Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND: The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Glofitamab is a bispecific antibody that recruits T cells to tumor cells. METHODS: In the phase 2 part of a phase 1-2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously. Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles total). The primary end point was complete response according to assessment by an independent review committee. Key secondary end points included duration of response, survival, and safety. RESULTS: Of the 155 patients who were enrolled, 154 received at least one dose of any study treatment (obinutuzumab or glofitamab). At a median follow-up of 12.6 months, 39% (95% confidence interval [CI], 32 to 48) of the patients had a complete response according to independent review. Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy (35% of whom had a complete response). The median time to a complete response was 42 days (95% CI, 42 to 44). The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. The most common adverse event was cytokine release syndrome (in 63% of the patients). Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher cytokine release syndrome in 4% and grade 3 or higher neurologic events in 3%. CONCLUSIONS: Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT03075696.).

A systematic review of ambulance service-based randomised controlled trials in stroke.

BACKGROUND: Treatment for stroke is time-dependent, and ambulance services play a vital role in the early recognition, assessment and transportation of stroke patients. Innovations which begin in ambulance services to expedite delivery of treatments for stroke are developing. However, research delivery in ambulance services is novel, developing and not fully understood. AIMS: To synthesise literature encompassing ambulance service-based randomised controlled interventions for acute stroke with consideration to the characteristics of the type of intervention, consent modality, time intervals and issues unique to research delivery in ambulance services. Online searches of MEDLINE, EMBASE, Web of Science, CENTRAL and WHO IRCTP databases and hand searches identified 15 eligible studies from 538. Articles were heterogeneous in nature and meta-analysis was partially available as 13 studies reported key time intervals, but terminology varied. Randomised interventions were evident across all points of contact with ambulance services: identification of stroke during the call for help, higher dispatch priority assigned to stroke, on-scene assessment and clinical interventions, direct referral to comprehensive stroke centres and definitive care delivery at scene. Consent methods ranged between informed patient, waiver and proxy modalities with country-specific variation. Challenges unique to the prehospital setting comprise the geographical distribution of ambulance resources, low recruitment rates, prolonged recruitment phases, management of investigational medicinal product and incomplete datasets. CONCLUSION: Research opportunities exist across all points of contact between stroke patients and ambulance services, but randomisation and consent remain novel. Early collaboration and engagement between trialists and ambulance services will alleviate some of the complexities reported. REGISTRATION NUMBER: PROSPERO 2018CRD42018075803.

Challenges and Experiences in Multicenter Prehospital Stroke Research: Narrative Data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2).

BACKGROUND: Ambulance services are increasingly research active and the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is the largest United Kingdom (UK) ambulance-based randomized controlled trial in stroke. We explore the complexities and challenges encountered during RIGHT-2. METHODS: Five hundred and sixteen of 1487 paramedics from eight UK ambulance services serving 54 comprehensive or primary stroke care centers screened and consented 1149 patients presenting within 4 h of FAST-positive stroke and with systolic blood pressure >120 mmHg; participants were randomized to treatment with transdermal glyceryl trinitrate versus sham patch in the ambulance. KEY FINDINGS: Working with multiple ambulance services demanded flexibility in the trial protocol to overcome variation in operating procedures to ensure deliverability. Many paramedics are novice researchers, and research concepts and practices are emerging including consent strategies in emergency stroke care. Regional variation in hospital participation and hours/days of operation presented paramedics with additional considerations prior to patient recruitment. The working hours of hospital research staff often do not reflect the 24/7 nature of ambulance work, which challenged deliverability until trial processes became fully embedded. Management of investigational medicinal product between ambulance stations, in-transit when on ambulance vehicles and on handover at hospital, necessitated an in-depth review to maintain accountability. CONCLUSION: RIGHT-2 demonstrated that although there are significant practical challenges to conducting multicenter ambulance-based research in a time-dependent environment, careful planning and management facilitated delivery. Lessons learned here will help inform the design and conduct of future ambulance-based trials.

