Showing papers by "Newcastle University published in 2003"

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

Abstract: Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

A DNA damage checkpoint response in telomere-initiated senescence

Abstract: Most human somatic cells can undergo only a limited number of population doublings in vitro. This exhaustion of proliferative potential, called senescence, can be triggered when telomeres--the ends of linear chromosomes-cannot fulfil their normal protective functions. Here we show that senescent human fibroblasts display molecular markers characteristic of cells bearing DNA double-strand breaks. These markers include nuclear foci of phosphorylated histone H2AX and their co-localization with DNA repair and DNA damage checkpoint factors such as 53BP1, MDC1 and NBS1. We also show that senescent cells contain activated forms of the DNA damage checkpoint kinases CHK1 and CHK2. Furthermore, by chromatin immunoprecipitation and whole-genome scanning approaches, we show that the chromosome ends of senescent cells directly contribute to the DNA damage response, and that uncapped telomeres directly associate with many, but not all, DNA damage response proteins. Finally, we show that inactivation of DNA damage checkpoint kinases in senescent cells can restore cell-cycle progression into S phase. Thus, we propose that telomere-initiated senescence reflects a DNA damage checkpoint response that is activated with a direct contribution from dysfunctional telomeres.

Essential Bacillus subtilis genes

Abstract: To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among ≈4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden–Meyerhof–Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Biological activity in the deep subsurface and the origin of heavy oil

Abstract: At temperatures up to about 80 °C, petroleum in subsurface reservoirs is often biologically degraded, over geological timescales, by microorganisms that destroy hydrocarbons and other components to produce altered, denser 'heavy oils'. This temperature threshold for hydrocarbon biodegradation might represent the maximum temperature boundary for life in the deep nutrient-depleted Earth. Most of the world's oil was biodegraded under anaerobic conditions, with methane, a valuable commodity, often being a major by-product, which suggests alternative approaches to recovering the world's vast heavy oil resource that otherwise will remain largely unproduced.

IAHS Decade on Predictions in Ungauged Basins (PUB), 2003–2012: Shaping an exciting future for the hydrological sciences

Abstract: Drainage basins in many parts of the world are ungauged or poorly gauged, and in some cases existing measurement networks are declining. The problem is compounded by the impacts of human-induced changes to the land surface and climate, occur-ring at the local, regional and global scales. Predictions of ungauged or poorly gauged basins under these conditions are highly uncertain. The IAHS Decade on Predictions in Ungauged Basins, or PUB, is a new initiative launched by the International Association of Hydrological Sciences (IAHS), aimed at formulating and implementing appropriate science programmes to engage and energize the scientific community, in a coordinated manner, towards achieving major advances in the capacity to make predictions in ungauged basins. The PUB scientific programme focuses on the estimation of predictive uncertainty, and its subsequent reduction, as its central theme. A general hydrological prediction system contains three components: (a) a model that describes the key processes of interest, (b) a set of parameters that represent those landscape properties that govern critical processes, and (c) appropriate meteorological inputs (where needed) that drive the basin response. Each of these three components of the prediction system, is either not known at all, or at best known imperfectly, due to the inherent multi-scale space-time heterogeneity of the hydrological system, especially in ungauged basins. PUB will therefore include a set of targeted scientific programmes that attempt to make inferences about climatic inputs, parameters and model structures from available but inadequate data and process knowledge, at the basin of interest and/or from other similar basins, with robust measures of the uncertainties involved, and their impacts on predictive uncertainty. Through generation of improved understanding, and methods for the efficient quantification of the underlying multi-scale heterogeneity of the basin and its response, PUB will inexorably lead to new, innovative methods for hydrological predictions in ungauged basins in different parts of the world, combined with significant reductions of predictive uncertainty. In this way, PUB will demonstrate the value of data, as well as provide the information needed to make predictions in ungauged basins, and assist in capacity building in the use of new technologies. This paper presents a summary of the science and implementation plan of PUB, with a call to the hydrological community to participate actively in the realization of these goals.

Collaborative Planning in Perspective

Abstract: This article presents a personal review by the author of Collaborative Planning: Shaping Places in Fragmented Societies, published in 1997. It explains how the book came to be written and makes some comments on the various criticisms it has attracted. The first section introduces key experiences that fed into the book followed by a brief summary of the key ideas that underpin its arguments. In reviewing the critiques, the article focuses in particular on the treatment of `context', the emphasis on `process', the use of `social theory', and `power', and the development of `institutionalist' analysis. This is followed by a comment on the normative biases in the work. In conclusion, the author makes a plea for continuing attention to the complexity and diversity of urban governance contexts and the importance for practical action of grasping the particularities of situated governance dynamics.

