International orienteering experts' consensus on the definition, development, cause, impact and methods to reduce mental fatigue in orienteering: A Delphi study.

Orienteering is an outdoor activity wherein participants use a map and compass to locate control points and choose the quickest path to the next control point in a natural environment. Attentional focus, rapid decision-making, and high aerobic fitness may influence orienteering performance. Therefore, this research aimed to seek international orienteering expert consensus regarding the definition, development, causes, influences and methods to reduce mental fatigue (MF) in orienteering based on practical experience. Following ethical approval, a three-round Delphi survey was conducted online with twenty-four orienteering coaches and athletes (or former athletes) from 10 different countries with international orienteering competition experience. The threshold of consensus was ≥ 70% agreement among respondents. The experts agreed that MF exists in daily life and orienteering with a substantial negative effect on their conscious decision-making performance and psychological responses. The experts disagreed that the form of MF that athletes experienced in orienteering training are similar to the competition. However, there was no agreement that MF would impact endurance and high-speed running performance during orienteering. This research refines the definition of MF and summarises the distinctions in what causes MF in orienteering training and competition, implying that MF should be addressed separately.

A Concussion Education Programme for Motorsport Drivers: A Field-Based Exploratory Pilot Study.

OBJECTIVE: Concussion education strategies that improve knowledge and attitudes long term are needed. This exploratory study piloted an interactive concussion education program, adopting concepts from the learning sciences and attitude change literature, for the underserved and high-risk population of motorsports. METHOD: Forty UK motorsport drivers (ages 16-20 years) participated. The workshop group received a two-phased workshop-based program. The comparison group received a concussion leaflet. Participants completed an adapted version of the Rosenbaum Concussion Knowledge and Attitudes Survey (RoCKAS-ST) at pre-, post- and 2-month follow-up. Within-group analysis for the workshop group explored the differential effect of the individual difference variable, Need for Cognition (NfC), and effectiveness was explored through post-workshop questionnaires and interviews. RESULTS: Unlike the comparison group, the workshop group showed a significant improvement in knowledge over time (F(2,58) = 45.49, p < .001, η2p = .61). Qualitative data indicated workshop-program participants developed safer attitudes toward concussion following programming. Preliminary evidence suggested individuals' responses to concussion education aligned with differences in NfC. CONCLUSION: This study piloted the first concussion education program for motorsport drivers and explored whether aligning educational provision with the NfC construct may help to improve program effectiveness. Findings are relevant to addressing the public health issue of concussion through educational approaches.

Concussion in Motorsport? Experience, Knowledge, Attitudes, and Priorities of Medical Personnel and Drivers.

OBJECTIVE: To assess concussion experiences, knowledge, and attitudes of motorsport medical personnel and drivers and to determine priority areas regarding concussion within the sport. DESIGN: Sequential mixed-method design. Part 1: stakeholder interviews; part 2: cross-sectional online survey. SETTING: United Kingdom. PARTICIPANTS: Part 1: key motorsport stakeholders (N = 8); part 2: motorsport medical personnel and drivers (N = 209) representing amateur and/or professional 4-wheeled motorsport. MAIN OUTCOME MEASURES: Concussion experience, knowledge, attitudes, and perceived priority areas. RESULTS: Thirty-one percent of surveyed drivers (age = 37.91 ± 13.49 years: 89% male) reported suffering from concussion in motorsport. Eighty-seven percent of surveyed medical personnel (age = 48.60 ± 10.68 years: 74% male) reported experience with concussed drivers, and 34% reported feeling pressured to clear a driver with concussion. Gaps in knowledge and misperceptions about concussion were reported in both groups, and disparity between concussion attitudes emerged between drivers and medical personnel. Application of assessment and management procedures varied between medical personnel and there was evidence motorsport policy and concussion guidelines may not be directly followed. According to both medical personnel (77%) and drivers (85%), "education and training" is the top priority area for the sport. CONCLUSIONS: There is clear evidence of concussions in motorsport, but accurate knowledge about this injury is missing. Concussion education and training for all drivers and medical personnel is required. Additional investigations into concussion attitudes are advised to complement and advance simple educational initiatives. Further investigation is also required to determine how to best support motorsport medical personnel, and general practitioners, who hold significant responsibility in guiding drivers from diagnosis to return to racing, and to support the effective implementation of policy.

