bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of lunar cycles on the activity patterns and depth use of a temperate sport fish, the largemouth bass, Micropterus salmoides
Authors: HANSON K. C. , ARROSA S. , HASLER C. T. , SUSKI C. D. , PHILIPP D. P. , NIEZGODA G. , COOKE S. J.
Published: September 2010

Abstract  The behaviour of free‐swimming, telemetered, adult largemouth bass, Micropterus salmoides (L.), was monitored using a whole lake, three‐dimensional acoustic telemetry array to test the hypothesis that fish activity and depth distribution are influenced by lunar phase. The percent of lunar face shining and whether the moon was waxing or waning were significant determinants of swimming activity and depth distribution during most of the lunar cycles evaluated, although these patterns were not consistent across the year. In spring and summer, daily depth distribution followed a pattern in which the fish inhabited greater depths on the 26–50% and 51–75% waxing moon. Fish daily movement distances were five times greater during spring and summer than in winter, but no repeatable patterns were noted in relation to lunar periodicity. This research suggests that solunar tables frequently consulted by recreational anglers may have little predictive value for identifying peak fishing time.
Home range of an estuarine‐dependent fish species Pomadasys commersonnii in a South African estuary
Authors: CHILDS A.‐R. , BOOTH A. J. , COWLEY P. D. , POTTS W. M. , NÆSJE T. F. , THORSTAD E. B. , ØKLAND F.
Published: September 2010

Abstract  The home range and area use of spotted grunter, Pomadasys commersonnii (Haemulidae) (Lacepède), were investigated in the Great Fish estuary, South Africa. Forty individuals (263–698 mm TL) were surgically implanted with acoustic‐coded transmitters and manually tracked during two periods in 2003. Tagged fish spent on average 68 and 77% of the time in the estuary and the remaining time at sea during the two periods, respectively. While in the estuary, there was large variation in home range size, home range length and the number of home range areas amongst individuals. Larger fish had larger home ranges and more core areas than smaller fish. The home ranges of 29 individuals (74%) occurred in the lower reaches of the estuary, suggesting that the proclamation of a no‐take zone in this high use area could benefit this over‐exploited estuarine fishery species.
Rapid evolution as a possible constraint on emerging infectious diseases
Authors: PENCZYKOWSKI RACHEL M. , FORDE SAMANTHA E. , DUFFY MEGHAN A.
Published: September 2010

1. Emerging infectious diseases may decimate populations or become endemic, but such worst‐case scenarios do not occur as frequently as might be expected, even for virulent parasites.

2. One explanation for this apparent paradox is that rapid evolution of host resistance may diminish or terminate epidemics. Theoretical and empirical studies have shown that evolution in host–parasite systems can dramatically alter the prevalence and intensity of infection.

3. The potential for rapid evolution to protect host populations from negative effects of virulent parasites depends on the type of parasite‐driven evolution that occurs. In some host–parasite systems, evolution of increased host resistance can terminate epidemics. However, evolution resulting from parasite‐mediated disruptive selection might actually allow a disease to persist in the host population. Epidemics may also be sustained through coevolution of the parasite.

4. The rate of evolution and subsequent disease dynamics will be affected by both the diversity of the host population and the community context in which the host–parasite interaction is embedded. Predators, competitors and food resources can all affect the rates of evolution of hosts and parasites and interact with evolution to determine the outcome of epidemics.

5. Freshwater organisms have played an important role in the studies of eco‐evolutionary dynamics. Rapid evolution in response to parasitism has been demonstrated in multiple freshwater host species, which appears to have protected some of these populations from the virulent effects of infectious diseases.

6. Studies of emerging infectious diseases in freshwater ecosystems should consider the possibility of evolution of hosts and/or parasites on ecological timescales, since this phenomenon can profoundly affect disease dynamics.
Seismic attenuation in Faroe Islands basalts
Authors: Shaw F. , Worthington M.H. , White R.S. , Andersen M.S. , Petersen U.K. ,   the Seifaba Group
Published: September 2010

We analysed vertical seismic profiling (VSP) data from two boreholes at Glyvursnes and Vestmanna on the island of Streymoy, Faroe Islands, to determine the magnitude and causes of seismic attenuation in sequences of basalt flows. The work is part of SeiFaBa, a major project integrating data from vertical and offset VSP, surface seismic surveys, core samples and wireline log data from the two boreholes. Values of effective seismic quality factor (Q) obtained at Glyvursnes and Vestmanna are sufficiently low to significantly degrade the quality of a surface reflection seismic image. This observation is consistent with results from other VSP experiments in the North Atlantic region. We demonstrate that the most likely cause of the low values of effective Q at Glyvursnes and Vestmanna is a combination of 1D scattering and intrinsic attenuation due to seismic wave‐induced fluid flow within pores and micro‐cracks. Tests involving 3D elastic wave numerical modelling with a hypothetical basalt model based on field observations, indicate that little scattering attenuation is caused by lateral variations in basalt structure.
Land‐use impact on ecosystem functioning in eastern Colorado, USA
Authors: Paruelo J. M. , Burke I. C. , Lauenroth W. K.
Published: September 2010

