important issue in the contingent valuation mortality risk reduction literature. A number of studies find that willingness-to-pay for mortality risk reduction is not sensitive to the scope of the risk change. We present the scope test as a difference in the number of lives saved by the program, instead of small changes in risk, and find that referendum votes are responsive to scope. A third feature of this article is that we identify those at-risk respondents who would most benefit from the policy and decompose willingness-to-pay into use values and altruistic nonuse values. We find that willingness-to-pay per life saved ranges from $3.95 million to $7.69 million for the private good of lives saved when the respondent is at risk (i.e., use values). Willingness-to-pay per life saved including both use and altruistic nonuse values ranges from $6.89 million to $12.87 million.

Resolving the chromatin impact of mosaic variants with targeted Fiber-seq.

Accurately quantifying the functional consequences of non-coding mosaic variants requires the pairing of DNA sequence with both accessible and closed chromatin architectures along individual DNA molecules-a pairing that cannot be achieved using traditional fragmentation-based chromatin assays. We demonstrate that targeted single-molecule chromatin fiber sequencing (Fiber-seq) achieves this, permitting single-molecule, long-read genomic and epigenomic profiling across targeted >100 kilobase loci with ~10-fold enrichment over untargeted sequencing. Targeted Fiber-seq reveals that pathogenic expansions of the DMPK CTG repeat that underlie Myotonic Dystrophy 1 are characterized by somatic instability and disruption of multiple nearby regulatory elements, both of which are repeat length-dependent. Furthermore, we reveal that therapeutic adenine base editing of the segmentally duplicated γ-globin (HBG1/HBG2) promoters in primary human hematopoietic cells induced towards an erythroblast lineage increases the accessibility of the HBG1 promoter as well as neighboring regulatory elements. Overall, we find that these non-protein coding mosaic variants can have complex impacts on chromatin architectures, including extending beyond the regulatory element harboring the variant.

The regulatory potential of transposable elements in maize.

Since their initial discovery in maize, transposable elements (TEs) have emerged as being integral to the evolution of maize, accounting for 80% of its genome. However, the repetitive nature of TEs has hindered our understanding of their regulatory potential. Here, we demonstrate that long-read chromatin fiber sequencing (Fiber-seq) permits the comprehensive annotation of the regulatory potential of maize TEs. We uncover that only 94 LTR retrotransposons contain the functional epigenetic architecture required for mobilization within maize leaves. This epigenetic architecture degenerates with evolutionary age, resulting in solo TE enhancers being preferentially marked by simultaneous hyper-CpG methylation and chromatin accessibility, an architecture markedly divergent from canonical enhancers. We find that TEs shape maize gene regulation by creating novel promoters within the TE itself as well as through TE-mediated gene amplification. Lastly, we uncover a pervasive epigenetic code directing TEs to specific loci, including that locus that sparked McClintock's discovery of TEs.

Cost-comparison study of reusable and disposable rhinolaryngoscopes in a large English teaching hospital.

OBJECTIVE: This study aimed to compare the cost per use of video-rhinolaryngoscopy using reusable and disposable devices in a tertiary referral centre. METHODS: A cost-comparison study was performed that utilised retrospective cost data and prospective utilisation data to compare the total costs of using reusable video-rhinolaryngoscopes versus a single-use alternative. RESULTS: It was estimated that 4776 and 1821 procedures were performed annually with reusable and disposable video-rhinolaryngoscopes, respectively. The cost per use was £66.61 for reusable devices versus £150.00 for disposable devices. The break-even point (i.e. when cost per use was equal, occurred at 1374 procedures per year). Thereafter, it was cheaper to use reusable devices. CONCLUSION: Disposable rhinolaryngoscopes may present a cheaper solution to services with low rates of rhinolaryngoscope utilisation. However, for larger services considering replacement of their reusable rhinolaryngoscopes with disposable units, it is likely that the recurring costs will be prohibitive in the medium to long term.

Clinical performance and Willingness To Pay for soft toric contact lenses in low and moderate astigmats.

PURPOSE: To determine clinical performance and the 'Willingness To Pay' for toric vs. spherical soft contact lenses in an astigmatic population. METHODS: In the clinical study, subjects with binocular low to moderate astigmatism (-0.75DC to -1.50DC) wore pairs of soft toric (Biofinity toric) and spherical (Biofinity) contact lenses in random sequence. Visual acuity (high and low contrast, monocular and binocular), subjective comfort and subjective vision were recorded. In the economics study, first subjects who had participated in the clinical study were presented with a series of randomised economic scenarios in order to determine their Willingness To Pay a premium (i.e. an increase) for toric lenses. Then, a similar set of scenarios were presented to a much larger group of online respondents and again, Willingness To Pay was established. RESULTS: For the four measures of visual acuity, the Biofinity toric lens out-performed the Biofinity spherical lens by 0.6 to 1.1 lines.. Subjective vision performance was statistically significantly better with the toric lens for the distance task only. Comfort scores were not significantly different. Similar findings for Willingness To Pay were established for the clinical subjects and for the online respondents. The Willingness To Pay premium (additional fee) for a monthly supply of toric lenses (over spherical lenses) was between £13 and £16, if a toric lens provides better vision and similar comfort, as shown in the clinical study. CONCLUSION: Consumers are willing to pay a monthly premium of around 50% to benefit from the typical experience of better vision and similar comfort for toric vs. spherical lenses. The level of additional cost for toric lenses compared to their spherical equivalents is less than this in the market, so eye care professionals should consider that toric lenses are delivering a greater clinical return than anticipated by wearers for the relatively small increase in price.