Advancing drug development in pediatric oncology, a focus on cancer biology and targeted therapies: iMATRIX platform.

With the development of novel treatment therapies as well as evolving and innovative approaches to conduct clinical trials, the landscape of pediatric oncology drug development has dramatically changed in recent years. Despite this change, approvals for new drugs and labeling updates to ensure availability of proper treatment for pediatric patients with cancer remain slow. The context of drug development in pediatric tumors has also changed with regulatory initiatives in the US and Europe, creating a great need for faster development of novel drugs. Today, conventional study designs have been replaced or complemented by novel clinical trial designs, such as master protocols and platform trials, to optimize cancer drug development and enable faster regulatory approval. The iMATRIX platform is a mechanism-of-action (MOA)-based phase 1/2 trial framework for concurrently studying multiple molecules across a range of relevant pediatric tumor types, taking into account the biology of each pediatric tumor type. Six studies have been conducted, ongoing, or planned on the iMATRIX platform - investigating atezolizumab, cobimetinib, entrectinib, idasanutlin, alectinib, and glofitamab. A brief overview of study designs and characteristics are shared in this article, along with learnings from them.

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.

BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known. METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated. RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant. CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).

Cognitive-behavioral therapy for insomnia for primary care: Review of components and application for residents in primary care.

Healthy sleep patterns are a significant component of good physical and mental health. Quality sleep can be affected by such things as stress, age, pregnancy, physical health problems, and shift work. Behaviors related to sleep problems can be one of three types: predisposing, precipitating, and perpetuating. Additionally, cognitive processes related to sleep quality tend to be predominated by sleep thinking or insomnia thinking. Multiple medical organizations promote Cognitive Behavioral Therapy for Insomnia as a best practice for clinical management of sleep problems and disorders. Cognitive Behavioral Therapy for Insomnia consists of five components aimed at addressing both the behavioral and cognitive impediments to high quality sleep. These components are sleep hygiene, relaxation, sleep restriction, stimulus control, and cognitive therapy. This paper will address each component, as well as provide a patient education pattern well suited for primary care settings.

Motivational Interviewing and Self-Determination Theory in Suicide Assessment: A Practical Application to Aid Residents' Management of Suicide.

Suicide is a problem on the rise in the United States. One significant avenue to help reverse the trend is through family medicine and interventions within primary care clinics. This can be a significant stressor for many family medicine physicians to manage patients experiencing suicidal ideation within their busy schedule. Motivational Interviewing is an evidence-based method of interacting with patients in a healthy and collaborative manner. The literature is growing on how to use Motivational Interviewing in assessments of suicidal ideation. Additionally, Self-Determination Theory proposes that individuals have three basic needs: a sense of connection, a level of autonomy, and a degree of competence. These needs and the associated principles of intrinsic and extrinsic motivation help to explain why Motivational Interviewing can be so helpful in the change process. By examining the principles of Motivational Interviewing and Self-Determination Theory residents will be able to better create an environment conducive to collaborative sharing, honest discussion, and meaningful assessment to ensure safety for patients in primary care.

Pre-hospital transdermal glyceryl trinitrate in patients with stroke mimics: data from the RIGHT-2 randomised-controlled ambulance trial.

