Socioeconomic inequalities in the quality of primary care under Brazil's national pay-for-performance programme: a longitudinal study of family health teams.

BACKGROUND: Many governments have introduced pay-for-performance programmes to incentivise health providers to improve quality of care. Evidence on whether these programmes reduce or exacerbate disparities in health care is scarce. In this study, we aimed to assess socioeconomic inequalities in the performance of family health teams under Brazil's National Programme for Improving Primary Care Access and Quality (PMAQ). METHODS: For this longitudinal study, we analysed data on the quality of care delivered by family health teams participating in PMAQ over three rounds of implementation: round 1 (November, 2011, to March, 2013), round 2 (April, 2013, to September, 2015), and round 3 (October, 2015, to December, 2019). The primary outcome was the percentage of the maximum performance score obtainable by family health teams (the PMAQ score), based on several hundred (ranging from 598 to 914) indicators of health-care delivery. Using census data on household income of local areas, we examined the PMAQ score by income ventile. We used ordinary least squares regressions to examine the association between PMAQ scores and the income of each local area across implementation rounds, and we did an analysis of variance to assess geographical variation in PMAQ score. FINDINGS: Of the 40 361 family health teams that were registered as ever participating in PMAQ, we included 13 934 teams that participated in the three rounds of PMAQ in our analysis. These teams were located in 11 472 census areas and served approximately 48 million people. The mean PMAQ score was 61·0% (median 61·8, IQR 55·3-67·9) in round 1, 55·3% (median 56·0, IQR 47·6-63·4) in round 2, and 61·6% (median 62·7, IQR 54·4-69·9) in round 3. In round 1, we observed a positive socioeconomic gradient, with the mean PMAQ score ranging from 56·6% in the poorest group to 64·1% in the richest group. Between rounds 1 and 3, mean PMAQ performance increased by 7·1 percentage points for the poorest group and decreased by 0·8 percentage points for the richest group (p<0·0001), with the gap between richest and poorest narrowing from 7·5 percentage points (95% CI 6·5 to 8·5) to -0·4 percentage points over the same period (-1·6 to 0·8). INTERPRETATION: Existing income inequalities in the delivery of primary health care were eliminated during the three rounds of PMAQ, plausibly due to a design feature of PMAQ that adjusted financial payments for socioeconomic inequalities. However, there remains an important policy agenda in Brazil to address the large inequities in health. FUNDING: UK Medical Research Council, Newton Fund, and CONFAP (Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa).

Far-infrared observations of a massive cluster forming in the Monoceros R2 filament hub⋆.

We present far-infrared observations of Monoceros R2 (a giant molecular cloud at approximately 830 pc distance, containing several sites of active star formation), as observed at 70 µm, 160 µm, 250 µm, 350 µm, and 500 µm by the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) instruments on the Herschel Space Observatory as part of the Herschel imaging survey of OB young stellar objects (HOBYS) Key programme. The Herschel data are complemented by SCUBA-2 data in the submillimetre range, and WISE and Spitzer data in the mid-infrared. In addition, C18O data from the IRAM 30-m Telescope are presented, and used for kinematic information. Sources were extracted from the maps with getsources, and from the fluxes measured, spectral energy distributions were constructed, allowing measurements of source mass and dust temperature. Of 177 Herschel sources robustly detected in the region (a detection with high signal-to-noise and low axis ratio at multiple wavelengths), including protostars and starless cores, 29 are found in a filamentary hub at the centre of the region (a little over 1% of the observed area). These objects are on average smaller, more massive, and more luminous than those in the surrounding regions (which together suggest that they are at a later stage of evolution), a result that cannot be explained entirely by selection effects. These results suggest a picture in which the hub may have begun star formation at a point significantly earlier than the outer regions, possibly forming as a result of feedback from earlier star formation. Furthermore, the hub may be sustaining its star formation by accreting material from the surrounding filaments.

Ultrasound and magnetic resonance imaging of healthy paediatric ankles and knees: a baseline for comparison with haemophilic joints.