DNA-m6A calling and integrated long-read epigenetic and genetic analysis with fibertools.

Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule and single-nucleotide resolution. Long-read epigenetic studies encompass both the direct identification of native cytosine methylation as well as the identification of exogenously placed DNA N6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using single-molecule sequencing, as well as co-processing single-molecule genetic and epigenetic architectures, is limited by computational demands and a lack of supporting tools. Here, we introduce fibertools, a state-of-the-art toolkit that features a semi-supervised convolutional neural network for fast and accurate identification of m6A-marked bases using PacBio single-molecule long-read sequencing, as well as the co-processing of long-read genetic and epigenetic data produced using either PacBio or Oxford Nanopore sequencing platforms. We demonstrate accurate DNA-m6A identification (>90% precision and recall) along >20 kilobase long DNA molecules with a ~1,000-fold improvement in speed. In addition, we demonstrate that fibertools can readily integrate genetic and epigenetic data at single-molecule resolution, including the seamless conversion between molecular and reference coordinate systems, allowing for accurate genetic and epigenetic analyses of long-read data within structurally and somatically variable genomic regions.

The regulatory landscape of Arabidopsis thaliana roots at single-cell resolution.

The scarcity of accessible sites that are dynamic or cell type-specific in plants may be due in part to tissue heterogeneity in bulk studies. To assess the effects of tissue heterogeneity, we apply single-cell ATAC-seq to Arabidopsis thaliana roots and identify thousands of differentially accessible sites, sufficient to resolve all major cell types of the root. We find that the entirety of a cell's regulatory landscape and its transcriptome independently capture cell type identity. We leverage this shared information on cell identity to integrate accessibility and transcriptome data to characterize developmental progression, endoreduplication and cell division. We further use the combined data to characterize cell type-specific motif enrichments of transcription factor families and link the expression of family members to changing accessibility at specific loci, resolving direct and indirect effects that shape expression. Our approach provides an analytical framework to infer the gene regulatory networks that execute plant development.

Performance of Risk Assessment Models for Prevalent or Undiagnosed Type 2 Diabetes Mellitus in a Multi-Ethnic Population-The Helius Study.

Background: Most risk assessment models for type 2 diabetes (T2DM) have been developed in Caucasians and Asians; little is known about their performance in other ethnic groups. Objectives: We aimed to identify existing models for the risk of prevalent or undiagnosed T2DM and externally validate them in a multi-ethnic population currently living in the Netherlands. Methods: A literature search to identify risk assessment models for prevalent or undiagnosed T2DM was performed in PubMed until December 2017. We validated these models in 4,547 Dutch, 3,035 South Asian Surinamese, 4,119 African Surinamese, 2,326 Ghanaian, 3,598 Turkish, and 3,894 Moroccan origin participants from the HELIUS (Healthy LIfe in an Urban Setting) cohort study performed in Amsterdam. Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test). We identified 25 studies containing 29 models for prevalent or undiagnosed T2DM. C-statistics varied between 0.77-0.92 in Dutch, 0.66-0.83 in South Asian Surinamese, 0.70-0.82 in African Surinamese, 0.61-0.81 in Ghanaian, 0.69-0.86 in Turkish, and 0.69-0.87 in the Moroccan populations. The C-statistics were generally lower among the South Asian Surinamese, African Surinamese, and Ghanaian populations and highest among the Dutch. Calibration was poor (Hosmer-Lemeshow p < 0.05) for all models except one. Conclusions: Generally, risk models for prevalent or undiagnosed T2DM show moderate to good discriminatory ability in different ethnic populations living in the Netherlands, but poor calibration. Therefore, these models should be recalibrated before use in clinical practice and should be adapted to the situation of the population they are intended to be used in.

Assessing public health risk in the London polonium-210 incident, 2006.