Current epidemiology of cerebrospinal fluid shunt surgery in the UK and Ireland (2004-2013).

OBJECTIVES: To determine current epidemiology and clinical characteristics of cerebrospinal fluid (CSF) shunt surgery, including revisions. METHODS: A retrospective, multicentre, registry-based study was conducted based on 10 years' data from the UK Shunt Registry, including primary and revision shunting procedures reported between 2004 and 2013. Incidence rates of primary shunts, descriptive statistics and shunt revision rates were calculated stratified by age group, geographical region and year of operation. RESULTS: 41 036 procedures in 26 545 patients were submitted during the study period, including 3002 infants, 4389 children and 18 668 adults. Procedures included 20 947 (51.0%) primary shunt insertions in 20 947 patients, and 20 089 (49.0%) revision procedures. Incidence rates of primary shunt insertions for infants, children and adults were 39.5, 2.4 and 3.5 shunts per 100 000 person-years, respectively. These varied by geographical subregion and year of operation. The most common underlying diagnoses were perinatal intraventricular haemorrhage (35.3%) and malformations (33.9%) in infants, tumours (40.5%) and malformations (16.3%) in children, and tumours (24.6%), post-haemorrhagic hydrocephalus (16.2%) and idiopathic normal pressure hydrocephalus (14.2%) in adults. Ninety-day revision rates were 21.9%, 18.6% and 12.8% among infants, children and adults, respectively, while first-year revision rates were 31.0%, 25.2% and 17.4%. The main reasons for revision were underdrainage and infection, but overdrainage and mechanical failure continue to pose problems. CONCLUSIONS: Our report informs patients, carers, clinicians, providers and commissioners of healthcare, researchers and industry of the current epidemiology of shunting for CSF disorders, including the potential risks of complications and frequency of revision.

Doppler Non-invasive Monitoring of ICP in an Animal Model of Acute Intracranial Hypertension.

BACKGROUND: In many neurological diseases, intracranial pressure (ICP) is elevated and needs to be actively managed. ICP is typically measured with an invasive transducer, which carries risks. Non-invasive techniques for monitoring ICP (nICP) have been developed. The aim of this study was to compare three different methods of transcranial Doppler (TCD) assessment of nICP in an animal model of acute intracranial hypertension. METHODS: In 28 rabbits, ICP was increased to 70-80 mmHg by infusion of Hartmann's solution into the lumbar subarachnoid space. Doppler flow velocity in the basilar artery was recorded. nICP was assessed through three different methods: Gosling's pulsatility index PI (gPI), Aaslid's method (AaICP), and a method based on diastolic blood flow velocity (FVdICP). RESULTS: We found a significant correlation between nICP and ICP when all infusion experiments were combined (FVdICP: r = 0.77, AaICP: r = 0.53, gPI: r = 0.54). The ability to distinguish between raised and 'normal' values of ICP was greatest for FVdICP (AUC 0.90 at ICP >40 mmHg). When infusion experiments were considered independently, FVdICP demonstrated again the strongest correlation between changes in ICP and changes in nICP (mean r = 0.85). CONCLUSIONS: TCD-based methods of nICP monitoring are better at detecting changes of ICP occurring in time, rather than absolute prediction of ICP as a number. Of the studied methods of nICP, the method based on FVd is best to discriminate between raised and 'normal' ICP and to monitor relative changes of ICP.

Cessation of diastolic cerebral blood flow velocity: the role of critical closing pressure.

