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German universities built over the years highly specialized book collections for use by faculty and graduate students. The German term,seminarbibliothek, is often applied to these types of collections, although examples can be found in universities across Europe. The purpose of this article is to examine a similar type of collection using ebooks in veterinary science and to compare this collection to the standard subject classified ebook collections. Most collection development in college and university libraries focuses on academic subjects. The type of collection being described here focuses on a mission. A mission-focused collection increases the use of library holdings and greatly benefits the stakeholders within the institution. This study looks at how such a collection might be formed and defined and what possible effects this might have on the use of collections of this type. [ABSTRACT FROM PUBLISHER]

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles. [ABSTRACT FROM AUTHOR]

Objective: To identify techniques commonly used in the management of periradicular disease by general dental practitioners and to ascertain views on continuing professional education in endodontics.Design: Data was collected via a postal questionnaire distributed to 617 general dental practitioners in Scotland (33% of practitioners registered with the Dental Practice Board).Results: 417 (69%) questionnaires were completed and returned. Only 24.9% of respondents used rubber dam routinely. The majority of respondents used hand instruments for preparation with either sodium hypochlorite or local anaesthetic being used most frequently for irrigation. The mean time for treatment of a single rooted tooth was 71 minutes. The demand for continuing education courses was high with 340 and 197 respondents requesting endodontic and rubber dam courses, respectively.Conclusions: Traditional methods for preparing the root canal using hand instruments were favoured by most dentists. The major disincentive to the use of rotary instruments and new techniques for obturating with thermally softened gutta-percha was expense. The importance of rubber dam isolation requires reiteration and more continuing education courses are required to update clinical skills. [ABSTRACT FROM AUTHOR]

Objective: To identify factors influencing the diagnosis and management of periradicular disease by general dental practitioners.Design: The study was conducted in two stages. 1. Analysis of recent returns to the Scottish Dental Practice Board. 2. Data collection via a postal questionnaire distributed to 617 general dental practitioners in Scotland (33% of practitioners registered with the Dental Practice Board).Results: 417 (69%) questionnaires were completed and returned. The majority of respondents undertook root canal treatment and the number of cases treated had increased in the last five years. The vast majority of the respondents (89.3%) were confident in their diagnosis of periradicular disease and 77.1% were confident of their treatment of the disease. A referral system for treatment was used by 31% of respondents of whom the majority used a specialist in a hospital. Over 50% of the respondents undertook surgical root canal treatment. Only 40% of respondents followed up their completed cases for longer than six months. Constraints on the provision of treatment included the time available and the low level of fees.Conclusions: Current arrangements for the treatment of periradicular disease in general dental practice are less than optimal. The fiscal arrangements for the provision of these treatments must be developed to encourage a high standard of treatment to be performed thereby maximising the likelihood of success. In addition, efforts to inform patients of the benefits of the treatment of periradicular disease should be increased. [ABSTRACT FROM AUTHOR]

Background:Prostate cancer (PrCa) is one of the most common diseases to affect men worldwide and among the leading causes of cancer-related death. The purpose of this study was to use second-generation sequencing technology to assess the frequency of deleterious mutations in 22 tumour suppressor genes in familial PrCa and estimate the relative risk of PrCa if these genes are mutated.Methods:Germline DNA samples from 191 men with 3 or more cases of PrCa in their family were sequenced for 22 tumour suppressor genes using Agilent target enrichment and Illumina technology. Analysis for genetic variation was carried out by using a pipeline consisting of BWA, Genome Analysis Toolkit (GATK) and ANNOVAR. Clinical features were correlated with mutation status using standard statistical tests. Modified segregation analysis was used to determine the relative risk of PrCa conferred by the putative loss-of-function (LoF) mutations identified.Results:We discovered 14 putative LoF mutations in 191 samples (7.3%) and these mutations were more frequently associated with nodal involvement, metastasis or T4 tumour stage (P=0.00164). Segregation analysis of probands with European ancestry estimated that LoF mutations in any of the studied genes confer a relative risk of PrCa of 1.94 (95% CI: 1.56-2.42).Conclusions:These findings show that LoF mutations in DNA repair pathway genes predispose to familial PrCa and advanced disease and therefore warrants further investigation. The clinical utility of these findings will become increasingly important as targeted screening and therapies become more widespread. [ABSTRACT FROM AUTHOR]