OBJECTIVES: Mr Alexander Litvinenko died in a London hospital on 23 November 2006, allegedly from poisoning with the radionuclide polonium-210 ((210)Po). Associated circumstances required an integrated response to investigate the potential risk of internal contamination for individuals exposed to contaminated environments. STUDY DESIGN: Descriptive study. METHODS: Contaminated locations presenting a potential risk to health were identified through environmental assessment by radiation protection specialists. Individuals connected with these locations were identified and assessed for internal contamination with (210)Po. RESULTS: In total, 1029 UK residents were identified, associated with the 11 most contaminated locations. Of these, 974 were personally interviewed and 787 were offered urine tests for (210)Po excretion. Overall, 139 individuals (18%) showed evidence of probable internal contamination with (210)Po arising from the incident, but only 53 (7%) had assessed radiation doses of 1mSv or more. The highest assessed radiation dose was approximately 100mSv. CONCLUSIONS: Although internal contamination with (210)Po was relatively frequent and was most extensive among individuals associated with locations judged a priori to pose the greatest risk, a high degree of assurance could be given to UK and international communities that the level of health risk from exposure to the radionuclide in this incident was low.

Cross-strand disulfides in the hydrogen bonding site of antiparallel ß-sheet (aCSDhs): Forbidden disulfides that are highly strained, easily broken.

Some disulfide bonds perform important structural roles in proteins, but another group has functional roles via redox reactions. Forbidden disulfides are stressed disulfides found in recognizable protein contexts, which currently constitute more than 10% of all disulfides in the PDB. They likely have functional redox roles and constitute a major subset of all redox-active disulfides. The torsional strain of forbidden disulfides is typically higher than for structural disulfides, but not so high as to render them immediately susceptible to reduction under physionormal conditions. Previously we characterized the most abundant forbidden disulfide in the Protein Data Bank, the aCSDn: a canonical motif in which disulfide-bonded cysteine residues are positioned directly opposite each other on adjacent anti-parallel ß-strands such that the backbone hydrogen-bonded moieties are directed away from each other. Here we perform a similar analysis for the aCSDh, a less common motif in which the opposed cysteine residues are backbone hydrogen bonded. Oxidation of two Cys in this context places significant strain on the protein system, with the ß-chains tilting toward each other to allow disulfide formation. Only left-handed aCSDh conformations are compatible with the inherent right-handed twist of ß-sheets. aCSDhs tend to be more highly strained than aCSDns, particularly when both hydrogen bonds are formed. We discuss characterized roles of aCSDh motifs in proteins of the dataset, which include catalytic disulfides in ribonucleotide reductase and ahpC peroxidase as well as a redox-active disulfide in P1 lysozyme, involved in a major conformation change. The dataset also includes many binding proteins.

Osteoarthritis in England: Incidence Trends From National Health Service Hospital Episode Statistics.

OBJECTIVE: It is typical in epidemiological research of osteoarthritis (OA) to collect data for the hand, hip, and knee. However, little population-based data exist for this disease in the foot. Thus, we addressed patterns of OA for the foot compared with the hand, hip, and knee spanning 2000/2001 to 2017/2018 in England. METHODS: Secondary-care data from 3 143 928 patients with OA of the foot, hand, hip, and knee were derived from the National Health Service (NHS) Hospital Episode Statistics (HES) database. Distribution, population prevalence, and incidence of joint-specific OA were stratified by age and sex. RESULTS: OA incidence increased significantly at the foot [3.8% (95% confidence interval [CI] 3.0, 4.6)], hand [10.9% (10.1, 11.7)], hip [3.8% (2.9, 4.7)], and knee [2.9% (2.2, 3.6)] per year from 2000/2001 to 2017/2018. A higher proportion of women were diagnosed with OA, whereas greater incidence in men was estimated for the hand and hip. Foot OA presented comparable diagnosis numbers to the hand. More recently during 2012/2013 to 2017/2018, a significant rise in hip OA was estimated among younger adults, whereas knee OA decreased across all age groups. Incidence of OA in the foot and hand were particularly significant among the 75 or older age group, though bimodal age distributions were observed for both sites. CONCLUSION: The significant increase in secondary care records for OA in England underscores the importance of exploring possible causative factors and identifying groups most at risk. Further detailed data may be particularly important for the hip, which represents significant incidence among younger adults. Greater incidence of OA in the foot compared with the knee emphasizes the need for well-conducted epidemiological research in this area. Monitoring the performance of surgical outcomes at the population-level for this frequently affected yet understudied site could have substantial potential to reduce the socioeconomic burden it represents to the NHS.

Accelerating structure-function mapping using the ViVa webtool to mine natural variation.