Land‐cover change associated with agriculture has had an enormous effect on the structure and functioning of temperate ecosystems. However, the empirical evidence for the impact of land use on ecosystem functioning at the regional scale is scarce. Most of our knowledge on land‐use impact has been derived from simulation studies or from small plot experiments. In this article we studied the effects of land use on (i) the seasonal dynamics and (ii) the interannual variability of the Normalized Difference Vegetation Index (NDVI), a variable linearly related to the fraction of the photosynthetically active radiation (PAR) intercepted by the canopy. We also analysed the relative importance of environmental factors and land use on the spatial patterns of NDVI. We compared three cultivated land‐cover types against native grasslands. The seasonal dynamics of NDVI was used as a descriptor of ecosystem functioning. In order to reduce the dimensionality of our data we analysed the annual integral (NDVI‐I), the date of maximum NDVI (DMAX) and the quarterly average NDVI. These attributes were studied for 7 years and for 346 sites distributed across eastern Colorado (USA).

   Land use did modify ecosystem functioning at the regional level in eastern Colorado. The seasonal dynamics of NDVI, a surrogate for the fraction of PAR intercepted by the canopy, were significantly altered by agricultural practices. Land use modified both the NDVI integral and the seasonal dynamics of this spectral index. Despite the variability within land‐cover categories, land use was the most important factor in explaining regional differences of the NDVI attributes analysed. Within the range of environmental conditions found in eastern Colorado, land use was more important than mean annual precipitation, mean annual temperature and soil texture in determining the seasonal dynamics of NDVI.
Eco‐hydrological controls on summertime convective rainfall triggers
Authors: JUANG JEHN‐YIH , KATUL GABRIEL G. , PORPORATO AMILCARE , STOY PAUL C. , SIQUEIRA MARIO S. , DETTO MATTEO , KIM HYUN‐SEOK , OREN RAM
Published: September 2010

Triggers of summertime convective rainfall depend on numerous interactions and feedbacks, often compounded by spatial variability in soil moisture and its impacts on vegetation function, vegetation composition, terrain, and all the complex turbulent entrainment processes near the capping inversion. To progress even within the most restricted and idealized framework, many of the governing processes must be simplified and parameterized. In this work, a zeroth‐order representation of the dynamical processes that control convective rainfall triggers – namely land surface fluxes of heat and moisture – is proposed and used to develop a semianalytical model to explore how differential sensitivities of various ecosystems to soil moisture states modify convective rainfall triggers. The model is then applied to 4 years (2001–2004) of half‐hourly precipitation, soil moisture, environmental, and eddy‐covariance surface heat flux data collected at a mixed hardwood forest (HW), a maturing planted loblolly pine forest (PP), and an abandoned old field (OF) experiencing the same climatic and edaphic conditions. We found that the sensitivity of PP to soil moisture deficit enhances the trigger of convective rainfall relative to HW and OF, with enhancements of about 25% and 30% for dry moisture states, and 5% and 15% for moist soil moisture states, respectively. We discuss the broader implications of these findings on potential modulations of convective rainfall triggers induced by projected large‐scale changes in timberland composition within the Southeastern United States.
Environmental variation is directly responsible for short‐ but not long‐term variation in forest‐atmosphere carbon exchange
Authors: RICHARDSON ANDREW D. , HOLLINGER DAVID Y. , ABER JOHN D. , OLLINGER SCOTT V. , BRASWELL BOBBY H.
Published: September 2010

Tower‐based eddy covariance measurements of forest‐atmosphere carbon dioxide (CO2) exchange from many sites around the world indicate that there is considerable year‐to‐year variation in net ecosystem exchange (NEE). Here, we use a statistical modeling approach to partition the interannual variability in NEE (and its component fluxes, ecosystem respiration, Reco, and gross photosynthesis, Pgross) into two main effects: variation in environmental drivers (air and soil temperature, solar radiation, vapor pressure deficit, and soil water content) and variation in the biotic response to this environmental forcing (as characterized by the model parameters). The model is applied to a 9‐year data set from the Howland AmeriFlux site, a spruce‐dominated forest in Maine, USA. Gap‐filled flux measurements at this site indicate that the forest has been sequestering, on average, 190 g C m−2 yr−1, with a range from 130 to 270 g C m−2 yr−1. Our fitted model predicts somewhat more uptake (mean 270 g C m−2 yr−1), but interannual variation is similar, and wavelet variance analyses indicate good agreement between tower measurements and model predictions across a wide range of timescales (hours to years). Associated with the interannual variation in NEE are clear differences among years in model parameters for both Reco and Pgross. Analysis of model predictions suggests that, at the annual time step, about 40% of the variance in modeled NEE can be attributed to variation in environmental drivers, and 55% to variation in the biotic response to this forcing. As model predictions are aggregated at longer timescales (from individual days to months to calendar year), variation in environmental drivers becomes progressively less important, and variation in the biotic response becomes progressively more important, in determining the modeled flux. There is a strong negative correlation between modeled annual Pgross and Reco (r=−0.93, P≤0.001); two possible explanations for this correlation are discussed. The correlation promotes homeostasis of NEE: the interannual variation in modeled NEE is substantially less than that for either Pgross or Reco
Determination of haemophilia A carrier status by mutation analysis
Authors: Oranwiroon S. , Akkarapatumwong V. , Pung‐Amritt P. , Treesucon A. , Veerakul G. , Mahasandana C. , Panyim S. , Yenchitsomanus P.
Published: September 2010

