Amoebic gill disease increases energy requirements and decreases hypoxia tolerance in Atlantic salmon (Salmo salar) smolts.

Globally, Atlantic salmon (Salmo salar Linnaeus) aquaculture is now routinely affected by amoebic gill disease (AGD; Neoparamoeba perurans). The disease proliferates throughout the summer and is implicated in decreasing tolerance of salmon to environmental perturbations, yet little empirical evidence exists to support these observations. Using salmon acclimated to 15 or 19 °C, our aim was to determine the effects of clinically light-moderate (industry-relevant) AGD on metabolism (MO2rest and MO2max), aerobic scope (MO2max - MO2rest), excess post-exercise oxygen consumption (EPOC), and hypoxia tolerance. An increase in MO2rest (~8% and ~ 13% increase within the 15 and 19 °C acclimation groups, respectively) with increasing disease signs demonstrated an increase in baseline energy requirements as the disease progressed. Conversely, MO2max remained stable at both temperatures (~364 mg O2 kg-1 h-1), resulting in a decline in aerobic scope by 13 and 19% in the 15 and 19 °C groups, respectively. There was evidence of a decrease in hypoxia tolerance as the dissolved oxygen concentrations at loss of equilibrium increased by ~8% with more severe lesion coverage of the gills. These results suggest an increase in basal energy requirements and reduction in hypoxia tolerance as AGD proliferates, lending support to the idea that AGD reduces environmental tolerance. However, the lack of an effect of acclimation temperature indicates that the temperature-disease interaction may be more complicated than currently thought.

An Economic Evaluation of the Costs and Benefits of Providing Comprehensive Supports to Students in Elementary School.

There is growing evidence that out-of-school factors, such as physical and mental health, family support, and social and emotional development, significantly affect student learning (Berliner 2009). To address challenges related to poverty, schools are being charged with serving as a focal point in providing and coordinating support services for students and their families (Adelman and Taylor 2002; Dryfoos 2002). In many schools these support services are provided in fragmented ways that do not address the needs of all students or engage teachers in connecting these services to the academic mission of the school (Walsh and DePaul 2008). An emerging school-based model, broadly termed "comprehensive student support" (Walsh et al. 2016), is designed to overcome such fragmentation. In this paper, we build upon previous effectiveness work with an economic evaluation of a successful support model, City Connects. We find that the benefits of the program exceed the costs, indicating that the program is a sound investment and should be considered an option to address the needs of students and to prevent future crises from disrupting their learning.

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies.

Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM.

Horse owners' knowledge, and opinions on recognising colic in the horse.

BACKGROUND: Colic is the most common emergency problem in the horse. An owner's ability to recognise colic and seek assistance is a critical first step in determining case outcome. OBJECTIVES: The aim of this study was to assess horse owners' knowledge and opinions on recognising colic. STUDY DESIGN: Cross-sectional study. METHODS: An online questionnaire was distributed to horse owners with open and closed questions on their knowledge of normal clinical parameters in the horse, confidence and approach to recognising colic (including assessment through case scenarios), and their demographics. Descriptive and chi squared statistical analyses were performed. RESULTS: There were 1564 participants. Many respondents either did not know or provided incorrect estimates for their horse's normal clinical parameters: only 45% (n = 693/1540) gave correct normal values for heart rate, 45% (n = 694/1541) for respiratory rate and 67% (n = 1028/1534) for rectal temperature. Knowledge of normal values was statistically associated with participants' educational qualifications (P<0.01). Owners said if they suspected their horse had colic they would assess faecal output (76%; n = 1131/1486), gastrointestinal sounds (75%; n = 1113/1486), respiratory rate (65%; n = 967/1486) and heart rate (54%; n = 797/1486). There was a lack of consensus on whether to call a vet for behavioural signs of colic, unless the signs were severe or persistent. The majority of participants (61%) were confident that they could recognise most types of colic. In the case scenarios, 49% were confident deciding that a surgical case had colic, but 9% were confident deciding an impaction case had colic. MAIN LIMITATIONS: Most respondents were UK based; risk of self-selection bias for owners with previous experience of colic. CONCLUSIONS: There was marked variation in horse owners' recognition and responses to colic, and significant gaps in knowledge. This highlights the need for the development of accessible educational resources to support owners' decision-making.

