Packed red blood cells suppress myeloid dendritic cell and monocyte inflammatory responses in a whole blood model of transfusion

Purpose/Objective: The basis for poor outcomes in some patients post transfusion remains largely unknown. Despite leukodepletion, there is still evidence of immunomodulatory effects of transfusion that require further study. In addition, there is evidence that the age of blood components transfused significantly affects patient outcomes. Myeloid dendritic cell (DC) and monocyte immune function were studied utilising an in vitro whole blood model of transfusion. Materials and methods: Freshly collected (‘recipient’) whole blood was cultured with ABO compatible leukodepleted PRBC at 25% blood replacement-volume (6hrs). PRBC were assayed at [Day (D) 2, 14, 28and 42 (date-of expiry)]. In parallel, LPS or Zymosan (Zy) were added to mimic infection. Recipients were maintained for the duration of the time course (2 recipients, 4 PRBC units, n = 8).Recipient DC and monocyte intracellular cytokines and chemokines (IL-6, IL-10, IL-12,TNF-a, IL-1a, IL-8, IP-10, MIP-1a, MIP-1b, MCP-1) were measured using flow cytometry. Changes in immune response were calculated by comparison to a parallel no transfusion control (Wilcoxin matched pairs). Influence of storage age was calculated using ANOVA. Results: Significant suppression of DC and monocyte inflammatory responses were evident. DC and monocyte production of IL-1a was reduced following exposure to PRBC regardless of storage age (P < 0.05 at all time points). Storage independent PRBC mediated suppression of DC and monocyte IL-1a was also evident in cultures costimulated with Zy. In cultures co-stimulated with either LPS or Zy, significant suppression of DC and monocyte TNF-a and IL-6 was also evident. PRBC storage attenuated monocyte TNF-a production when co-cultured with LPS (P < 0.01 ANOVA). DC and monocyte production of MIP-1a was significantly reduced following exposure to PRBC (DC: P < 0.05 at D2, 28, 42; Monocyte P < 0.05 all time points). In cultures co-stimulated with LPS and zymosan, a similar suppression of MIP-1a production was also evident, and production of both DC and monocyte MIP-1b and IP-10 were also significantly reduced. Conclusions: The complexity of the transfusion context was reflected in the whole blood approach utilised. Significant suppression of these key DC and monocyte immune responses may contribute to patient outcomes, such as increased risk of infection and longer hospital stay, following blood transfusion.

Dengue fever viral exposure rates among blood donors during outbreaks in North Queensland

Introduction: Dengue poses a problem for safe transfusion of blood components with confirmed reports of transfusion-transmission in Hong Kong and Singapore. The largest outbreak in 50 years occurred in North Queensland during 2008/2009 with more than 1,000 confirmed cases in Cairns and Townsville. During this outbreak, supplementary questioning for all donors was implemented, and fresh components were not manufactured from at risk donors. We aim to determine the seroprevalence of dengue exposure in this population during this epidemic. Methods: Samples were collected from blood donors during the 2008/2009 epidemic and 3 months after the last confirmed case. These samples were tested for anti-Dengue IgM, IgG and NS1 antigen with commercially available ELISA based assay kits from PanBio. Results: Initial analyses revealed 2.7% of samples from deferred donors were IgM repeat reactive. Of these, 16% were also positive for anti-dengue IgG, while none of these were positive for the NS1 viral antigen. However, two NS1 positives were found in samples collected from deferred donors. Conclusions: This initial analysis represents recent and cumulative past exposure in a presumed asymptomatic population, and will provide documentation of the rate of asymptomatic dengue infection during the epidemic. This data can also be used to assess the risk of dengue becoming endemic in North Queensland given that the mosquito vector is established in this region.