A reliable method for determination of carrier status and genetic counselling is required for effective control of haemophilia. Linkage analysis is currently the most widely used method for this purpose; however, in cases where there is no prior family history and/or unavailability of informative polymorphic markers it is less applicable. Detection of a mutation characterized in each family may be an alternative method for determination of the carrier status. In this study, linkage analysis using four polymorphic DNA markers, and direct mutation analysis were compared to determine the carrier status in six unrelated Thai haemophilia A families, two with a family history and four without. In the two families with a family history of haemophilia A, the carrier and noncarrier statuses could readily be determined in eight females by either linkage or direct mutation analysis. In the four families without a family history, the polymorphic DNA markers for linkage analysis were informative in two families and uninformative in the other two. The carrier status could be excluded in all four female siblings of the patients in the former. However, the specific FVIII gene mutation was not observed in the mother of one patient, who should have carried the mutation. In the remaining two families with uninformative polymorphic DNA markers, the carrier and noncarrier statuses of four female members could only be determined by direct mutation analysis. Therefore, direct mutation analysis could circumvent the limitations of linkage analysis in the determination of haemophilia A carrier status in families without a previous history or informative polymorphic markers.
Detection of all anti‐factor VIII antibodies in haemophilia A patients by the Bethesda assay and a more sensitive immunoprecipitation assay
Authors: Klinge J. , Auerswald G. , Budde U. , Klose H. , Kreuz W. , Lenk H. , Scandella D. ,   THE PAEDIATRIC INHIBITOR STUDY GROUP OF THE GERMAN SOCIETY ON THROMBOSIS and HAEMOSTASIS
Published: September 2010

Plasmas from 40 haemophilia A patients enrolled in a study by the paediatric group of the German Society on Thrombosis and Hemostasis were tested by the Bethesda assay for inhibitor antibodies and by a more sensitive immunoprecipitation assay (IP) for all antifactor VIII antibodies. Of the 26 severe, 11 moderate and three mild haemophiliacs, 18, two, and none, respectively, had positive Bethesda titres after several factor VIII infusions. In 275 plasmas with Bethesda titres of 0, 0.6–1.0, > 1–5, and > 5–655, the IP responses were 0–238, 0–61, 0–786, and 43–6141, respectively, and a reliable positive IP titre was > 4.2. The overlapping ranges of IP titres indicated large differences in the ratio of inhibitory to noninhibitory antibodies in individual plasmas. In five of seven patients with Bethesda titres of 0.6–1, the IP titres were < 4.2, suggesting a lack of precision of Bethesda titres ≤ 1. Detection of the primary immune response was found in only three patients by IP assay before a positive Bethesda assay. This precludes early, reliable testing of which patients will be immunologically responsive. In four patients undergoing immune tolerance therapy, antifactor VIII antibodies were still detectable by the IP assay in the absence of a Bethesda titre, which indicates that antibodies were completely eradicated in none of the patients. Our results show that the use of both the Bethesda and IP assays can provide more accurate detection of antifactor VIII antibodies in all patients.
The French haemophilia cohort: rationale and organization of a long‐term national pharmacosurveillance system
Authors: Calvez T. , Biou M. , Costagliola D. , Jullien A‐M. , Laurian Y. , Rossi F. , Rothschild C. , SiÉ P. ,   FOR THE SUIVI THÉRAPEUTIQUE NATIONAL DES HÉMOPHILES GROUP
Published: September 2010

Medicinal products of biological origin still carry a specific iatrogenic risk, mainly because of their starting material, mode of preparation and variability. Careful postmarketing surveillance systems are therefore necessary. To assess the long‐term safety of haemophilia treatment with plasma‐derived and recombinant clotting factor products, a cohort study was set up in France in 1994. Participants were patients with haemophilia A and B, with or without previous clotting factor therapy. Clinical events, treatments, biological data and adverse events were recorded on standard forms. Blood samples were separated into serum, plasma and peripheral blood mononuclear cells, frozen, and banked in a central laboratory. The same data and samples were collected at yearly follow‐up visits. As of December 1999, 1234 haemophiliacs were enrolled in 39 haemophilia centres. At enrolment, 50.2% of patients were under 15 years of age, and the cumulative number of days of exposure to the product was below 50 in 35.1% of cases. The median duration of follow‐up was 26.9 months, with a total of 2729 patient‐years (135 947 days of exposure and 211 million units of factor VIII or IX). To date, only 17 patients were lost to follow‐up. The initial results show good compliance with this health‐watch policy among patients and clinicians specializing in haemophilia. The regular follow‐up data and centralized sample bank will serve to investigate rapidly any suspected outbreaks as soon as reliable biological tests become available in the future.
Low factor VIII recovery in haemophilia A patients without inhibitor titre is not due to the presence of anti‐factor VIII antibodies undetectable by the Bethesda assay
Authors: Mondorf W. , Klinge J. , Luban N. L. C. , Bray G. , Saenko E. , Scandella D. ,   THE RECOMBINATE PUP STUDY GROUP
Published: September 2010