BACKGROUND: Prehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2). METHODS: RIGHT-2 was a prospective, multicentre, paramedic-delivered, ambulance-based, sham-controlled, participant-and outcome-blinded, randomised-controlled trial of transdermal glyceryl trinitrate (GTN) in adults with ultra-acute presumed stroke in the UK. Final diagnosis (intracerebral haemorrhage, ischaemic stroke, transient ischaemic attack, mimic) was determined by the hospital investigator. This pre-specified subgroup analysis assessed the safety and efficacy of transdermal GTN (5 mg daily for 4 days) versus sham patch among stroke mimic patients. The primary outcome was the 7-level modified Rankin Scale (mRS) at 90 days. RESULTS: Among 1149 participants in RIGHT-2, 297 (26%) had a final diagnosis of mimic (GTN 134, sham 163). The mimic group were younger, mean age 67 (SD: 18) vs 75 (SD: 13) years, had a longer interval from symptom onset to randomisation, median 75 [95% CI: 47,126] vs 70 [95% CI:45,108] minutes, less atrial fibrillation and a lower systolic blood pressure and Face-Arm-Speech-Time tool score than the stroke group. The three most common mimic diagnoses were seizure (17%), migraine or primary headache disorder (17%) and functional disorders (14%). At 90 days, the GTN group had a better mRS score as compared to the sham group (adjusted common odds ratio 0.54; 95% confidence intervals 0.34, 0.85; p = 0.008), a difference that persisted at 365 days. There was no difference in the proportion of patients who died in hospital, were discharged to a residential care facility, or suffered a serious adverse event. CONCLUSIONS: One-quarter of patients suspected by paramedics to have an ultra-acute stroke were subsequently diagnosed with a non-stroke condition. GTN was associated with unexplained improved functional outcome observed at 90 days and one year, a finding that may represent an undetected baseline imbalance, chance, or real efficacy. GTN was not associated with harm. TRIAL REGISTRATION: This trial is registered with International Standard Randomised Controlled Trials Number ISRCTN 26986053 .

Suicide in primary care: How to screen and intervene.

Suicide is significant public health concern within the United States. Research results are mixed about the effectiveness of universal screening and interventions with patients who are at-risk for suicide. Primary care is a logical intervention point to mitigate risk among patients in each of these areas. The Department of Veterans Affairs and Department of Defense have developed comprehensive guidelines for the assessment and management of suicidal patients. This approach involves specific screening tools, risk stratification by categories and interventions used by clinicians to help reduce risk levels in their patients. This article aims to provide a model, built on the principles of these guidelines, which primary care physicians can use to identify, assess and intervene with patients who are at-risk for suicide.

Quantification and Valuation of Nitrogen Removal Services Provided by Commercial Shellfish Aquaculture at the Subwatershed Scale.

Eutrophication is a global environmental challenge, and diverse watershed nitrogen sources require multifaceted management approaches. Shellfish aquaculture removes nitrogen, but the extent and value of this ecosystem service have not been well-characterized at the local scale. A novel approach was employed to quantify and value nitrogen reduction services provided by the shellfish aquaculture industry to a municipality. Cultivated hard clam and eastern oyster nitrogen removal in Greenwich Bay, Connecticut, was valued using the replacement cost methodology and allocated by municipal nitrogen source. Using the preferred analysis allocating replacement costs by nitrogen source, aquaculture-based removal of 14 006 kg nitrogen was valued at $2.3-5.8 (2.3-6.4€) million year-1. This nitrogen removal represents 9% of the total annual Greenwich-specific nitrogen load, 16% of the combined nonpoint sources, 38% of the fertilizer sources, 51% of the septic sources, 98% of the atmospheric deposition to the watershed, or 184% of the atmospheric deposition to the embayments that discharge to Greenwich Bay. Our approach is transferable to other coastal watersheds pursuing nitrogen reduction goals, both with and without established shellfish aquaculture. It provides context for decisions related to watershed nitrogen management expenditures and suggests a strategy to comprehensively evaluate mechanisms to achieve nitrogen reduction targets.

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage: Data From the RIGHT-2 Trial.

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

The Pillow Project, Infant Choking, and Basic Life Support Training for Prospective Parents: A Low-Cost Intervention for Widespread Application.