BACKGROUND: Reducing cerebral perfusion pressure (CPP) below the lower limit of autoregulation (LLA) causes cerebral blood flow (CBF) to become pressure passive. Further reductions in CPP can cause cessation of CBF during diastole. We hypothesized that zero diastolic flow velocity (FV) occurs when diastolic blood pressure becomes less than the critical closing pressure (CrCP). METHODS: We retrospectively analyzed studies of 34 rabbits with CPP below the LLA, induced with pharmacologic sympathectomy (N = 23) or cerebrospinal fluid infusion (N = 11). Basilar artery blood FV and cortical Laser Doppler Flow (LDF) were monitored. CrCP was trended using a model of cerebrovascular impedance. The diastolic closing margin (DCM) was monitored as the difference between diastolic blood pressure and CrCP. LDF was recorded for DCM values greater than and less than zero. RESULTS: Arterial hypotension caused a reduction of CrCP (p < 0.001), consistent with decreased wall tension (p < 0.001) and a drop in intracranial pressure (ICP; p = 0.004). Cerebrospinal infusion caused an increase of CrCP (p = 0.002) accounted for by increasing ICP (p < 0.001). The DCM was compromised by either arterial hypotension or intracranial hypertension (p < 0.001 for both). When the DCM reached zero, diastolic FV ceased for a short period during each heart cycle (R = 0.426, p < 0.001). CBF pressure passivity accelerated when DCM decreased below zero (from 1.51 ± 0.51 to 2.17 ± 1.17 % ΔLDF/ΔmmHg; mean ± SD; p = 0.010). CONCLUSIONS: The disappearance of diastolic CBF below LLA can be explained by DCM reaching zero or negative values. Below this point the decrease in CBF accelerates with further decrements of CPP.

Psychological distress does not compromise outcome in spinal surgery.

SUMMARY OF BACKGROUND DATA: Physical outcomes following surgery for degenerative spine disease have been well studied whereas the importance of psychological factors has only recently been acknowledged. Previous studies suggest that pre-operative psychological distress predicts poor outcome from spinal surgery. In the drive to identify patients who will not benefit, these patients risk being denied surgery. STUDY DESIGN: This is a prospective series from a spinal surgical register. AIM: The study examines the relationship between the physical symptoms, pre-operative psychological distress and outcome following surgery. METHODS: The Short Form 36 (SF36) Health Survey Questionnaire and the Hospital Anxiety and Depression Scale (HADS) were administered to patients undergoing elective surgery for degenerative spine disease pre-operatively and at 3 and 12 months post-operatively. Levels of physical disability (SF-36 physical functioning (SF36PF) and bodily pain (SF36BP) scores) and psychological distress (HADS-anxiety and HADS-depression scores) before and after surgery were compared. RESULTS: A total of 302 patients were included (169 men, 133 women, mean age 55 years). Pre-operatively patients had worse physical scores than age-matched controls (SF36PF normative mean (S.D.) 80.97 (12.69) vs. pre-op 33.31 (24.7) P < 0.05). Of the 302 patients, 117 (39%) had significant anxiety or depression. Increased levels of anxiety or depression pre-operatively correlated with worse physical (SF-36PF and SF-36BP) scores pre-operatively (Spearman's r P < 0.05). Levels of anxiety and depression were reduced post-operatively and physical outcomes improved post-operatively. Physical function remained worse in those groups who had high levels of anxiety and depression pre-operatively but when matched for pre-operative physical function, psychological distress did not have any additional effect on outcome. CONCLUSIONS: Poor physical function pre-operatively correlates with psychological distress. Both physical and psychological symptoms improve after surgery. Physical outcome after surgery is strongly influenced by pre-operative physical functioning but not independently by psychological distress. Anxious and depressed patients should continue to be offered surgery if clinically indicated.

Exploring the use of high and low demand simulation for human performance assessment during multiorgan retrieval with the joint scrub practitioner.

