Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.

INTRODUCTION: This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. METHODS: A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. RESULTS: Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). CONCLUSIONS: Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.

Mid-infrared interference coatings with excess optical loss below 10 ppm.

We present high-reflectivity substrate-transferred single-crystal GaAs/AlGaAs interference coatings at a center wavelength of 4.54 µm with record-low excess optical loss below 10 parts per million. These high-performance mirrors are realized via a novel microfabrication process that differs significantly from the production of amorphous multilayers generated via physical vapor deposition processes. This new process enables reduced scatter loss due to the low surface and interfacial roughness, while low background doping in epitaxial growth ensures strongly reduced absorption. We report on a suite of optical measurements, including cavity ring-down, transmittance spectroscopy, and direct absorption tests to reveal the optical losses for a set of prototype mirrors. In the course of these measurements, we observe a unique polarization-orientation-dependent loss mechanism which we attribute to elastic anisotropy of these strained epitaxial multilayers. A future increase in layer count and a corresponding reduction of transmittance will enable optical resonators with a finesse in excess of 100 000 in the mid-infrared spectral region, allowing for advances in high resolution spectroscopy, narrow-linewidth laser stabilization, and ultrasensitive measurements of various light-matter interactions.

Physiological performance and inflammatory markers as indicators of complications after oesophageal cancer surgery.

BACKGROUND: The extent to which physiological factors influence outcome following oesophageal cancer surgery is poorly understood. This study aimed to evaluate the extent to which cardiorespiratory fitness and selected metabolic factors predicted complications after surgery for carcinoma. METHODS: Two hundred and twenty-five consecutive patients underwent preoperative cardiopulmonary exercise testing to determine peak oxygen uptake ( V ˙ o2peak ), anaerobic threshold and the ventilatory equivalent for carbon dioxide ( V ˙ e/ V ˙ co2 ). Cephalic venous blood was assayed for serum C-reactive protein (CRP) and albumin levels, and a full blood count was done. The primary outcome measure was the Morbidity Severity Score (MSS). RESULTS: One hundred and ninety-eight patients had anatomical resection. A high MSS (Clavien-Dindo grade III or above) was found in 48 patients (24·2 per cent) and was related to an increased CRP concentration (area under the receiver operating characteristic (ROC) curve (AUC) 0·62, P = 0·001) and lower V ˙ o2peak (AUC 0·36, P = 0·003). Dichotomization of CRP levels (above 10 mg/l) and V ˙ o2peak (below 18·6 ml per kg per min) yielded adjusted odds ratios (ORs) for a high MSS of 2·86 (P = 0·025) and 2·92 (P = 0·002) respectively. Compared with a cohort with a low Combined Inflammatory and Physiology Score (CIPS), the OR was 1·70 (95 per cent c.i. 0·85 to 3·39) for intermediate and 27·47 (3·12 to 241·69) for high CIPS (P < 0·001). CONCLUSION: CRP and V ˙ o2peak were independently associated with major complications after potentially curative oesophagectomy for cancer. A composite risk score identified a group of patients with a high risk of developing complications.

