Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

Every minute counts: A comparison of thawing times and haemostatic quality of plasma thawed at 37°C and 45°C using four different methods.

BACKGROUND: Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and it might remove the need to have extended pre-thawed plasma: thus, reducing unnecessary plasma wastage. STUDY DESIGN AND METHODS: The aims of this study were to assess (a) the thawing times and (b) in vitro haemostatic quality of thawed plasma using Barkey Plasmatherm V (PTV) at 37 and 45°C versus Barkey Plasmatherm Classic (PTC) at 37 and 45°C, Sarstedt Sahara-III Maxitherm (SS-III) at 37°C and Helmer Scientific Thermogenesis Thermoline (TT) at 37°C. Haemostatic quality was assessed using LG-Octaplas at three different time points: baseline (5 min), 24 and 120 h after thawing. RESULTS: The thawing time (SD) of 2 and 4 units was significantly different between different thawers. PTV at 45°C was the fastest method for both 2 and 4 units (7.06 min [0.68], 9.6 min [0.87], respectively). SS-III at 37°C being the slowest method (24.69 min [2.09] and 27.18 min [4.4], respectively) (p = < 0.05). Baseline measurements for all assays showed no significant difference in the prothrombin time, fibrinogen, FII, FV, protein C activity or free protein S antigen between all methods tested. However, at baseline PTV (both 37°C and 45°C) had significantly higher levels of FVII, FVIII and FXI and shortened activated partial thromboplastin time. DISCUSSION: PTV was the quickest method at thawing plasma at both 37 and at 45°C. The haemostatic quality of plasma thawed at 45 versus 37°C was not impaired. Thawing frozen plasma at 45°C should be considered.

Advancing the social return on investment framework to capture the social value of public health interventions: semistructured interviews and a review of scoping reviews.

OBJECTIVES: Investment in public health has far-reaching impacts, not only on physical health but also on communities, economies and the environment. There is increasing demand to account for the wider impact of public health and the social value that can be created, which can be captured through the use of the social return on investment (SROI) framework. This study aims to explore the application of SROI and identify areas of advancement for its use in public health. STUDY DESIGN AND METHODS: Publically available SROI studies of public health interventions previously identified through published systematic scoping reviews were examined through a methodological lens. This was complemented by semistructured interviews with key public health academic experts with experience in the field of SROI. The results were thematically analysed and triangulated. RESULTS: In total, 53 studies and nine interviews were included in the analysis. All interviewees agreed that SROI is a suitable framework to demonstrate the social value of public health interventions. Developmental aspects were also identified through the analysis. This included a more systematic use of SROI principles and methodological developments. Lastly, it was identified that further advancements were needed to promote awareness of SROI and how it can be used to generate investment. CONCLUSION: By identifying key areas for advancement, the results from this study can be used to further refine the SROI framework for use within the speciality to promote investment in services and interventions that demonstrate maximum value to people, communities, economies and the environment.

A systematic review of whether Health Impact Assessment frameworks support best practice principles.

OBJECTIVES: Health Impact Assessment (HIA) is an evidence-based approach to assess the likely public health impacts of a policy or plan in any sector. Several HIA frameworks are available to guide practitioners doing a HIA. This systematic review sought to determine whether these support practitioners to meet best practice principles defined by the International Association for Impact Assessment. STUDY DESIGN: This was a systematic review. METHODS: Three complementary search strategies were used to identify frameworks in June 2022. We used three databases to find completed HIAs published in the last five years and hand-searched their reference lists for frameworks. We also searched 23 HIA repositories using Google's Advanced function and contacted HIA practitioners via two international mailing lists. We used a bespoke quality appraisal tool to assess frameworks against the principles. RESULTS: The search identified 24 HIA frameworks. None of the frameworks achieved a 'good' rating for all best practice principles. Many identified the principles but did not provide guidance on how to meet them at all HIA steps. The highest number of frameworks were rated 'good' for ethical use of evidence and comprehensive approach to health (n = 15). Eight frameworks were rated as 'good' for participation, and two for equity. The highest number of frameworks rated 'poor' for sustainability (n = 11). CONCLUSIONS: There is marked variation in the degree to which HIA frameworks support the best practice principles. HIA practitioners could select elements from different frameworks for practical guidance to meet all the best practice principles.