Background:Prostate cancer (PrCa) is one of the most common cancers affecting men but its aetiology is poorly understood. Family history of PrCa, particularly at a young age, is a strong risk factor. There have been previous reports of increased PrCa risk in male BRCA1 mutation carriers in female breast cancer families, but there is a controversy as to whether this risk is substantiated. We sought to evaluate the role of germline BRCA1 mutations in PrCa predisposition by performing a candidate gene study in a large UK population sample set.Methods:We screened 913 cases aged 36-86 years for germline BRCA1 mutation, with the study enriched for cases with an early age of onset. We analysed the entire coding region of the BRCA1 gene using Sanger sequencing. Multiplex ligation-dependent probe amplification was also used to assess the frequency of large rearrangements in 460 cases.Results:We identified 4 deleterious mutations and 45 unclassified variants (UV). The frequency of deleterious BRCA1 mutation in this study is 0.45%; three of the mutation carriers were affected at age 65 years and one developed PrCa at 69 years. Using previously estimated population carrier frequencies, deleterious BRCA1 mutations confer a relative risk of PrCa of ∼3.75-fold, (95% confidence interval 1.02-9.6) translating to a 8.6% cumulative risk by age 65.ConclusionThis study shows evidence for an increased risk of PrCa in men who harbour germline mutations in BRCA1. This could have a significant impact on possible screening strategies and targeted treatments. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Ecology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: A family history of prostate cancer (PrCa) is a strong risk factor for the disease, indicating that inherited factors are important in this disease. We previously estimated that about 2% of PrCa cases diagnosed ≤ 55 years harbour a BRCA2 mutation and PrCa among BRCA2 carriers has been shown to be more aggressive, with poorer survival.Methods: To further evaluate the role of BRCA2 in PrCa predisposition, we screened 1864 men with PrCa aged between 36 and 88 years. We analysed the BRCA2 gene using a novel high-throughput multiplex fluorescence heteroduplex detection system developed for the ABI3130xl genetic analyzer.Results: We identified 19 protein-truncating mutations, 3 in-frame deletions and 69 missense variants of uncertain significance (UV) in our sample set. All the carriers of truncating mutations developed PrCa at ≤ 65 years, with a prevalence of BRCA2 mutation of 1.20% for cases in this age group.Conclusion: Based on the estimated frequency of BRCA2 mutations in the United Kingdom we estimate that germline mutations in the BRCA2 gene confer an ∼ 8.6-fold increased risk of PrCa by age 65, corresponding to an absolute risk of ∼ 15% by age 65. These results suggest that routine testing of early onset PrCa cases for germline BRCA2 mutations will further help to refine the prevalence and risk associated with BRCA2 mutations and may be useful for guiding management options. [ABSTRACT FROM AUTHOR]

KEY POINTS AND PRACTICAL RECOMMENDATIONS: •  β-Blockers are appropriate treatment for patients with hypertension and those who have concomitant ischemic heart disease, heart failure, obstructive cardiomyopathy, or certain arrhythmias. •  β-Blockers can be used in combination with other antihypertensive drugs to achieve maximal blood pressure control. Labetalol can be used in hypertensive emergencies and urgencies. •  β-Blockers may be useful in patients having hyperkinetic circulation (palpitations, tachycardia, hypertension, and anxiety), migraine headache, and essential tremor. •  β-Blockers are highly heterogeneous with respect to various pharmacologic effects: degree of intrinsic sympathomimetic activity, membrane-stabilizing activity, β(1) selectivity, α(1) -adrenergic-blocking effect, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific effects may be important in the selection of a drug for clinical use. •  β-Blocker usage to reduce perioperative ischemia and cardiovascular complications may not benefit as many patients as was once hoped and may actually cause harm in some individuals. Currently the best evidence supports β-blocker use in two patient groups: patients undergoing vascular surgery with known ischemic heart disease or multiple risk factors for it and for patients already receiving β-blockers for known cardiovascular conditions. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk. [ABSTRACT FROM AUTHOR]

The article discusses the need for the development of a more comprehensive sustainable energy law that will cater future challenges of renewable development in the U.S., focusing on the utility-scale renewables. It describes the conflicting laws used by federal, state, and local levels for each stage of renewable development, as well as identify the gaps and suggests how such laws should be enhanced to deal with the challenges. It claims the more scholarly and legislative focus should be given to the formulation of renewable energy law to address the eternal conflict between flexibility and predictability of laws. It adds that development of such a law must not only balance environmental and economic interests but protect human safety and health as well.