Assessment of damages for wrongful birth and consolidation in advance care directives

The recent decision of Waller v James involved a claim by the plaintiff parents for damages for wrongful birth against the defendant doctor, Dr James, a gynaecologist with a practice in infertility and IVF procedures, who had been consulted by the plaintiffs. The second plaintiff, Mr Waller suffered an inherited anti-thrombin deficiency (ATD), a condition which results in a propensity for the blood to clot, at least in adults. Dr James subsequently recommended IVF treatment. The first plaintiff, Mrs Waller became pregnant after the first cycle of IVF treatment. Her son Keeden was born on 10 August 2000 with a genetic anti-thrombin deficiency. Keeden was released from hospital on 14 August 2000. However, he was brought back to the hospital the next day with cerebral thrombosis (CSVT). As a result of the thrombosis, he suffered permanent brain damage, cerebral palsy and related disabilities. The plaintiffs alleged that the defendant was in breach of contract and his common law duty of care to the plaintiffs in failing to inform them, or cause them to be informed, of the hereditary aspects of ATD. They further alleged that, had they been properly informed, they would not have proceeded to conceive a child using the male plaintiff’s sperm and therefore avoided the harm that had befallen them. The plaintiffs claimed damages to compensate them for their losses, including psychiatric and physical injuries and the costs of having, raising and caring for Keeden. The defendant was held to be not liable in negligence by Justice Hislop of the Supreme Court of New South Wales because a finding was made on medical causation which was adverse to the plaintiffs claim.

Shadows : Re-visualising the shark. Developing a framework for hybrid photography in the illumination of nonhuman animal and ecological perspectives at Heron Island and Gladstone, Great Barrier Reef

This study investigated how and to what degree “hybrid photography”—the simultaneous use of indexical and fictional properties and strategies— innovates the representation of animals within animalcentric, ecocentric frameworks. Design theory structured this project’s Practice-led, Visual research methodology framework. Grounded theory processes articulated emerging categories of hybrid photography through systematically and comparatively treating animal photography works for reflexive analysis. Design theory then applied and clarified categories, developing practice that re-visualised shark perspectives as new ecological discourse. Shadows, a creative practice installation, realised a full-scale photographic investigation into shark and marine animal realities of a specific environment—Heron Island and Gladstone, Great Barrier Reef—facing ecological crisis from dredging and development at Gladstone Harbour. Works rendered and explored hybrid photography’s capacity for illuminating nonhuman animals, in particular, sharks, and comprise 65% of this project’s weighting. This exegetical paper offers a definition, strategies and evaluation of hybrid photography in unsettling animal perspectives as effective ecological discourse, and comprises 35%.

Fluid-structure interaction analysis of full scale vehicle-barrier impact using coupled SPH-FEA

Portable water-filled barriers (PWFB) are roadside structures used to separate moving traffic from work-zones. Numerical PWFB modelling is preferred in the design stages prior to actual testing. This paper aims to study the fluid-structure interaction of PWFB under vehicular impact using several methods. The strategy to treat water as non-structural mass was proposed and the errors were investigated. It was found that water can be treated with the FEA-NSM model for velocities higher than 80kmh-1. However, full SPH/FEA model is still the best treatment for water and necessary for lower impact velocities. The findings in this paper can be used as guidelines for modelling and designing PWFB.

Effect of aerobic interval training and caffeine on blood platelet function

Purpose: Hyperactive platelets contribute to the thrombotic response in humans, and exercise transiently increases platelet function. Caffeine is routinely used by athletes as an ergogenic aid, but the combined effect of exercise and caffeine on platelet function has not been investigated. Methods: Twelve healthy males were randomly assigned to one of four groups and undertook four experimental trials of a high-intensity aerobic interval training (AIT) bout or rest with ingestion of caffeine (3 mg·kg-1) or placebo. AIT was 8 × 5 min at approximately 75% peak power output (approximately 80% V?O2peak) and 1-min recovery (approximately 40% peak power output, approximately 50% V?O2peak) intervals. Blood/urine was collected before, 60, and 90 min after capsule ingestion and analyzed for platelet aggregation/activation. Results: AIT increased platelet reactivity to adenosine diphosphate (placebo 30.3%, caffeine 13.4%, P < 0.05) and collagen (placebo 10.8%, caffeine 5.1%, P < 0.05) compared with rest. Exercise placebo increased adenosine diphosphate-induced aggregation 90 min postingestion compared with baseline (40.5%, P < 0.05), but the increase when exercise was combined with caffeine was small (6.6%). During the resting caffeine protocol, collagen-induced aggregation was reduced (-4.3%, P < 0.05). AIT increased expression of platelet activation marker PAC-1 with exercise placebo (P < 0.05) but not when combined with caffeine. Conclusion: A single bout of AIT increases platelet function, but caffeine ingestion (3 mg·kg) does not exacerbate platelet function at rest or in response to AIT. Our results provide new information showing caffeine at a dose that can elicit ergogenic effects on performance has no detrimental effect on platelet function and may have the potential to attenuate increases in platelet activation and aggregation when undertaking strenuous exercise.

