bluuebunny/crossref_metadata_2025 huggingface dataset:
Why are estimates of the terrestrial carbon balance so different?
Authors: HOUGHTON R. A.
Published: December 2004

The carbon balance of the world's terrestrial ecosystems is uncertain. Both top‐down (atmospheric) and bottom‐up (forest inventory and land‐use change) approaches have been used to calculate the sign and magnitude of a net terrestrial flux. Different methods often include different processes, however, and comparisons can be misleading. Differences are not necessarily the result of uncertainties or errors, but often result from incomplete accounting inherent in some of the methods. Recent estimates are reviewed here. Overall, a northern mid‐latitude carbon sink of approximately 2 Pg C yr−1 appears robust, although the mechanisms responsible are uncertain. Several lines of evidence point to environmentally enhanced rates of carbon accumulation. Other lines suggest that recovery from past disturbances is largely responsible for the sink. The tropics appear to be a small net source of carbon or nearly neutral, and the same uncertainties of mechanism exist. In addition, studies in the tropics do not permit an unequivocal choice between two alternatives: large emissions of carbon from deforestation offset by large sinks in undisturbed forests, or moderate emissions from land‐use change with essentially no change in the carbon balance in undisturbed forests. Resolution of these uncertainties is most likely to result from spatially detailed historical reconstructions of land‐use change and disturbance in selected northern mid‐latitude regions where such data are available, and from systematic monitoring of changes in the area of tropical forests with satellite data of high spatial resolution collected over the last decades and into the future.
The annual carbon budget of a French pine forest (Pinus pinaster) following harvest
Authors: KOWALSKI S. , SARTORE M. , BURLETT R. , BERBIGIER P. , LOUSTAU D.
Published: December 2004

Eddy covariance measurements of net ecosystem exchange (NEE) of carbon dioxide and sensible and latent heat have operated since clear felling of a 50‐year old maritime pine stand in Les Landes, in Southwestern France. Turbulent fluxes from the closed‐path system are computed via different methodologies, including those recommended from EUROFLUX (Adv. Ecol. Res. 30 (2000) 113; Agric. Forest Meteorol. 107 (2001a, b) 43 and 71), and sensitivity analysis demonstrates the merit of post‐processing for accurate flux calculation. Footprint modeling, energy balance closure, and empirical modeling corroborate the eddy flux measurements, indicating best reliability in the daytime.

The ecosystem, a net source of atmospheric CO2, is capable of fixing carbon during fair weather during any season due to the abundance of re‐growing species (mostly grass), formerly from the understorey. Annual carbon loss of 200–340 g m−2 depends on the period chosen, with inter‐annual variability evident during the 18‐month measurement period and apparently related to available light. Empirical models, with weekly photosynthetic parameters corresponding to seasonal vegetation and respiration depending on soil temperature, fit the data well and allow partitioning of annual NEE into GPP and TER components. Comparison with a similar nearby mature forest (Agric. Forest Meteorol. 108 (2001) 183) indicates that clear‐cutting reduces GPP by two thirds but TER by only one third, transforming a strong forest sink into a source of CO2. Likewise, the loss of 50% of evapotranspiration (by the trees) leads to increased temperatures and thus reduced net radiation (by one third), and a 50% increase in sensible heat loss by the clear cut.
Climate and CO2 controls on global vegetation distribution at the last glacial maximum: analysis based on palaeovegetation data, biome modelling and palaeoclimate simulations
Authors: HARRISON SANDY P. , PRENTICE COLIN I.
Published: December 2004

The global vegetation response to climate and atmospheric CO2 changes between the last glacial maximum and recent times is examined using an equilibrium vegetation model (BIOME4), driven by output from 17 climate simulations from the Palaeoclimate Modelling Intercomparison Project. Features common to all of the simulations include expansion of treeless vegetation in high northern latitudes; southward displacement and fragmentation of boreal and temperate forests; and expansion of drought‐tolerant biomes in the tropics. These features are broadly consistent with pollen‐based reconstructions of vegetation distribution at the last glacial maximum. Glacial vegetation in high latitudes reflects cold and dry conditions due to the low CO2 concentration and the presence of large continental ice sheets. The extent of drought‐tolerant vegetation in tropical and subtropical latitudes reflects a generally drier low‐latitude climate. Comparisons of the observations with BIOME4 simulations, with and without consideration of the direct physiological effect of CO2 concentration on C3 photosynthesis, suggest an important additional role of low CO2 concentration in restricting the extent of forests, especially in the tropics. Global forest cover was overestimated by all models when climate change alone was used to drive BIOME4, and estimated more accurately when physiological effects of CO2 concentration were included. This result suggests that both CO2 effects and climate effects were important in determining glacial‐interglacial changes in vegetation. More realistic simulations of glacial vegetation and climate will need to take into account the feedback effects of these structural and physiological changes on the climate.
Uncertainties in interpretation of isotope signals for estimation of fine root longevity: theoretical considerations
Authors: LUO YIQI
Published: December 2004