Trade-offs between succulent and non-succulent epiphytes underlie variation in drought tolerance and avoidance.

Epiphyte communities comprise important components of many forest ecosystems in terms of biomass and diversity, but little is known regarding trade-offs that underlie diversity and structure in these communities or the impact that microclimate has on epiphyte trait allocation. We measured 22 functional traits in vascular epiphyte communities across six sites that span a microclimatic gradient in a tropical montane cloud forest region in Costa Rica. We quantified traits that relate to carbon and nitrogen allocation, gas exchange, water storage, and drought tolerance. Functional diversity was high in all but the lowest elevation site where drought likely limits the success of certain species with particular trait combinations. For most traits, variation was explained by relationships with other traits, rather than differences in microclimate across sites. Although there were significant differences in microclimate, epiphyte abundance, and diversity, we found substantial overlap in multivariate trait space across five of the sites. We found significant correlations between functional traits, many of which related to water storage (leaf water content, leaf thickness, hydrenchymal thickness), drought tolerance (turgor loss point), and carbon allocation (specific leaf area, leaf dry matter content). This suite of trait correlations suggests that the epiphyte community has evolved functional strategies along with a drought avoidance versus drought tolerance continuum where leaf succulence emerged as a pivotal overall trait.

Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomised trial.

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

A pooled analysis of randomized, controlled, phase 3 trials investigating the efficacy and safety of a novel, fixed dose calcipotriene and betamethasone dipropionate cream for the topical treatment of plaque psoriasis.

BACKGROUND: Plaque psoriasis is a common, chronic and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP). OBJECTIVES: Pooled analysis of two different phase 3 clinical trails to compare superiority regarding efficacy, safety and quality of life (QoL) between CAL/BDP PAD-cream and CAL/BDP TS. METHODS: The data from two phase 3, multicentre, randomized, investigator-blind, active and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS) and cream vehicle, which were applied once daily for 8 weeks. RESULTS: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy end points after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%; P < 0.0001), the mean per cent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (P < 0.0001) and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (P = 0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream. CONCLUSIONS: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favourable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel.

Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

A Feeling for the Human Subject: Margaret Lasker and the Genetic Puzzle of Pentosuria.

In 1933 Margaret Lasker, a biochemist who worked at the labs of Montefiore Hospital in New York, developed an accurate method for the differentiation between pentosuria and diabetes. Research into pentosuria, and mostly its genetic aspects, became Lasker's lifelong passion. Since research was not part of her job description, she conducted the chief part of her study in her home kitchen. Lasker's extensive and personal correspondence with her patients and their families may be the secret key for her success in maintaining a prolonged research career against all odds. Laker's last article was published in 1955 in Human Biology, presenting data on 72 cases of pentosuria, which occurs almost exclusively in Ashkenazi Jews. More than half a century later, and long after Lasker was gone, her well kept data and family records allowed the discovery of two mutations in the DCXR gene, by Mary-Claire King and her team.

Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials.

BACKGROUND: Obesity is associated with psoriasis and negatively affects response to therapy. OBJECTIVES: To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. METHODS: This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo- and active-comparator-controlled AMAGINE-2 and AMAGINE-3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12-week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m-2 ) and efficacy was evaluated using the physician-rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. RESULTS: In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab-treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6-17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. CONCLUSIONS: The efficacy and safety of brodalumab did not differ between patients with moderate-to-severe psoriasis who had a BMI < 30 kg m-2 or a BMI ≥ 30 kg m-2 .

Classroom sound can be used to classify teaching practices in college science courses.

