Challenges and opportunities of sharing animal health data for research and disease management: a case study of bovine tuberculosis.

The sharing of animal disease data should be encouraged. The analysis of such data will broaden our knowledge of animal diseases and potentially provide insights into their management. However, the need to conform to data protection rules in the sharing of such data for analysis purposes often poses practical difficulties. This paper sets out the challenges and the methods used for the sharing of animal health data in England, Scotland and Wales - Great Britain - using bovine tuberculosis (bTB) data as a case study. The data sharing described is undertaken by the Animal and Plant Health Agency on behalf of the Department for Environment, Food and Rural Affairs and the Welsh and Scottish Governments. It should be noted that animal health data are held at the level of Great Britain (rather than the United Kingdom - which includes Northern Ireland), as Northern Ireland's Department of Agriculture, Environment and Rural Affairs has its own separate data systems. Bovine tuberculosis is the most significant and costly animal health problem facing cattle farmers in England and Wales. It can be devastating for farmers and farming communities and the control costs for taxpayers in Great Britain are over £150 million a year. The authors describe two methods of data sharing - first, where data are requested by, and delivered to, an academic institution for epidemiological or scientific analysis, and second, where data are proactively published in an accessible and meaningful way. They provide details of an example of the second method, namely, the free-to-access website â€Ëœinformation bovine TB' (https://ibtb.co.uk), which publishes bTB data for the benefit of the farming community and veterinary health professionals.

L'échange et le partage de données sur les maladies animales sont des pratiques à encourager. En effet, l'analyse de ces données permet d'étoffer les connaissances sur les maladies animales et peut aussi apporter un nouvel éclairage sur leur gestion. Néanmoins, la nécessité de se conformer aux règles sur la protection des données pose souvent des difficultés pratiques lors des échanges de ce type de données à des fins d'analyse. Les auteurs expliquent les difficultés rencontrées en matière d'échange de données de santé animale en Angleterre, en écosse et au Pays de Galles (Grande-Bretagne), ainsi que les méthodes utilisées, à partir de l'exemple concret des données relatives à la tuberculose bovine. L'échange et le partage de données sont réalisés par l'Agence britannique de santé animale et végétale, pour le compte du ministère britannique de l'Environnement, de l'Alimentation et des Affaires rurales et des gouvernements gallois et écossais. Il convient de préciser que les données de santé animale dont il s'agit sont celles conservées au niveau de la Grande-Bretagne seulement (et non du Royaume-Uni, qui inclut l'Irlande du Nord), étant donné que le ministère de l'Agriculture, de l'Environnement et des Affaires rurales de l'Irlande du Nord possède ses propres systèmes de données. La tuberculose bovine est le principal problème de santé animale auquel sont confrontés les éleveurs de bovins en Angleterre et au Pays de Galles, et le plus coûteux à traiter. La survenue de la tuberculose bovine est une catastrophe pour les éleveurs affectés et leur communauté. En outre, le coût annuel de son contrôle s'élève à plus de 150 millions de livres pour le contribuable britannique. Les auteurs décrivent deux méthodes d'échange et de partage de données : la première est celle où une institution de recherche demande et obtient l'accès à des données particulières afin de réaliser une étude épidémiologique ou scientifique ; la deuxième consiste à publier les données de manière proactive et constructive, en les rendant facilement accessibles. Un exemple concret de cette deuxième méthode est décrit en détail : il s'agit du site web d'information sur la tuberculose bovine (https://ibtb.co.uk), d'accès libre, qui diffuse des informations sur cette maladie à l'intention des éleveurs et des professionnels de la santé animale.