The Purdue University Libraries was an early implementer of purchasing books requested through interlibrary loan rather than borrowing the requested books. The service, called Books on Demand, began in January 2000. An analysis of the requests at the end of the first two years of service indicated that these patron-selected books were more likely to have repeat circulations than the books acquired through normal collection development processes. When the program reached its tenth year, the authors analyzed and compared the books purchased through Books on Demand with all other purchased books during the same period. Findings indicate that books acquired through this user-initiated program have higher circulation rates than books acquired through the normal selection channels. The difference is quite large, a mean of 4.1 compared to a mean of 2.4, when the first interlibrary loan use is included as a circulation. Therefore, the authors recommend that libraries investigate a service of purchasing books requested via interlibrary loan as a complement to other collection development efforts. [ABSTRACT FROM AUTHOR]

In solid organ transplantation, CYA dosing is based on the area under the concentration vs time curve (AUCinf). This study aimed to develop a guideline for the initial i.v. CYA dose for pediatric hematopoietic SCT (HSCT) patients to achieve the target AUCinf recommended in solid organ transplantation. Whole-blood CYA concentrations were determined in 24 patients (0.5–16.9 years) after the first i.v. dose given over 2 h, 1 day before HSCT. The i.v. CYA dose predicted to achieve an AUCinf of 4200 μg × h/l was calculated for each patient and expressed as a function of each patient's actual weight and body surface area (BSA). In patients 9 and >9 years of age, the mean i.v. CYA dose predicted to achieve the target AUC was 2.6±0.94 and 2.1±1.21 mg/kg, respectively. When these doses were expressed in terms of BSA, the mean dose was 65±23.1 and 68±35.0 mg/m2 in children 9 and >9 years of age, respectively. In children 0.5–17 years of age undergoing HSCT, we recommend an initial i.v. CYA dose of 65 mg/m2 infused over 2 h to achieve an AUCinf of approximately 4200 μg × h/l.Bone Marrow Transplantation (2008) 42, 455–459; doi:10.1038/bmt.2008.189; published online 14 July 2008 [ABSTRACT FROM AUTHOR]

The article presents a study on meeting academic needs for information using a customer service approach. The study aimed to investigate whether academic libraries should seek to improve general satisfaction with their services or are services more relevant than others. The study asserted that faculty and students mainly want information services. It analyzed the LibQual+(trademark) data to identify which other resources contribute to information satisfaction among users. The results indicated that access mechanisms were very relevant predictors of information satisfaction and that library facilities and staff were negligible predictors.

Robust protocols for microarray gene expression profiling of archival formalin-fixed paraffin-embedded tissue (FFPET) are needed to facilitate research when availability of fresh-frozen tissue is limited. Recent reports attest to the feasibility of this approach, but the clinical value of these data is poorly understood. We employed state-of-the-art RNA extraction and Affymetrix microarray technology to examine 34 archival FFPET primary extremity soft tissue sarcomas. Nineteen arrays met stringent QC criteria and were used to model prognostic signatures for metastatic recurrence. Arrays from two paired frozen and FFPET samples were compared: although FFPET sensitivity was low ( approximately 50%), high specificity (95%) and positive predictive value (92%) suggest that transcript detection is reliable. Good agreement between arrays and real time (RT)-PCR was confirmed, especially for abundant transcripts, and RT-PCR validated the regulation pattern for 19 of 24 candidate genes (overall R(2)=0.4662). RT-PCR and immunohistochemistry on independent cases validated prognostic significance for several genes including RECQL4, FRRS1, CFH and MET - whose combined expression carried greater prognostic value than tumour grade - and cmet and TRKB proteins. These molecules warrant further evaluation in larger series. Reliable clinically relevant data can be obtained from archival FFPET, but protocol amendments are needed to improve the sensitivity and broad application of this approach. [ABSTRACT FROM AUTHOR]