Dissemination of pediatric basic life support skills, while recommended, is not done routinely for pregnant women and their partners within the maternity services. This study evaluates an e-learning program coupled with the use of a novel infant pillow mannequin to determine whether a low-cost intervention with potential for widespread application could enable training in the event of an infant choking and the provision of basic life support. A prospective cohort study with an uncontrolled pre- and posttest design was used following institutional ethical approval. A 4-week cycle of antenatal education classes in a regional Maternity Hospital in Ireland and a purposive sample of pregnant women and their partners attending the antenatal education classes were used. The following measures were assessed: (1) confidence in knowing what to do in the event of an infant choking; (2) confidence in performing infant cardiopulmonary resuscitation (CPR); (3) ability to perform the requisite skills; and (4) the perceived acceptability of the infant pillow mannequin as a means of practice. Twenty-four individuals completed a pre- and postprogram questionnaire. The e-learning program along with practice on the pillow mannequin significantly affected confidence (P < .001) in the actions to take in the event of an infant choking and in performing infant CPR. Forty-four participants used the pillow mannequin for practice and volunteered to have their skills assessed. More than 90% demonstrated correct positioning of the infant in the event of choking, correctly identified the correct ratio of chest compressions to breaths, and conducted chest compressions to the required depth. Three distinct categories of comment were identified: usefulness of the program; simplicity of the program/pillow mannequin; and accessibility for practice at home. A self-instructional e-learning program coupled with an infant pillow mannequin enables parents to learn the procedure in the event of an infant choking and to demonstrate basic life support. This low-cost intervention has the potential for widespread application within developed and developing countries.

Effects of Management Treatments on Regeneration of a Geographically Disjunct, Relictual Hybrid Aspen (Populus xsmithii) Population in the Central Great Plains, USA.

Populus xsmithii is an uncommon hybrid of quaking aspen (Populus tremuloides) and bigtooth aspen (Populus grandidentata). Like its parents, Populus xsmithii is an early successional member of boreal forest communities, dependent on disturbance events that clear areas of competitive stems and spur an increase in clonal suckering. In recent years, aspen dieback has been noted across much of the western United States, a condition characterized by mortality of older stems and a lack of recruitment of suckers to maturity. In the Niobrara River Valley of Cherry County, Nebraska, USA, a disjunct population of Pleistocene relict Populus xsmithii has been targeted for management via clearing of competitive conifer species and establishment of fenced refugia to protect suckers from herbivory. The stands currently contain abundant suckers, which occur in three types of sites: the fenced refugia created by managers, the open habitat cleared of other species in the stands, and the woodpiles left by said clearing. This study assessed the growth and vigor of these aspen suckers over a nine-month period (summer 2013-spring 2014) and compared the effects of different site treatments. We found that aspen suckers in the open areas were significantly shorter, had smaller basal diameter, and had higher damage scores than those in the two protected site types (fenced and woodpile). Because this population is on the margin of the distribution for aspen, evaluating the effectiveness of management techniques will provide valuable information for those who seek to ensure the survival of this aspen population and others.

Assessment of consent models as an ethical consideration in the conduct of prehospital ambulance randomised controlled clinical trials: a systematic review.

BACKGROUND: We sought to understand the main ethical considerations when conducting clinical trials in the prehospital ambulance based setting. METHODS: A systematic review of the literature on randomised controlled trials in ambulance settings was undertaken. A search of eight databases identified published studies involving recruitment of ambulance service users. Four independent authors undertook abstract and full-text reviews to determine eligibility and extract relevant data. The data extraction concentrated on ethical considerations, with any discussion of ethics being included for further analysis. The resultant data were combined to form a narrative synthesis. RESULTS: In all, 56 papers were identified as meeting the inclusion criteria. Issues relating to consent were the most significant theme identified. Type of consent differed depending on the condition or intervention being studied. The country in which the research took place did not appear to influence the type of consent, apart from the USA where exception from consent appeared to be most commonly used. A wide range of terms were used to describe consent. CONCLUSIONS: Consent was the main ethical consideration in published ambulance based research. A range of consent models were used ranging from informed consent to exception from consent (waiver of consent). Many studies cited international guidelines as informing their choice of consent model but diverse and sometimes confused terms were used to describe these models. This suggests that standardisation of consent models and the terminology used to describe them is warranted.

Cultivation of the Ribbed Mussel (Geukensia demissa) for Nutrient Bioextraction in an Urban Estuary.