Convendría alentar la puesta en común de datos zoosanitarios, pues el análisis de estos datos nos ayudará a conocer más y mejor las enfermedades animales y, a la postre, puede darnos pistas sobre la mejor manera de afrontarlas. Ocurre a menudo, sin embargo, que el prescriptivo cumplimiento de las reglas de protección de datos plantee dificultades prácticas para poner estos datos en común con fines de análisis. Los autores, empleando como ejemplo un estudio sobre la tuberculosis bovina, describen esas dificultades y los métodos utilizados para compartir datos zoosanitarios en Inglaterra, Escocia y Gales (Gran Bretaña). En el ejemplo descrito, la Agencia de Sanidad Animal y Vegetal del Reino Unido fue la instancia que impulsó la puesta en común de los datos en nombre del Departamento de Medio Ambiente, Alimentación y Asuntos Rurales del Reino Unido y de los gobiernos galés y escocés. Conviene puntualizar que los datos zoosanitarios cubren el territorio de Gran Bretaña (y no de todo el Reino Unido, que incluye Irlanda del Norte), ya que el Departamento de Medio Ambiente, Alimentación y Asuntos Rurales norirlandés dispone de su propio sistema de datos independiente. La tuberculosis bovina es el problema zoosanitario más importante y oneroso al que hacen frente las explotaciones de vacuno en Inglaterra y Gales. Esta enfermedad no solo puede ser devastadora para los productores y profesionales del sector, sino que la lucha contra ella cuesta al contribuyente británico más de 150 millones de libras al año. Los autores describen dos métodos para compartir de datos: en el primero de ellos, un establecimiento universitario solicita y recibe los datos con fines de análisis científico o epidemiológico; en el segundo, una entidad toma la iniciativa de hacer públicos los datos de forma accesible y coherente. Los autores exponen en detalle un ejemplo del segundo procedimiento, a saber, el sitio web de información sobre la tuberculosis bovina (https://ibtb.co.uk) en libre acceso, en el cual se publican datos sobre la enfermedad dirigidos a los profesionales del sector pecuario y la sanidad animal.

Well-being in wounds inventory (WOWI): development of a valid and reliable measure of well-being in patients with wounds.

OBJECTIVE: Physical and psychosocial deficits have been reported in people living with chronic wounds. While the negative impact of these factors on an individual's quality of life (QoL) is well documented, there has been little research into the well-being of those living with chronic wounds, despite recent calls for increased attention to this related, yet distinct construct. This paper introduces the Well-being in Wounds Inventory (WOWI) and provides support for the WOWI as a valid and reliable measure of well-being in patients living with chronic wounds. METHOD: A draft questionnaire was administered to a convenience sample of individuals with chronic wounds (n=85) and the resulting data subject to factor analysis in order to refine the structure of the questionnaire. The reliability, validity and responsiveness of the resulting questionnaire were then tested by administration to a second sample of individuals with wounds (n=49). Socio-demographic data, issues affecting patient well-being and well-being factors, such as, emotions; perceived coping skills; social support; personal control; hope for the future, were measured. RESULTS: Results confirmed the WOWI as a reliable and valid measure of well-being. Items loaded onto two subscales, 'personal resources' and 'wound worries'. Analysis revealed the WOWI to be highly feasible measure of well-being, with good test-retest reliability and responsiveness to changes in health status. CONCLUSION: The current study highlights the importance of assessing well-being factors in individuals living with chronic wounds. It introduces the WOWI as a valid and reliable measure of well-being in chronic wound patients. The authors recommend health-care practitioners take account of well-being as part of a holistic treatment plan in order to maximise patient outcomes. DECLARATION OF INTEREST: This project was funded by Urgo Medical. The authors have no conflict of interest to declare.

Contribution of the Leg Club model of care to the well-being of people living with chronic wounds.

OBJECTIVE: Social support impacts well-being. Higher levels of social support encourage treatment adherence and aid healing in people living with chronic wounds. The Leg Club model of care harnesses social support mechanisms to improve patient outcomes. This study investigated whether social support mechanisms available through a Leg Club environment influenced well-being. METHOD: Participants were community Leg Club members. Socio-demographic data was collected, and the Well-being in Wounds Inventory (WOWI) administered to assess 'wound worries,' 'personal resources,' and 'well-being'. Participants' perceived social situation, length of time attending a Leg Club, wound duration, and feelings about their physical appearance were also measured. RESULTS: The subjects recruited (n=49) were aged between 50 and 94 years (mean=75.34, standard deviation=10.31). Membership of a Leg Club did impact well-being factors. Time spent at a Leg Club improved 'personal resources' over time. 'Perceived social situation' predicted key aspects of well-being, as did 'time spent attending a Leg Club' and 'feelings about physical appearance.' Social support and relief from social isolation were important aspects of Leg Club membership for participants. CONCLUSION: Attending a Leg Club enhances well-being in people living with a chronic wound; social support has an important role to play in this relationship. Future research should consider the specific interplay of social support mechanisms of Leg Club, and other relevant wound-related variables to optimise patient well-being and treatment outcomes. DECLARATION OF INTEREST: The Urgo Foundation funded this project. The authors have no conflicts of interest to declare.