This paper examines uncertainties in the interpretation of isotope signals when estimating fine root longevity, particularly in forests. The isotope signals are depleted δ13C values from elevated CO2 experiments and enriched Δ14C values from bomb 14C in atmospheric CO2. For the CO2 experiments, I explored the effects of six root mortality patterns (on–off, proportional, constant, normal, left skew, and right skew distributions), five levels of nonstructural carbohydrate (NSC) reserves, and increased root growth on root δ13C values after CO2 fumigation. My analysis indicates that fitting a linear equation to δ13C data provides unbiased estimates of longevity only if root mortality follows an on–off model, without dilution of isotope signals by pretreatment NSC reserves, and under a steady state between growth and death. If root mortality follows the other patterns, the linear extrapolation considerably overestimates root longevity. In contrast, fitting an exponential equation to δ13C data underestimates longevity with all the mortality patterns except the proportional one. With either linear or exponential extrapolation, dilution of isotope signals by pretreatment NSC reserves could result in overestimation of root longevity by several‐fold. Root longevity is underestimated if elevated CO2 stimulates fine root growth. For the bomb 14C approach, I examined the effects of four mortality patterns (on–off, proportional, constant, and normal distribution) on root Δ14C values. For a given Δ14C value, the proportional pattern usually provides a shorter estimate of root longevity than the other patterns. Overall, we have to improve our understanding of root growth and mortality patterns and to measure NSC reserves in order to reduce uncertainties in estimated fine root longevity from isotope data.
Soil arthropods as indicators of water stress in Antarctic terrestrial habitats?
Authors: Convey Peter , Block William , Peat Helen J.
Published: December 2004

Abiotic features of Antarctic terrestrial habitats, particularly low temperatures and limited availability of liquid water, strongly influence the ecophysiology and life histories of resident biota. However, while temperature regimes of a range of land microhabitats are reasonably well characterized, much less is known of patterns of soil water stress, as current technology does not allow measurement at the required scale. An alternative approach is to use the water status of individual organisms as a proxy for habitat water status and to sample over several years from a population to identify seasonal or long‐term patterns. This broad generalization for terrestrial invertebrates was tested on arthropods in the maritime Antarctic. We present analyses of a long‐term data set of body water content generated by monthly sampling for 8–11 years of seven species of soil arthropods (four species of Acari, two Collembola and one Diptera) on maritime Antarctic Signy Island, South Orkney Islands. In all species, there was considerable within‐ and between‐sample variability. Despite this, clear seasonal patterns were present in five species, particularly the two collembolans and a prostigmatid mite. Analyses of monthly water content trends across the entire study period identified several statistically significant trends of either increase or decrease in body water content, which we interpret in the context of regional climate change. The data further support the separation of the species into two groups as follows: firstly, the soft‐bodied Collembola and Prostigmata, with limited cuticular sclerotization, which are sensitive to changes in soil moisture and are potentially rapid sensors of microhabitat water status, secondly, more heavily sclerotized forms such as Cryptostigmata (=Oribatida) and Mesostigmata mites, which are much less sensitive and responsive to short‐term fluctuations in soil water availability. The significance of these findings is discussed and it is concluded that annual cycles of water content were driven by temperature, mediated via radiation and precipitation, and constituted reliable indicators of habitat moisture regimes. However, detailed ecophysiological studies are required on particular species before such information can be used to predict over long timescales.
Soil and rhizosphere microorganisms have the same Q10 for respiration in a model system
Authors: Bååth Erland , Wallander Håkan
Published: December 2004

We compared the Q10 relationship for root‐derived respiration (including respiration due to the root, external mycorrhizal mycelium and rhizosphere microorganisms) with that of mainly external ectomycorrhizal mycelium and that of bulk soil microorganisms without any roots present. This was studied in a microcosm consisting of an ectomycorrhizal Pinus muricata seedling growing in a sandy soil, and where roots were allow to colonize one soil compartment, mycorrhizal mycelium another compartment, and the last compartment consisted of root‐ and mycorrhiza‐free soil. The respiration rate in the bulk soil compartment was 30 times lower than in the root compartment, while that in the mycorrhizal compartment was six times lower. There were no differences in Q10 (for 5–15°C) between the different compartments, indicating that there were no differences in the temperature relationship between root‐associated and non‐root‐associated organisms. Thus, there are no indications that different Q10 values should be used for different soil organism, bulk soil or rhizosphere‐associated microorganisms when modelling the effects of global climate change.
Soil nitrogen transformations under Populus tremuloides, Betula papyrifera and Acer saccharum following 3 years exposure to elevated CO2 and O3
Authors: Holmes William E. , Zak Donald R. , Pregitzer Kurt S. , King John S.
Published: December 2004