Effect of interval training intensity on fat oxidation, blood lactate and the rate of perceived exertion in obese men

Purpose The objectives of this study were to examine the effect of 4-week moderate- and high-intensity interval training (MIIT and HIIT) on fat oxidation and the responses of blood lactate (BLa) and rating of perceived exertion (RPE). Methods Ten overweight/obese men (age = 29 ±3.7 years, BMI = 30.7 ±3.4 kg/m2) participated in a cross-over study of 4-week MIIT and HIIT training. The MIIT training sessions consisted of 5-min cycling stages at mechanical workloads 20% above and 20% below 45%VO2peak. The HIIT sessions consisted of intervals of 30-s work at 90%VO2peak and 30-s rest. Pre- and post-training assessments included VO2max using a graded exercise test (GXT) and fat oxidation using a 45-min constant-load test at 45%VO2max. BLa and RPE were also measured during the constant-load exercise test. Results There were no significant changes in body composition with either intervention. There were significant increases in fat oxidation after MIIT and HIIT (p ≤ 0.01), with no effect of intensity. BLa during the constant-load exercise test significantly decreased after MIIT and HIIT (p ≤ 0.01), and the difference between MIIT and HIIT was not significant (p = 0.09). RPE significantly decreased after HIIT greater than MIIT (p ≤ 0.05). Conclusion Interval training can increase fat oxidation with no effect of exercise intensity, but BLa and RPE decreased after HIIT to greater extent than MIIT.

HPLC method for preliminary analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus

An HPLC with SPE method has been developed for analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus (ASE). The plasma sample was prepared by SPE method equipped with Oasis HLB cartridge (3cc, 60 mg). The analysis was performed on a Dikma Diamonsil RP(18) column (4.6 mmx150 mm, 5 microm) with the gradient elution of solvent A (ACN) and solvent B (0.1% aqueous phosphoric acid, v/v) and the detection wavelength was set at 270 nm. The calibration curve was linear over the range of 0.156-15.625 microg/mL. The LOD was 60 ng/mL. The intraday precision was less than 5.80%, and the interday precision was less than 6.0%. The recovery was (87.30 +/- 1.73)%. As a result, 19 constituents were detected in rat plasma after oral administration of the ASE, including 11 original compounds in ASE and eight metabolites, and three of the metabolites originated from syringin in ASE. Six constituents were identified by comparing with the corresponding reference compounds.

The effect of varied test instructions on neuropsychological performance following mild traumatic brain injury : an investigation of ‘diagnosis threat’

Diagnosis threat is a psychosocial factor that has been proposed to contribute to poor outcomes following mild traumatic brain injury (mTBI). This threat is thought to impair the cognitive test performance of individuals with mTBI because of negative injury stereotypes. University students (N= 45, 62.2% female) with a history of mTBI were randomly allocated to a diagnosis threat (DT, n=15), reduced threat (DT-reduced, n=15) or neutral (n=15) group. The reduced threat condition invoked a positive stereotype (i.e., that people with mTBI can perform well on cognitive tests). All participants were given neutral instructions before they completed baseline tests of: a) objective cognitive function across a number of domains; b) psychological symptoms; and, c) PCS symptoms, including self-reported cognitive and emotional difficulties. Participants then received either neutral, DT or DT-reduced instructions, before repeating the tests. Results were analyzed using separate mixed model ANOVAs; one for each dependent measure. The only significant result was for the 2 X 3 ANOVA on an objective test of attention/working memory, Digit Span, p<.05, such that the DT-reduced group performed better than the other groups, which were not different from each other. Although not consistent with predictions or earlier DT studies, the absence of group differences on most tests fits with several recent DT findings. The results of this study suggest that it is timely to reconsider the role of DT as a unique contributor to poor mTBI outcome.