Venous leg ulcers: what about well-being?

The impact of having a leg ulcer is well-documented in terms of the pain, restrictions and psychosocial difficulties that patients experience. However, the current focus on quality of life as a patient reported outcome measure overlooks the importance of the individual's well-being. In this article, we argue that a shift in focus from quality of life to well-being will contribute to the more proactive patient centred approach to care to which we should all aspire in contemporary care settings.

The effectiveness of local child weight management programmes: an audit study.

BACKGROUND: Many different child weight management programmes exist, with varying degrees of evaluation to provide evidence of their success. The purpose of this research was to use a standardized approach to audit the effectiveness of weight management intervention programmes in the West Midlands region of the UK, specifically to assess the benefits to participating children in terms of health improvement and behaviour change. METHODS: An audit of seven family-based intervention programmes currently in place in the West Midlands. Programmes were audited against the Standard Evaluation Framework. RESULTS: The programmes provided a partial data set relating to a change in weight from the baseline to the end of the programme; none of the programmes provided all of the measures indicated by the Standard Evaluation Form as being essential for evaluation. Weight change ranged from an increase in group mean of 0.4 kg to a decrease of 0.9 kg. Body Mass Index SD decreased by 0.1-0.2 points in four programmes and remained unchanged in two programmes. Four programmes collected long-term follow-up data at 6 months. This was often limited because of participant dropout. Improvement in diet and exercise were reported by participants in all programmes which measured these behaviours. CONCLUSIONS: Ongoing evaluation of all programmes, using a standard approach, is essential in order to improve the evidence base and support future commissioning.

Fruit and vegetable intake of primary school children: a study of school meals.

BACKGROUND: Despite an increasing focus on the nutritional content of school meals and initiatives such as the School Fruit and Vegetable Scheme, children are not meeting the recommended levels of fruit and vegetable consumption. The present study aimed to examine children's fruit and vegetable consumption in 15 primary schools across the West Midlands region. METHODS: A total of 1296 children, aged 4-11 years, were observed for five consecutive days and the consumption of all food items was measured using the weighed intake method. Differences in the mean intake of fruit, vegetables and foods high in fat and sugar between Key Stages 1 and 2 were determined. RESULTS: Two-thirds of the children in the present study did not consume any fruit at lunchtime and only 3% of children consumed at least one portion as part of their school meal. The proportion of children consuming some quantity of vegetable at lunchtime was more than double that consuming fruit. Children in Key Stage 1 consumed significantly more vegetables on average than children in Key Stage 2 (P ≤ 0.05); however, no significant differences were found for the consumption of fruit. CONCLUSIONS: Despite the introduction of food-based standards for school meal provision; children are not consuming adequate portions of fruit and vegetables at lunchtime. The importance of strategies used by catering staff to promote the consumption of fruit and vegetables should be harnessed to encourage children to taste fruit and vegetables provided. Further research is recommended to increase the evidence base on strategies aiming to promote fruit and vegetable consumption in children.

Critical energy-density profile near walls.

We examine critical adsorption for semi-infinite thermodynamic systems of the Ising universality class when they are in contact with a wall of the so-called normal surface universality class in spatial dimension d=3 and in the mean-field limit. We apply local-functional theory and Monte Carlo simulations in order to quantitatively determine the properties of the energy density as the primary scaling density characterizing the critical behaviors of Ising systems besides the order parameter. Our results apply to the critical isochore, near two-phase coexistence, and along the critical isotherm if the surface and the weak bulk magnetic fields are either collinear or anticollinear. In the latter case, we also consider the order parameter, which so far has yet to be examined along these lines. We find the interface between the surface and the bulk phases at macroscopic distances from the surface, i.e., the surface is "wet." It turns out that in this case the usual property of monotonicity of primary scaling densities with respect to the temperature or magnetic field scaling variable does not hold for the energy density due to the presence of this interface.