Clinical implications of germline mutations in breast cancer genes: RECQL.

BACKGROUND: The identification of new hereditary breast cancer genes is an area of highly active research. In 2015, two independent studies provided initial evidence for a novel breast cancer susceptibility gene, RECQL, a DNA helicase which plays an important role in the DNA damage response. Several subsequent studies in independent patient cohorts have provided further data on RECQL variant frequency in additional populations, some of which have brought in to question the increased breast cancer risk associated with RECQL mutations. RESULTS: The initial reports present findings from whole exome sequencing of high-risk familial breast cancer cases in the French-Canadian, Polish and Han Chinese populations and estimate the carrier frequency of pathogenic RECQL mutations in high-risk breast cancer patients who have previously tested negative for BRCA1 and BRCA2 mutations to be approximately 1-2%. Proposed founder mutations were identified in French-Canadian and Polish populations. Functional studies support loss of function of the helicase activity of RECQL for some of the reported pathogenic mutations. An additional study in a cohort of Southern Chinese high-risk breast cancer patients estimated the frequency of pathogenic RECQL mutations to be 0.54%. A possible Chinese founder mutation was identified, but only a small number of controls were sequenced. Subsequent case-control studies screening for the Polish founder mutation in patients from Germany and Belarus did not find any evidence for increased breast cancer risk for this variant. An Australian case-control study also failed to identify an increased risk of breast cancer associated with RECQL loss of function variants. CONCLUSIONS: RECQL plays an important role in DNA repair, and is a plausible candidate breast cancer susceptibility gene. Initial studies showed evidence of an association between variants in this gene and an increased breast cancer risk in three separate populations, and identified founder mutations with significantly increased odds ratios. However, several subsequent studies have failed to support the association. With the limited and conflicting evidence available, there remains debate as to whether there is an increased breast cancer risk in individuals carrying RECQL loss of function variants. Further studies are required to better quantify the risks associated with RECQL variants and the current evidence base is not sufficient to justify routine inclusion of RECQL on breast cancer gene panels in clinical use. Management of patients in whom RECQL variants have been identified should be based on clinician assessment, in the context of the family history. Further studies are required to better quantify the risks to RECQL mutation carriers and may also guide management and potential therapeutic targeting for patients.

Principles for the safety evaluation of cosmetic powders.

Consumer exposure to cosmetic (personal care) products is mostly by dermal contact, however additional considerations with regards to potential inhalation exposure from some cosmetics, such as sprays and powders, may be needed for a robust and reliable safety assessment. To get a deeper understanding of the exposure to airborne particles and droplets during product application, a team of international experts was founded under the umbrella of the European Association of the Cosmetic Industry "Cosmetics Europe" (CE) in Brussels. This expert team has worked out a pragmatic strategy how small and medium sized enterprises (SMEs), but also relevant authorities, could handle the safety evaluation of cosmetic powder products. Sufficient information on the aerodynamic diameter of sprayed droplets and here specifically of airborne particles is essential in addition to knowing the exposure after typical product application. The current article is focused on the determination of inhalation exposure to solids, and the derivation of safe exposure levels for cosmetic powder products found in the market. The principles described herein are very similar to spray products as published earlier and should be applied in a similar way (Steiling et al., 2014). Prediction models for the best estimate of inhalation exposure, developed with data from computer simulation programs, individual real-time measurements or finally by experience from the market were introduced and applied. Safety assessment approaches for exposure from powder spray products were developed and have been already considered in regulatory guidelines like the EC Cosmetics Regulation.

UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following 24weeks of treatment.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) lead to accumulation of high concentrations of potentially toxic fatty acid intermediates. Newborn screening and early intervention have reduced mortality, but most patients continue to experience frequent hospitalizations and significant morbidity despite treatment. The deficient energy state can cause serious liver, muscle, and heart disease, and may be associated with an increased risk of sudden death. Triheptanoin is a medium odd-chain fatty acid. Anaplerotic metabolites of triheptanoin have the potential to replace deficient tricarboxylic acid (TCA) cycle intermediates, resulting in net glucose production as a novel energy source for the treatment of LC-FAOD. STUDY DESIGN: A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks. RESULTS: Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period. CONCLUSIONS: In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: Colic is the most common equine emergency problem, and one of the main causes of equid deaths. The horse owners' ability to recognise colic is a critical first step in determining case outcome. OBJECTIVES: To assess equine owners' knowledge and recognition of colic. STUDY DESIGN: Online questionnaire of horse owners. METHODS: An online survey was designed to evaluate owners' approach to colic in the horse. The survey included questions on owner demographics, their recognition of colic (including owner's opinions of their ability to recognise colic, their approach, and their recognition of colic using case vignettes), and their knowledge of normal ranges for clinical parameters. Descriptive and chi squared statistical analysis was performed. RESULTS: The survey was completed by 1061 UK respondents. Six per cent of owners thought they could recognise all types of colic, 61% said they could recognise most cases and 30% said they could recognise some but not all cases. Owners said they would assess faecal output (73% of respondents), gastrointestinal sounds (69%), respiratory rate (62%) and heart rate (50%) in horses with suspected colic. One fifth (22%) of owners would call a vet immediately without assessing any parameters. Many respondents either did not know, or provided incorrect estimates of normal values for clinical parameters: 30.4% were 'unsure' of the normal heart rate and 35.5% gave heart rate values which were outside reference ranges; only 24.5% gave appropriate values for normal respiratory rates and only 31% gave normal temperature values. There was no statistical significance between participants' age, educational qualifications, or their experience with horses and their knowledge of normal clinical parameters. CONCLUSIONS: Owners varied in their approach and ability to recognise colic, and many had significant gaps in their knowledge of normal parameters. Educational materials and/or training to assist owners could help address these issues. Ethical animal research: The study did not involve animal research. The study was reviewed and approved by the Ethics Committee, School of Veterinary Medicine and Science, University of Nottingham. The questionnaire was conducted in accordance with the 1998 Data Protection Act, and the British Educational Research Association's Revised Ethical Guidelines for Educational Research (2004). SOURCE OF FUNDING: Adelle Bowden's studentship is funded by the School of Veterinary Medicine and Science, University of Nottingham. Competing interests: None declared.

Alterations in gill structure in tropical reef fishes as a result of elevated temperatures.

Tropical regions are expected to be some of the most affected by rising sea surface temperatures (SSTs) because seasonal temperature variations are minimal. As temperatures rise, less oxygen dissolves in water, but metabolic requirements of fish and thus, the demand for effective oxygen uptake, increase. Gill remodelling is an acclimation strategy well documented in freshwater cyprinids experiencing large seasonal variations in temperature and oxygen as well as an amphibious killifish upon air exposure. However, no study has investigated whether tropical reef fishes remodel their gills to allow for increased oxygen demands at elevated temperatures. We tested for gill remodelling in five coral reef species (Acanthochromis polyacanthus, Chromis atripectoralis, Pomacentrus moluccensis, Dascyllus melanurus and Cheilodipterus quinquelineatus) from populations in northern Papua New Guinea (2° 35.765' S; 150° 46.193' E). Fishes were acclimated for 12-14 days to 29 and 31°C (representing their seasonal range) and 33 and 34°C to account for end-of-century predicted temperatures. We measured lamellar perimeter, cross-sectional area, base thickness, and length for five filaments on the 2nd gill arches and qualitatively assessed 3rd gill arches via scanning electron microscopy (SEM). All species exhibited significant differences in the quantitative measurements made on the lamellae, but no consistent trends with temperature were observed. SEM only revealed alterations in gill morphology in P. moluccensis. The overall lack of changes in gill morphology with increasing temperature suggests that these near-equatorial reef fishes may fail to maintain adequate O2 uptake under future climate scenarios unless other adaptive mechanisms are employed.

