Youth organizations, social mobility and health in middle age: evidence from a Scottish 1950s prospective cohort study.

BACKGROUND: Informal educational programmes focused on youth development appear to improve health and well-being at time of involvement. Less is known about long-term effects. We investigate their impact on self-reported general health in mid-life using the Aberdeen Children of the 1950s (ACONF) cohort. METHODS: We use a subset (n = 1333) of the ACONF cohort, born 1950-56, in Aberdeen Scotland, who took part in Family and Reading Surveys in 1964 and a follow-up questionnaire in 2001. We explore exposure to youth development focused clubs in childhood on self-reported general health around age 50 mediated by adult socioeconomic position. Logistic regression and mediation analysis were used to report odds ratios and natural direct and indirect effects, respectively, on multiply imputed data. RESULTS: Being a member of the Scouts/Guides (G&S) was associated with a 53% (95% confidence interval 1.03-2.27) higher odds of 'excellent' general health in adulthood compared to children attending 'other clubs'. Indirect effects of G&S and Boys'/Girls' Brigade (B&GB) on general health acting via higher socioeconomic position show positive associations; 12% and 6% higher odds of 'excellent' general health in adulthood compared to children attending 'other clubs', respectively. Comparison of indirect with direct effects suggests 27% of this association is mediated through a higher adult socioeconomic position in adulthood. CONCLUSIONS: These results suggest a beneficial association between attending G&S and B&GB clubs in childhood and adult general health. As these organizations are volunteer-led, this may represent a cost-effective method for improving population health.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Superatom Picture of Collective Nonclassical Light Emission and Dipole Blockade in Atom Arrays.

We show that two-time, second-order correlations of scattered photons from planar arrays and chains of atoms display nonclassical features that can be described by a superatom picture of the canonical single-atom g_{2}(τ) resonance fluorescence result. For the superatom, the single-atom linewidth is replaced by the linewidth of the underlying collective low light-intensity eigenmode. Strong light-induced dipole-dipole interactions lead to a correlated response, suppressed joint photon detection events, and dipole blockade that inhibits multiple excitations of the collective atomic state. For targeted subradiant modes, the nonclassical nature of emitted light can be dramatically enhanced even compared with that of a single atom.

Prognostic factors of functional outcome after hip fracture surgery: a systematic review.

Objective: this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery. Design: systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections. Results: from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome. Conclusion: we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.

Coarsening Dynamics of an Isotropic Ferromagnetic Superfluid.

In zero magnetic field the ground-state manifold of a ferromagnetic spin-1 condensate is SO(3) and exhibits Z_{2} vortices as topological defects. We investigate the phase-ordering dynamics of this system after being quenched into this ferromagnetic phase from a zero-temperature unmagnetized phase. Following the quench, we observe the ordering of both magnetic and gauge domains. We find that these domains grow diffusively, i.e., with domain size L(t)∼t^{1/2}, and exhibit dynamic scale invariance. The coarsening dynamics progresses as Z_{2} vortices annihilate; however, we find that at finite energy a number of these vortices persist in small clumps without influencing magnetic or gauge order. We consider the influence of a small nonzero magnetic field, which reduces the ground-state symmetry, and show that this sets a critical length scale such that when the domains reach this size the system dynamically transitions in order parameter and scaling behavior from an isotropic to an anisotropic ferromagnetic superfluid.

Transfusion in adults: 10-year survival of red cell, plasma and platelet recipients following transfusion.

OBJECTIVE: To determine the long-term survival of adult recipients (>16 years) transfused with red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) in England and Wales. STUDY DESIGN AND METHODS: The EASTR study (Epidemiology and Survival of Transfusion Recipients) was a national multi-centre epidemiological study with cross-sectional sampling from 29 representative hospitals in England supplied by NHS Blood and Transplant (NHSBT). Three separate groups of RBC (n = 9142), FFP (n = 4232) and PLT (3584) recipients were sampled over 1 year (1 October 2001-30 September 2002), with prospective survival monitoring for 10 years. This study presents the data for adult recipients (>16 years of age). RESULTS: The median age interquartile range (IQR) of adult transfusion recipients was RBC 70 (54-79), FFP 66 (51-76), PLT 62 (48-72). The 10-year survival for adult RBC, FFP and PLT recipients was highest for RBC recipients at 36% confidence interval (CI 35-37%, n = 8675), compared with 30% for both FFP (CI 29-32%, n = 3849) and PLT (CI 28-30%, n = 3110) recipients. In all groups, post-transfusion survival decreased with age, and a risk-adjusted analysis showed that reason for transfusion, transfusion type (surgical or medical) and cancer diagnosis (presence or absence) were all significantly associated with survival. Older patients with cancer receiving a medical rather than surgical transfusion had the highest hazard of death. CONCLUSION: This study shows that survival following transfusion in England is broadly similar to that reported in other wealthy nations. More than 70% of recipients die within 10 years of transfusion, but long-term survival is common in younger patients (>80% 10-year survival in RBC recipients aged 16-39 years).