The study was undertaken to document cartilage and soft tissue changes/findings in ankles and knees of normal children of different age groups to be used for comparison in the assessment of children with haemophilia. Cartilage thickness and soft tissue changes were recorded at predetermined sites of ankles/knees on both US and MRI in healthy boys in three age groups: 7-9; 10-14; and 15-18 years. To assess the validity of the ultrasound and MRI measurements, an ex vivo study was done using agar phantoms with techniques and scanners similar to those applied in vivo. Twenty (48%) knees and 22 (52%) ankles of 42 boys, were evaluated. There was a reduction in the thickness of joint cartilage with age. A difference in cartilage measurements was noted in most sites between the age groups on both US and MRI (P < 0.05 each), but such difference was not noted for joint fluid in ankles or knees (P = 0.20, P = 0.68 or P = 0.75, P = 0.63 for US, MRI, respectively). Although cartilage measurements were smaller on US than on MRI for both ankles and knees (P < 0.05 each), this observation was not recorded for fluid in knees (P = 0.02). For diminutive measurements (2 mm) mean US measurements were smaller than corresponding phantom's measurements, P = 0.02. Age-related measurements were noted for cartilage thickness on US and MRI in ankles and knees. US measurements were smaller than corresponding MRI measurements at most joint sites, which were supported by results on small-diameter phantoms.

Is the elusive Gymnothorax polyuranodon really a freshwater moray?

Analysis of 36 records of the rarely encountered moray Gymnothorax polyuranodon indicate that juveniles and adults inhabit fresh and mildly brackish habitats (salinity < 5) in streams of the Australian Wet Tropics Eighty-one per cent of these records were from freshwater streams and collectively demonstrate that this species inhabits fresh water throughout all seasons. A survey of fish researchers, each with at least 100 h of field experience in Australia's Wet Tropics, revealed that 33% of researchers working in fresh waters (nine of 27 researchers) had encountered the species and 15% of researchers with substantial experience working in estuaries (two of 13 researchers) had encountered the species. The species was not sampled or observed in the nearshore marine environment. The only record of an elver of this species was, however, found in an estuary at a salinity of 33·4. This preliminary evidence suggests adult G. polyuranodon occupy freshwater habitats, but further research is required to understand the complete life cycle, including movements, habitat use and reproductive ecology of the species.

Flightless I deficiency enhances wound repair by increasing cell migration and proliferation.

Wound healing disorders are a therapeutic problem of increasing clinical importance involving substantial morbidity, mortality, and rising health costs. Our studies investigating flightless I (FliI), a highly conserved actin-remodelling protein, now reveal that FliI is an important regulator of wound repair whose manipulation may lead to enhanced wound outcomes. We demonstrate that FliI-deficient + /- mice are characterized by improved wound healing with increased epithelial migration and enhanced wound contraction. In contrast, FliI-overexpressing mice have significantly impaired wound healing with larger less contracted wounds and reduced cellular proliferation. We show that FliI is secreted in response to wounding and that topical application of antibodies raised against the leucine-rich repeat domain of the FliI protein (FliL) significantly improves wound repair. These studies reveal that FliI affects wound repair via mechanisms involving cell migration and proliferation and that FliI might represent an effective novel therapeutic factor to improve conditions in which wound healing is impaired.

ArrayExpress--a public database of microarray experiments and gene expression profiles.

UNLABELLED: ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts--the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50,000 hybridizations and >1,500,000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. AVAILABILITY: www.ebi.ac.uk/arrayexpress.

ArrayExpress--a public repository for microarray gene expression data at the EBI.

ArrayExpress is a public repository for microarray data that supports the MIAME (Minimum Information About a Microarray Experiment) requirements and stores well-annotated raw and normalized data. As of November 2004, ArrayExpress contains data from approximately 12,000 hybridizations covering 35 species. Data can be submitted online or directly from local databases or LIMS in a standard format, and password-protected access to prepublication data is provided for reviewers and authors. The data can be retrieved by accession number or queried by various parameters such as species, author and array platform. A facility to query experiments by gene and sample properties is provided for a growing subset of curated data that is loaded in to the ArrayExpress data warehouse. Data can be visualized and analysed using Expression Profiler, the integrated data analysis tool. ArrayExpress is available at http://www.ebi.ac.uk/arrayexpress.

Effect of healing on the expression of transforming growth factor beta(s) and their receptors in chronic venous leg ulcers.