Pentacoordinate silicon complexes with dynamic motion resembling a pendulum on the S(N)2 reaction pathway.

A series of glutarimide derivatives which has two carbonyl coordination sites for intramolecular pentacoordination at silicon with a X(1+n)SiC(3-n)O moiety have been synthesised and characterized. The substituent (leaving group) effects on the Si-O bond exchange between the two coordination sites (resembling a pendulum) have been studied by comparison of the differently substituted (X = F, Cl, OTf, Br and I) structures. The activation parameters for the Si-O bond exchange process were measured by NMR and separately computed and are consistent with the strength of Si-O bond coordination and the nature of the leaving group, X. The temperature-dependent (29)Si NMR spectroscopy is supported by X-ray crystallography and shows that the tetrahedral reactant is converted into pentacoordinate intermediates by intramolecular O-Si association followed by reversion to a tetrahedral geometry by Si-X dissociation. The two association/dissociation patterns offer a model for nucleophilic substitution at a silicon atom. A continuum of structures on the S(N)2 reaction profile from the glutarimide derivatives correlates reasonably well with the structural data obtained from derivatives of lactams, diketopiperazines and quinolones.

The National Neonatal Transport Programme (NNTP) 2004-2009.

A retrospective analysis of all National Neonatal Transport Programme (NNTP) transport data from 2004-2009 was performed. 1621 transports were conducted during this period with a yearly average of 271. The majority (96%) were ground transports. 1118 (69%) were forward transfers. Of the 446 (27.5%) retrotransfers, 411 (91%.) were to tertiary centres. When transported, 592 infants (36.5%) were <48 hours old and 770 (47.5%) were <1 week old. 902 transports (55%) involved infants <32 wks birth-gestation and 720 (44%) involved infants weighing <1500gms. Transport for management of patent ductus arteriosus accounted for 357 (22%). The average mobilisation time was 34 minutes. 54% of transports were completed after scheduled service hours. The NNTP currently transports similar numbers of critically ill infants during its 8hr service compared with neonatal transport services that operate 24hr services. Performing PDA ligations in a tertiary neonatal unit would significantly reduce the number of neonatal transports required annually.

Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma.

BACKGROUND: Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4Ralpha and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum-sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. METHODS: Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. RESULTS: Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC(100) relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05-0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC(100) relative to control (P < 0.05) at nominal b.i.d. doses of 3-100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. CONCLUSION: Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma.

Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkey.

BACKGROUND: Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics. OBJECTIVE: Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey. METHODS: Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8-24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes. RESULTS: The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02). CONCLUSION: Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis.

Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI, diffusion and perfusion MRI and MRS.

Prolonged hemiparetic migraine aura can cause diagnostic confusion and be mistaken for ischaemic stroke occurring during the course of a migraine--'migrainous infarction'. We report a case of prolonged hemiparesis occurring during the course of a migraine attack. Though initially confused with migrainous infarction, we suggest with sequential magnetic resonance imaging, magnetic resonance angiography, diffusion, perfusion images and magnetic resonance spectroscopy that the hemiplegia was not of vascular origin and that the patient had sporadic hemiplegic migraine. We hypothesize that the mechanisms of sporadic hemiplegic migraine probably lie at a cellular level, similiar to familial hemiplegic migraine.

Validation of a micro-CT technique for measuring volumetric wear in retrieved acetabular liners.