ANTECEDENTES: El grado en el que los factores fisiológicos influyen en el resultado tras la cirugía del cáncer de esófago no se conoce bien. Este estudio tuvo como objetivo evaluar en qué medida el estado cardiorrespiratorio y los factores metabólicos seleccionados predecían complicaciones después de cirugía por cáncer. MÉTODOS: Pacientes consecutivos fueron sometidos a una prueba de ejercicio cardiopulmonar preoperatoria para determinar el consumo pico de oxígeno (peak oxygen uptake, V ̇ O2Peak ), el umbral anaeróbico (anaerobic threshold, AT) y el equivalente ventilatorio de dióxido de carbono (ventilatory equivalent for carbon dioxide, V ̇ E / V ̇ CO2 ). Se extrajo sangre de la vena cefálica para analizar la proteína C reactiva (C-reactive protein, CRP) sérica, albumina y hemograma completo. La medida de resultado primario fue la puntuación de la gravedad de la morbilidad (Morbidity Severity Score, MSS). RESULTADOS: Se observó MSS (Clavien-Dindo > 2) en 33 (17,7%) pacientes, relacionándose con CRP elevada (AUC 0,69, P = 0,001) y V ̇O2Peak baja (AUC 0,33, P = 0,003). La dicotomización de la CRP (por encima de 10 mg/L) y V ̇O2Peak (por debajo de 18,6 mL/kg/min) se asociada a una razón de oportunidades (odds ratio, OR) de 4,01 (P = 0,002) y 3,74 (P = 0,002) para MSS y CD > 2, respectivamente. En comparación con la cohorte con una puntuación combinada inflamatoria y fisiológica (Combined Inflammatory and Physiology Score, CIPS) baja, el OR fue de 1,70 (i.c. del 95% 0,85-3,39) para una CIPS intermedia y de 27,47 (3,12-241,69, P < 0,001) para CIPS elevada. CONCLUSIÓN: CRP y V ̇O2Peak se asociaron de forma independiente con complicaciones mayores tras esofaguectomía potencialmente curativa por cáncer. Una puntuación combinada de riesgo identificó a un grupo de pacientes con un riesgo elevado de desarrollar complicaciones.

Cardiorespiratory fitness fails to predict short-term postoperative mortality in patients undergoing elective open surgery for abdominal aortic aneurysm.

INTRODUCTION: Preoperative cardiopulmonary exercise testing aids surgical risk stratification and is an established predictor of mid- to long-term survival in patients undergoing elective open abdominal aortic aneurysm repair. Whether cardiopulmonary exercise testing also predicts 30-day mortality in this population remains to be established. MATERIALS AND METHODS: Data for 109 patients (mean age 72 years) who underwent cardiopulmonary exercise testing to assess risk for surgical abdominal aortic aneurysm repair was analysed. Patients were classified according to cardiopulmonary fitness as fit (peak oxygen uptake ≥ 15ml O2.kg-1.min-1) or unfit (peak oxygen uptake less than 15ml O2.kg-1.min-1) and further stratified according to clamp position (infrarenal or suprarenal). Between-group postoperative outcomes were compared for in-hospital 30-day mortality, postoperative morbidity scale scores (day 5) and hospital length of stay. RESULTS: Seventy-nine patients underwent open surgery and 30 patients were treated conservatively. No deaths were recorded at 30 days post-surgery. Unfit patients with infrarenal clamping exhibited higher postoperative morbidity scale scores (64% vs 26%) and longer length of stay (four days) than fit patients (p < 0.05). Conversely, with suprarenal clamping, postoperative morbidity scale scores were similar and length of stay longer (three days) in fit compared with unfit patients (p < 0.05). DISCUSSION AND CONCLUSION: Preoperative fitness level defined by peak oxygen uptake failed to identify patients at risk of 30-day mortality when undergoing elective abdominal aortic aneurysm repair. Postoperative morbidity and length of stay in patients with suprarenal clamping was high independent of cardiopulmonary fitness. These findings suggest that cardiopulmonary exercise testing may be a useful predictor of complications following infrarenal rather than suprarenal clamping but may not be a good predictor of 30-day mortality.

Cardiorespiratory fitness is impaired and predicts mid-term postoperative survival in patients with abdominal aortic aneurysm disease.