The transforming growth factor betas are of major importance in the wound repair process; however, no studies to date have investigated the role of the transforming growth factor beta receptors in chronic venous leg ulcers or what effect healing has on these proteins. To determine whether the transforming growth factor beta peptides and their receptors are expressed in chronic venous wounds, we used immunofluorescent analysis and quantitative competitive reverse transcription polymerase chain reaction to identify the protein and mRNA expression, respectively. Biopsy samples from wounds and normal skin were collected from 12 patients with chronic venous leg ulcers and three patients undergoing reconstructive surgery, respectively. Additionally four of the chronic venous leg ulcer patients were re-biopsied between 2 and 8 wk after the first biopsy when the wounds had entered the healing phase. The tissue excised from the ulcers included the surrounding intact skin, the ulcer edge, and the ulcer base. Immunofluorescent staining for transforming growth factors beta1, beta2, and beta3 was observed within the epidermis of the skin surrounding the chronic venous ulcers and in fibroblasts and inflammatory cells of the dermis, although this staining was not as strong as that seen in normal unwounded skin. Very little staining could be seen within the ulcers for any of the ligands, however. In contrast the transforming growth factor beta type I receptor was observed throughout the ulcers and the normal unwounded skin biopsies, particularly in the basal epidermal cells. No immunofluorescence for the type II transforming growth factor beta receptor was observed in any of the ulcer biopsies investigated, although it was observed throughout the epidermis and in fibroblasts and inflammatory cells in the surrounding skin. Quantitative, competitive reverse transcription polymerase chain reaction was used to analyze mRNA expression for transforming growth factor beta1 and the type II receptor in the nonhealing ulcers and normal unwounded skin biopsies. These studies revealed that transforming growth factor beta1 and transforming growth factor beta receptor II mRNA was expressed in all the chronic nonhealing ulcers albeit at very low levels for the type II receptor. In marked contrast to the staining observed in nonhealing chronic ulcers, positive immunostaining was observed for the transforming growth factor betas and both the type I and type II receptors in healing ulcers. These results suggest that the absence of a viable receptor complex for the transforming growth factor betas in nonhealing chronic venous ulcers may contribute to wound chronicity.

Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds.

The ability of single growth factors to promote healing of normal and compromised wounds has been well described, but wound healing is a process requiring the coordinated action of multiple growth factors. Only the synergistic effect on wound healing of combinations containing at most two individual growth factors has been reported. We sought to assess the ability of a novel milk-derived growth factor-enriched preparation ¿mitogenic bovine whey extract (MBWE), which contains six known growth factors, to promote repair processes in organotypic in vitro models and incisional wounds in vivo. MBWE stimulated the contraction of fibroblast-populated collagen lattices in a dose-dependent fashion and promoted the closure of excisional wounds in embryonic day 17 fetal rat skin. Application of MBWE increased incisional wound strength in normal animals on days 3, 5, 7, and 10 and reversed the decrease in wound strength observed following steroid treatment. Wound histology showed increased fibroblast numbers in wounds from normal and steroid-compromised animals. These data suggest the mixture of factors present in bovine milk exerts a direct action on the cells of cutaneous wound repair to enhance both normal and compromised healing.

High-resolution magnetic relaxation dispersion measurements of solute spin probes using a dual-magnet system.

The magnetic field dependence of the nuclear spin-lattice relaxation rate provides a detailed report of the spectral density functions that characterize the intra- and intermolecular fluctuations that drive magnetic relaxation. We have addressed the difficult sensitivity and resolution problems associated with low magnetic field strengths by using two magnets in close proximity and shielded from each other. The sample is stored in the high magnetic field, pneumatically driven to the variable satellite field, then returned to the high field for detection at high resolution. A magnetic shield effectively decouples the two magnets so that varying the satellite field strength has minimal effect on the field strength and shim of the high field magnet. The disadvantage of the sample-shuttle magnet-pair system is the restriction imposed on the relaxation times by the finite shuttle times. Experiments not described here have shown this rate maximum to be about 20 s(-1) for most practical solutions. However, we demonstrate here that the sensitivity gains over switched-current magnet systems permit characterization of solute inter- and intramolecular dynamics over the time scale range from tens of microseconds to less than a picosecond. This range permits investigation of a number of crucial chemical dynamics questions, while high sensitivity permits examination of a variety of solute spins. Representative data are presented for (1)H, (111)Cd, and (7)Li.

Identification and characterization of the KlCMD1 gene encoding Kluyveromyces lactis calmodulin.