To determine graft-versus-leukemia (GVL) effect after hematopoietic stem cell transplantation (HSCT), we studied the outcome of consecutive children with acute lymphoblastic leukemia (ALL) who received fully matched marrow allografts comparing relapse rate post HSCT between matched sibling donor (MSD) and matched unrelated donor (MUD) recipients. Furthermore, we estimated event-free survival (EFS) on the basis of the occurrence of acute graft-versus-host disease (aGVHD). Between 1998 and 2006 we performed 37 fully MSD and 36 fully MUD HSCTs. All patients received identical conditioning regimens with cyclophosphamide/total body irradiation and dual GVHD prophylaxis with cyclosporine (CSA) and methotrexate (MTX). Three-year cumulative incidence of relapse for the MSD and MUD groups were 55.6±12.3 and 22.0±8.1%, respectively (P=0.03). Three-year EFS according to aGVHD was 32.7±12.2% for no aGVHD, 61.2±10.0% for grade I–II aGVHD and 66.7±11.1% for grade III–IV aGVHD. Three-year EFS and overall survival (OS) were 40.5±11.6, 49.1±9.5% for the MSD group, and 60.5±8.7, 62.3±8.4% for the MUD group. In children with ALL receiving dual GVHD prophylaxis, relapse rate is significantly higher among recipients of MSD compared to MUD transplantation, which may in part be attributed to a better GVL effect with the unrelated graft.Bone Marrow Transplantation (2007) 40, 951–955; doi:10.1038/sj.bmt.1705853; published online 17 September 2007 [ABSTRACT FROM AUTHOR]

The article talks about LibQUAL+, an assessment tool that can be used by libraries in assessing their services. The LibQUAL+ was developed by the Association of Research Libraries (ARL) which will be used in developing a survey that allowed local libraries to discover their particular strengths and deficiencies. LibQUAL+ enables libraries to compare their results with results of peer institutions and they can use a proved and tested survey instrument. Libraries can also use the new tool for help in strategic planning.

To compare the outcome of hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) conditioned with two different regimens: (1) single dose of VP16 (60 mg/kg over 4 h) and total body irradiation (TBI; 1200 cGy, in six fractions) or (2) Cyclophosphamide 50 mg/kg over 1 h daily for 4 days followed by the same dose of TBI. One hundred and seven children with ALL received fully matched HSCT from 1990 to 2003 in the Hospital for Sick Children, Toronto. All received cyclosporin A and a short course of methotrexate for graft-versus-host disease (GVHD) prophylaxis. The VP16 group, there were 36 matched related donor transplants (MRD) and 26 matched unrelated donor transplants (MUD), and in the cyclophosphamide group there were 23 MRD and 22 MUD transplants. Neutrophil engraftment occurred at a median of 18 and 17 days for the VP16/TBI and the CY/TBI groups, respectively. The 3 year event-free survival and overall survival were 47±7 and 55±7% for those receiving VP16/TBI, and 51±8 and 53±8% for the CY/TBI group. There were no significant differences in the prevalence of acute or chronic GVHD and transplant-related mortality between the two groups. Both VP16/FTBI and CY/FTBI regimen are equally effective regimens.Bone Marrow Transplantation (2006) 38, 739–743. doi:10.1038/sj.bmt.1705515; published online 2 October 2006 [ABSTRACT FROM AUTHOR]