Measurements of factor VIII (FVIII) recovery in previously untreated patients with haemophilia A were done as part of the clinical trial of safety and efficacy of the recombinant FVIII, Recombinate™. In 22 of 72 assessable patients, positive inhibitor titres ≥ 0.6 Bethesda units mL−1 were detected by the Bethesda assay in one or more plasma samples, and the remaining 50 patients were negative at all timepoints. Of the latter group, 16 individuals without inhibitors unexpectedly had both normal (111) and low (52) recoveries during the study. We investigated the possibility that other antibodies not detectable in the Bethesda assay were responsible for the low recovery, by using a highly sensitive immunopreciptation (IP) assay for detection of all antiFVIII antibodies. Eight of the 16 patients with low and normal recoveries did indeed have antibodies detected by the IP assay, and the remaining eight were negative. Four antibody‐positive individuals had insignificantly low titres, and the other four had modest to high titres. In the latter group, antibodies were found with similar frequencies and titre in plasmas from patients with low or normal recovery. Low recovery in haemophilia A patients without inhibitor titres must therefore be attributed to factors other than antiFVIII.
Product choice and haemophilia treatment in the Netherlands
Authors: Mauser‐Bunschoten E. P. , Roosendaal G. , Van Den Berg H. M.
Published: September 2010

In the Netherlands, there is a free choice of product for the treatment of haemophilia. Which product is chosen depends on the following considerations: medical, psychological, availability of clotting products, economics and government guidelines. Since the introduction of recombinant product in 1995, the percentage of Dutch patients treated with it has increased from 8% in 1995 to 20% in 1998. In 1999, an average of 48% of patients visiting the Van Creveldkliniek were treated with recombinant product. Children are more often treated with recombinant product than adults; 93% of children between 0 and 5 years, 53% of children between 6 and 20 years and 40% of adults are treated with recombinant product.
Immune tolerance induction: recombinant vs. human‐derived product
Authors: Berntorp E.
Published: September 2010

The ultimate goal in the treatment of high‐responding inhibitors in congenital haemophilia is to induce immune tolerance (IT). Since the advent of highly purified factor VIII products, especially recombinant ones, the issue has been raised of whether the type of product has an impact on treatment success. It is clear that IT induction is possible to achieve with both recombinant products and human‐derived products, but there is a lack of comparative studies. Different theoretical aspects indicate that human‐derived concentrate, especially of low purity, and with a high content of von Willebrand factor, may have a better tolerizing effect.
Choice of factor concentrates for haemophilia: a developing world perspective
Authors: Srivastava A.
Published: September 2010

Provision of factor concentrates continues to be the single greatest challenge in providing effective haemophilia care in the developing world. While concerns for ultimate safety and very high purity dominate the selection of factor concentrates in developed countries, availability and cost are the pressing issues in developing countries. There certainly is concern for reasonable safety but purity is often considered an unaffordable luxury. Cost‐effective protocols need to be designed for factor replacement in these countries where liberal on‐demand therapy and prophylaxis are not possible. It is also essential to establish a good transfusion service for collecting adequate quantities of safe plasma. Support from government and health insurance is required to allow access to at least modest quantities of virus‐inactivated factor concentrates. Depending on the situation in each country, factor concentrates may be imported, contract‐fractionated or locally produced. Paradigms of effective management of this problem exist within the developing world. Untill such time as these examples are widely emulated, less safe products will continue to be used in situations where a distinction frequent needs to be made between what is ideal and what is practical.
Clinical severity of disease, functional disability and health‐related quality of life. Three‐year follow‐up study of 150 Finnish patients with coagulation disorders
Authors: Solovieva S.
Published: September 2010

A questionnaire‐based follow‐up study of 150 Finnish patients with coagulation disorders was conducted to evaluate the changes in clinical manifestation of the disease, pain intensity, functional disability and patient’s health‐related quality of life, occurring during a 3‐year period. Health‐related quality of life was assessed using the MOS‐36 health survey. The clinical severity of the disease manifestation was estimated using the frequency of bleeding episodes into joints and soft tissue during the previous 12 months. Severity of musculoskeletal morbidity, which reflects simultaneous presence of pain and disability, was estimated using intensity of pain and level of disability. Results showed that clinical severity of the disease remained unchanged during the 3‐year period for the majority of patients. Nonetheless, the annual number of bleeds in patients with severe or moderately severe haemophilia was still disconcertingly high and the number of bleeding episodes into soft tissue had increased. The clinical severity of the disease manifestation, rather than the severity of the disease based on molecular classification, was a factor that negatively influenced the intensity of pain (both acute and chronic), as well as level of disability. Severity of musculoskeletal morbidity at time 1 and changes in severity of musculoskeletal morbidity over time were found to be significant predictors of physical role, bodily pain, vitality and social functioning. In conclusion, the disease can be relatively well controlled by the availability of coagulation products, thus stabilizing the clinical severity of the disease manifestation during the 3‐year period studied. The findings stress the importance of preventing haemorrhages to avoid resulting permanent joint impairment and disability.
Viral markers and use of factor products among Finnish patients with bleeding disorders
Authors: Ebeling F. , Rasi V. , Laitinen H. , Krusius T.
Published: September 2010