The KlCMD1 gene was isolated from a Kluyveromyces lactis genomic library as a suppressor of the Saccharomyces cerevisiae temperature-sensitive mutant spc110-124, an allele previously shown to be suppressed by elevated copy number of the S. cerevisiae calmodulin gene CMD1. The KlCMD1 gene encodes a polypeptide which is 95% identical to S. cerevisiae calmodulin and 55% identical to calmodulin from Schizosaccharomyces pombe. Complementation of a S. cerevisiae cdm1 deletion mutant by KlCMD1 demonstrates that this gene encodes a functional calmodulin homologue. Multiple sequence alignment of calmodulins from yeast and multicellular eukaryotes shows that the K. lactis and S. cerevisiae calmodulins are considerably more closely related to each other than to other calmodulins, most of which have four functional Ca2+-binding EF hand domains. Thus like its S. cerevisiae counterpart Cmd1p, the KlCMD1 product is predicted to form only three Ca2+-binding motifs.

Regulation of insulin-like growth factor-binding protein-5 by insulin-like growth factor I and interleukin-1alpha in ovine articular chondrocytes.

Insulin-like growth factors (IGFs) contribute to the maintenance of the cartilage matrix by stimulating proteoglycan synthesis. In contrast, interleukin-1 (IL-1), an inflammatory cytokine, suppresses the synthesis of proteoglycans. In pathological conditions the chondrocytes' responsiveness to IGF-I is decreased, and elevated levels of IGF-binding proteins (IGFBPs) have been implicated as a possible cause. The aim of this study was to investigate the effects of IGF-I and IL-1 on IGFBP production by ovine articular chondrocytes (OAC) and the roles of these IGFBPs in the regulation of proteoglycan synthesis. As revealed by Western ligand and immunoblotting, OACs secreted IGFBP-2 and a 24-kDa IGFBP in culture medium under basal conditions. Exposure of the cells to IGF-I for 48 h resulted in the appearance of IGFBP-5 in the medium. Des(1-3)IGF-I, an IGF-I analog with reduced affinity for IGFBPs, also increased the level of IGFBP-5, but to a lesser extent than IGF-I, whereas LR3IGF-I, which has virtually no affinity for IGFBPs, had no effect on IGFBP-5. Furthermore, IGFBP-5 underwent a time-dependent limited proteolysis when incubated with OAC-conditioned medium, degrading into 22- and 16-kDa fragments. The degradation of IGFBP-5 was significantly inhibited by IGF-I, but not by des(1-3)IGF-I or LR3IGF-I. Basic fibroblast growth factor, transforming growth factor-beta, and platelet-derived growth factor had no effect on OAC IGFBPs. However, IL-1alpha increased the IGFBP-5 level in a dose-dependent manner, showing maximum activity at 200 U/ml. Furthermore, IL-1alpha, but not IGF-I, induced IGFBP-5 messenger RNA expression, as assessed by Northern blot analysis. Coincubation of IGF-I with IL-1alpha resulted in a substantially increased IGFBP-5 protein level, suggesting a synergism between the mechanisms of action of these two factors. Des(1-3)IGF-I and LR3IGF-I were 10 times more potent than IGF-I in stimulating proteoglycan synthesis, indicating inhibition of IGF-I activity by endogenous IGFBPs. IL-1alpha reduced the IGF-I bioactivity, but had no effect on the activities of the IGF-I analogs, thus implying that locally produced IGFBPs, particularly IGFBP-5, which was substantially increased when IGF-I and IL-1alpha were coincubated, mediated the reduction of the IGF-I activity. Our results demonstrate that IGF-I and IL-1alpha synergistically increase the level of IGFBP-5 in OAC by inhibiting the proteolysis and stimulating the expression of IGFBP-5, respectively. Furthermore, the attenuation of IGF-I-stimulated proteoglycan synthesis by IL-1alpha in OAC appears to be mediated by chondrocyte IGFBPs. We conclude that locally produced IGFBPs, in particular IGFBP-5, may play a critical role in the regulation of cartilage matrix degradation in inflammatory and degenerative arthritides.

Mutations which block the binding of calmodulin to Spc110p cause multiple mitotic defects.