Bovine TB infection status in cattle in Great Britain in 2015.

This report, provided by the APHA, presents the key descriptive epidemiological parameters of bovine TB in cattle in Great Britain from January 1 to December 31, 2015, providing summary information on the epidemic, including key statistics and epidemiological parameters as presented in the annual surveillance report for Great Britain, with supporting detail from specific reports for England and Wales. It updates the previous annual summaries for 2012 to 2014, also published in Veterinary Record.

Step dynamics on vicinal surfaces using discrete interface models.

Fluctuations of a single step on a vicinal surface are investigated using a discrete model designed to go further in capturing atomistic effects than usually achieved with continuum models. Variants of the model to incorporate the following three types of adatom dynamics are studied: attachment-detachment; periphery (step-edge) diffusion; and terrace diffusion. The dynamic exponent z is determined for each type as well as crossover functions joining three distinct scaling regimes.

Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions.

One of the most prevalent lesions in DNA is the apurinic/apyrimidinic (AP) site, which is derived from the cleavage of the N-glycosyl bond by DNA glycosylase or by spontaneous depurination. AP sites are repaired by AP endonucleases during the process of base excision repair; however, an imbalance in this DNA repair system may cause mutations as well as cell death. We have established a sensitive and convenient slot-blot method to detect AP sites in genomic DNA using a novel aldehyde reactive probe (ARP), which reacts with the aldehydic group of ring-opened AP sites. The reaction of 1 mM of ARP with 15 microg of genomic DNA containing AP sites at 37 degrees C was completed within 1 min. The AP site-ARP complex was remarkably stable during incubation in TE buffer, even at 100 degrees C for 60 min. The sensitivity of this assay enables detection of 2.4 AP sites per 10(7) bases. By using this ARP-slot-blot assay, the rate of spontaneous depurination of calf thymus DNA was determined. Under physiological conditions, AP sites were increased at 1.54 AP sites/10(6) nucleotides/day (9000 AP sites/cell/day). This highly sensitive assay allows us to determine the endogenous level of AP sites in genomic DNA, as well as to investigate whether DNA-damaging agents cause imbalances of base excision/AP endonuclease repair in vivo and in vitro.

Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice.

The formation of 7-(2-hydroxyethyl)guanine (7-HEG) in DNA of target and nontarget tissues was investigated in male B6C3F1 mice (20/group) and F344 rats (10/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) and mice exposed to 100 ppm ETO for 1 or 3 days or 1, 2, or 4 weeks (5 days/week). The persistence of 7-HEG was studied in mice killed up to 7 days after cessation of the 4-week time-course study. In addition, the formation of O6-(2-hydroxyethyl)guanine and 3-(2-hydroxyethyl)adenine was evaluated in rats exposed to 300 ppm ETO. DNA samples from control and treated animals were analyzed for 7-HEG using neutral thermal hydrolysis, microconcentration, and high-performance liquid chromatography separation with fluorescence detection. Fluorescence-linked high-performance liquid chromatography was used for O6-(2-hydroxyethyl)guanine quantitation, and immunochromatography and gas chromatography-mass spectrometry were used for 3-(2-hydroxyethyl)adenine detection. Analysis of DNA from tissues of control mice and rats revealed the presence of peaks equivalent to 2-6 pmol 7-HEG/mg DNA. In mice exposed to 100 ppm ETO, 7-HEG accumulated to a similar extent in target and nontarget tissues, with adduct concentrations ranging from 17.5 +/- 3.0 (SE) (testis) to 32.9 +/- 1.9 (lung) pmol adduct/mg DNA after 4 weeks of exposure. Concurrent exposures of mice and rats to 100 ppm ETO for 4 weeks led to 2- to 3-fold lower concentrations of 7-HEG in mouse DNA in all tissues compared to rat DNA. 7-HEG disappeared slowly in a nearly linear fashion from the DNA of mouse kidney (t1/2 = 6.9 days) and rat brain and lung (t1/2 = 5.4-5.8 days), which was consistent with the loss of adduct mainly by chemical depurination. In contrast, a more rapid removal of 7-HEG from other mouse (t1/2 = 1.0-2.3 days) and rat (t1/2 = 2.9-4.8 days) tissues was consistent with adduct loss by depurination and DNA repair. Dose-response relationships for 7-HEG were nonlinear in both mice and rats, with the alkylating efficiency of ETO increasing at high exposures.(ABSTRACT TRUNCATED AT 400 WORDS)

Bovine TB surveillance in Great Britain in 2014.