In the seventh national voluntary cross‐sectional survey (in 1999) of Finnish patients with haemophilia A or B, type 3 von Willebrand disease or factor XIII deficiency, a plasma sample was received from 193 patients (67%). The samples were tested for hepatitis B and C, human immunodeficiency virus (HIV) and human T‐cell leukaemia virus (HTLV) antibodies. Fifty‐one percent of the patients were hepatitis C antibody positive and 34% hepatitis B core antibody positive. None of the patients had antibodies against HIV or HTLV. Eighteen percent of the patients had an elevated alanine aminotransferase activity. Abnormal alanine aminotransferase was significantly associated with hepatitis C seropositivity. No new seroconversions were detected among the haemophiliacs or patients with type 3 von Willebrand disease when compared with the last two surveys in 1993 and 1996, and there was no seroconversion in sole users of solvent/detergent‐treated factor products. Currently, 32% of the patients use prophylactic factor treatment as their principal mode of therapy, particularly the younger patients with severe forms of the bleeding diseases.
Purity of factor VIII product and incidence of inhibitors in previously untreated patients with haemophilia A
Authors: Mauser‐Bunschoten E. P. , Van Der Bom J. G. , Bongers M. , Twijnstra M. , Roosendaal G. , Fischer K. , Van Den Berg H M.
Published: September 2010

It has been suggested that ultrapure clotting factor products carry a greater risk for inhibitor development in patients with haemophilia. We compared the incidence of inhibitors in 59 previously untreated patients (PUPs) with severe haemophilia (endogenous factor VIII < 0.01 U L–1) A, who were initially treated with cryoprecipitate or intermediate purified products, with that in 22 patients exclusively treated with monoclonally purified and recombinant factor VIII. Persistent inhibitors were those with 1 Bethesda unit per mL or more, on more than one occasion, combined with a decrease in recovery. Incidences of persistent inhibitors were 17% (10/59) for patients who were treated with cryoprecipitate or intermediate‐purity products and 9% (2/10) for monoclonally purified and recombinant factor VIII. Transient inhibitors appeared to develop earlier during treatment with ultrapure products as compared to treatment with intermediate/low‐purity products. In conclusion, ultrapure products appear not to carry a higher risk for inhibitor development.
Improvement of patient education and information: development of a patient’s information dossier
Authors: Mauser‐Bunschoten E. P. , Hamers M. J. , De Roode D. , Terlingen‐Van Baaren G. , De Kleijn P. , Bos R. , Van Den Berg H. M.
Published: September 2010

The demand for patient information in modern medical care is increasing and sound information for patients is becoming a necessity. For haemophilia patients, information about their disease and its complications is already widely available. In order to increase the organization of this information, a ‘Patient Information Dossier’ (PID) and communication check lists were developed at the Dutch National Hemophilia Center, the Van Creveldkliniek, in cooperation with the Department of Patient Education of the University Medical Center Utrecht. The PID has an unique double function: (1) it contains patient tailored information about the practical facts of hospital care; and (2) it provides a communication checklist used by various members of the comprehensive care team, in order to supply patients with more uniform information. In order to gain a better insight of the gaps in information supply, according to patients and healthcare workers, the Department of Patient Education formulated a questionnaire. The PID itself was written by a study group consisting of members of the comprehensive care team. The entire process was developed, edited and coordinated by an advisor of the Department of Patient Education. The above‐mentioned study group developed a specific PID on haemophilia care. Its 10 chapters provide information and guidelines, and advise patients where to find more information about this subject. Each chapter includes a checklist for patients, enabling them to prepare subjects for discussion during clinical visits. The team also developed a communication checklist to be used by various team members during a patient’s visit to the clinic, as well as specific checklists covering the possible problem subjects of the PID. The PID is the lifelong property of the patient, and can be used during each visit to the clinic. The PID was implemented in February 2000, and within 4 months, was distributed among 200 patients visiting the Van Creveldkliniek. Evaluation by use of a questionnaire showed that most patients found the information in the PID sufficient and in accordance with that which they had received previously.
Acquired haemophilia in the elderly is a severe disease: report of five new cases
Authors: Godreuil S. , Navarro R. , Quittet P. , Landreau L. , Schved J‐F. , Biron‐Andréani C.
Published: September 2010