Increases in atmospheric CO2 and tropospheric O3 may affect forest N cycling by altering plant litter production and the availability of substrates for microbial metabolism. Three years following the establishment of our free‐air CO2–O3 enrichment experiment, plant growth has been stimulated by elevated CO2 resulting in greater substrate input to soil; elevated O3 has counteracted this effect. We hypothesized that rates of soil N cycling would be enhanced by greater plant productivity under elevated CO2, and that CO2 effects would be dampened by O3. We found that elevated CO2 did not alter gross N transformation rates. Elevated O3 significantly reduced gross N mineralization and microbial biomass N, and effects were consistent among species. We also observed significant interactions between CO2 and O3: (i) gross N mineralization was greater under elevated CO2 (1.0 mg N kg−1 day−1) than in the presence of both CO2 and O3 (0.5 mg N kg−1 day−1) and (ii) gross NH4+ immobilization was also greater under elevated CO2 (0.8 mg N kg−1 day−1) than under CO2 plus O3 (0.4 mg N kg−1 day−1). We used a laboratory 15N tracer method to quantify transfer of inorganic N to organic pools. Elevated CO2 led to greater recovery of NH4+‐15N in microbial biomass and corresponding lower recovery in the extractable NO3− pool. Elevated CO2 resulted in a substantial increase in NO3−‐15N recovery in soil organic matter. We observed no O3 main effect and no CO2 by O3 interaction effect on 15N recovery in any soil pool. All of the above responses were most pronounced beneath Betula papyrifera and Populus tremuloides, which have grown more rapidly than Acer saccharum. Although elevated CO2 has increased plant productivity, the resulting increase in plant litter production has yet to overcome the influence of the pre‐existing pool of soil organic matter on soil microbial activity and rates of N cycling. Ozone reduces plant litter inputs and also appears to affect the composition of plant litter in a way that reduces microbial biomass and activity.
Analysis of the haemophilia A mutation in sporadic patients registered at the Royal London Hospital and their families
Authors: TAGLIAVACCA L. , ROWLEY G. , GREEN P. M. , HAYDEN S. , WOOSEY C. , COLVIN B. , GIANNELLI F.
Published: December 2004

Summary. The families of sporadic haemophilia A patients registered at the Royal London Hospital and with living grandparents were selected for study. Twelve of the 13 known families agreed to collaborate. Of these 11 had a patient with severe and one a patient with mild haemophilia. Five of the severely affected patients had inversions of type 1, that is involving int22h‐1 and int22h‐3, and two had inversions of type 2, that is involving int22h‐1 and int22h‐2. The remaining four patients with severe disease had single base substitutions causing two different non‐sense (Gln592→Stop; Trp2313→Stop) and two different mis‐sense mutations (His267→Pro; Arg2209→Gln). A single base substitution causing a mis‐sense mutation (His1961→Asp) was also found in the patient with mild haemophilia. The Arg2209→Gln mutation has previously been found in other patients while the other single base substitutions have not hitherto been observed. Three mutations (all single base substitutions) appear to have arisen in the germline of the patient’s mother, while seven mutations originated in the gonad of one of the patient’s grandparents. In two of the latter families (both with inversion type 2) the origin of muta‐tions could be clearly assigned to the grandpaternal gonad. Data on parental age at the onset of mutation were ob‐tained in the families investigated. In addition, further evidence was obtained that the int‐22h‐related inversions arise by intrachromatid, intrachromosome homologous re‐combination as the int22h repeat sequences of a patient were found to be identical to those of the maternal grand‐father whose germline represents the origin of mutation.
The introduction of high‐purity products in Canada
Authors: Growe G. H. , Rivet C.
Published: December 2004

Summary. In October 1993, the Canadian Blood Agency, the agent for the provinces/territories in Canada, agreed to the introduction of high‐purity coagulation products, either recombinant or highly purified factor concentrates, for the management of coagulation deficiencies. This represented a cost increase of approximately $30 million (40%) for the national coagulation product inventory.

Representatives of the relevant recipients of the products, some of the treaters, the distributor and the funders met on a regular basis in order to monitor the impact of these new products. The Association of Hemophilia Clinic Directors of Canada also agreed to include some specific outcome studies over a longer period of time to include evaluation of inhibitor formation, prophylaxis regimens, immune status and the incidence of thrombosis. The ‘Hemophilia and Von Willebrand’s Disease’ clinical practice guidelines were also developed under their auspices. A usage monitoring system has been implemented and has been continuously managed by the Canadian Blood Agency. This resulted in trends of practice and rationales for unexpected use being identified early for planning and funding purposes.