A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome

Abstract: Seckel syndrome (OMIM 210600) is an autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly and mental retardation. Clinically, Seckel syndrome shares features in common with disorders involving impaired DNA-damage responses, such as Nijmegen breakage syndrome (OMIM 251260) and LIG4 syndrome (OMIM 606593). We previously mapped a locus associated with Seckel syndrome to chromosome 3q22.1–q24 in two consanguineous Pakistani families1. Further marker analysis in the families, including a recently born unaffected child with a recombination in the critical region, narrowed the region to an interval of 5 Mbp between markers D3S1316 and D3S1557 (145.29 Mbp and 150.37 Mbp). The gene encoding ataxia–telangiectasia and Rad3–related protein (ATR) maps to this region2,3. A fibroblast cell line derived from an affected individual displays a defective DNA damage response caused by impaired ATR function. We identified a synonymous mutation in affected individuals that alters ATR splicing. The mutation confers a phenotype including marked microcephaly (head circumference 12 s.d. below the mean) and dwarfism (5 s.d. below the mean). Our analysis shows that UV-induced ATR activation can occur in non-replicating cells following processing by nucleotide excision repair.

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

Abstract: Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with β-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and β-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and β-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.

Precise dating of Dansgaard–Oeschger climate oscillations in western Europe from stalagmite data

Abstract: The signature of Dansgaard-Oeschger events--millennial-scale abrupt climate oscillations during the last glacial period--is well established in ice cores and marine records. But the effects of such events in continental settings are not as clear, and their absolute chronology is uncertain beyond the limit of (14)C dating and annual layer counting for marine records and ice cores, respectively. Here we present carbon and oxygen isotope records from a stalagmite collected in southwest France which have been precisely dated using 234U/230Th ratios. We find rapid climate oscillations coincident with the established Dansgaard-Oeschger events between 83,000 and 32,000 years ago in both isotope records. The oxygen isotope signature is similar to a record from Soreq cave, Israel, and deep-sea records, indicating the large spatial scale of the climate oscillations. The signal in the carbon isotopes gives evidence of drastic and rapid vegetation changes in western Europe, an important site in human cultural evolution. We also find evidence for a long phase of extremely cold climate in southwest France between 61.2 +/- 0.6 and 67.4 +/- 0.9 kyr ago.

Research designs for studies evaluating the effectiveness of change and improvement strategies

Abstract: The methods of evaluating change and improvement strategies are not well described. The design and conduct of a range of experimental and non-experimental quantitative designs are considered. Such study designs should usually be used in a context where they build on appropriate theoretical, qualitative and modelling work, particularly in the development of appropriate interventions. A range of experimental designs are discussed including single and multiple arm randomised controlled trials and the use of more complex factorial and block designs. The impact of randomisation at both group and individual levels and three non-experimental designs (uncontrolled before and after, controlled before and after, and time series analysis) are also considered. The design chosen will reflect both the needs (and resources) in any particular circumstances and also the purpose of the evaluation. The general principle underlying the choice of evaluative design is, however, simple-those conducting such evaluations should use the most robust design possible to minimise bias and maximise generalisability.

α-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma

Abstract: Parkinson's disease (PD) and other related disorders are characterized by the accumulation of fibrillar aggregates of alpha-synuclein protein (alpha-syn) inside brain cells. It is likely that the formation of alpha-syn aggregates plays a seminal role in the pathogenesis of at least some of these diseases, because two different mutations in the gene encoding alpha-syn have been found in inherited forms of PD. alpha-Syn is mainly expressed by neuronal cells and is generally considered to exist as a cytoplasmic protein. Here, we report the unexpected identification of alpha-syn in conditioned culture media from untransfected and alpha-syn-transfected human neuroblastoma cells, as well as in human cerebrospinal fluid and blood plasma. The method used was immunocapture by using anti-alpha-syn antibodies coupled to magnetic beads, followed by detection on Western blots. In all cases, alpha-syn was identified as a single 15 kDa band, which co-migrated with a recombinant form of the protein and reacted with five different antibodies to alpha-syn. Our findings suggest that cells normally secrete alpha-syn into their surrounding media, both in vitro and in vivo. The detection of extracellular alpha-syn and/or its modified forms in body fluids, particularly in human plasma, offers new opportunities for the development of diagnostic tests for PD and related diseases.