Acquired haemophilia is a rare but life‐threatening bleeding disease that can be observed in males or females at various ages. In the present study, we report on five cases of acquired factor (F) VIII inhibitors diagnosed in the elderly population over a period of 5 years between 1995 and 1999 in our hospital. The median age of the patients at the time of diagnosis was 76.2 years (66–92 years). In all cases, the diagnosis was suggested by mild to severe bleeding with no previous bleeding history. While the absence of associated conditions is frequently reported especially among the elderly, in our series an underlying disease was found in four out of the five cases: kidney tumour (two cases) and autoimmune disease (two cases). The bleeding was controlled in four patients using porcine FVIII (two cases) or recombinant FVIIa (two cases). The inhibitors were completely resolved in two patients (kidney tumour, GoodPasture syndrome) by treatment of the underlying disease. However, three patients died as direct or indirect consequence of having an inhibitor. Our series confirms and extends previous data reporting the complexity and severity of this disorder. Because bleeding is often severe, a prompt and correct diagnosis is required to provide adequate therapeutic options that take the advanced age of the patients into account.
Barriers to compliance with prophylaxis therapy in haemophilia
Authors: Hacker M. R. , Geraghty S. , Manco‐Johnson M.
Published: September 2010

Prophylaxis, or the practice of routine replacement infusions of clotting factor concentrate in persons with severe haemophilia, is a demanding medical regimen. Prophylactic infusions require direct venepuncture or sterile entry into a central venous access device on a regular basis. A telephone survey was conducted to elicit information regarding the barriers to compliance with prophylaxis. The Mountain States Regional Haemophilia and Thrombosis Center has recommended prophylaxis to 52 male patients with haemophilia A or B. The haemophilia nurse attempted to contact all of these patients or their parents, and contact was made with 38 (73.1%) of them. Respondents were asked about the following issues: their decision to initiate prophylaxis; their self‐rated compliance; the challenges, barriers, and facilitators of prophylaxis; and their perceived value of the therapy. Four patients (10.5%) elected not to begin prophylaxis. Of the 34 persons who began prophylaxis, 20 respondents (58.8%) rated their compliance as excellent. Nearly one‐third of the families with excellent compliance (giving 75–100% of prescribed infusions) stated that the time‐consuming nature of prophylaxis was the most significant challenge of the regimen. In addition, 58.3% of the families that gave less than the prescribed number of infusions reported that the time commitment was the primary reason for missing infusions. Knowledge of the benefits of prophylaxis was the primary facilitator of compliance for 44.1% of families. Ninety‐seven percent of respondents rated prophylaxis as very valuable. These data show that despite the known benefits of prophylaxis, it is a demanding medical regimen, and compliance is imperfect. In addition, this study underscores the importance of providing continuing support and education for patients and families who are implementing prophylaxis.
Creutzfeldt‐Jakob disease: reflections on the risk from blood product therapy
Authors: BROWN P.
Published: September 2010

Abstract  Creutzfeldt‐Jakob disease (CJD) was first described as a clinical entity in the 1920s, first transmitted experimentally in 1968, and first transmitted iatrogenically in 1972 (corneal transplant). Numerous experimental studies in rodents, sheep and primates have since revealed very low levels of infectivity in blood (about 1/100 000th the level in brain tissue) that can appear as early as half‐way through the incubation period, with 5–10 fold higher concentrations in leucocytes than plasma. Transfused blood from individuals incubating the variant form of CJD has transmitted infection to four recipients in the United Kingdom, and several dozen other recipients remain at risk. Plasma and plasma proteins have not been implicated in any transmissions, and no instance of transmission from the blood of individuals incubating other forms of CJD has been recognized. Strategies to prevent iatrogenic transmissions include low‐risk sourcing, leucodepletion, and a variety of infectivity‐reducing plasma processing steps; screening tests to detect infection in preclinical donors are under development.
Safety procedures of coagulation factors
Authors: JORQUERA J. I.
Published: September 2010

Abstract  Two main types of safety procedures must be applied to biological products, including plasma derivatives: (i) preventive procedures and (ii) elimination procedures.Prevention includes epidemiological control of donor populations; checks on each donor’s health condition; analysis of each donation for the main pathogens using serological methods; additional analysis of all plasma for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis A virus (HAV) and the B19 virus, using nucleic acid amplification techniques (NAT). A 60 days or longer inventory hold of all plasma donations is applied, to allow additional time to discard previous donations from potential seroconverting or otherwise rejectable donors.Elimination procedures minimize the low residual risk of transmitting pathogens, including unknown or previously undetected ones. Since the introduction 20 years ago of solvent‐detergent treatment, very effective against enveloped viruses (HIV, HBV, HCV, West Nile virus, SARS, avian influenza virus etc), there have been no known cases of transmission of this type of pathogens by products manufactured according to this procedure. Other inactivation procedures such as pasteurization, dry‐heat or nanofiltration may prove equally effective. In addition, dry‐heat treatment and nanofiltration are capable of effectively eliminating non‐enveloped viruses (HAV, B19 virus). Recent studies show that the B19 virus is much more sensitive to heat (in lyophilized state or by pasteurization) and acid pH than previously thought.Although there is no evidence for the transmission of classic transmissible spongiform encephalopathies (TSEs) through blood or blood‐products transfusion, four possible cases have been reported in the United Kingdom involving transmission by non‐leukoreduced blood components of the agent that causes variant Creutzfeldt‐Jakob Disease (vCJD), a disease linked to the outbreak of bovine spongiform encephalopathy (BSE) which took place in that country. However, there are no cases of human TSE (classic or variant) transmission by plasma‐derived products. Analytical methods capable of detecting the vCJD agent in patients’ brains (where high titres are found) and other tissues (such as the spleen, appendix and lymph nodes, where much lower concentrations are found) are unable to detect the agent in blood or plasma from patients with vCJD, even in the clinical phase of the disease. Experiments by Grifols and other groups show that the capacity of the production processes to eliminate vCJD agent models is many orders of magnitude greater than the maximum expected load of the agent. In this regard, the efficacy of precipitation, affinity chromatography, depth filtration and nanofiltration are particularly notable.
Desmopressin for the treatment of haemophilia
Authors: CASTAMAN G.
Published: September 2010

