Optimised XUV holography using spatially shaped high harmonic beams.

We present a novel method for controlling the transverse positions and relative powers of multiple high-order harmonic beams. A phase-only spatial light modulator is used to produce multiple infrared foci, the positions and intensities of which can be controlled programmably, enabling the generation and control of multiple HHG beams. To demonstrate the utility of this method we perform Fourier transform holography with separate illumination of the object and reference pinhole by a pair of HHG beams, which makes optimal use of the available photon flux. The programmable control of the spatial distribution of HHG beams demonstrated here offers new opportunities for experiments at extreme ultraviolet (XUV) wavelengths, particularly for photon intensive applications such as imaging.

Spatially resolved common-path high-order harmonic interferometry.

Spatially resolved interference is observed between high-order harmonics generated in two longitudinally separated gas targets. High-contrast modulations in the intensity of each harmonic order up to the cutoff are observed on-axis in the far field of the source as the separation between the gas targets is increased. For low-order harmonics, additional off-axis modulations are observed, which are attributed to the interference between the contributions from the long quantum trajectories from each gas target. The inherent synchronization of this setup offers the prospect for high-stability metrology of quantum states with ultrafast temporal resolutions.

Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation.

There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively.

Beyond the randomized clinical trial: citrate for continuous renal replacement therapy in clinical practice.

BACKGROUND: Premature circuit clotting is a major problem during continuous renal replacement therapy (CRRT). Six randomized controlled trials confirmed that regional anticoagulation with citrate is superior to heparin. Our objective was to compare circuit patency with citrate, heparin and epoprostenol in routine clinical practice. METHODS: We retrospectively analysed data on circuit patency of all circuits used in a single centre between September 2008 and August 2009. We differentiated between premature filter clotting, elective discontinuation and waste. RESULTS: 309 patients were treated with CRRT (n = 2,059 circuits). The mean age was 65.7; 63.8% were male. The methods to maintain circuit patency were unfractionated heparin (42.3%), epoprostenol (23.0%), citrate (14.7%), combinations of different anticoagulants (14.6%) and no anticoagulation (4.7%). Premature clotting was the most common reason for circuit discontinuation among circuits anticoagulated with heparin, epoprostenol or combinations of different anticoagulants (59-62%). Among circuits anticoagulated with citrate the main reason for discontinuation was elective (61%). Hazard regression analysis confirmed significantly better circuit survival with citrate. Changing from heparin to citrate decreased the risk of premature circuit clotting by 75.8%. CONCLUSION: In routine clinical practice, regional anticoagulation with citrate is associated with significantly better circuit patency than heparin or epoprostenol.

Metabolic effects of intensive insulin therapy in critically ill patients.

Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.

Neutrophils in development of multiple organ failure in sepsis.

Multiple organ failure is a major threat to the survival of patients with sepsis and systemic inflammation. In the UK and in the USA, mortality rates are currently comparable with and projected to exceed those from myocardial infarction. The immune system combats microbial infections but, in severe sepsis, its untoward activity seems to contribute to organ dysfunction. In this Review we propose that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure. We further suggest that targeting neutrophils and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.

Erythrocyte zinc in hospital patients.

BACKGROUND: Abnormal thyroid function tests (serum thyrotropin [TSH], free thyroxine [T(4)] and free triiodothyronine [T(3)]) are frequently seen in hospitalized patients. Assessment of thyroid function in these patients is difficult. It has been suggested that acutely ill patients may be hypothyroid at the tissue level. Erythrocyte zinc (EZn) has been shown to be increased in hypothyroidism. The aim of this study was to examine EZn as an index of thyroid status of hospital patients. METHODS: In order to assess the thyroid status at tissue level, we measured EZn in 26 healthy subjects, 39 critically ill patients and 19 hospitalized geriatric patients. EZn was measured in young cells, as the effect of illness is likely to be seen in the newly formed cells. RESULT: TSH and free T(3) were lower in critically ill patients and serum free T(3) was lower in geriatric patients. EZn in young cells was higher in both patient groups (by 13% and 23%, respectively). EZn in old cells was also higher in the geriatric group. CONCLUSION: We conclude that EZn is higher in hospitalized patients, suggesting that these patients may be hypothyroid at the tissue level.

Relationship between TISS and ICU cost.