This report, provided by the APHA, summarises the key descriptive epidemiological parameters of bovine TB in cattle in Great Britain from January 1 to December 31, 2014. It summarises some of the temporal trends observed over a longer period and highlights some differences and similarities between Scotland, Wales and the three bovine TB risk areas of England. It updates the previous annual summaries for 2012 and 2013, also published inVeterinary Record(VR, June 14, 2014, vol 174, pp 600-604; March 28, 2015, vol 176, pp 326-330).

Responses to diagnostic tests for bovine tuberculosis in dairy and non-dairy cattle naturally exposed to Mycobacterium bovis in Great Britain.

Field surveillance of British cattle using the single intradermal comparative cervical tuberculin (SICCT) test shows a higher incidence rate of bovine tuberculosis (bTB) in dairy compared to beef herds, but a lower probability of post-mortem examination confirmed (PMC) Mycobacterium bovis infection in dairy herds. A cross-sectional study was conducted to compare animal level differences in bTB detection between dairy and non-dairy cattle in Great Britain. During the period from 2002 to 2005, 200 (41% dairy) reactors in the SICCT test (standard interpretation) were randomly selected, and 200 in-contact cattle (43% dairy) were purposively selected from bTB-infected herds. Interferon (IFN)-γ responses in blood to bovine and avian purified protein derivative (PPD), and early secretory antigen target 6 kDa and culture filtrate protein 10 (ESAT-6/CFP10), were measured. The post-mortem examination included gross pathological examination, mycobacterial culture and histopathology. The proportions of cattle positive to ESAT6/CFP10 were 26% (95% confidence interval, CI, 15-39%) in dairy reactors and 62% (95% CI 51-72%) in non-dairy reactors (P <0.001). PMC risk was 34% (95% CI 24-45%) in dairy reactors and 69% (95% CI 60-78%) in non-dairy reactors (P <0.001). The odds ratio for PMC risk in dairy reactors compared to non-dairy reactors, after controlling for bTB prevalence, herd size and SICCT test response, was 0.27 (95% CI 0.14-0.53; P <0.001). In surveillance data, adjusted animal level PMC risks were lower for dairy reactors than for beef reactors aged >2 years (P <0.001).

Farm characteristics and farmer perceptions associated with bovine tuberculosis incidents in areas of emerging endemic spread.

While much is known about the risk factors for bovine tuberculosis (bTB) in herds located in high incidence areas, the drivers of bTB spread in areas of emerging endemicity are less well established. Epidemiological analysis and intensive social research identified natural and social risk factors that may prevent or encourage the spread of disease. These were investigated using a case-control study design to survey farmers in areas defined as recently having become endemic for bTB (from or after 2006). Telephone surveys were conducted for 113 farms with a recent history of a bTB incident where their officially tuberculosis free status had been withdrawn (OTFW) (cases) and 224 controls with no history of a bTB incident, matched on location, production type and the rate of endemic bTB spread. Farmers were questioned about a range of farm management strategies, farm characteristics, herd health, wildlife and biosecurity measures with a focus on farmer attitudes and behaviours such as farmers' perception of endemicity and feelings of control, openness and social cohesion. Data generated in the telephone surveys was supplemented with existing herd-level data and analysed using conditional logistic regression. Overall, herd size (OR 1.07), purchasing an animal at a cattle market compared to purchasing outside of markets (OR 2.6), the number of contiguous bTB incidents (2.30) and the number of inconclusive reactors detected in the 2 years prior to the case incident (OR 1.95) significantly increased the odds of a bTB incident. Beef herds using a field parcel more than 3.2km away from the main farm and dairy herds reporting Johne's disease in the previous 12 months were 3.0 and 4.7 times more likely to have a recent history of a bTB incident, respectively. Beef herds reporting maize growing near, but not on, their farm were less likely to be case herds. Operating a closed farm in the two years prior to the case breakdown did not reduce the odds of a bTB incident. Farmers that had recently experienced a bTB incident were more likely to have implemented badger biosecurity in the previous year, but no more likely than control farms to have implemented cattle biosecurity. Case farmers felt significantly less likely to be influenced by government, vets or other farmers compared to those with no history of bTB. This suggests that alternative methods of engaging with farmers who have recently had a breakdown may need to be developed.

Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells.

BACKGROUND: Prostacyclin has proved to be a beneficial treatment for patients with severe pulmonary hypertension. We postulated that the response may reflect, at least in part, inhibition of pulmonary artery smooth muscle cell (PASMC) growth. METHODS AND RESULTS: Human PASMCs were derived from distal (<1-mm external diameter, n=8) and proximal (>8-mm external diameter, n=12) pulmonary arteries obtained at transplant surgery and pneumonectomy. The effects of the stable prostacyclin analogues on [methyl-(3)H]thymidine incorporation and cell proliferation were investigated by using immunohistochemically characterized cells. Distal cells proliferated faster than did proximal PASMCs and displayed a distinct sensitivity to cicaprost and iloprost. Both analogues inhibited thymidine uptake over 24 hours (20% to 60%, P<0.001; n=8) and abolished stimulation of DNA synthesis by platelet-derived growth factor-BB (10 ng/mL) in distal but not proximal cells. The inhibitory effect of cicaprost was mimicked by isoproterenol (10(-5) mol/L), forskolin (10(-5) mol/L), and dibutyryl cAMP (5x10(-4) mol/L) and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (5x10(-5) mol/L). Cicaprost (10(-10) to 10(-6) mol/L) inhibited the proliferation of PASMCs, which had been stimulated with either platelet-derived growth factor-BB or serum, and increased cAMP production. These effects were potentiated by 3-isobutyl-1-methylxanthine and attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (10(-5) to 10(-4) mol/L). CONCLUSIONS: ++Cicaprost and iloprost inhibit DNA synthesis and proliferation to a greater extent in distal compared with proximal human PASMCs, acting at least in part via a cAMP-dependent mechanism. The results are consistent with the hypothesis that prostacyclin analogues inhibit vascular remodeling in pulmonary hypertension and demonstrate heterogeneity among human PASMCs.

Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins.

BACKGROUND: Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-beta (TGF-beta) superfamily, underlie many cases of familial and sporadic primary pulmonary hypertension (PPH). We postulated that pulmonary artery smooth muscle cells (PASMCs) from patients with PPH might demonstrate abnormal growth responses to TGF-beta superfamily members. METHODS AND RESULTS: For studies of (3)H-thymidine incorporation or cell proliferation, PASMCs (passages 4 to 8) were derived from main pulmonary arteries. In control cells, 24-hour incubation with TGF-beta(1) (10 ng/mL) or bone morphogenetic protein (BMP)-2, -4, and -7 (100 ng/mL) inhibited basal and serum-stimulated (3)H-thymidine incorporation, and TGF-beta(1) and BMPs inhibited the proliferation of serum-stimulated PASMCs. In contrast, TGF-beta(1) stimulated (3)H-thymidine incorporation (200%; P<0.001) and cell proliferation in PASMCs from PPH but not from patients with secondary pulmonary hypertension. In addition, BMPs failed to suppress DNA synthesis and proliferation in PASMCs from PPH patients. Reverse transcription-polymerase chain reaction of PASMC mRNA detected transcripts for type I (TGF-betaRI, Alk-1, ActRI, and BMPRIB) and type II (TGF-betaRII, BMPR-II, ActRII, ActRIIB) receptors. Receptor binding and cross-linking studies with (125)I-TGF-beta(1) confirmed that the abnormal responses in PPH cells were not due to differences in TGF-beta receptor binding. Mutation analysis of PASMC DNA failed to detect mutations in TGF-betaRII and Alk-1 but confirmed the presence of a mutation in BMPR-II in 1 of 5 PPH isolates. CONCLUSIONS: We conclude that PASMCs from patients with PPH exhibit abnormal growth responses to TGF-beta(1) and BMPs and that altered integration of TGF-beta superfamily growth signals may contribute to the pathogenesis of PPH.