The Working Group set up under the auspices of the Canadian Blood Agency was an effective vehicle to evaluate the conversion and the impact of these new products in the country and can serve as a model for future endeavours.
Clinical outcome of HIV‐infected haemophiliac patients in Hong Kong
Authors: LEE C. K. , HUI C. H. , LIE A. K. W. , LIANG R. , CHAN T. K.
Published: December 2004

Summary. About half of the haemophiliacs in Hong Kong have been infected by human immunodeficiency virus (HIV). This study aimed to determine their clinical course of progression. Forty‐seven adult patients with congenital coagulation factor deficiency being followed up regularly from January 1992 onward in the Department of Medicine of Queen Mary Hospital, Hong Kong, were included in this study. Twenty were positive for HIV antibody and the remaining 27 were negative. Three other HIV‐positive patients who died before 1992 were excluded. From January 1992 to June 1996, the 47 patients included in the study were followed up in the clinic every 3–6 months with regular CD4, CD8 lymphocyte counts and β2 microglobulin levels. At the initiation of the study in January 1992, the HIV‐infected patients had already a lower mean CD4 count (360.4 μL−1 versus 658.8 μL−1, P<0.01), a reversed CD4/CD8 ratio (0.53) and a higher mean serum β2 microglobulin level (1.853 μg mL−1 versus 1.315 μg mL−1, P>0.05). On regular follow‐up, HIV‐positive patients had a more significant progressive fall in their mean CD4 count (301.6 μL−1 versus 360.4 μL−1, P<0.01) and rise in their mean serum β2 microglobulin level (2.60 μg mL−1, versus 1.853 μg mL−1, P<0.05). The CD4 and CD8 counts of HIV‐positive patients were falling at a rate of 1.44 μL−1 month−1 and 4.03 μL−1 month−1 respectively. During the follow‐up period, two of the 20 HIV‐positive patients developed clinical acquired immunodeficiency syndrome (AIDS) at 15 and 36 months from the initiation of the study. Both patients had typical features of AIDS with a low CD4 count, reversed CD4/CD8 ratio and elevated β2 microglobulin level. The former patient eventually died of fungal brain abscess. The remaining 18 HIV‐positive patients so far remained clinically asymptomatic. Eleven patients were put on antiretroviral drug therapy when their CD4 counts fell below 200 μL−1. Only two of the 20 HIV‐infected patients developed AIDS during the observation period of 4 years; this figure of 10% is relatively slow. Two of our patients died of AIDS before the study was initiated in 1992. Even if they were included, still only 17.4% had progressed. The figure is in the lowest rate of progression expected from Western experience. Although our study population is small, it remains unclear why our HIV‐infected Chinese haemophiliacs have a slow rate of progression to AIDS.
The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients
Authors: SUWANNURAKS M. , CHUANSUMRIT A. , SRIUDOMPORN N.
Published: December 2004

Controlling haemorrhage by using a celluloid splint as an adjunctive therapy in patients with bleeding disorders is very beneficial in dental extraction. However, this technique still requires specific replacement therapy. The use of fibrin glue as a local treatment in dental extraction, without the use of any blood product replacement, recommended to improve efficiency in controlling haemorrhage during dental extraction. This method was modified using a combination of celluloid splint and fibrin glue for use in dental extraction in bleeding disorder patients. It was found that this method was effective in controlling bleeding, was cost effective, did not require replacement therapy and posed no risk of viral transmission.
Anaphylaxis following the use of a plasma‐derived immunopurified Monoclate‐P®, and the recombinant Recombinate® and Kogenate® factor VIII: a therapeutic challenge
Authors: PERNOD G. , ARMARI C. , BARRO C. , PLANTAZ D. , CAPERAN D. , JACQUOT C. , POLACK B.
Published: December 2004

We report the first case of an anaphylactic shock to three different FVIII concentrates, one immuopurified plasma‐derived (Monoclate‐P®) and two recombinant FVIII products (Recombinate® and Kogenate®). These shocks appeared despite the use of antihistaminic drugs. The use of a highly purified plasma‐derived FVIII allowed successful on‐demand therapy without any antiallergic drug or desensitization.
Painless urethral bleeding: an unusual presentation of Von Willebrand disease
Authors: Armenian S. , Raffel J. L. , Nugent D. J. , Young G.
Published: December 2004