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having a few faculty completely transform their teaching, but the extent to which STEM faculty are changing their teaching methods is unclear. Here, we describe the development and application of the machine-learning-derived algorithm Decibel Analysis for Research in Teaching (DART), which can analyze thousands of hours of STEM course audio recordings quickly, with minimal costs, and without need for human observers. DART analyzes the volume and variance of classroom recordings to predict the quantity of time spent on single voice (e.g., lecture), multiple voice (e.g., pair discussion), and no voice (e.g., clicker question thinking) activities. Applying DART to 1,486 recordings of class sessions from 67 courses, a total of 1,720 h of audio, revealed varied patterns of lecture (single voice) and nonlecture activity (multiple and no voice) use. We also found that there was significantly more use of multiple and no voice strategies in courses for STEM majors compared with courses for non-STEM majors, indicating that DART can be used to compare teaching strategies in different types of courses. Therefore, DART has the potential to systematically inventory the presence of active learning with ∼90% accuracy across thousands of courses in diverse settings with minimal effort.

Hierarchies of evidence applied to lifestyle Medicine (HEALM): introduction of a strength-of-evidence approach based on a methodological systematic review.

BACKGROUND: Current methods for assessing strength of evidence prioritize the contributions of randomized controlled trials (RCTs). The objective of this study was to characterize strength of evidence (SOE) tools in recent use, identify their application to lifestyle interventions for improved longevity, vitality, or successful aging, and to assess implications of the findings. METHODS: The search strategy was created in PubMed and modified as needed for four additional databases: Embase, AnthropologyPlus, PsycINFO, and Ageline, supplemented by manual searching. Systematic reviews and meta-analyses of intervention trials or observational studies relevant to lifestyle intervention were included if they used a specified SOE tool. Data was collected for each SOE tool. Conditions necessary for assigning the highest SOE grading and treatment of prospective cohort studies within each SOE rating framework were summarized. The expert panel convened to discuss the implications of findings for assessing evidence in the domain of lifestyle medicine. RESULTS AND CONCLUSIONS: A total of 15 unique tools were identified. Ten were tools developed and used by governmental agencies or other equivalent professional bodies and were applicable in a variety of settings. Of these 10, four require consistent results from RCTs of high quality to award the highest rating of evidence. Most SOE tools include prospective cohort studies only to note their secondary contribution to overall SOE as compared to RCTs. We developed a new construct, Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM), to illustrate the feasibility of a tool based on the specific contributions of diverse research methods to understanding lifetime effects of health behaviors. Assessment of evidence relevant to lifestyle medicine requires a potential adaptation of SOE approaches when outcomes and/or exposures obviate exclusive or preferential reliance on RCTs. This systematic review was registered with the International Prospective Register of Systematic Reviews, PROSPERO [CRD42018082148].

The impact of providing blood to the scene of an accident on transfusion laboratory practice.

BACKGROUND: Haemorrhage is the leading cause of mortality during trauma. In 2012, London's Air Ambulance introduced Blood on Board (BOB), transfusing group O red cells (RBC) to trauma patients at the scene. OBJECTIVES: This study assessed the impact of BOB on the number of mixed field samples received by the laboratory, the number of group O RBC transfused to non-group O patients and the ratio of RBC to fresh frozen plasma (FFP) transfused in the initial 24 h. METHODS: Three major trauma centres collected data on patients for whom the major haemorrhage protocol was activated between August 2008 and February 2012 pre-BOB and March 2012 and December 2013 post-BOB. RESULTS: A total of 233 trauma patients were identified pre-BOB and 119 post-BOB. There was no significant difference in the percentage of group O units transfused to non-group O patients (75 vs 82%, P = 0·21) or the RBC : FFP ratio (pre-BOB mean 1·6 [interquartile range (IQR) 1·0-2·0]; post-BOB mean 1·7 [IQR 1·1-2·2], P = 0·24). There was no significant difference in the percentage of mixed field samples received (23% vs 27%, P = 0·3). CONCLUSION: The introduction of BOB did not change the proportion of group O RBC transfused or the RBC : FFP ratio; however, the proportion of acceptable samples decreased. This is largely due to an increase in blood samples not received from the post-BOB cohort, which we believe is probably due to patients who died at the scene. We have introduced robust systems to indicate reasons for not obtaining samples.

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study.