NEW FINDINGS: What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of <13.1 ml O2  kg-1  min-1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥34 are associated with increased risk of postoperative mortality at 2 years. These findings demonstrate that cardiorespiratory fitness can predict mid-term postoperative survival in AAA patients, which may help to direct care provision. ABSTRACT: Preoperative cardiopulmonary exercise testing is a standard assessment of cardiorespiratory fitness (CRF) and risk stratification. However, to what extent CRF is impaired in patients undergoing surgical repair of abdominal aortic aneurysm (AAA) disease and the corresponding implications for postoperative outcome requires further investigation. We measured CRF during an incremental exercise test to exhaustion using online respiratory gas analysis in patients with AAA disease (n = 124, aged 72 ± 7 years) and healthy sedentary control subjects (n = 104, aged 70 ± 7 years). Postoperative survival was examined for association with CRF, and threshold values were calculated for independent predictors of mortality. Patients who underwent preoperative cardiopulmonary exercise testing before surgical repair had lower CRF [age-adjusted mean difference of 12.5 ml O2  kg-1  min-1 for peak oxygen uptake ( V ̇ O 2 peak ), P < 0.001 versus control subjects]. After multivariable analysis, both V ̇ O 2 peak and the ventilatory equivalent for carbon dioxide at anaerobic threshold ( V ̇ E / V ̇ C O 2 - AT ) were independent predictors of mid-term postoperative survival (2 years). Hazard ratios of 5.27 (95% confidence interval 1.62-17.14, P = 0.006) and 3.26 (95% confidence interval 1.00-10.59, P = 0.049) were observed for V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34, respectively. Thus, CRF is lower in patients with AAA, and those with a V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34 are associated with a markedly increased risk of postoperative mortality. Collectively, our findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients, which may help to direct care provision.

The cardiopulmonary exercise test grey zone; optimising fitness stratification by application of critical difference.

BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification. METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V˙O2-AT): 11 ml O2 kg-1 min-1, peak oxygen uptake (V˙O2 peak): 16 ml O2 kg-1 min-1, and ventilatory equivalent for carbon dioxide at AT (V̇E/V̇CO2-AT): 36]. RESULTS: The critical difference for V˙O2-AT, V˙O2 peak, and V˙E/V˙CO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and ≥13.6 ml O2 kg-1 min-1, V˙O2 peak <14.2 and ≥18.3 ml kg-1 min-1, V˙E/V˙CO2-AT ≥40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness. CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for.

Effects of submaximal and supramaximal interval training on determinants of endurance performance in endurance athletes.

We compared the effects of submaximal and supramaximal cycling interval training on determinants of exercise performance in moderately endurance-trained men. Maximal oxygen consumption (VO2max ), peak power output (Ppeak ), and peak and mean anaerobic power were measured before and after 6 weeks (3 sessions/week) of submaximal (85% maximal aerobic power [MP], HIIT85 , n = 8) or supramaximal (115% MP, HIIT115 , n = 9) interval training to exhaustion in moderately endurance-trained men. High-intensity training volume was 47% lower in HIIT115 vs HIIT85 (304 ± 77 vs 571 ± 200 min; P < 0.01). Exercise training was generally associated with increased VO2max (HIIT85 : +3.3 ± 3.1 mL/kg/min; HIIT115 : +3.3 ± 3.6 ml/kg/min; Time effect P = 0.002; Group effect: P = 0.95), Ppeak (HIIT85 : +18 ± 9 W; HIIT115 : +16 ± 27 W; Time effect P = 0.045; Group effect: P = 0.49), and mean anaerobic power (HIIT85 : +0.42 ± 0.69 W/kg; HIIT115 : +0.55 ± 0.65 W/kg; Time effect P = 0.01; Group effect: P = 0.18). Six weeks of submaximal and supramaximal interval training performed to exhaustion seems to equally improve VO2max and anaerobic power in endurance-trained men, despite half the accumulated time spent at the target intensity.

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals.

BACKGROUND: Exercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development. METHODS: df was measured in 24 healthy individuals prior to, after 5min of submaximal exercise, following maximal exercise, 45min of passive recovery and following 60min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. RESULTS: Significantly increased df was observed following exercise, returning to resting values following 60min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. CONCLUSION: This study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

High resolution study of the spatial distributions of abyssal fishes by autonomous underwater vehicle.