Transfusion in children: epidemiology and 10-year survival of transfusion recipients.

OBJECTIVE: To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival. STUDY DESIGN AND METHODS: The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children <16 years. RESULTS: Children <16 years comprised 449 (5%) of the RBC, 362 (9%) of the FFP and 452 (13%) of the PLT recipients. In children 54% of RBC, 63% FFP and 45% PLT recipients were under 1 year of age and 57% RBC, 60% FFP and 52% PLT were male. Median (IQR) DEduring the study year was 3(2-8); 5(2-13) and 11(6-21) in the RBC, FFP and PLT cohorts, respectively. A total of 20% of RBC, 31% of FFP and 54% of PLT recipients had been exposed to >10 donors. Perinatal conditions were the commonest indication for transfusion in the RBC (36%) and FFP (44%) cohorts and comprised 31% of the PLT cohort. Medical conditions (48%), predominantly malignancy (33%), were the most frequent indication in the PLT cohort. The 10 year (95% CI) survival rates were 81% (77-85%), 72% (67-76%) and 71% (66-75%)for RBC, FFP and PLT cohorts, respectively. CONCLUSIONS: Around half of paediatric transfusion recipients are under 1 year of age. Exposure to components from multiple donors is common. At least 70% of paediatric recipients are long survivors and are at risk for late complications of transfusion.

A clinical governance framework for blood services.

BACKGROUND AND OBJECTIVES: The elements of clinical governance, which ensure excellence in clinical care, can be applied to blood services. In this survey, their application in a range of blood providers was gauged, with the aim of identifying best practice and producing a generalizable framework. MATERIALS AND METHODS: The Medical Directors of members of the Alliance of Blood Operators surveyed how different elements of clinical governance operated within their organizations and developed recommendations applicable in the blood service environment. RESULTS: The recommendations that emerged highlighted the importance of an organization's culture, with the delivery of optimal clinical governance being a corporate responsibility. Senior management must agree and promote a set of values to ensure that the system operates with the patient and donor at its heart. All staff should understand how their role fits into the 'journey to the patient', and a culture of openness promoted. Thus, reporting of errors and risks should be actively sought and praised, with penalties applied for concealment. Systems should exist to collect, analyse and escalate clinical outcomes, safety data, clinical risk assessments, incident reports and complaints to inform organizational learning. CONCLUSION: Clinical governance principles from general health care can be applied within blood services to complement good manufacturing practice. This requires leadership, accountability, an open culture and a drive for continuous improvement and excellence in clinical care.

Blood use in neurosurgical cases at the university hospital of the west indies.

OBJECTIVE: Many neurosurgical cases are done without the need for blood transfusion, yet blood is unnecessarily cross-matched, resulting in wasted resources. This study was undertaken to document and compare the number of units of blood components requested, cross-matched and transfused in neurosurgical cases at the University Hospital of the West Indies (UHWI). METHODS: A prospective, observational study was undertaken over one year. Data collected for each patient included demographic information, relevant perioperative data, and blood banking data including blood components requested, cross-matched and transfused. Data were analysed using SPSS version 16. RESULTS: Data were analysed on 152 patients, 71 females (46.7%) and 81 males (53.3%). The mean age was 48.7 ± 19.6 years and 100 of the procedures were done electively (65.8%). Blood components were ordered in 114 (75%) cases, red cells more commonly in 113 (74.3%) patients, and plasma in 19 (12.5%) patients. Overall, 20 patients (13.2%) were transfused. Most patients (90.9%) needed one to two units of blood. Of the 236 units of blood components that were cross-matched or prepared, only 62 were transfused. The cross-match/preparation to transfusion ratio (CTR/PTR) was 6.00 for red cells and 1.31 for plasma. Preoperative haemoglobin ≤ 10.0 g/dL (p = 0.001), estimated blood loss of ≥ 1 litre (p < 0.001), higher American Society of Anesthesiologists (ASA) physical status score (p < 0.03) and a resident as lead surgeon (p < 0.05), were significant predictors of blood transfusion. CONCLUSION: The transfusion rate was low with a high cross-match to transfusion ratio, suggesting that less cross-matching is needed. A new approach to blood ordering for neurosurgical cases is recommended.

Strategies for screening blood donors to source convalescent H1N1v plasma for intervention therapy.