BACKGROUND: Apremilast, an oral phosphodiesterase-4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. OBJECTIVE: To evaluate long-term efficacy and safety of apremilast in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial. METHODS: Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0-72), Scalp Physician Global Assessment (ScPGA; 0-5) and Nail Psoriasis Severity Index (NAPSI; 0-8); patient-reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0-32) and pruritus visual analog scale (VAS; 0-100 mm). RESULTS: The apremilast-extension phase (Weeks 16-104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last-observation-carried-forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%-59.2% of patients; NAPSI mean change from baseline was -48.1% to -51.1%; DLQI score ≤5 was achieved by 66.0%-72.5% of patients; and pruritus VAS mean change from baseline was -24.4 to -32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure. CONCLUSIONS: Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast.

The contribution of previous lameness events and body condition score to the occurrence of lameness in dairy herds: A study of 2 herds.

It has been demonstrated that low body condition and previous occurrence of lameness increase the risk of future lameness in dairy cows. To date the population attributable fraction (PAF), which provides an estimate of the contribution that a risk factor makes toward the total number of disease events in a population, has not been explored for lameness using longitudinal data with repeated measures. Estimation of PAF helps to identify control measures that could lead to the largest improvements on-farm. The aim of this study was to use longitudinal data to evaluate the proportion of lameness that could be avoided in 2 separate herds (2 populations) through (1) reduced recurrence of previous lameness events, (2) and moving body condition score (BCS) into more optimal ranges. Data were obtained from 2 UK dairy herds: herd A, a 200-cow herd with 8 yr of data from a total of 724 cows where lameness events were based on weekly locomotion scores (LS; 1 to 5 scale), and herd B, a 600-cow herd with data recorded over 44 mo from a total of 1,040 cows where treatment of clinical cases was used to identify lameness events. The PAF for categories of BCS were estimated using a closed equation appropriate for multiple exposure categories. Simulation models were used to explore theoretical scenarios to reflect changes in BCS and recurrence of previous lameness events in each herd. For herd A, 21.5% of the total risk periods (cow-weeks) contained a lameness event (LS 3, 4, or 5), 96% of which were repeat events and 19% were recorded with BCS <2 (3 wk previously; 0 to 5 scale). When lameness events were based on 2 consecutive weeks of LS 4 or 5, 4% of risk periods were recorded as lame, of which 89.5% were repeat events. For herd B, 16.3% of the total risk periods (consecutive 30 d) contained a lameness event (72.6% were repeat events) and 20% were recorded with BCS ≤2 (0 to 120 d previously). The median PAF for all previous lameness was between 79 and 83% in the 2 herds. Between 9 and 21% of lameness events could be attributed to previous lameness occurring >16 wk before a risk period. The median PAF estimated for changes in BCS were in the region of 4 to 11%, depending on severity of lameness. Repeated bouts of lameness made a very large contribution to the total number of lameness events. This could either be because certain cows are initially susceptible and remain susceptible, due to the increased risk associated with previous lameness events, or due to interactions with environmental factors. This area requires further research.

On-Disc Observations of Flux Rope Formation Prior to Its Eruption.

Coronal mass ejections (CMEs) are one of the primary manifestations of solar activity and can drive severe space weather effects. Therefore, it is vital to work towards being able to predict their occurrence. However, many aspects of CME formation and eruption remain unclear, including whether magnetic flux ropes are present before the onset of eruption and the key mechanisms that cause CMEs to occur. In this work, the pre-eruptive coronal configuration of an active region that produced an interplanetary CME with a clear magnetic flux rope structure at 1 AU is studied. A forward-S sigmoid appears in extreme-ultraviolet (EUV) data two hours before the onset of the eruption (SOL2012-06-14), which is interpreted as a signature of a right-handed flux rope that formed prior to the eruption. Flare ribbons and EUV dimmings are used to infer the locations of the flux rope footpoints. These locations, together with observations of the global magnetic flux distribution, indicate that an interaction between newly emerged magnetic flux and pre-existing sunspot field in the days prior to the eruption may have enabled the coronal flux rope to form via tether-cutting-like reconnection. Composition analysis suggests that the flux rope had a coronal plasma composition, supporting our interpretation that the flux rope formed via magnetic reconnection in the corona. Once formed, the flux rope remained stable for two hours before erupting as a CME. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11207-017-1093-4) contains supplementary material, which is available to authorized users.