Summary.  The synthetic vasopressin analogue (1–deamino‐8‐d‐arginine‐vasopressin) increases plasma concentration of factor VIII and von Willebrand factor in normal subjects and patients with mild haemophilia A and von Willebrand disease. Since its first clinical use in 1977, desmopressin has become the treatment of choice for patients with haemophilia A and factor VIII coagulant activity (FVIII:C) > 5% and has spared several patients the risk of acquiring blood‐borne viral infections due to the use of non‐virally inactivated plasma‐derived FVIII concentrates. An average two to sixfolds FVIII:C increase is typically observed in most patients and return to baseline occurs usually within 8 hours. Several clinical studies have demonstrated the clinical efficacy and safety of desmopressin and the availability of concentrated formulation for subcutaneous injection and of a nasal spray has paved the way to home‐treatment. However, overall it appears that haemophilic children may have a lower rate of biologic response compared to adults and a minority of adult patients are not able to attain clinically useful FVIII:C levels post‐desmopressin administration. Thus, in every patient with haemophilia A likely to be treated or candidate to an elective invasive procedure, a test‐infusion/injection should be carried out to assess the future usefulness of the compound.
The use of desmopressin in open‐heart surgery
Authors: CATTANEO M.
Published: September 2010

Summary.  Desmopressin (l‐deamino‐8‐d‐arginine vasopressin, DDAVP) is a synthetic analogue of the antidiuretic hormone vasopressin. Like the natural antidiuretic hormone, desmopressin increases the plasma levels of factor VIII and von Willebrand factor (vWF), with the advantage, compared to vasopressin, that it produces little or no vasoconstriction, no increase in blood pressure, and no contraction of the uterus or gastrointestinal tract, so that it is well tolerated when administered to humans. In 1977, desmopressin was used for the first time in patients with mild hemophilia A and von Willebrand disease (vWD) for the prevention and treatment of bleeding, first during dental extractions and then during major surgical procedures. The clinical indications for desmopressin rapidly expanded beyond hemophilia and vWD. The compound was shown to be efficacious even in bleeding disorders not involving a deficiency or dysfunction of factor VIII or vWF, including congenital and acquired defects of platelet function and such frequent abnormalities of hemostasis as those associated with chronic kidney and liver diseases. Desmopressin has also been used prophylactically in patients undergoing surgical operations characterized by large blood loss and transfusion requirements.
The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977–2007)
Authors: FEDERICI A. B.
Published: September 2010

Summary.  The aim of the treatment for von Willebrand disease (VWD) is to correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion as a result of reduced and/or dysfunctional von Willebrand factor (VWF) and the abnormal coagulation expressed by low levels of factor VIII (FVIII). Correction of both deficiencies can be achieved by administering the synthetic peptide desmopressin (DDAVP) or, in cases unresponsive to this agent, the plasma concentrates containing VWF and FVIII (VWF/FVIII). DDAVP is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments, but the drug can be clinically useful also in other VWD types, including acquired von Willebrand syndrome (AVWS). A test dose of DDAVP at the time of diagnosis is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding and surgery. DDAVP is not effective in VWD type 3 and in severe forms of VWD 1 and 2. It can induce transient thrombocytopenia in patients with VWD type 2B. The results of several retrospective studies on the use of DDAVP in VWD management have been reported by many authors in different countries for the last 30 years. However, despite the widespread use of DDAVP in the treatment of VWD, there are only a few prospective clinical trials in a large number of cases on DDAVP efficacy and safety aimed at determining benefits and limits of this therapeutic approach. An investigator‐driven observational prospective study on clinical efficacy of DDAVP in 200 patients with VWD types 1 and 2 has been recently organized: the effectiveness and safety of DDAVP will be evaluated prospectively for 24 months during bleeding episodes and minor or major surgeries in the VWD patients who were exposed to an infusion trial at enrollment.
YKL‐40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis
Authors: Richter Benedikte , Roslind Anne , Hesse Ulrik , Nordling Jørgen , Johansen Julia Sidenius , Horn Thomas , Hansen Alastair Bierre
Published: September 2010

Richter B, Roslind A, Hesse U, Nordling J, Johansen J S, Horn T & Hansen A B (2010) Histopathology 57, 371–383 YKL‐40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis

Aims:  Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL‐40. The aims were to examine YKL‐40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL‐40 could be a non‐invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity.