Neurocognitive impairment in drug-free patients with major depressive disorder

Abstract: Background Although neurocognitive impairment has been widely reported in major depressive disorder (MDD), confounding factors, such as the effects of psychotropic medication, have rarely been controlled for. Aims To examine neurocognitive function in medication-free patients with MDD and healthy controls. Method Forty-four patients meeting DSM—IV criteria for MDD, all psychotropic-medication-free for at least 6 weeks, and 44 demographically matched, healthy comparison subjects completed a comprehensive neurocognitive battery. Results Patients with depression were impaired significantly in a range of cognitive domains, including attention and executive function and visuospatial learning and memory, compared with controls. Motor and psychomotor functions were intact. Severity of depression correlated with learning and memory performance, but not executive function. Conclusions Pronounced neurocognitive impairment was found in this sample of young adult out-patients with MDD. This is not attributable to the confounding effects of psychotropic medication and could therefore provide an objective marker of brain dysfunction in depression.

Mitochondrial DNA mutations in human colonic crypt stem cells

Abstract: The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.

Structure and energetics of the vacancy in graphite

Abstract: We determine properties of the vacancy in graphite from first principles calculations. The ground-state structure is associated with a formation energy of 7.4 eV and arises through a combination of symmetric relaxation and symmetry-breaking Jahn-Teller distortion to one of three degenerate, symmetry-related structures. The distortion results in a weak reconstructed bond and small out-of-plane atomic displacements. Dynamic switching between degenerate structures is activated by a barrier of 0.1 eV and we interpret scanning tunneling microscopy observations on the basis of thermal averaging between structures. The calculated migration energy of 1.7 eV is lower than that widely accepted from experiment, and we propose that the discrepancy is explained by a revised picture of trapping during vacancy transport, dependent on concentration. We discuss the significance of these findings in understanding defect behavior in irradiated graphite and related graphitic materials, in particular single-walled nanotubes.

Learning and teaching in the clinical environment

Abstract: Clinical teaching—that is, teaching and learning focused on, and usually directly involving, patients and their problems—lies at the heart of medical education. At undergraduate level, medical schools strive to give students as much clinical exposure as possible; they are also increasingly giving students contact with patients earlier in the course. For postgraduates, “on the job” clinical teaching is the core of their professional development. How can a clinical teacher optimise the teaching and learning opportunities that arise in daily practice? ![][1] Clinical teaching in general practice Learning in the clinical environment has many strengths. It is focused on real problems in the context of professional practice. Learners are motivated by its relevance and through active participation. Professional thinking, behaviour, and attitudes are “modelled” by teachers. It is the only setting in which the skills of history taking, physical examination, clinical reasoning, decision making, empathy, and professionalism can be taught and learnt as an integrated whole. Despite these potential strengths, clinical teaching has been much criticised for its variability, lack of intellectual challenge, and haphazard nature. In other words, clinical teaching is an educationally sound approach, all too frequently undermined by problems of implementation. #### Common problems with clinical teaching #### Challenges of clinical teaching [1]: /embed/graphic-1.gif

Nihilism in the 1990s: The True Mortality of Congenital Diaphragmatic Hernia

Abstract: Objective Reported survival in congenital diaphragmatic hernia (CDH) fails to allow for case selection bias. This study reports the incidence of CDH in a geographically defined population over 11 years and assesses the effect of new therapies (high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, inhaled nitric oxide, and delayed surgery) on survival when case selection is avoided. Methods A retrospective review of cases from a regional case registry, the Northern Region Congenital Anomaly Survey, was conducted. Results A total of 185 cases were identified. Mortality was 62% and did not vary significantly during the study period. Mortality was unaffected by the introduction of new therapies. There was a significant inverse correlation between the rate of elective termination and survival of live borns. The presence of an additional anomaly increased mortality to 79%. Conclusions The mortality of CDH when complete case ascertainment is achieved is unaffected by new therapies. The survival rate is principally determined by the rate of antenatal termination and the incidence of associated anomalies. Reports of improved survival of CDH should be interpreted with caution, as variations in outcome are more likely to be explained by case selection artifact.

The epidemiology of Leber hereditary optic neuropathy in the North East of England.

Abstract: We performed the first population-based clinical and molecular genetic study of Leber hereditary optic neuropathy (LHON) in a population of 2,173,800 individuals in the North East of England. We identified 16 genealogically unrelated families who harbor one of the three primary mitochondrial DNA (mtDNA) mutations that cause LHON. Two of these families were found to be linked genetically to a common maternal founder. A de novo mtDNA mutation (G3460A) was identified in one family. The minimum point prevalence of visual failure due to LHON within this population was 3.22 per 100,000 (95% CI 2.47–3.97 per 100,000), and the minimum point prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.38–13.27 per 100,000). These results indicate that LHON is not rare but has a population prevalence similar to autosomally inherited neurological disorders. The majority of individuals harbored only mutant mtDNA (homoplasmy), but heteroplasmy was detected in ∼12% of individuals. Overall, however, ∼33% of families with LHON had at least one heteroplasmic individual. The high incidence of heteroplasmy in pedigrees with LHON raises the possibility that a closely related maternal relative of an index case may not harbor the mtDNA mutation, highlighting the importance of molecular genetic testing for each maternal family member seeking advice about their risks of visual failure.

Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome

Abstract: Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits complement activation by regulating C3b deposition on targets. Factor H mutations occur in 10–20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP mutations could predispose to HUS, and we sequenced MCP coding exons in affected individuals from 30 families. MCP mutations were detected in affected individuals of three families: a deletion of two amino acids (D237/S238) in family 1 (heterozygous) and a substitution, S206P, in families 2 (heterozygous) and 3 (homozygous). We evaluated protein expression and function in peripheral blood mononuclear cells from these individuals. An individual with the D237/S238 deletion had reduced MCP levels and ≈50% C3b binding compared with normal controls. Individuals with the S206P change expressed normal quantities of protein, but demonstrated ≈50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. MCP expression and function was evaluated in transfectants reproducing these mutations. The deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies.

The importance of patient preferences in treatment decisions - Challenges for doctors

Abstract: The expectation that patients will become increasingly involved in making treatment decisions poses new challenges for doctors. This article discusses what these are and how doctors might face them Health professionals are increasingly encouraged to involve patients in treatment decisions, recognising patients as experts with a unique knowledge of their own health and their preferences for treatments, health states, and outcomes.1 2 Increased patient involvement, a result of various sociopolitical changes,w1 is an important part of quality improvement since it has been associated with improved health outcomes3 w1-w9 and enables doctors to be more accountable to the public. However, this poses challenges for doctors. We discuss these in relation to the competences for shared decision making that have been proposed.4 w10 We made literature searches using Medline, Web of Science, PsychINFO, CINAHL, the Cochrane Library, and HMIC (key words “consumer participation,” “patient participation,” “decision making,” “patient preferences,” “shared decision making,” “patient involvement in decision making”). We also searched references of articles, indexes of key journals, important texts about patient involvement, and key reviews. We conducted informal interviews with doctors from a range of specialties (general practice, orthopaedics, stroke medicine, accident and emergency, and vascular surgery) and recorded their opinions to provide a focus to this discussion (quotes in italics). For patients' views about treatment options to be valued and necessary, there must be a partnership between doctor and patient, but establishing one requires both time and certain skills. “There's not enough time”— The pressure of time is a perpetual challenge; doctors are particularly concerned about the implications of informing patients without allowing extra time for this.5 However, involving patients more in treatment decisions may have no significant effect on consultation length3: adequate discussion at an early stage may allow more succinct discussion later …

The Genetic Heritage of the Earliest Settlers Persists Both in Indian Tribal and Caste Populations

Abstract: Two tribal groups from southern India—the Chenchus and Koyas—were analyzed for variation in mitochondrial DNA (mtDNA), the Y chromosome, and one autosomal locus and were compared with six caste groups from different parts of India, as well as with western and central Asians. In mtDNA phylogenetic analyses, the Chenchus and Koyas coalesce at Indian-specific branches of haplogroups M and N that cover populations of different social rank from all over the subcontinent. Coalescence times suggest early late Pleistocene settlement of southern Asia and suggest that there has not been total replacement of these settlers by later migrations. H, L, and R2 are the major Indian Y-chromosomal haplogroups that occur both in castes and in tribal populations and are rarely found outside the subcontinent. Haplogroup R1a, previously associated with the putative Indo-Aryan invasion, was found at its highest frequency in Punjab but also at a relatively high frequency (26%) in the Chenchu tribe. This finding, together with the higher R1a-associated short tandem repeat diversity in India and Iran compared with Europe and central Asia, suggests that southern and western Asia might be the source of this haplogroup. Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations. Taken together, these results show that Indian tribal and caste populations derive largely from the same genetic heritage of Pleistocene southern and western Asians and have received limited gene flow from external regions since the Holocene. The phylogeography of the primal mtDNA and Y-chromosome founders suggests that these southern Asian Pleistocene coastal settlers from Africa would have provided the inocula for the subsequent differentiation of the distinctive eastern and western Eurasian gene pools.