Aetiology and outcome of massive transfusion in two large London teaching hospitals over a 3-year period (2012-2014).

OBJECTIVES: The objectives of this study were to determine: (i) the incidence of massive transfusion (MT) (defined as transfusion of ≥5 red-blood-cell (RBC) units within 4 h, and/or ≥10 RBC units within 24 h of bleeding) over a 3-year period; (ii) the cause, and mortality rate of patients who received MT (from any cause); and (iii) the risk factors for death. BACKGROUND: MT can occur in different clinical settings, yet little is known about its epidemiology/clinical outcomes. METHODS: Data was extracted using transfusion laboratory information management system (LIMS) and patients' electronic databases. RESULTS: We identified 701 episodes (incidence 1.7 per 1000 admissions [95% confidence interval (CI): 1.6-1.9], belonging to 678 patients (225 females and 453 males, median age 61). Main causes of MT were cardiac surgery (35%), trauma (28%), medical (10%) and vascular surgery (9%). The overall mortality was 32%, and the median number of days spent in hospital was 14 and 2 for those who survived and those who died, respectively. Multivariable analysis showed that cardiac surgery was associated with 56% (95% CI: 9-78%) lower odds of death compared to other surgery, and transfusion of 10-14 RBC and >15 RBC units (compared with 5-9 RBC units) were associated with 2.1 (95% CI: 1.4-3.3) and 9.9 (95% CI: 4.6-21.1) times higher odds of dying, respectively. CONCLUSION: In-hospital morbidity and mortality of MT is high. Future research should focus on unifying the definition of MT, and early identification of the MT markers in order to improve outcomes.

The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE).

BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). METHODS: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons. RESULTS: At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast. CONCLUSION: Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52.

The Economic Impact of Space Weather: Where Do We Stand?

Space weather describes the way in which the Sun, and conditions in space more generally, impact human activity and technology both in space and on the ground. It is now well understood that space weather represents a significant threat to infrastructure resilience, and is a source of risk that is wide-ranging in its impact and the pathways by which this impact may occur. Although space weather is growing rapidly as a field, work rigorously assessing the overall economic cost of space weather appears to be in its infancy. Here, we provide an initial literature review to gather and assess the quality of any published assessments of space weather impacts and socioeconomic studies. Generally speaking, there is a good volume of scientific peer-reviewed literature detailing the likelihood and statistics of different types of space weather phenomena. These phenomena all typically exhibit "power-law" behavior in their severity. The literature on documented impacts is not as extensive, with many case studies, but few statistical studies. The literature on the economic impacts of space weather is rather sparse and not as well developed when compared to the other sections, most probably due to the somewhat limited data that are available from end-users. The major risk is attached to power distribution systems and there is disagreement as to the severity of the technological footprint. This strongly controls the economic impact. Consequently, urgent work is required to better quantify the risk of future space weather events.

Optimized automated data analysis for the cytokinesis-block micronucleus assay using imaging flow cytometry for high throughput radiation biodosimetry.

The cytokinesis-block micronucleus (CBMN) assay is a well-established technique that can be employed in triage radiation biodosimetry to estimate whole body doses of radiation to potentially exposed individuals through quantitation of the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using traditional microscope-based methods and most recently has been modified for application on the ImageStream(X) (IS(X) ) imaging flow cytometer. This modification has allowed for a similar number of BNCs to be automatically scored as compared to traditional microscopy in a much shorter time period. However, the MN frequency measured was much lower than both manual and automated slide-based methods of performing the assay. This work describes the optimized analysis template which implements newly developed functions in the IDEAS(®) data analysis software for the IS(X) that enhances specificity for BNCs and increases the frequency of scored MN. A new dose response calibration curve is presented in which the average rate of MN per BNC is of similar magnitude to those presented in the literature using automated CBMN slide scoring methods. In addition, dose estimates were generated for nine irradiated, blinded samples and were found to be within ±0.5 Gy of the delivered dose. Results demonstrate that the improved identification accuracy for MN and BNCs in the IS(X) -based version of the CBMN assay will translate to increased accuracy when estimating unknown radiation doses received by exposed individuals following large-scale radiological or nuclear emergencies. © 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.