Study Objectives. To compare the disposition of cyclosporine after the administration of two oral formulations to children undergoing hematopoietic stem cell transplantation, and to evaluate the relationship between whole blood cyclosporine concentrations during the dosing interval and the area under the whole blood concentration-time curve. Design. Prospective, descriptive, crossover study. Setting. Hematopoietic stem cell transplantation unit in a tertiary-quaternary university-affiliated pediatric hospital. Patients. Twenty-four pediatric patients aged 0.5-16.9 years undergoing allogeneic hematopoietic stem cell transplantation. Intervention. The modified oral formulation of cyclosporine was given on the first day (divided as two doses), and a single identical dose of the original oral formulation was given on the morning of the second day. Measurements and Main Results. Blood samples were obtained at 0, 0.5, 1.25, 2, 4, 6, 9, and 12 hours after the morning close from the lumen of the central venous catheter not previously used for intravenous cyclosporine administration. Cyclosporine concentration-time data were analyzed by using noncompartmental methods. Mean ± SD maximum concentrations were significantly higher after administration of the modified form than after administration of the original form (594.9 ± 349.7 vs 483.0 ± 363.0 µg/L, p=0.003), as was the area under the concentration-time curve from 0-12 hours (AUC0-12; 3432 ± 1563 vs 3144 ± 1780 µg/L⋅hr, p=0.022). For both formulations, cyclosporine concentrations at 4 hours after administration were most strongly correlated with the AUC0-12. Unlike that of the original formulation, the trough cyclosporine concentration of the modified form had the weakest relationship with AUC (Spearman p coefficient 0.584, p=0.003). Conclusion. Cyclosporine absorption is lower in children undergoing hematopoietic stem cell transplantation than in children receiving solid organ transplants. Dosage adjustment for the modified formulation based on trough concentration may not be appropriate because its relationship with the AUC was weak. The link between pharmacokinetic parameters and clinical outcomes, such as graft-versus-bust disease, must be further studied. [ABSTRACT FROM AUTHOR]

The feasibility of using the electrically evoked compound action potential (ECAP), measured with the NRT system (Neural Response Telemetry) and the NRT software (version 2.04), to quantify the longitudinal spread of neural excitation was examined in four subjects fitted with the Nucleus C124M cochlear implant. The ECAP and psychophysical forward-masking profiles were measured using stimulation on each of three electrodes, in basal, middle and apical positions. Spatial spread profiles derived from the ECAP measure produced broader functions than those derived from the psychophysical measure. These results, together with investigation of the change of ECAP spread pattern with stimulation current, suggest that functions derived from this 'simple' method were more influenced by the spread of electric field from excited neuron to electrode array than by breadth of the neural excitation pattern. The recently released NRT version 3.0 permits the masker and probe pulses to be delivered to separate electrodes, thus removing a fundamental limitation of version 2.04. Results from a pilot study, in which this capability was exploited, suggest that the spatial functions from this 'advanced' method may provide a better correlation with results from psychophysical forward masking. [ABSTRACT FROM AUTHOR]

A basic principle of information literacy programs is that skills needed to use computers and skills needed to find and evaluate information are two separate sets of skills. Outside the library this is not always the view. The claim is sometimes made that information skills are acquired by learning computer skills. This article uses data from a survey of computer and information skills to determine whether or not these skills are separate entities. The survey was given to incoming freshmen at Purdue University in West Lafayette, Indiana, in 1999 and 2000.

Summary:Allogeneic bone marrow transplant (BMT) with an MRD in complete remission (CR)1 is the preferred treatment for children with Philadelphia-positive (Ph+) ALL. The role of MUD BMT in CR1 is still controversial. We compared the outcomes of two treatment strategies: BMT using an MRD or MUD vs chemotherapy in children with Ph+ ALL in CR1. In total, 21 children were treated from 1985 to 2001. In all, 10 received chemotherapy and 11 received allogeneic BMT: four MRD, seven MUD. In the MRD group, one relapsed 12 months after BMT and died; the remaining three are long-term event-free survivors (median follow-up, 6.1 years). In the MUD group four died; the remaining three are long-term event-free survivors (median follow-up, 7.2 years). The 4-year event-free survival (EFS) for the BMT group was 53±15%. In the chemotherapy group, seven relapsed after a median period of 12.5 months and three remain in continuous CR (median follow-up, 2.4 years). Four chemotherapy patients received CR2 transplants; all died. The 4-year EFS for the chemotherapy and MUD groups was 33±17 and 35.7±20%, respectively. This difference was not statistically significant. We continue to support treating children with Ph+ ALL with MRD BMT in CR1. The effectiveness of MUD BMT vs chemotherapy merits further study.Bone Marrow Transplantation (2004) 33, 39-45. doi:10.1038/sj.bmt.1704319 Published online 20 October 2003 [ABSTRACT FROM AUTHOR]

Discusses the effect of bibliographic instruction on the demand for reference services. Purpose of the bibliographic program; Results of a research study on the topic using data from 83 Association of Research Libraries members; Impact of bibliographic skills instruction on library user.