BACKGROUND AND OBJECTIVES: During the 1918, pandemic blood components were successfully used to treat severe influenza pneumonia. A Proof of Principle trial investigating the clinical benefit of convalescent plasma was proposed in the 2009 H1N1v epidemic with the aim of screening donors for high titre antibody in order to stockpile plasma packs to be used for treatment for severe pneumonia. MATERIALS AND METHODS: Serum samples were collected from donors. IgG antibody capture format enzyme-linked immunoassays using recombinant proteins (GACELISAs) were compared with microneutralization (MN) and haemagglutination inhibition (HAI). The influence of age and history of influenza-like illness (ILI) on the detection of high titre antibody was examined. RESULTS: 1598 unselected donor sera collected in October and December 2009 were tested by HAI. The HAI and demographic data defined a possible strategy for selective donor screening. One of the GACELISAs was highly specific for recent infection but showed lower sensitivity than HAI. CONCLUSIONS: During the 2009 pandemic screening 17- to 30-year-old donors by HAI delivered around 10% with high antibody levels. The ELISA using a short recombinant H1N1v HA detected fewer reactives but was more specific for high titre antibody (≥1:256). Screening strategies are proposed based on using HAI on serum or GACELISA on plasma.

HIV testing trends among gay men in Scotland, UK (1996-2005): implications for HIV testing policies and prevention.

OBJECTIVE: To examine trends in the HIV testing behaviour of gay men in Scotland over a 10-year period. METHODS: Seven cross-sectional surveys in commercial gay venues in Glasgow and Edinburgh (1996-2005). 9613 men completed anonymous, self-completed questionnaires (70% average response rate). RESULTS: Among 8305 respondents included in these analyses, HIV testing increased between 1996 and 2005, from 49.7% to 57.8% (p<0.001). The proportion of men who had tested recently (in the calendar year of, or immediately before, the survey) increased from 28.4% in 1996 to 33.2% in 2005, when compared with those who have tested but not recently, and those who have never tested (adjusted odds ratio 1.31, 95% CI 1.13 to 1.52). However, among ever testers, there was no increase in rates of recent testing. Recent testing decreased with age: 31.3% of the under 25, 30.3% of the 25-34, 23.2% of the 35-44 and 21.2% of the over 44 years age groups had tested recently. Among men reporting two or more unprotected anal intercourse partners in the previous year, only 41.4% had tested recently. CONCLUSIONS: HIV testing among gay men in Scotland increased between 1996 and 2005, and corresponds with the Scottish Government policy change to routine, opt-out testing in genitourinary medicine clinics. Testing rates remain low and compare unfavourably with near-universal testing levels elsewhere. The limited change and decline across age groups in recent HIV testing rates suggest few men test repeatedly or regularly. Additional, innovative efforts are required to increase the uptake of regular HIV testing among gay men.

AIDS mortality in African migrants living in Portugal: evidence of large social inequalities.

OBJECTIVE: To examine infectious disease and AIDS mortality among African migrants in Portugal, gender and socio-economic differences in AIDS mortality risk, and differences between African migrants to Portugal and to England and Wales. METHODS: Data from death registrations, 1998-2002, and the 2001 Census were used to derive standardised death rates by country of birth, occupational class (men only), and marital status. RESULTS: Compared with people born in Portugal, African migrants had higher mortality for infectious diseases including AIDS. There was considerable heterogeneity among Africans, with those from Cape Verde having the highest mortality. Death rates were more than five times higher among those who were unmarried than those who were. A larger proportion of Africans were unmarried accounting for some excess mortality. Death rates were also higher among men from manual occupational classes than among men from non-manual. A comparison with England and Wales shows that death rates for infectious disease and AIDS in Portugal are much higher and Africans in Portugal also fare worse than Africans in England and Wales. CONCLUSION: AIDS mortality rates were higher among Africans than those born in Portugal and were associated with socio-environmental factors. Further research is required to interpret the excess mortality among Africans and there is a need to ensure the inclusion of relevant data items on ethnicity in national monitoring and surveillance systems.

Botulinum neurotoxin A blocks synaptic vesicle exocytosis but not endocytosis at the nerve terminal.

The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K(+)-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K(+) depolarization, in the presence of Ca(2+), triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A-blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca(2+) is required for synaptic vesicle membrane retrieval.

The EASTR study: a new approach to determine the reasons for transfusion in epidemiological studies.