Introduction: The National Organ Retrieval Service (NORS) 2015 review recommended a Joint Scrub Practitioner for abdominal and cardiac teams during combined organ retrieval. To evaluate the feasibility of this role, and to understand the functional implications, this study explores the use of simulation and provides a novel and comprehensive approach to assess individual and team performance in simulated multiorgan retrievals. Methods: Two high-fidelity simulations were conducted in an operating theatre with porcine organs, en bloc, placed in a mannequin. For donation after brainstem death (DBD) simulation, an anaesthetic machine provided simulated physiological output. Retrievals following donation after circulatory death (DCD) began with rapid arrival in theatre of the mannequin. Cardiothoracic (lead surgeon) and abdominal (lead and assistant surgeons; joint scrub practitioner, n=9) teams combined for the retrievals. Data collected before, during and after simulations used self-report and expert observers to assess: attitudinal expectations, mental readiness, mental effort, non-technical skills, teamwork, task workload and social validation perceptions. Results: Attitudinal changes regarding feasibility of a joint scrub practitioner for DBD and DCD are displayed in the main body. There were no significant differences in mental readiness prior to simulations nor in mental effort indicated afterwards; however, variance was noted between simulations for individual team members. Non-technical skills were slightly lower in DCD than in DBD. Global ratings of teamwork were significantly (p<0.05) lower in DCD than in DBD. Measures of attitude indicated less support for the proposed joint scrub practitioner role for DCD than for DBD. Discussion: The paper posits that the joint scrub practitioner role in DCD multiorgan retrieval may bring serious and unanticipated challenges. Further work to determine the feasibility of the NORS recommendation is required. Measures of team performance and individual psychological response can inform organ retrieval feasibility considerations nationally and internationally.

The Vanguard Study: Human Performance Evaluation of UK National Organ Retrieval Service Teams Utilizing a Single Scrub Practitioner in Multiorgan Retrieval.

BACKGROUND: The National Organ Retrieval Service (NORS) 2015 review recommended a single scrub practitioner provide support simultaneously to abdominal and cardiothoracic teams in UK multiorgan retrieval. Previously, this model had been used only by the combined abdominal and cardiac team in Scotland. This study reports the impact on performance as part of the Vanguard project, which utilized the single scrub practitioner role with 5 NORS teams, to determine applicability United Kingdom wide. METHODS: Participants comprised members of abdominal (n = 56) and cardiothoracic (n = 54) teams attending UK thoraco-abdominal retrievals. Data were collected by validated psychometric scales to assess individual workload, anxiety, confidence, demands/coping resources, and teamwork. Additional data were collected through open comments and quantitative data describing context and outcome of retrieval. RESULTS: Abdominal and cardiothoracic teams showed different responses when using single (Vanguard) or dual scrub practitioners (Standard). Vanguard configuration was associated with significantly higher anxiety for abdominal but not cardiothoracic teams. Perceived workload increased for abdominal teams during Vanguard but decreased for cardiothoracic teams. Scrub practitioners reported elevated anxiety and decreased confidence in retrievals using Vanguard configuration. CONCLUSIONS: This is the first large study examining human performance during organ retrieval in the United Kingdom. Despite previous regional success, this study showed a significant negative impact of the single scrub practitioner when extrapolated widely to UK teams. As a result of this study, NORS declined to implement the single scrub model. These data support the use of human performance analysis as an essential part of successful development in organ retrieval practice.

Hypertonic saline in patients with poor-grade subarachnoid hemorrhage improves cerebral blood flow, brain tissue oxygen, and pH.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia and infarction due to reduced CBF remains the leading cause of poor outcome after aneurysmal subarachnoid hemorrhage. Hypertonic saline (HS) is associated with an increase in CBF. This study explores whether CBF enhancement with HS in patients with poor-grade subarachnoid hemorrhage is associated with improved cerebral tissue oxygenation. METHODS: Continuous monitoring of arterial blood pressure, intracranial pressure, cerebral perfusion pressure, brain tissue oxygen, carbon dioxide, pH, and middle cerebral artery flow velocity was performed in 44 patients. Patients were given an infusion (2 mL/kg) of 23.5% HS. In 16 patients, xenon CT scanning was also performed. CBF in a region surrounding the tissue oxygen sensor was calculated. Data are mean+/-SD. RESULTS: Thirty minutes postinfusion, a significant increase in arterial blood pressure, cerebral perfusion pressure, flow velocity, brain tissue pH, and brain tissue oxygen was seen together with a decrease in intracranial pressure (P<0.05). Intracranial pressure remained reduced for >300 minutes and flow velocity elevated for >240 minutes. A significant increase in brain tissue oxygen persisted for 240 minutes. Average baseline regional CBF was 33.9+/-13.5 mL/100 g/min, rising by 20.3%+/-37.4% (P<0.05) after HS. Patients with favorable outcome responded better to HS in terms of increased CBF, brain tissue oxygen, and pH and reduced intracranial pressure compared with those with an unfavorable outcome. A sustained increase in brain tissue oxygen (beyond 210 minutes) was associated with favorable outcome (P<0.023). CONCLUSIONS: HS augments CBF in patients with poor-grade subarachnoid hemorrhage and significantly improves cerebral oxygenation for 4 hours postinfusion. Favorable outcome is associated with an improvement in brain tissue oxygen beyond 210 minutes.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes. METHODS: We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294). FINDINGS: Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups. INTERPRETATION: Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months. FUNDING: Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).