On abyssal plains, demersal fish are believed to play an important role in transferring energy across the seafloor and between the pelagic and benthic realms. However, little is known about their spatial distributions, making it difficult to quantify their ecological significance. To address this, we employed an autonomous underwater vehicle to conduct an exceptionally large photographic survey of fish distributions on the Porcupine Abyssal Plain (NE Atlantic, 4850 m water depth) encompassing two spatial scales (1-10 km(2)) on and adjacent to a small abyssal hill (240 m elevation). The spatial distributions of the total fish fauna and that of the two dominant morphotypes (Coryphaenoides sp. 1 and C. profundicolus) appeared to be random, a result contrary to common expectation but consistent with previous predictions for these fishes. We estimated total fish density on the abyssal plain to be 723 individuals km(-2) (95% CI: 601-844). This estimate is higher, and likely more precise, than prior estimates from trawl catch and baited camera techniques (152 and 188 individuals km(-2) respectively). We detected no significant difference in fish density between abyssal hill and plain, nor did we detect any evidence for the existence of fish aggregations at any spatial scale assessed.

An assessment of juvenile Atlantic cod Gadus morhua distribution and growth using diver operated stereo-video surveys.

Stereo-video scuba transects were conducted during daylight hours from June to September 2013 within a proposed marine protected area (MPA) in the Firth of Clyde, west of Scotland. More juvenile Atlantic cod Gadus morhua of fork length (LF ) range 6-11 cm were observed in substrata containing mixed gravel, including maerl, than in boulder-cobble substrata with high algal cover, or sand with low density seagrass. Community composition was significantly different between substratum types. A decrease in G. morhua abundance was observed over the period of data collection. Over time, mean and variance in G. morhua LF increased, indicating multiple recruitment events. Protecting mixed gravel substrata could be a beneficial management measure to support the survival and recruitment of juvenile G. morhua; other substrata might be important at night given their diel migratory behaviour. Stereo-video cameras provide a useful non-destructive fisheries-independent method to monitor species abundance and length measurements.

On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans.

AIM: The aim of this study was to examine if erythropoietin (EPO) has the potential to act as a biological antioxidant and determine the underlying mechanisms. METHODS: The rate at which its recombinant form (rHuEPO) reacts with hydroxyl (HO˙), 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) and peroxyl (ROO˙) radicals was evaluated in-vitro. The relationship between the erythopoietic and oxidative-nitrosative stress response to poikilocapneic hypoxia was determined separately in-vivo by sampling arterial blood from eleven males in normoxia and following 12 h exposure to 13% oxygen. Electron paramagnetic resonance spectroscopy, ELISA and ozone-based chemiluminescence were employed for direct detection of ascorbate (A(˙-) ) and N-tert-butyl-α-phenylnitrone spin-trapped alkoxyl (PBN-OR) radicals, 3-nitrotyrosine (3-NT) and nitrite (NO2-). RESULTS: We found rHuEPO to be a potent scavenger of HO˙ (kr = 1.03-1.66 × 10(11) m(-1) s(-1) ) with the capacity to inhibit Fenton chemistry through catalytic iron chelation. Its ability to scavenge DPPH˙ and ROO˙ was also superior compared to other more conventional antioxidants. Hypoxia was associated with a rise in arterial EPO and free radical-mediated reduction in nitric oxide, indicative of oxidative-nitrosative stress. The latter was confirmed by an increased systemic formation of A˙(-) , PBN-OR, 3-NT and corresponding loss of NO2- (P < 0.05 vs. normoxia). The erythropoietic and oxidative-nitrosative stress responses were consistently related (r = -0.52 to 0.68, P < 0.05). CONCLUSION: These findings demonstrate that EPO has the capacity to act as a biological antioxidant and provide a mechanistic basis for its reported cytoprotective benefits within the clinical setting.

Neutrophil to lymphocyte ratio predicts perioperative mortality following open elective repair of abdominal aortic aneurysms.