Presents a study that examined the effectiveness of antiemetic prophylaxis in children receiving antineoplastic agents prior to undergoing bone marrow transplantation (BMT). Percentage of BMT patients who experienced nausea during the conditioning regimen; Components of BMT supportive therapy; Symptoms in women with breast cancer undergoing BMT.

Summary. Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)-matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre-BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft-versus-host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell-replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II–IV acute GVHD (58% versus 24% in the MRD group; P = 0·02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P = 0·06). Three years post BMT, the probabilities of transplant-related mortality were 33 ± 11% and 20 ± 8% in MUD and MRD groups respectively (P = 0·38); the probabilities of relapse were 28 ± 12% and 41 ± 9% respectively (P = 0·19). Lansky or Karnofsky performance scores in event-free survivors were 90–100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3–97), 3-year event-free survival was 49 ± 11% and 47 ± 9% in the MUD and MRD BMT groups respectively (P = 0·71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD. [ABSTRACT FROM AUTHOR]

We used a novel digital autoradiographic technique that enabled, for the first time, simultaneous visualization and quantification of spatial and temporal changes in carbon allocation patterns in ectomycorrhizal mycelia. Mycorrhizal plants of Pinus sylvestris L. were grown in microcosms containing non-sterile peat. The time course and spatial distribution of carbon allocation by P. sylvestris to mycelia of its mycorrhizal partners,Paxillus involutus (Batsch) Fr. and Suillus bovinus (L.): Kuntze, were quantified following 14C pulse labeling of the plants. Litter patches were used to investigate the effects of nutrient resource quality on carbon allocation. The wood-decomposer fungus Phanerochaete velutina (D.C.: Pers.) Parmasto was introduced to evaluate competitive and territorial interactions between its mycelial cords and the mycelial system of S. bovinus.Growth of ectomycorrhizal mycelium was stimulated in the litter patches. Nearly 60% of the C transferred from host plant to external mycorrhizal mycelium (> 2 mm from root surfaces) was allocated to mycelium in the patches, which comprised only 12% of the soil area available for mycelial colonization. Mycelia in the litter patch most recently colonized by mycorrhizal mycelium received the largest investment of carbon, amounting to 27 to 50% of the total 14C in external mycorrhizal mycelium.The amount of C transfer to external mycelium of S. bovinus following pulse labeling was reduced from a maximum of 167 nmol in systems with no saprotroph to a maximum of 61 nmol in systems interacting with P. velutina. The 14C content of S. bovinus mycelium reached a maximum 24–36 h after labeling in control microcosms, but allocation did not reach a peak until 56 h after labeling, when S. bovinus interacted with mycelium of P. velutina. The mycelium of S. bovinus contained 9% of the total 14C in the plants (including mycorrhizae) at the end of the experiment, but this was reduced to 4% in the presence of P. velutina.The results demonstrate the dynamic manner in which mycorrhizal mycelia deploy C when foraging for nutrients. The inhibitory effect of the wood-decomposer fungus P. velutina on C allocation to external mycorrhizal mycelium has important implications for nutrient cycling in forest ecosystems. [ABSTRACT FROM AUTHOR]

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m2 p.o. or by nasogastric tube. Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (auc) and an individualized dose which would achieve an auc of 1300 μm/min were calculated. mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. the relationship between the busulfan concentration at hour 6 and auc was determined using linear regression. thirty-nine courses of busulfan were evaluated in 38 patients. a change from the initial busulfan dose was required to achieve the target auc in 34 courses (87%). most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions. Obesity did not significantly affect busulfan dose requirements. Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r2 = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique. Bone Marrow Transplantation (2000) 26, 1143–1147. [ABSTRACT FROM AUTHOR]