Modelling human drug abuse and addiction with dedicated small animal positron emission tomography.

Drug addiction is a chronically relapsing brain disorder, which causes substantial harm to the addicted individual and society as a whole. Despite considerable research we still do not understand why some people appear particularly disposed to drug abuse and addiction, nor do we understand how frequently co-morbid brain disorders such as depression and attention-deficit hyperactivity disorder (ADHD) contribute causally to the emergence of addiction-like behaviour. In recent years positron emission tomography (PET) has come of age as a translational neuroimaging technique in the study of drug addiction, ADHD and other psychopathological states in humans. PET provides unparalleled quantitative assessment of the spatial distribution of radiolabelled molecules in the brain and because it is non-invasive permits longitudinal assessment of physiological parameters such as binding potential in the same subject over extended periods of time. However, whilst there are a burgeoning number of human PET experiments in ADHD and drug addiction there is presently a paucity of PET imaging studies in animals despite enormous advances in our understanding of the neurobiology of these disorders based on sophisticated animal models. This article highlights recent examples of successful cross-species convergence of findings from PET studies in the context of drug addiction and ADHD and identifies how small animal PET can more effectively be used to model complex psychiatric disorders involving at their core impaired behavioural self-control.

Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article.

OBJECT: Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH. METHODS: Within 72 hours of aSAH, 80 patients (age range 24-82 years) were randomized to receive intravenous EPO (30,000 U) or placebo every 48 hours for a total of 90,000 U. Primary end points were the incidence, duration, and severity of vasospasm and impaired autoregulation on transcranial Doppler ultrasonography. Secondary end points were incidence of DIDs and outcome at discharge and at 6 months. RESULTS: Randomization characteristics were balanced except for age, with the EPO group being older (mean age 59.6 vs 53.3 years, p=0.034). No differences were demonstrated in the incidence of vasospasm and adverse events; however, patients receiving EPO had a decreased incidence of severe vasospasm from 27.5 to 7.5% (p=0.037), reduced DIDs with new cerebral infarcts from 40.0 to 7.5% (p=0.001), a shortened duration of impaired autoregulation (ipsilateral side, p<0.001), and more favorable outcome at discharge (favorable Glasgow Outcome Scale score, p=0.039). Among the 71 survivors, the EPO group had fewer deficits measured with National Institutes of Health Stroke Scale (median Score 2 vs 6, p=0.008). CONCLUSIONS: This preliminary study showed that EPO seemed to reduce delayed cerebral ischemia following aSAH via decreasing severity of vasospasm and shortening impaired autoregulation.

Investigation of the hydrodynamic properties of a new MRI-resistant programmable hydrocephalus shunt.