OBJECTIVES: This study assesses the predictive value of neutrophil to lymphocyte ratio (NLR) in relation to 30-day and overall mortality following open abdominal aortic aneurysm (AAA) repairs. In addition, it assess assesses any correlation between NLR and age, size of the AAA and gender. METHODS: Patients undergoing elective or urgent open repair of their AAA by a single surgeon during a 10-year period were included. A pre-operative NLR of >5 was regarded as abnormal. RESULTS: 350 consecutive patients underwent AAA repair. 52 had an NLR>5. 30-day mortality rate was 12/52 (23%) in the NLR>5 group and 20/298 (6.7%) in the NLR<5 group (p = 0.0007). All deaths in the NLR>5 group were due to myocardial infarction. The median NLR was higher in those that died within 30 days at 4.2 [IQR: 2.6-7.5] versus 2.8 [IQR: 2.1-3.8] (p = 0.0001). Overall mortality at 10 years, in the NLR>5 group - 26/52 (50%) was significantly greater than that of the NLR<5 group - 102/298 (34.2%) (p = 0.043). Median NLR of those dying during follow-up was significantly higher in those with a baseline NLR>5 at 3.2 (IQR 2.5-4.6) versus 2.6 (IQR: 2.0-3.6) in those surviving (p = 0.00004). No difference was found between NLR and age, aneurysm size or gender. CONCLUSION: Pre-operative NLR>5 appears to be a significant predictor of both 30-day mortality and long-term outcome in elective and urgent open AAA surgery. It is plausible the NLR is identifying a group with sub-clinical cardiovascular disease at risk of peri-operative myocardial infarction.

Internal carotid artery occlusion: its natural history including recanalization and subsequent neurological events.

OBJECTIVE: To determine the incidence of recanalization of the occluded internal carotid artery (ICA) and establish its natural history. METHODS: Patients with duplex-confirmed ICA occlusions were identified, and a subgroup offered repeat scanning. The antemortem condition and cause of death of patients who died were recorded. RESULTS: Of 153 patients identified, 77 underwent follow-up at a median of 35 months (interquartile range [IQR]: 14-61).In all, 8 (10.3%) demonstrated recanalization at a median of 53 months (IQR: 35-114). Of 8, 7 underwent carotid endarterectomy with histopathological confirmation of recanalization. Of the 153 patients, 45 (29%) had further neurological events, and 38 (25%) were within the territory of the occluded ICA. In all, 76 patients died, and of the 53 with a confirmed cause of death, 12 (23%) were attributed to a cerebrovascular accident corresponding to the territory of the occluded artery. CONCLUSION: Recanalization of ICA occlusion is common and leads to significant neurological events. Duplex ultrasound follow-up appears mandatory.

Aging blunts hyperventilation-induced hypocapnia and reduction in cerebral blood flow velocity during maximal exercise.

Cerebral blood flow (CBF) increases from rest to ∼60% of peak oxygen uptake (VO(2peak)) and thereafter decreases towards baseline due to hyperventilation-induced hypocapnia and subsequent cerebral vasoconstriction. It is unknown what happens to CBF in older adults (OA), who experience a decline in CBF at rest coupled with a blunted ventilatory response during VO(2peak). In 14 OA (71 ± 10 year) and 21 young controls (YA; 23 ± 4 years), we hypothesized that OA would experience less hyperventilation-induced cerebral vasoconstriction and therefore an attenuated reduction in CBF at VO(2peak). Incremental exercise was performed on a cycle ergometer, whilst bilateral middle cerebral artery blood flow velocity (MCA V (mean); transcranial Doppler ultrasound), heart rate (HR; ECG) and end-tidal PCO(2) (P(ET)CO(2)) were monitored continuously. Blood pressure (BP) was monitored intermittently. From rest to 50% of VO(2peak), despite greater elevations in BP in OA, the change in MCA V(mean) was greater in YA compared to OA (28% vs. 15%, respectively; P < 0.0005). In the YA, at intensities >70% of VO(2peak), the hyperventilation-induced declines in both P(ET)CO(2) (14 mmHg (YA) vs. 4 mmHg (OA); P < 0.05) and MCA V(mean) (-21% (YA) vs. -7% (OA); P < 0.0005) were greater in YA compared to OA. Our findings show (1), from rest-to-mild intensity exercise (50% VO(2peak)), elevations in CBF are reduced in OA and (2) age-related declines in hyperventilation during maximal exercise result in less hypocapnic-induced cerebral vasoconstriction.

Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function.