Summary.  Von Willebrand disease (vWD) is the most common bleeding disorder, and usually presents with either easy bruising or mucus membrane bleeding. Many patients are also diagnosed as a result of abnormal pre‐operative laboratory tests. In this report, we describe two patients presenting with painless, persistent urethral bleeding as their initial manifestation of vWD. The first patient began bleeding after a Foley catheter was placed during a hospital admission for status epilepticus. A urologic examination demonstrated a wound in the posterior urethra. Despite repeated attempts at controlling the bleeding with cautery, the bleeding persisted. The second patient presented with spontaneous urethral bleeding and a normal urologic examination. Due to persistent bleeding, both patients underwent a coagulation evaluation that demonstrated the presence of type 1 vWD. The first patient had resolution of his bleeding following 5 weeks of Alphanate, a von Willebrand factor containing factor VIII concentrate, and aminocaproic acid. The second patient initially responded to desmopressin, but subsequently required Humate‐P to achieve complete resolution. These cases illustrate the importance of an evaluation for bleeding disorders in patients with persistent bleeding from any site.
A new ELISA assay for diagnosis of acquired von Willebrand Syndrome
Authors: Siaka C. , Rugeri L. , Caron C. , Goudemand J.
Published: December 2004

Summary. The pathophysiology of acquired von Willebrand syndrome (AVWS), a rare bleeding disorder, is not fully understood. Circulating antibodies to Von Willebrand factor (VWF) are found in patients with AVWS associated with lymphoproliferative disorders but these autoantibodies are difficult to detect with routine laboratory tests and neutralisation assays. We have developed a simple enzyme‐linked immunosorbent assay (ELISA) to detect serum antibody binding to VWF protein immobilized on polystyrene plates. Ten patients with AVWS were studied, eight of whom also had lymphoproliferative disorders. We found antibodies in eight patients; all of them were positive for IgG and five were also positive for IgM. This simple method appears to be more sensitive than functional assays, which failed to identify two of the patients who were positive with the ELISA. In conjunction with other tests, this ELISA method may be useful for demonstrating the immunological mechanism underlying some cases of AVWS. Such patients would qualify for intravenous immunoglobulin therapy, which can correct the clotting disorder.
Prophylaxis for severe haemophilia: clinical and economical issues
Authors: Fischer K. , Berg Van den M.
Published: December 2004

Summary.  Patients with severe haemophilia are treated either in case of bleeds only (on demand), or with regular infusions of clotting factor to prevent bleeds (prophylaxis). The introduction of prophylaxis has been hampered by issues of cost and viral safety. In order to compare results and treatment cost of different treatment strategies in adults, three cohorts of patients with severe haemophilia (born 1970–1980) were compared.

106 French patients were treated on demand, 49 Dutch patients were treated with intermediate dose prophylaxis, and 24 Swedish patients were treated with high dose prophylaxis. The annual number of joint bleeds, and the radiological Petterson score were used to compare outcome, annual clotting factor consumption was used to compare costs.

Prophylaxis reduced bleeds and arthropathy: patients treated on demand had a median of 11.5 joint bleeds/year and a median Pettersson score of 16 points, for intermediate dose prophylaxis median bleeds were 2.8 and Pettersson score was 7 points, and for high dose prophylaxis median bleeds were 0.5 joint bleeds and Pettersson score was 4 points. All differences were statistically significant, except the Pettersson scores in both prophylactic regimens. Treatment cost was only increased for high dose prophylaxis: mean clotting factor consumption was 1612 IU kg−1 yr−1 for on demand treatment, 1488 IU kg−1 yr−1 for intermediate dose prophylaxis, and 4012 IU kg−1 yr−1 for high dose prophylaxis.

In young adults, the cost of intermediate dose prophylaxis is similar, but outcome is better than for on demand treatment. The cost of high dose prophylaxis is twofold higher, further improving outcome only slightly.
Continuous infusion
Authors: Schulman S.
Published: December 2004

Summary.  There is evidence, albeit scientifically weak, for improved cost/benefit with administration of factor concentrates by continuous infusion when high‐dose replacement is necessary, as several studies have shown a reduced requirement for the concentrate. There is evidence from only one study for fewer bleeding complications with continuous infusion. There is evidence from two studies that additional therapy with tranexamic acid reduces the risk of bleeding complications in patients receiving continuous infusion.