We have generated three temperature-sensitive alleles of SPC110, which encodes the 110 kDa component of the yeast spindle pole body (SPB). Each of these alleles carries point mutations within the calmodulin (CaM) binding site of Spc110p which affect CaM binding in vitro; two of the mutant proteins fail to bind CaM detectably (spc110-111, spc110-118) while binding to the third (spc110-124) is temperature-sensitive. All three alleles are suppressed to a greater or lesser extent by elevated dosage of the CaM gene (CMD1), suggesting that disruption of CaM binding is the primary defect in each instance. To determine the consequences on Spc110p function of loss of effective CaM binding, we have therefore examined in detail the progression of synchronous cultures through the cell division cycle at the restrictive temperature. In each case, cells replicate their DNA but then lose viability. In spc110-124, most cells duplicate and partially separate the SPBs but fail to generate a functional mitotic spindle, a phenotype which we term 'abnormal metaphase'. Conversely, spc110-111 cells initially produce nuclear microtubules which appear well-organised but on entry into mitosis accumulate cells with 'broken spindles', where one SPB has become completely detached from the nuclear DNA. In both cases, the bulk of the cells suffer a lethal failure to segregate the DNA.

Dietary fish oil prevents the development of renal damage in salt-loaded stroke-prone spontaneously hypertensive rats.

1. Stroke-prone spontaneously hypertensive rats (SHRSP) fed a high salt diet rapidly develop proteinuria, a marker of renal damage. We have recently shown that supplementing the diet of these rats with pure omega-3 fatty acids can inhibit the development of proteinuria. The aim of the present study was to examine the underlying renal pathology and to see whether a similar benefit could be obtained with fish oil or canola oil. 2. Diets containing sodium (2% by weight) and 5% fish oil, canola oil, olive oil or safflower oil (the latter two serving as controls) were fed to groups of eight young SHRSP and the development of hypertension and proteinuria was monitored. After 9 weeks, rats were killed and their kidneys were taken for histological examination and fatty acid analysis. Urinary protein was characterized electrophoretically. 3. Patterns of protein excretion were consistent with the appearance of pathological changes in both glomeruli and tubules. Fish oil inhibited the elevation of blood pressure, prevented the development of proteinuria and minimized histological lesions. However, in rats fed canola oil, hypertension and renal damage were equally severe as in rats fed olive or safflower oil. 4. The prevention of hypertensive renal damage by dietary fish oil may be attributable to the increased incorporation of long-chain omega-3 fatty acids in the kidney.

The cardiovascular protective role of docosahexaenoic acid.

Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.

Purified omega-3 fatty acids retard the development of proteinuria in salt-loaded hypertensive rats.

OBJECTIVE: To determine whether purified omega-3 and omega-6 fatty acids influence the progression of hypertensive renal failure in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with established hypertension or during the developmental stage of their hypertension. DESIGN: Groups of eight SHRSP aged 1 or 4 months were fed, for 12 weeks, synthetic diets containing 2% sodium (wt:wt) and either 5% olive oil or 4.5% gamma-linolenic acid (omega-6), eicosapentaenoic acid (omega-3) or docosahexaenoic acid (omega-3). METHODS: Urinary protein excretion and blood pressure were measured after 6, 9 and 12 weeks. The rats were killed and their tissues were collected for fatty acid and eicosanoid analysis. RESULTS: Young rats (aged 1 month) fed diets containing gamma-linolenic acid or olive oil developed marked proteinuria by 9 weeks, whereas no change was observed after 12 weeks in rats fed docosahexaenoic acid or eicosapentaenoic acid. Blood pressure was lower in those fed docosahexaenoic acid or eicosapentaenoic acid than in the gamma-linolenic acid or olive oil groups. Adult rats (aged 4 months) fed the docosahexaenoic acid diet had significantly lower proteinuria than those fed gamma-linolenic acid, eicosapentaenoic acid or olive oil, but there were no differences in blood pressure among the groups. Kidneys from rats fed omega-3 fatty acids had increased levels of docosahexaenoic acid or eicosapentaenoic acid, or both, whereas those from rats fed gamma-linolenic acid and olive oil contained virtually no omega-3 fatty acids. Thromboxane B2 and 12-hydroxyeicosatetraenoic acid production in renal cortex extracts was lowest in rats fed docosahexaenoic acid and eicosapentaenoic acid. CONCLUSION: Dietary omega-3 fatty acids retard the development of hypertension-induced proteinuria. This may be caused by a favourable influence on fatty acid and eicosanoid metabolism and reduction of blood pressure.