Thousands of sequenced genomes are now publicly available capturing a significant amount of natural variation within plant species; yet, much of these data remain inaccessible to researchers without significant bioinformatics experience. Here, we present a webtool called ViVa (Visualizing Variation) which aims to empower any researcher to take advantage of the amazing genetic resource collected in the Arabidopsis thaliana 1001 Genomes Project (http://1001genomes.org). ViVa facilitates data mining on the gene, gene family, or gene network level. To test the utility and accessibility of ViVa, we assembled a team with a range of expertise within biology and bioinformatics to analyze the natural variation within the well-studied nuclear auxin signaling pathway. Our analysis has provided further confirmation of existing knowledge and has also helped generate new hypotheses regarding this well-studied pathway. These results highlight how natural variation could be used to generate and test hypotheses about less-studied gene families and networks, especially when paired with biochemical and genetic characterization. ViVa is also readily extensible to databases of interspecific genetic variation in plants as well as other organisms, such as the 3,000 Rice Genomes Project ( http://snp-seek.irri.org/) and human genetic variation ( https://www.ncbi.nlm.nih.gov/clinvar/).

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response.

When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic-pituitary-adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic-pituitary-adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic-pituitary-interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR (nr3c2). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic-pituitary-adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior.

Exposures and reported symptoms associated with occupational deployment to the Buncefield fuel depot fire, England 2005.

OBJECTIVES: An explosion at the Buncefield fuel depot outside London occurred on 11 December 2005. We conducted a retrospective cohort study of airborne exposures and health status for workers deployed. METHODS: Deployed individuals were identified through their occupational health departments. We sent a self-completion questionnaire asking about health symptoms during the burn and post-burn phases. The prevalence of health symptoms in workers was compared to symptoms in local residents not under the smoke plume. RESULTS: Of 1949 eligible individuals, 815 returned questionnaires (response rate 44%). Respiratory protection was used by 39%. Symptoms were reported by 41% of individuals during the burn phase compared with 26% in the post-burn phase. In a final multivariable model, reporting of any symptoms was associated with deployment inside the inner fire cordon during the burn phase (OR 2.07, 95% CI 1.24 to 3.47) and wearing a face mask (OR 2.33, 95% CI 1.67 to 3.26). Compared with the general public, eye irritation (prevalence ratio (PR) 2.1, 95% CI 1.5 to 3.0), coughing (PR 1.3, 95% CI 1.0 to 1.8) and headaches (PR 1.7, 95% CI 1.2 to 2.5) were more common in workers deployed during the burn phase but not the post-burn phase. CONCLUSIONS: Increased reporting of symptoms close to the fire during the burn phase was consistent with increased exposure to products of combustion, although no major acute illness was reported. That only a minority of individuals used face masks, which were not protective for symptoms, raises questions about the availability of adequate respiratory protection for such incidents.

Evolving care of HIV-infected pregnant women in Jamaica--from nevirapine to HAART.

BACKGROUND: The Ministry of Health, Jamaica, is scaling-up programmes to improve the health of HIV-positive pregnant women according to the modified WHO recommended preventative mother to child transmission (pMTCT) regimens of therapy based upon the mother's clinical and immunological status. Highly-active antiretroviral drugs (HAART) can result in successful pMTCT to < 1%. We report the clinical and immunological characteristics of HIV/AIDS in an era of evolving treatment and care of HIV-infected pregnant Jamaican women. SUBJECTS AND METHOD: Clinical records were reviewed of patients registered in antenatal clinics in Greater Kingston and St. Catherine, Jamaica (annual birth cohort--20,000) between September 2002 and August 2006. Disease status was determined using the Centers for Disease Control and Prevention (CDC) classification system for adult HIV/AIDS. Demographic, clinical and laboratory data were documented and analyzed. RESULTS: During the four-year period, 571 HIV-infected women were enrolled; 62% from Victoria Jubilee Hospital, 25% from Spanish Town Hospital and 13% from the University Hospital of the West Indies. Mean age was 27-29 (range 15-41) years, median parity was 2 (range 0-9) and 68-70% were unemployed. Ninety-five per cent had live births. CDC categories of illnesses were A--mild disease in 82% (n=473), B--moderate disease in 4.4% (n=24) and C--severe disease in 1.4% (n=8) while 12% (n=66) had insufficient data. During the first three years, CD4+ cell counts were evaluated in only 2.5% (10 of 406) of patients with median of 344 cells/microL, compared to CD4 evaluation in 50% (83 of 165 women) in the last year with median of573 cells/uL. Antiretroviral (ARV) medications primarily for pMTCT were given to 89% (n=506) ofwomen. Of these, uptake of HAART increased during years 1-3 from 2-3% to 62% in year four Within two years post-partum, 24 women died, 92% (n=22)from the direct complications of HIV/AIDS. CONCLUSION: A comprehensive system of care of HIV in the peripartum period has been developed in Jamaica. Detailed medical evaluation during pregnancy is performed with modern guidelines and increasing laboratory availability of CD4+ cell counts and viral loads. We believe declining HIV infection rates in Jamaican infants and healthier mothers are a direct consequence of increased testing in pregnancy with early diagnosis and initiation of HAART-based pMTCT regimens in pregnant women.