Future studies should address the question of minimum steady‐state levels required for haemostasis, comparisons with bolus injection using a randomized design and investigate the risk of inhibitor formation.
Potential role of the dynamic properties of whole blood coagulation in assessment of dosage requirements in haemophilia
Authors: Ingerslev J. , Poulsen L. H. , Sørensen B.
Published: December 2004

Summary. In the clinical setting, patients suffering from haemophilia are classified according to the residual level of the deficient coagulation factor. Patients suffering from the severe form of haemophilia (critical factor level <0.01 IU mL−1) display some heterogeneity in their tendency to bleeding despite the uniform factor level. Utilizing a new thrombelastographic method in which coagulation is activated by very small amounts of tissue factor and where resulting data are processed with new software, we studied the whole blood coagulation profile in 11 patients with severe haemophilia A and 11 patients with moderate haemophilia. In both groups of patients, we found a considerable degree of heterogeneity in the coagulation signal. In moderate haemophilia with factor VIII (FVIII):C levels between 0.01 and 0.05 IU mL−1, variance was expected, whereas a quite substantial diversity had not been forecasted in patterns of the whole blood coagulation profiles in patients with the severe form of haemophilia A. Ex vivo substitution to patient's blood to reach various theoretical levels of recombinant factor VIII (rFVIII) revealed that the coagulation response to FVIII supplementation varied substantially. In some severely affected patients levels of FVIII:C close to 0.05 IU mL−1 was sufficient to normalize the coagulation profile, while others required a dose giving >0.50 IU mL−1 of FVIII to achieve a normal whole blood clotting profile. In conclusion, our study revealed that severe haemophilia A seems not to be a single entity, but rather several different clinical and biochemical phenotypes, and that the response to added FVIII varies amongst patients.
Social adjustment in three cultures: data from families affected by chronic blood disorders. A sibling study
Authors: Clemente C. , Tsiantis J. , Kolvin I. , Ba G. , Christogiorgos S. , Lee C. , Taylor B. , Miller R.
Published: December 2004

Summary.  This study explores the rate of psychosocial dysfunction in affected and unaffected children from families with haemophilia or β‐thalassaemia, as part of a cross‐sectional, multicentre study into the resilience of 115 families with blood disorders. Sociodemographic and developmental data were collected from the parents using a standardized and semi‐structured interview format, and medical data were obtained from the clinician. The children's social functioning over the year prior to the assessment was assessed with The Social Adjustment Scale adapted for school‐aged children. Children with β‐thalassaemia showed significantly higher rates of social dysfunction than their unaffected siblings or children with haemophilia and their siblings. Older children showed significantly higher social dysfunction at school. The high rate of social dysfunction in children with β‐thalassaemia compared with unaffected siblings is likely to have a basis in the negative experiences associated with their medical problems. In contrast, the therapeutic advances in haemophilia allows boys to lead an almost normal life. Overall, the rates of social dysfunction in families with both these disorders proved commoner than reported in population surveys, but with the unavailability of local population controls, caution needs to be exercised in the interpretation of this finding.
The management of inhibitors in haemophilia A: introduction and systematic review of current practice
Authors: Paisley S. , Wight J. , Currie E. , Knight C.
Published: December 2004

Summary.  Haemophilia is the commonest bleeding disorder in the UK, affecting approximately 5400 people, almost all of them male. In haemophiliacs, reduced levels, or absence, of factor VIII (FVIII) cause bleeding episodes, typically into joint spaces or muscles. Haemophilia is generally treated with exogenous FVIII. However, in some haemophiliacs, therapeutically administered FVIII comes to be recognized as a foreign protein, stimulating the production of antibodies (inhibitors), which react with FVIII to render it ineffective. Alternative treatment strategies then have to be used to manage bleeding episodes. In addition, strategies have been developed to attempt to abolish inhibitor production through the induction of immune tolerance. A systematic review was undertaken of current international practice for the clinical management of haemophilia A patients with inhibitors to FVIII, concentrating on literature published from 1995 onwards. Although it can be difficult to determine what constitutes current practice, current guidelines indicate that immune tolerance induction is seen as desirable, with the choice of regimen dependent on patient characteristics, familiarity with regimens and cost. Various approaches, based on similar factors, are used to control bleeding episodes.
The epidemiology of inhibitors in haemophilia A: a systematic review
Authors: Wight J. , Paisley S.
Published: December 2004

Summary.  This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5–7%. The cumulative risk of inhibitor development varied (0–39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma‐derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies.
Cranial Pseudotumour in Haemophilia
Authors: Libby E. N. , White G. C.
Published: December 2004

Summary.  Intracranial pseudotumour has rarely been reported in haemophilia. We present the fourth case describing this complication.
Treatment of acquired haemophilia with factor eight inhibitor bypassing activity
Authors: Sallah S.
Published: December 2004