Previous studies of blood use have used different methods to obtain and classify transfusion indications. Before undertaking a national study of transfusion recipients, a pilot study was performed over 2 months at two teaching and two district general hospitals to match information from hospital transfusion laboratories with clinical coding data from the hospital's Patients Administration System to determine the indication for transfusion in 2468 recipients. Data analysis revealed major limitations in the conventional use of primary diagnostic International Statistical Classification of Disease and Related Health Problems 10th Revision (ICD-10) or procedure Office of Population, Censuses and Surveys - Classification of Surgical Operations and Procedures - 4th Revision (OPCS-4) codes alone in allocating transfusion indications. A novel algorithm was developed, using both types of code, to select the probable indication for transfusion for each patient. A primary OPCS-4 code was selected for recipients transfused in relation to surgery (43%) and either the primary (36%) or the secondary (12%) ICD-10 code was chosen for recipients transfused for medical reasons. The remaining patients were unclassified. Selected codes were then collated into Epidemiology and Survival of Transfusion Recipients (EASTR) casemix groups (E-CMGs). The most frequent E-CMGs were haematology (15% of recipients), musculoskeletal (14%), digestive system (12%) and cardiac (10%). The haematology E-CMG includes patients with malignant and non-malignant blood disorders and recipients transfused for anaemia where no cause was listed. Recipients undergoing hip and knee replacement and coronary artery bypass grafting are within the musculoskeletal and cardiac E-CMGs. The digestive E-CMG includes recipients transfused for gastrointestinal (GI) bleeds and those undergoing GI surgery. This methodology provides a more useful means of establishing the probable indication for transfusion and arranging recipients into clinically relevant groups.

The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

Lymphocyte blastogenic response to ovalbumin in a model for canine allergy.

Lymphocyte stimulation tests (LST) were performed in five dogs sensitised with ovalbumin (OVA) and seven healthy dogs. In addition, all five OVA-sensitised and two control dogs were tested after two in vivo provocations with OVA-containing eye drops. The isolated cells were suspended in culture media containing OVA and were cultured for up to 12 days. Proliferation was measured as reduction in 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity by flow cytometry on days 0, 3, 6, 9 and 12. A cell proliferation index (CPI) for each day and the area under the curve (AUC) of the CPI was calculated for each dog. All OVA-sensitised dogs demonstrated increased erythema after conjunctival OVA application. The presence of OVA-specific lymphocytes was demonstrated in 2/5 OVA-sensitised dogs before and 4/5 after in vivo provocation. Using the AUC, the difference between OVA-sensitised and control dogs was significant in all three LST before in vivo provocation (P<0.05) and borderline significant (P=0.053) in 2/3 LST after provocation. The most significant difference in CPI was observed after 9 days of culture (P=0.001). This pilot study indicates that the LST allows detection of rare antigen specific memory T-cells in dogs previously sensitised to, but not concurrently undergoing challenge by a specific antigen.

Exercise- and hypoxia-induced anaerobic metabolism and recovery: a student laboratory exercise using teleost fish.

Anaerobic metabolism is recruited in vertebrates under conditions of intense exercise or lowered environmental oxygen availability (hypoxia), typically resulting in the accumulation of lactate in blood and tissues. Lactate will be cleared over time after the reoxygenation of tissues, eventually returning to control levels. Here, we present a laboratory exercise developed as part of an upper-level vertebrate physiology class that demonstrates the effects of exercise and hypoxia exposure on blood lactate in fish and the subsequent decrease in lactate during recovery. Typically, the results obtained by students demonstrate that both treatments cause significant increases in blood lactate concentrations (two to three times higher than control values) that decrease back to normal values within 3 h of recovery under normoxia. The procedures described are generally applicable to other fish species and provide an alternative to using humans or other mammalian species to investigate anaerobic metabolism.

The dynamics of clot formation in fresh-frozen plasma.

BACKGROUND: Factor VIII (FVIII) levels are used as a quality marker of fresh-frozen plasma (FFP); however, other clotting factors are not routinely measured. METHODS: We assessed additional haemostatic parameters and the dynamics of coagulation using Thrombelastography (TEG) and a thrombin generation test (TGT). FFP was prepared on the day of donation (Day 0) or after overnight hold at 4 degrees C (Day 1). RESULTS: Factor VIII in Day 1 FFP was 18% lower than in Day 0. TEG parameters in Day 1 FFP were consistent with increased coagulability and did not correlate with altered levels of clotting factors, but were consistent with the increased levels of microparticles seen in the Day 1 samples. TGT studies exhibited increased lag time, time to peak and reduced peak thrombin generation, but no change in endogenous thrombin potential (ETP) on Day 1. There was a weak association between FVIII level and both ETP and peak thrombin (ETP r(s)> or = 0.22, P< or = 0.003; peak thrombin r(s)> or = 0.48, P< or = 0.0001), which was influenced by ABO group, with the lowest levels in group O. CONCLUSION: We conclude that levels of FVIII do not predict the haemostatic potential of FFP and that there may be a role for alternative technologies in monitoring the quality of FFP.