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vsimmunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group. Bone Marrow Transplantation (2000) 26, 1149–1156. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated excessive telomeric shortening in peripheral blood leucocytes of bone marrow transplant (BMT) recipients. This finding has raised concerns about accelerated haemopoietic ageing that might predispose to clonal disorders and late graft failure. We studied the peripheral blood neutrophils and T cells of 14 fully engrafted long-term survivors of BMT. We found that in both neutrophils and T cells there was significant telomere shortening in the recipient (0.6 and 0.5 kb, respectively; P < 0.001 and < 0.04, respectively). We found no relationship between degree of shortening and the nucleated cell dose given at the time of transplant. We also demonstrated significantly longer telomeres in T cells than neutrophils from the same individual (mean 11.6 kb and 10.6 kb, respectively; P=0.0001). We propose mechanisms to account for these observations. The replicative stress that causes this telomere shortening does not necessarily occur at the level of the most primitive haemopoietic stem cell. [ABSTRACT FROM AUTHOR]

Focuses on the archives of the Academie des Sciences in Paris, France. Collection, inventorying and conservation of manuscripts; Dossiers on individual members and meetings; Sponsorship of competitions.

Busulphan (BU) pharmacokinetic (PK) studies in children undergoing bone marrow transplantation suggest that individual BU dosing may be necessary to optimise BU systemic exposure. Optimising BU systemic exposure may improve outcome and decrease toxicity in BMT. Because of practical limitations in obtaining blood from children and for financial reasons, a limited sampling method (LSM) is needed. However, such methods for BU have not been validated in children. In the present study, we individualized oral BU dosing in 10 children to target an area under the curve of BU (BU AUC) of 900–1400 μ M/min based on BU AUC0–∞ calculated from nine serum BU concentrations performed after a BU test dose of 40 mg/m2. We validated a LSM using 3 BU concentrations to determine AUC. Six of nine patients studied (one patient non-evaluable), required their doses modified (3, lower; 3, higher). The mean percent dose change was 26.2% (range -33.3% to +45.3%). Our three sample LSM BU AUC0–∞ (1098 ± 344, mean ± 1 s.d.) correlated highly with our nine sample BU AUC0–∞ (1132 ± 389, Pearson r = 0.98, P = 0.0001) and was not significantly different by t-test (P = 0.3). The mean percentage difference between the three sample LSM AUCs and the nine sample AUCs in each of our patients was 7.5%, (range -10.99% to +9.4%). Trough levels correlated extremely well with AUC (r = 0.95, P = 0.0001). Individual BU dosing, based on AUC, is necessary in most children to achieve targeted levels of BU therapy. An LSM of three BU concentrations performed at 0.5 h, 1 h and 6 h post-BU test dose closely predicts the AUC calculated from nine sampling points. [ABSTRACT FROM AUTHOR]

Comments on several issues related to medical care in Great Britain. Safety and danger of pipe gases; Management of the elderly agitated demented patient; Prescribing costs of general practitioner.

Focuses on issues related to medicine in Great Britain. Influence of government policies on the practice of medical services; Attributes of estrogens in the causation of endometrial carcinoma; Effects of feeding infants with cows milk as a breast milk supplement.

The angiotensin-converting enzyme (ACE) inhibitor trandolapril, a non-sulfhydryl prodrug which is hydrolysed into trandolaprilat, was studied in 322 hypertensives of African-American descent using a double-blind, randomised, placebo-controlled, parallel study design. Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day trandolapril, an analysis of drug effect on trough blood pressure (BP) stratified by age, gender, weight, pre-treatment plasma renin activity, and trandolaprilat concentration was performed. Two mg was the lowest effective trandolapril dose, whereas doses above 4 mg did not significantly reduce trough BP. Reduction in BP did not correlate with trough plasma trandolaprilat concentration. Pre-treatment plasma renin activity was not a reliable indicator of anti-hypertensive response, as similar reductions in BP occurred even in patients with the lowest renin levels. There were no observable differences based on age, gender or measurements of the renin-angiotensin-aldosterone axis. In conclusion, neither age, gender or plasma renin activity influenced anti-hypertensive response to angiotensin-converting enzyme inhibition in African-Americans. [ABSTRACT FROM AUTHOR]