Summary.  Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if not recognized and treated appropriately. A retrospective analysis of the efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with acquired haemophilia treated in three medical centres in the past 10 years was conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The majority of patients received FEIBA at a dose of 75 u kg−1 every 8–12 h. The number of FEIBA doses administered was higher in patients with severe compared with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001. Complete response (CR) was achieved in 76% of severe and 100% of moderate bleeding episodes with a total CR of 86%. When compared with patients with human inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P < 0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor VIII concentrates prior to FEIBA had significantly higher maximum recorded human inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P = 0.0001. Treatment with FEIBA was very well tolerated and with very few side effects. This study provides evidence that FEIBA is an effective agent in acquired haemophilia and suitable for all types of patients regardless of severity of haemorrhage, underlying disease or inhibitor titre.
Activated prothrombin complex concentrate (FEIBA®) treatment during surgery in patients with inhibitors to FVIII/IX
Authors: Tjønnfjord G. E. , Brinch L. , Gedde‐Dahl T. , Brosstad F. R.
Published: December 2004

Summary.  Non‐activated and activated prothrombin complex concentrates (PCC/aPCC) have been used successfully to treat bleeds in haemophilia patients with inhibitors, but most physicians do not consider these products as effective as factor VIII/IX (FVIII/IX) concentrates in non‐inhibitor patients. Thus, surgical procedures in inhibitor patients have been performed reluctantly. We have performed 14 minor and five major surgical and invasive diagnostic procedures in eight patients with congenital haemophilia A and inhibitors and in two patients with acquired haemophilia. When a loading dose of 100 U kg−1 of FEIBA® was given followed by 200 U kg−1 day−1 in three divided doses every 8 h for 3 days, and then, when the daily dose was tapered to 100–150 U kg−1, no severe or unexpected bleeding complications were observed. However, one adverse event was observed. A 69‐year‐old man who suffered a myocardial infarction the third postoperative day following sigmoidectomy was managed safely with opiate analgesia, nitrates and diuretics, and the continued use of FEIBA®.
Radiological assessment of haemophilic arthropathy with emphasis on MRI findings
Authors: Kilcoyne R. F. , Nuss R.
Published: December 2004

Summary.  Medical imaging of haemophilic joints is important for detecting abnormalities, grading their severity and selecting the appropriate therapy. The plain‐film scoring systems for staging joint disease that were developed prior to the availability of magnetic resonance imaging (MRI) are inadequate for planning modern prevention and treatment. MRI is capable of delineating all of the soft tissue findings long before they are evident on plain radiographs. In this paper, an MRI scoring system is presented along with examples of joint effusion, haemarthrosis, synovial hypertrophy, haemosiderin deposition, erosions, cysts and cartilage loss. MRI is a powerful tool in the diagnosis, staging and treatment of patients with haemophilic joint disease.
Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective
Authors: Björkman S.
Published: December 2004

Summary. The high cost and limited availability of factor concentrates make dosing of factor VIII (FVIII) or factor IX (FIX) a crucial issue in the prophylactic treatment of haemophilia. It has often been recommended that this treatment should aim to maintain a minimum plasma level of 1% of normal coagulation factor activity (FVIII:C or FIX:C). The dosage needed is commonly given as 25–40 U kg−1three times weekly for FVIII or twice weekly for FIX. However, these guidelines are valid only with several qualifications. First, the actual trough levels required may vary considerably between patients. The clinical severity of haemophilia may depend on more factors than the endogenous level of FVIII:C or FIX:C. Secondly, interindividual variations in dose requirements are also due to variance in the pharmacokinetics of the coagulation factors. Pharmacokinetic calculations are useful to design optimal dosing schedules to achieve required trough levels of FVIII:C or FIX:C. Moreover, tailoring of the dosing of FVIII or FIX according to their disposition in the individual patient can markedly improve the cost‐effectiveness of prophylactic treatment. However, the usefulness ofin vivorecovery as a guide for prophylactic dosing seems questionable. It should be clearly understood that maintaining a certain trough level of FVIII:C or FIX:C is not an end in itself. Clinical outcome, not the achieved trough level, determines whether a dosage is adequate. Chiefly for economic reasons, the minimum effective dosage of coagulation factor should be determined and used in every patient. The dose requirement should also be re‐evaluated at appropriate times.
Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens
Authors: McLaren K M , Burnett R A , Goodlad J R , Howatson S R , Lang S , Lee F D , Lessells A M , Ogston S A , Robertson A J , Simpson J G , Smith G D , Tavadia H B , Walker F ,   (Scottish Pathology Consistency Group)
Published: December 2004

Aims:  The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists.

Methods:  A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid–Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens.

Results:  In both studies κ statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (κ 0.375).

Conclusions:  The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.
Barriers to patient information provision in primary care: patients' and general practitioners' experiences and expectations of information for low back pain
Authors: McIntosh Aileen , Shaw Clare F M
Published: December 2004

Background As patient involvement in health‐care increases, the role of information is crucial, especially in conditions where self‐management is considered an integral part of care. However, the suitability and applicability of much patient information has not been appraised in terms of how far it meets patients' information needs.