Shellfish aquaculture is gaining acceptance as a tool to reduce nutrient over enrichment in coastal and estuarine ecosystems through the feeding activity of the animals and assimilation of filtered particles in shellfish tissues. This ecosystem service, provided by the ribbed mussel (Geukensia demissa), was studied in animals suspended from a commercial mussel raft in the urban Bronx River Estuary, NY, in waters closed to shellfish harvest due to bacterial contamination. Naturally occurring populations of ribbed mussels were observed to be healthy and resilient in this highly urbanized environment. Furthermore, mussels grown suspended in the water column contained substantially lower concentrations of heavy metals and organic contaminants in their tissues than blue mussels (Mytilus edulis) collected at a nearby benthic site. Spat collection efforts from shore and within the water column were unsuccessful; this was identified as a key bottleneck to future large-scale implementation. Filtration experiments indicated that a fully stocked G. demissa raft would clear an average 1.2 × 107 L of Bronx River Estuary water daily, removing 160 kg of particulate matter from the water column, of which 12 kg would be absorbed into mussel digestive systems. At harvest, 62.6 kg of nitrogen would be sequestered in mussel tissue and shell. These values compare favorably to other resource management recovery methods targeting agricultural and stormwater nitrogen sources.

An Internal and Critical Review of the PEAK Relational Training System for Children with Autism and Related Intellectual Disabilities: 2014-2017.

The PEAK Relational Training System was designed as an assessment instrument and treatment protocol for addressing language and cognitive deficits in children with autism. PEAK contains four comprehensive training modules: Direct Training and Generalization emphasize a contingency-based framework of language development, and Equivalence and Transformation emphasize an approach to language development consistent with Relational Frame Theory. The present paper provides a comprehensive and critical review of peer-reviewed publications based on the entirety PEAK system through April, 2017. We describe both psychometric and outcome research, and indicate both positive features and limitations of this body of work. Finally, we note several research and practice questions that remain to be answered with the PEAK curriculum as well as other many other autism assessment and treatment protocols that are rooted within the framework of applied behavior analysis.

Near Misses in Slot Machine Gambling Developed Through Generalization of Total Wins.

The purpose of the present study was to evaluate the development of the near miss effect in slot machine gambling as a product of stimulus generalization from total wins. The study was conducted across two experiments. Twelve college students participated in the first experiment, which demonstrated that greater post-reinforcement pauses followed losing outcomes that were formally similar to total wins, relative to losing outcomes that were formally dissimilar [F (5, 7) = 5.24, p = .025] along a generalization gradient (R (2) = .96). Additionally, 11 out of 12 participants showed greater response latencies following near-misses than following total wins. Thirteen college students participated in the second experiment, which demonstrated that symbols that more saliently indicated a loss resulted in lower response latencies than functionally equivalent but visually dissimilar losing symbols [F (3, 10) = 15.50, p = .01]. A generalization gradient was observed across winning symbols (R (2) = .98), and an inverse of the gradient observed across winning symbols was observed across symbols that were the least formally similar (R (2) = .69). The present study replicates and extends previous research on near misses in slot machine gambling, and provides discussion around the clinical utility of such findings on the prevention of problem gambling.

Site Preparation Drives Long-Term Plant Community Dynamics in Restored Tallgrass Prairie: A Case Study in Southeastern South Dakota.

Most tallgrass prairies have been destroyed or altered, making restoration an important component to their conservation. Our goal was to evaluate progress 12-years post-restoration at Spirit Mound Historic Prairie and determine whether the outcomes varied based on different land use and restoration histories across the site. We examined changes in plant diversity, richness, evenness, non-native species relative abundance, and community composition from 2004 to 2013. Areas with different restoration treatments and land-use histories showed divergent results. Seventy percent of the site, previously annual row crop, was reconstructed using herbicide application followed by native seeding (hereafter reconstruction). Areas that were previously grazed, 15 % of the site, were restored with only partial seeding and no herbicide treatment (hereafter rehabilitation). Species richness and diversity increased over 40 % in the reconstruction since 2004 and remained over 1.9 times higher in the reconstructed areas than rehabilitated areas. Diversity did not change in the rehabilitation, but richness increased 47 % since 2004. Evenness decreased 11-26 % over time in both areas. Non-native species relative abundance did not change from 2004 to 2013, and remained five times higher in the rehabilitation than the reconstruction. Native C4 grass and forb abundance increased over time in the reconstruction, whereas non-native C3 grasses remained dominant in the rehabilitation. These results showed that restoration outcomes were radically different 12-years post-restoration among areas with different prior land uses that were subjected to different restoration practices. Long-term assessments are important to accurately determine restoration progress and inform management decisions.