There is considerable utility in the use of transcranial Doppler ultrasound (TCD) to assess cerebrovascular function. The brain is unique in its high energy and oxygen demand but limited capacity for energy storage that necessitates an effective means of regional blood delivery. The relative low cost, ease-of-use, non-invasiveness, and excellent temporal resolution of TCD make it an ideal tool for the examination of cerebrovascular function in both research and clinical settings. TCD is an efficient tool to access blood velocities within the cerebral vessels, cerebral autoregulation, cerebrovascular reactivity to CO(2), and neurovascular coupling, in both physiological states and in pathological conditions such as stroke and head trauma. In this review, we provide: (1) an overview of TCD methodology with respect to other techniques; (2) a methodological synopsis of the cerebrovascular exam using TCD; (3) an overview of the physiological mechanisms involved in regulation of the cerebral blood flow; (4) the utility of TCD for assessment of cerebrovascular pathology; and (5) recommendations for the assessment of four critical and complimentary aspects of cerebrovascular function: intra-cranial blood flow velocity, cerebral autoregulation, cerebral reactivity, and neurovascular coupling. The integration of these regulatory mechanisms from an integrated systems perspective is discussed, and future research directions are explored.

Temporal change in deep-sea benthic ecosystems: a review of the evidence from recent time-series studies.

Societal concerns over the potential impacts of recent global change have prompted renewed interest in the long-term ecological monitoring of large ecosystems. The deep sea is the largest ecosystem on the planet, the least accessible, and perhaps the least understood. Nevertheless, deep-sea data collected over the last few decades are now being synthesised with a view to both measuring global change and predicting the future impacts of further rises in atmospheric carbon dioxide concentrations. For many years, it was assumed by many that the deep sea is a stable habitat, buffered from short-term changes in the atmosphere or upper ocean. However, recent studies suggest that deep-seafloor ecosystems may respond relatively quickly to seasonal, inter-annual and decadal-scale shifts in upper-ocean variables. In this review, we assess the evidence for these long-term (i.e. inter-annual to decadal-scale) changes both in biologically driven, sedimented, deep-sea ecosystems (e.g. abyssal plains) and in chemosynthetic ecosystems that are partially geologically driven, such as hydrothermal vents and cold seeps. We have identified 11 deep-sea sedimented ecosystems for which published analyses of long-term biological data exist. At three of these, we have found evidence for a progressive trend that could be potentially linked to recent climate change, although the evidence is not conclusive. At the other sites, we have concluded that the changes were either not significant, or were stochastically variable without being clearly linked to climate change or climate variability indices. For chemosynthetic ecosystems, we have identified 14 sites for which there are some published long-term data. Data for temporal changes at chemosynthetic ecosystems are scarce, with few sites being subjected to repeated visits. However, the limited evidence from hydrothermal vents suggests that at fast-spreading centres such as the East Pacific Rise, vent communities are impacted on decadal scales by stochastic events such as volcanic eruptions, with associated fauna showing complex patterns of community succession. For the slow-spreading centres such as the Mid-Atlantic Ridge, vent sites appear to be stable over the time periods measured, with no discernable long-term trend. At cold seeps, inferences based on spatial studies in the Gulf of Mexico, and data on organism longevity, suggest that these sites are stable over many hundreds of years. However, at the Haakon Mosby mud volcano, a large, well-studied seep in the Barents Sea, periodic mud slides associated with gas and fluid venting may disrupt benthic communities, leading to successional sequences over time. For chemosynthetic ecosystems of biogenic origin (e.g. whale-falls), it is likely that the longevity of the habitat depends mainly on the size of the carcass and the ecological setting, with large remains persisting as a distinct seafloor habitat for up to 100 years. Studies of shallow-water analogs of deep-sea ecosystems such as marine caves may also yield insights into temporal processes. Although it is obvious from the geological record that past climate change has impacted deep-sea faunas, the evidence that recent climate change or climate variability has altered deep-sea benthic communities is extremely limited. This mainly reflects the lack of remote sensing of this vast seafloor habitat. Current and future advances in deep-ocean benthic science involve new remote observing technologies that combine a high temporal resolution (e.g. cabled observatories) with spatial capabilities (e.g. autonomous vehicles undertaking image surveys of the seabed).