BACKGROUND: The Polaris valve is a newly released hydrocephalus shunt that is designed to drain cerebrospinal fluid (CSF) from the brain ventricles or lumbar CSF space. The aim of this study was to bench test the properties of the Polaris shunt, independently of the manufacturer. METHODS: The Polaris Valve is a ball-on-spring valve, which can be adjusted magnetically in vivo. A special mechanism is incorporated to prevent accidental re-adjustment by an external magnetic field. The performance and hydrodynamic properties of the valve were evaluated in the UK Shunt Evaluation Laboratory, Cambridge, UK. RESULTS: The three shunts tested showed good mechanical durability over the 3-month period of testing, and a stable hydrodynamic performance over 45 days. The pressure-flow performance curves, operating, opening and closing pressures were stable. The drainage rate of the shunt increased when a negative outlet pressure (siphoning) was applied. The hydrodynamic parameters fell within the limits specified by the manufacturer and changed according to the five programmed performance levels. Hydrodynamic resistance was dependant on operating pressure, changing from low values of 1.6 mmHg/ml/min at the lowest level to 11.2 mmHg/ml/min at the highest performance level. External programming proved to be easy and reliable. Even very strong magnetic fields (3 Tesla) were not able to change the programming of the valve. However, distortion of magnetic resonance images was present. CONCLUSION: The Polaris Valve is a reliable, adjustable valve. Unlike other adjustable valves (except the Miethke ProGAV valve), the Polaris cannot be accidentally re-adjusted by an external magnetic field.

Effects of acute pravastatin treatment on intensity of rescue therapy, length of inpatient stay, and 6-month outcome in patients after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: We have previously demonstrated that acute pravastatin therapy after aneurysmal subarachnoid hemorrhage ameliorates vasospasm-related delayed ischemic deficits. This study assesses the effects of pravastatin on the frequency and intensity for rescue therapy, length of inpatient stay, and long-term outcome at 6 months. METHODS: Eighty aneurysmal subarachnoid hemorrhage patients (age 18 to 84 years, onset 1.8+/-1.3 days) were randomized to receive daily oral pravastatin (40 mg) or placebo for up to 14 days. Clinical events were recorded during the trial. Six-month outcome was assessed using the Short Form 36 and the modified Rankin Scale. RESULTS: Although no significant difference in the outcome at discharge was found between the trial groups, multivariate analysis showed pravastatin therapy reduced unfavorable outcome by 73% (P=0.041). The benefit persisted at 6 months (P=0.063) and was notable in the physical (P<0.001) and psychosocial (P<0.001) aspects measured using Short Form 36. Furthermore, the acute pravastatin therapy reduced the requirement for triple-H therapy (hypertensive, hypervolemic, hemodilution; P=0.045) and mortality related to vasospasm (P=0.02) and sepsis (P=0.001); no significant difference was found in the length of inpatient stay between the trial groups. CONCLUSIONS: This trial demonstrates that acute statin treatment reduces traditional rescue therapy for vasospasm after aneurysmal subarachnoid hemorrhage. Improvement in early outcome has proved robust at 6 months, particularly in relation to physical and psychosocial (Short Form 36) outcome.

Laboratory study on "intracranial hypotension" created by pumping the chamber of a hydrocephalus shunt.

BACKGROUND: It has been reported that pumping a shunt in situ may precipitate a proximal occlusion, and/or lead to ventricular over-drainage, particularly in the context of small ventricles. In the laboratory we measured the effect of pumping the pre-chamber of hydrocephalus shunts on intracranial hypotension. MATERIALS AND METHODS: A simple physical model of the CSF space in a hydrocephalic patient was constructed with appropriate compliance, CSF production and circulation. This was used to test eleven different hydrocephalus shunts. The lowest pressure obtained, the number of pumps needed to reach this pressure, and the maximum pressure change with a single pump, were recorded. RESULTS: All models were able to produce negative pressures ranging from -11.5 mmHg (Orbis-Sigma valve) to -233.1 mmHg (Sinu-Shunt). The number of pumps required reaching these levels ranged from 21 (PS Medical LP Reservoir) to 315 (Codman Hakim-Programmable). The maximum pressure change per pump ranged from 0.39 mmHg (Orbis-Sigma valve) to 23.1 (PS Medical LP Reservoir). CONCLUSION: Patients, carers and professionals should be warned that 'pumping' a shunt's pre-chamber may cause a large change in intracranial pressure and predispose the patient to ventricular catheter obstruction or other complications.