What's in it for me? Virtual conspicuous donation strategies as a source of value in blood donation

Providing an incentive is becoming common practice among blood service organisations. Driven by self-orientated motives rather than pure philanthropic intentions, research is showing that people increasingly want something in return for their support. It is contended that individuals donate conspicuously with the hope it will improve their social standing. Yet there is limited evidence for the effectiveness of conspicuous recognition strategies, and no studies, to the researcher’s knowledge, that have examined conspicuous donation strategies in an online social media context. There is a need to understand what value drives individuals to donate blood, and whether conspicuous donation strategies are a source of such value post blood donation. The purpose of this paper is to conceptualise how conspicuous donation strategies, in the form of virtual badges on social media sites, can be applied to the social behaviour of blood donation, as a value-adding tool, to encourage repeat behaviour.

Give some, get some: investigating the relationship between conspicuous donation behaviour on social media and customer value in a blood donation context

Previous research has questioned the role of altruism in charitable donation and suggests that such behaviour is also motivated by self-interest, such as public recognition or emotional satisfaction. Recognising this, not-for-profit organisations have developed strategies that allow individuals to donate conspicuously, and are at an embryonic stage of turning to social media to provide such recognition. Under investigation in this paper, is the relationship between conspicuous donation behaviour (CDB) on social media and customer value, in blood donation. Online survey results, from a sample of 186 Australian blood donors, support the proposed framework. Significant relationships between self-orientated CDB and emotional value, and other-orientated CDB and social value are demonstrated. The findings provide valuable insights into the use of conspicuous donation strategies on social media as a means to add value to the donation experience, and contribute to our understanding into the under-researched areas of CDB and customer value.

Beliefs underlying the intention to donate again among first-time blood donors who experience a mild adverse event

Using the belief basis of the theory of planned behavior (TPB), the current study explored the rate of mild reactions reported by donors in relation to their first donation and the intention and beliefs of those donors with regard to returning to donate again. A high proportion of first-time donors indicated that they had experienced a reaction to blood donation. Further, donors who reacted were less likely to intend to return to donate. Regression analyses suggested that targeting different beliefs for those donors who had and had not reacted would yield most benefit in bolstering donors’ intentions to remain donating. The findings provide insight into those messages that could be communicated via the mass media or in targeted communications to retain first-time donors who have experienced a mild vasovagal reaction.

Use of serum and blood samples on filter paper to improve the surveillance of dengue in Pacific Island Countries

Background In Pacific Island Countries (PICs) the epidemiology of dengue is characterized by long-term transmission of a single dengue virus (DENV) serotype. The emergence of a new serotype in one island country often indicates major outbreaks with this serotype will follow in other PICs. Objectives Filter paper (FP) cards on which whole blood or serum from dengue suspected patients had been dried was evaluated as a method for transportation of this material by standard mail delivery throughout the Pacific. Study design Twenty-two FP-dried whole blood samples collected from patients in New Caledonia and Wallis & Futuna Islands, during DENV-1 and DENV-4 transmission, and 76 FP-dried sera collected from patients in Yap State, Majuro (Republic of Marshall Islands), Tonga and Fiji, before and during outbreaks of DENV-2 in Yap State and DENV-4 in Majuro, were tested for the presence of DENV RNA, by serotype specific RT-PCR, at the Institut Louis Malardé in French Polynesia. Results The serotype of DENV could be determined, by a variety of RT-PCR procedures, in the FP-dried samples after more than three weeks of transport at ambient temperatures. In most cases, the sequencing of the envelope gene to genotype the viruses also was possible. Conclusions The serotype and genotype of DENV can be determined from FP-dried serum or whole blood samples transported over thousands of kilometers at ambient, tropical, temperatures. This simple and low-cost approach to virus identification should be evaluated in isolated and resource poor settings for surveillance for a range of significant viral diseases.

Platinum-based chemotherapy in metastatic breast cancer : current status

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently ∼60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer. © 2003 Elsevier Ltd. All rights reserved.

Platinum-based chemotherapy in metastatic breast cancer : the Leicester (UK) experience

Aims: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. Materials and methods: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n = 23), or cisplatin-etoposide (PE) (n = 19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m 2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m 2), and cisplatin (50 mg/m 2) all on day 1; and cisplatin (75 mg/m 2) and etoposide (100 mg/m 2) on day 1 and (100 mg/m 2) orally twice a day on days 2-3. Results: The response rate for 40 evaluable patients (MVP: n = 23; PE: n = 17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n = 19; PE: n = 18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer. © 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.