Methods and results:  Immunohistochemistry, immunoelectron microscopy and enzyme‐linked immunosorbent assay (ELISA) analyses in 45 patients showed YKL‐40 expression in detrusor mast cell granules and submucosal macrophages, and elevated YKL‐40 levels in serum and urine compared to healthy individuals (median 72 versus 7 μg/l, P < 0.001). Clinicopathological parameters showed associations of detrusor fibrosis with YKL‐40‐positive cells (P = 0.001), mast cells (P = 0.014) and urine YKL‐40 (P = 0.009). Bladder capacity correlated inversely with YKL‐40‐positive cells (P < 0.001) and mast cells (P = 0.029). Treatment intensity was not associated with YKL‐40.

Conclusion:  Serum and urine levels of YKL‐40 may be used as non‐invasive biomarkers in BPS/IC for the evaluation of bladder fibrogenesis.
Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers
Authors: Ianez Renata Fraga , Buim Marcilei E , Coutinho‐Camillo Claudia M , Schultz Regina , Soares Fernando A , Lourenço Silvia Vanessa
Published: September 2010

Ianez R F, Buim M E, Coutinho‐Camillo C M, Schultz R, Soares F A & Lourenço S V (2010) Histopathology 57, 410–417 Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers

Aims:  Myoepithelial cells are important components of salivary gland structure, aiding the expulsion of saliva from acinar lobules. The aim was to evaluate the expression of smooth muscle actin (SMA), calponin, caldesmon, CD10, CD29, S100 protein, glial fibrillary acidic protein (GFAP) and p63 in myoepithelial cells during salivary gland morphogenesis to understand the maturation process of these cells and their possible use in the diagnosis of salivary gland lesions.

Methods and results:  Major and minor human salivary glands at various stages of development, derived from fetuses at 8–26 weeks of gestation, were studied immunohistochemically. Fully developed salivary glands were used as controls. The protein p63 was present in all stages of salivary gland morphogenesis from initial bud to terminal bud stage. CD29, S100 and calponin were detected increasingly as salivary gland structure matured and in fully developed salivary gland. Proteins GFAP, CD10 and caldesmon were not observed in myoepithelial cells of salivary glands.

Conclusions:  The proteins SMA, calponin, CD29, S100 and p63, which are present from the earliest stages of salivary gland maturation, are valuable myoepithelial markers but, although very specific, are not exclusive markers for this cell type.
Annual and polyetic progression of citrus canker on trees protected with copper sprays
Authors: Behlau F. , Amorim L. , Belasque J. , Bergamin Filho A. , Leite R. P. , Graham J. H. , Gottwald T. R.
Published: September 2010

The effects of copper sprays on annual and polyetic progress of citrus canker, caused by Xanthomonas citri subsp. citri, in the presence of the Asian citrus leafminer (Phyllocnistis citrella), were evaluated in a study conducted in a commercial orchard in northwest Paraná state, Brazil, where citrus canker is endemic. Nonlinear monomolecular, logistic and Gompertz models were fitted to monthly disease incidence data (proportion of leaves with symptoms) for each treatment for three seasons. The logistic model provided the best estimate of disease progress for all years and treatments evaluated and logistic parameter estimates were used to describe polyetic disease dynamics. Although citrus canker incidence increased during each of the seasons studied, it decreased over the whole study period, more so in copper‐treated trees than in water‐sprayed controls. Copper treatment reduced disease incidence compared with controls in every year, especially 2004–2005, when incidence was ca. 10‐fold higher in controls than in treated plots (estimated asymptote values 0·82 and 0·07, respectively). Copper treatment also reduced estimated initial disease incidence and epidemic growth rates every year.
Maize dwarf mosaic virus diversity in the Johnsongrass native reservoir and in maize: evidence of geographical, host and temporal differentiation
Authors: Achon M. A. , Alonso‐Dueñas N. , Serrano L.
Published: September 2010

The genetic diversity and population structure of Maize dwarf mosaic virus (MDMV) was examined by analysis of the full coat protein gene of 539 isolates collected from maize and Johnsongrass (Sorghum halepense) from eight different maize‐growing areas in Spain. Restriction fragment length polymorphism analysis revealed that the MDMV population consisted of 49 genetic variants, with the three most frequent accounting for 44% of the isolates. This population was spatially structured according to the establishment of maize crops in the area. The highest nucleotide diversity values were observed in the old maize‐growing areas in the northeast of Spain (>0·211) and the lowest in the new maize‐growing areas in the west (<0·019). Moreover, the major genetic variants differed between the old and new maize‐growing areas. Evidence of host‐associated selection was found in the endemic area of the virus (Lleida), and aphid‐transmission studies suggested vector selection pressure. Assessment of the temporal evolution of the MDMV population in northeastern areas indicated that time was only significant in Lleida, where it explained 4·8% of the total variation over nine consecutive years.