Phonological development: A normative study of British English-speaking children

Abstract: This paper reports a normative study on the phonological development of British English-speaking children. Speech samples of 684 children, aged between 3;0 and 6;11 years, randomly selected from nurseries and schools in eight different areas throughout the UK, were collected and analysed to obtain normative data. This paper reports on two aspects of speech development: the age of acquisition of sounds (phonetic acquisition) and the age that error patterns were suppressed (phonemic acquisition). It discusses the effects of age, gender and socio-economic status on speech sound development. The study found that older children had more accurate production and fewer error patterns in their speech. It found no gender differences in the younger age groups. However, in the oldest age group, it found the phonological accuracy measures of girls' better than boys. It found no significant effects of socio-economic status on any of the phonological accuracy measures.

A regional frequency analysis of United Kingdom extreme rainfall from 1961 to 2000

Abstract: Multi-day rainfall events are an important cause of recent severe flooding in the UK, and any change in the magnitude of such events may have severe impacts upon urban structures such as dams, urban drainage systems and flood defences and cause failures to occur. Regional pooling of 1-, 2-, 5- and 10-day annual maxima for 1961 to 2000 from 204 sites across the UK is used in a standard regional frequency analysis to produce generalized extreme value growth curves for long return-period rainfall events for each of nine defined climatological regions. Temporal changes in 1-, 2-, 5- and 10-day annual maxima are examined with L-moments using both a 10 year moving window and the fixed decades of 1961–70, 1971–80, 1981–90 and 1991–2000. A bootstrap technique is then used to assess uncertainty in the fitted decadal growth curves and to identify significant trends in both distribution parameters and quantile estimates. There has been a two-part change in extreme rainfall event occurrence across the UK from 1961 to 2000. Little change is observed at 1 and 2 days duration, but significant decadal-level changes are seen in 5- and 10-day events in many regions. In the south of the UK, growth curves have flattened and 5- and 10-day annual maxima have decreased during the 1990s. However, in the north, the 10-day growth curve has steepened and annual maxima have risen during the 1990s. This is particularly evident in Scotland. The 50 year event in Scotland during 1961–90 has become an 8-year, 11-year and 25-year event in the East, South and North Scotland pooling regions respectively during the 1990s. In northern England the average recurrence interval has also halved. This may have severe implications for design and planning practices in flood control. Copyright © 2003 Royal Meteorological Society

Revealed comparative advantage and competitiveness in Hungarian agri-food sectors

Abstract: We examine the competitiveness of Hungarian agriculture and food processing, in relation to that of the EU, based on four indices of revealed comparative advantage, using highly disaggregate data for the period 1992 to 1998. Consistency tests suggest that the indices are less satisfactory as cardinal measures, but are useful in identifying the demarcation between comparative advantage and comparative disadvantage. Hungary is shown to have a comparative advantage in a range of agri-food products, including animals and meat. This complements the findings of those studies that have used price and cost based approaches in identifying competitiveness in cereals and crops. Results indicate that the RCA indices, when interpreted as a binary measure, have remained surprisingly stable during the period of transition, although there is evidence of a weakening in the level of comparative advantage as revealed in the Balassa index.

Outcome in adults with juvenile idiopathic arthritis: a quality of life study.

Abstract: Objective To evaluate quality of life (QOL) in adults with juvenile idiopathic arthritis (JIA), using validated measures of functional disability and generic health status, and to quantify their educational attainment and employment status. Methods The adult rheumatology departmental database was used to identify patients. Functional disability and generic health status/QOL were assessed by the Health Assessment Questionnaire (HAQ) and the Short Form 36-item health profile (SF-36), respectively. Educational achievement and employment status were assessed by questionnaire. Results Complete data were available for 82 of the 101 patients identified. The median age of patients was 30 years, and the median disease duration was 21 years. No deaths were recorded. All subtypes of JIA were represented. Thirty-nine percent of patients had active disease (based on the physician global assessment scale score). The median HAQ score was 1.125 (range 0–3). SF-36 scores for bodily pain, general health, physical functioning, vitality, emotion, and social isolation were significantly worse in patients compared with controls, and this trend increased with increasing age of the patients and disease duration. The SF-36 mental summation scores of patients were low compared with those of controls, for all subtypes of JIA, and this finding was independent of the degree of functional disability (by HAQ and SF-36 physical summation scores). The educational attainment of patients was comparable to that of local controls, but unemployment rates for patients were 3-fold higher than those for controls. Conclusion This is the largest study in which the SF-36 was used to assess generic health status and QOL in adults with JIA. Many patients had active disease in adulthood, and although the physical outcome of adults with JIA is relatively good, a profound effect on generic health status and QOL was demonstrated for all types of JIA. Furthermore, despite excellent educational attainment, there was a high rate of unemployment among patients.