In this study, a novel micro-CT-based technique for evaluating wear in retrieved acetabular liners was introduced and validated. Six UHMWPE acetabular components ranging in implantation time from 2.7 to 14.4 years were collected and evaluated with the use of a high-resolution micro-CT scanner. The components were scanned with a uniform volumetric resolution of 74 microns (16-bit precision) with the use of a 1,024 x 1,024 in-plane image matrix. Manual rigid 3D image registration of the interior hemispherical portion of the acetabular cup with geometric primitives by trained observers allowed for isolation, visualization, and measurement of the wear volume. Results for these six components indicated an average wear rate of 65 mm(3)/year. Overall scanner error was quantified gravimetrically and associated with a maximum uncertainty of 0.6%. Intra-- and interobserver uncertainty analysis showed the method to be both accurate and repeatable.

Systems biology may work when we learn to understand the parts in terms of the whole.

The first point to note about whether systems biology will work is that the essential idea of systems biology is not new: there has been interest in it, as well as efforts to apply it, since the middle of the 20th century. The difference now is that it has become fashionable, with an explosion in the number of publications using the two words, albeit not always with the same meaning. The reductionist approach remains dominant, however, and systems biology is often seen as no more than integration of diverse data into models of systems. This way of thinking needs to be changed if systems biology is to lead to an understanding of life and to provide the benefits that are expected from it. The emphasis ought to be on the needs of the system as a whole for understanding the components, not the converse. General properties of metabolic systems, such as feed-back inhibition, can be properly understood by taking account of supply and demand, i.e. the requirements of the system as a whole, but this is often overlooked. Metabolism tends to be viewed as static, although enzymes (and proteins in general) are continuously synthesized and degraded. The fact that they are themselves therefore metabolites introduces great complexity to metabolism, including an implication of infinite regress; understanding how living organisms escape from this will be an essential step towards understanding life.

Workflow improvement and impact of the new Beckman Coulter LH 1500 high throughput automated hematology workcell.

Our core laboratory at St. Joseph's Medical Center (SJMC) recently installed the new Beckman Coulter LH 1500 fully automated hematology workcell. Like many laboratories in North America and other parts of the world, we are under significant pressure to improve productivity, reduce costs, and improve service provision to our hospital and clinician bases. The difficulty of meeting this challenge is often further compounded by an increasing shortage of qualified technologist personnel. We recently reported on the significant productivity gains with the introduction of the LH 750 hematology system into the core laboratory, including a 23% reduction in slide review rate, automation of reticulocyte and nucleated red blood cell counts, and an 82% increase in the pass-through rate. Evolution to the next stage of automation has come much quicker than anticipated owing to a steep rise in workload and an ever increasing shortage of trained and experienced technologists to fill vacancies in the 24-hour core laboratory operation. We chose to upgrade our LH 750 analyzers to the newly introduced LH 1500 hematology workcell in order to cope with the increased workload and shortage of available experienced hematology technologists. The LH 1500 is a compact, high throughput, fully automated hematology workcell. It is designed to automate all manual process and handling steps associated with hematology analyses, including sample sorting, loading and unloading of cassettes, automatic rerun and reflex testing, sample storage, and tracking of samples. The LH 1500 is comprised of a minimum of 2, and up to 4, LH 750 instruments (with or without integrated slidemaker/stainers). The instruments are bidirectionally interfaced and linked to a fully automated conveyor track, specimen inlet and outlet stations, a sample stockyard, and a line controller. The configuration we chose at SJMC incorporates 1 LH 750 and 1 LH 755. We report that the upgrade to the LH 1500 was a relatively straightforward process and required no redesign of the core laboratory. Based on our evaluation, we estimate cost savings with the LH 1500 of between three quarters to 1 full-time equivalent, which eliminated or decreased many manual handling steps. In addition, this increase in efficiency has freed up our technologist resources to concentrate on the more difficult and clinically important samples. This is the first published report on the new LH 1500 hematology workcell. Our research indicates that the LH 1500 is the first hematology workcell to offer hematology laboratories the next level of automation and virtually eliminate preanalytical and postanalytical sample handling and sorting. For core laboratories and high-throughput hematology laboratories that face similar pressures to ours, the LH 1500 would appear as an attractive solution to maximize hematology productivity and improve service delivery.

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/