Aims To ascertain patients' and clinicians' experiences and expectations of information in low back pain in order to suggest a suitable ‘patient‐centred’ content for a patient information pack to be used in a primary care setting.

Methods A qualitative study using semi‐structured interviews with General Practitioners (GPs) (n = 15) and focus groups comprising patients with low back pain (n = 37).

Results Barriers to information‐giving for low back pain in primary care exist. Patients are dissatisfied with the information they receive from their GPs, especially regarding diagnosis and treatment. Patients tend to access information from a variety of other sources, which is often contradictory, conflicts with research evidence and leads to unreasonable expectations. GPs have varying views regarding the value of patient information and are equivocal about their roles as information providers. AlthoughThe Back Bookis generally acceptable as a patient information leaflet for low back pain, attention to the tone of the text is required.

Conclusions Barriers exist to patient information provision, both generally and for low back pain, which need to be addressed in order to close the gap between strategy and implementation. Improving clinician communication skills and involving patients in developing information materials which meet their needs are crucial to this process.
Putting partnership into practice: participatory wellbeing assessment on a south London housing estate
Authors: Cornwall Andrea , Lall Pawan , Kennedy Ken , Owen Felicity
Published: December 2004

Purpose  Bridging the gap between professionals and communities and establishing new forms of partnership is essential if service provision is to be made more responsive and accountable. This article describes an innovative approach to creating the basis for partnerships to address community wellbeing on an estate in south London.

Methods  Drawing on participatory appraisal and action planning methods, and drawing together residents and professionals within and beyond the health service, a participatory wellbeing assessment exercise was carried out on a housing estate with a population of around 6000 people, involving just under 10% of residents.

Results  The participatory wellbeing assessment exercise served as a means of seeking to bridge different perceptions, priorities and perspectives on wellbeing and forge new relationships, alliances and partnerships for change. Creating this vehicle for change also created opportunities for local people to participate in community wellbeing issues. This, in turn, strengthened connections between health policy, provision and grassroots community health development, broadening opportunities for service responsiveness and citizen involvement.

Conclusion  Broadening involvement in assessing and determining priorities for improving wellbeing can serve to do more than enable citizens to engage more directly in making and shaping the policies that affect their lives. It can also serve as a way of establishing new kinds of partnerships across and within the statutory and non‐statutory services, opening up space for new, more ‘joined up’ forms of work that help to bridge the gap between citizens and services.
Are patients' decision‐making preferences being met?
Authors: Ford Sarah , Schofield Theo , Hope Tony
Published: December 2004

Objective  To investigate the information and decision‐making expectations of general practice patients during real life consultations.

Design  Post‐consultation, quantitative patient preference and enablement questionnaire.

Setting and participants  Patients attending for routine appointments in general practice surgeries in Oxfordshire, UK.

Results  Thirteen Oxfordshire general practitioners (GPs) volunteered to take part and a total of 171 patients completed and returned the questionnaire. Between a quarter and one‐third of patients reported receiving less information than they desired, particularly in relation to the risks and benefits of medical treatments. Patients who preferred the doctor to make decisions for them (35%), were more likely to have their preferences met (64%) compared with patients wishing to share decisions (47%) or make their own (18%) who were less likely to achieve this role (52 and 41%, respectively). However, it could not be demonstrated unequivocally that these differences were statistically significant. In total, 61% of patients perceived that they achieved their preferred decision‐making role. No significant differences were found in post‐consultation enablement scores between any of the decision preference groups. Patients' assessments indicated that some doctors were more successful at achieving congruence than others.

Conclusion  The decision‐making preferences of general practice patients tend to vary. However, there was a substantial mismatch between the stated preferences of patients for the role they wanted to have in decision‐making and what they felt actually took place in their consultation. Therefore, it remains a challenge for doctors to match their consultation style to the decision‐making preferences of individual patients.
Modelling macroscopic imperfections for the prediction of flow localization and fracture
Authors: BARLAT F. , RICHMOND O.
Published: December 2004

Ductile materials subjected to plastic deformation experience the different stages of void nucleation, growth and coalescence that eventually lead to ductile fracture. Several models have been proposed to assess the influence of this damage on flow localization and fracture. In general, the plastic behaviour is represented by a constitutive model for porous or damaged materials. It is typical to introduce a material imperfection, with porosity higher than average, which evolves up to localization and fracture. However, the void volume fraction in the imperfection is chosen more or less arbitrarily. In the present work, a model that evaluates this void volume fraction more rigorously is developed. The forming limit diagram (FLD) for a dual phase‐steel is calculated using the damage‐based imperfection calculation and validated with experimental results. The effect of void shape on the imperfection porosity level and limit strains in sheet forming is also assessed with the present method.