Physiological and pathological changes in the eastern oyster Crassostrea virginica infested with the trematode Bucephalus sp. and exposed to the toxic dinoflagellate Alexandrium fundyense.

Effects of experimental exposure to Alexandrium fundyense, a Paralytic Shellfish Toxin (PST) producer known to affect bivalve physiological condition, upon eastern oysters, Crassostrea virginica with a variable natural infestation of the digenetic trematode Bucephalus sp. were determined. After a three-week exposure to cultured A. fundyense or to a control algal treatment with a non-toxic dinoflagellate, adult oysters were assessed for a suite of variables: histopathological condition, hematological variables (total and differential hemocyte counts, morphology), hemocyte functions (Reactive Oxygen Species (ROS) production and mitochondrial membrane potential), and expression in gills of genes involved in immune responses and cellular protection (MnSOD, CAT, GPX, MT-IV, galectin CvGal) or suspected to be (Dominin, Segon). By comparing individual oysters infested heavily with Bucephalus sp. and uninfested individuals, we found altered gonad and digestive gland tissue and an inflammatory response (increased hemocyte concentration in circulating hemolymph and hemocyte infiltrations in tissues) associated with trematode infestation. Exposure to A. fundyense led to a higher weighted prevalence of infection by the protozoan parasite Perkinsus marinus, responsible for Dermo disease. Additionally, exposure to A. fundyense in trematode-infested oysters was associated with the highest prevalence of P. marinus infection. These observations suggest that the development of P. marinus infection was advanced by A. fundyense exposure, and that, in trematode-infested oysters, P. marinus risk of infection was higher when exposed to A. fundyense. These effects were associated with suppression of the inflammatory response to trematode infestation by A. fundyense exposure. Additionally, the combination of trematode infestation and A. fundyense exposure caused degeneration of adductor muscle fibers, suggesting alteration of valve movements and catch state, which could increase susceptibility to predation. Altogether, these results suggest that exposure of trematode-infested oysters to A. fundyense can lead to overall physiological weakness that decrease oyster defense mechanisms.

Confirmation of suboptimal protocols in spinal immobilisation?

BACKGROUND: Spinal immobilisation during extrication of patients in road traffic collisions is routinely used despite the lack of evidence for this practice. In a previous proof of concept study (n=1), we recorded up to four times more cervical spine movement during extrication using conventional techniques than self-controlled extrication. OBJECTIVE: The objective of this study was to establish, using biomechanical analysis which technique provides the minimal deviation of the cervical spine from the neutral in-line position during extrication from a vehicle in a larger sample of variable age, height and mass. METHODS: A crew of two paramedics and four fire-fighters extricated 16 immobilised participants from a vehicle using six techniques for each participant. Participants were marked with biomechanical sensors and relative movement between the sensors was captured via high-speed infrared motion analysis cameras. A three-dimensional mathematical model was developed and a repeated-measures analysis of variance was used to compare movement across extrication techniques. RESULTS: Controlled self-extrication without a collar resulted in a mean movement of 13.33° from the neutral in-line position of the cervical spine compared to a mean movement of 18.84° during one of the equipment-aided extrications. Two equipment-aided techniques had significantly higher movement (p<0.05) than other techniques. Both height (p=0.003) and mass (p=0.02) of the participants were significant independent predictors of movement. CONCLUSIONS: These data support the findings of the proof of concept study, for haemodynamically stable patients controlled self-extrication causes less movement of the cervical spine than extrications performed using traditional prehospital rescue equipment.