Strategy for improved [(11)C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [(11)C]DAA1106.

INTRODUCTION: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [(11)C]DAA1106 ([(11)C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. METHODS: A four-step synthetic route was devised to prepare DAA1123, the precursor for [(11)C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [(11)C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [(11)C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [(11)C]CH(3)I trapped. Evaluation of [(11)C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. RESULTS: The standard solution method produced 2.6-5.2 GBq (n=19) of [(11)C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [(11)C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/micromol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [(11)C]DAA1106. In vivo microPET [(11)C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 micromol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. CONCLUSIONS: A robust, high yielding captive solvent method of [(11)C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model.

Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial.

OBJECT: The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects. METHODS: Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period. RESULTS: No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002). CONCLUSIONS: In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.

Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome in patients with poor-grade spontaneous subarachnoid hemorrhage.

OBJECT: Systemic administration of 23.5% hypertonic saline enhances cerebral blood flow (CBF) in patients with poor-grade spontaneous subarachnoid hemorrhage (SAH). Whether the increment of change in CBF correlates with changes in autoregulation of CBF or outcome at discharge remains unknown. METHODS: Thirty-five patients with poor-grade spontaneous SAH received 2 ml/kg 23.5% hypertonic saline intravenously, and they underwent bedside transcranial Doppler (TCD) ultrasonography and intracranial pressure (ICP) monitoring. Seventeen of them underwent Xe-enhanced computed tomography (CT) scanning for measuring CBF. Outcome was assessed using the modified Rankin Scale (mRS) at discharge from the hospital. The data were analyzed using repeated-measurement analysis of variance and Dunnett correction. A comparison was made between patients with favorable and unfavorable outcomes using multivariate logistic regression. RESULTS: The authors observed a maximum increase in blood pressure by 10.3% (p < 0.05) and cerebral perfusion pressure (CPP) by 21.2% (p < 0.01) at 30 minutes, followed by a maximum decrease in ICP by 93.1% (p < 0.01) at 60 minutes. Changes in ICP and CPP persisted for longer than 180 and 90 minutes, respectively. The results of TCD ultrasonography showed that the baseline autoregulation was impaired on the ipsilateral side of ruptured aneurysm, and increments in flow velocities were higher and lasted longer on the contralateral side (48.75% compared with 31.96% [p = 0.045] and 180 minutes compared with 90 minutes [p < 0.05], respectively). The autoregulation was briefly impaired on the contralateral side during the infusion. A dose-dependent effect of CBF increments on favorable outcome was seen on Xe-CT scans (mRS Score 1-3, odds ratio 1.27 per 1 ml/100 g tissue x min, p = 0.045). CONCLUSIONS: Bolus systemic hypertonic saline therapy may be used for reversal of cerebral ischemia to normal perfusion in patients with poor-grade SAH.

A Multidisciplinary Investigation of the Effects of Competitive State Anxiety on Serve Kinematics in Table Tennis.

Displays of anxiety in table tennis were assessed through subjective (a self-report questionnaire), physiological (heart-rate variability) and kinematic variables. Using a within-group crossover design, 9 university-level table tennis players completed a series of serves under low- and high-anxiety conditions. Anxiety manipulation was achieved through the introduction of a national standard table tennis player, known to the participants, to receive serves in the high-anxiety condition, whilst serves were received by no opponent in the low-anxiety condition. Automated motion capture systems consisting of high-speed 3D motion cameras and analytical software (QUALISYS) determined the subject's movement kinematics: bat face angle (degrees) and serve routine duration (s). Self-reported state anxiety (MRF-Likert) and heart rate measurements were collected to examine changes between conditions. Contrary to the hypothesis, bat face angles did not change significantly between anxiety conditions (F (1.8) = 2.791, p = 0.133) and movement times were faster in the high-anxiety condition. In light of these findings, research into other facets of movement behaviour must be analysed to gain further understanding of the effects of anxiety on performance, which remain unclear.