OBJECTIVE: To determine whether the therapeutic intervention scoring system (TISS) reliably reflects the cost of the overall intensive care unit (ICU) population, subgroups of that population and individual ICU patients. DESIGN: Prospective analysis of individual patient costs and comparison with TISS. SETTING: Adult, 12 bedded general medical and surgical ICU in a university teaching hospital. SUBJECTS: Two hundred fifty-seven consecutive patients including 52 coronary care (CCU), 99 cardiac surgery (CS) and 106 general ICU (GIC) cases admitted to the ICU during a 12-week period in 1994. A total of 916 TISS-scored patient days were analysed MAIN OUTCOME MEASURES: A variable cost (VC) that included consumables and service usage (nursing, physiotherapy, radiology and pathology staff costs) for individual patients was measured daily. Nursing costs were calculated in proportion to a daily nursing dependency score. A fixed cost (FC) was calculated for each patient to include medical, technical and clerical salary costs, capital equipment depreciation, equipment and central hospital costs. The correlation between cost and TISS was analysed using regression analysis. RESULTS: For the whole group (n = 257) the average daily FC was pound sterling 255 and daily VC was pound sterling 541 (SEM 10); range pound sterling 23-pound sterling 2,806. In the patient subgroups average daily cost (FC + VC) for CCU was pound sterling 476 (SEM 17.5), for CS pound sterling 766 (SEM 13.8) and for GIC pound sterling 873 (SEM 13.6). In the group as a whole, a strong correlation was demonstrated between VC and the TISS for each patient day (r = 0.87, p < 0.001) and this improved further when the total TISS score was compared with the total VC of the entire patient episode (r = 0.93, p < 0.001). This correlation was maintained in CCU, CS and GIC patient cohorts with only a small median difference between actual and predicted cost (2.2 % for GIC patients). However, in the individual patient, the range of error was up to +/- 65 % of the true variable cost. For the whole group the variable cost per TISS point was pound sterling 25. CONCLUSION: These results demonstrate that TISS reliably measures overall ICU population costs as well as those of the subgroups CCU, CS and GIC. However, the relationship between TISS and cost is less reliable for the individual patient.

Bicarbonate-based haemofiltration in the management of acute renal failure with lactic acidosis.

Continuous haemofiltration with lactate-based replacement fluid is widely used for the treatment of acute renal failure (ARF). In the presence of lactic acidosis, such treatment exacerbates rather than improves the clinical state. Continuous haemofiltration using a locally-prepared bicarbonate-based replacement fluid was performed in 200 patients over 7 years. All the patients had ARF with concomitant lactic acidosis, or demonstrated lactate intolerance after starting haemofiltration with lactate-based replacement fluids. In every case it was possible to correct the acidosis without inducing either extracellular volume expansion or hypernatraemia. In 89 patients (45%), the lactic acidosis resolved while being treated with bicarbonate-based haemofiltration. Fifty-seven patients (28.5%) survived. Significant differences at presentation in the group who survived, compared with those who died, were seen in age (50.8 vs. 57.1), mean arterial pressure (68.5 vs. 60.0 mmHg) and APACHE II score (32.1 vs. 38.9). Neither the severity of the presenting acidosis nor the arterial blood lactate appeared to predict outcome. Patients who developed ARF and lactic acidosis after cardiac surgery had a low survival rate. The combination of ARF and lactic acidosis that cannot safely be treated by haemofiltration using lactate-based replacement fluids can be managed with bicarbonate-based haemofiltration.

Critical illness poly-neuropathy following severe hyperpyrexia.

Two patients developed critical illness polyneuropathy after severe hyperpyrexia. Fever was secondary to a phaeochromocytoma in one patient and sepsis in the other. These observations suggest that high fever may be one possible aetiology of critical illness polyneuropathy.

The relationship between oxygen delivery and consumption.

The primary function of the heart and lungs is to generate a flow of oxygenated blood to respiring tissues to sustain aerobic metabolism. Teleologically, such a transport system has several basic requirements. It should be energy efficient, avoiding unnecessary cardiorespiratory work, but it should be sensitive to the fluctuating demands of cellular metabolism. Ideally, metabolic demand and oxygen distribution should be matched regionally when at rest, during exercise, and in different disease states. Finally, oxygen should pass efficiently across the extravascular tissue matrix. The mechanisms that control oxygen distribution are complex and not completely understood. In the critically ill patient, these mechanisms may have an important role in determining the clinical outcome. The relationship between oxygen delivery and consumption has not been clearly established despite considerable investigation during the last decade. However, these variables are often measured to define a population of critically ill patients in whom oxygen consumption is limited by oxygen delivery, the state of so-called delivery-dependent oxygen consumption or pathologic supply dependency. The recent literature in critical care and many leading intensive care units has emphasized the importance of raising oxygen delivery to "supranormal" levels in an attempt to satisfy the increased metabolic demands of these patients. This practice has been justified by the observation that increasing oxygen delivery improves oxygen debt and outcome in postoperative surgical patients requiring intensive care. In the severely hypovolemic patient, most physicians would agree that volume replacement to improve oxygen delivery must be beneficial. However, in patients with more complex problems, including sepsis, cardiovascular collapse, and hypoxic hypoxemia, controlled trials to examine the influence of such strategies on clinical outcome have produced conflicting data. Several methodologic factors may have contributed to these contradictory and often controversial results. These factors include failure to define the disease and patient population adequately, the relationship between the time of investigation and the evolution of the disease process, and the accuracy and frequency of measurement.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypoxic-ischaemic brain injury: imaging and neurophysiology abnormalities related to outcome.

BACKGROUND: The outcome for patients with hypoxic-ischaemic brain injury (HIBI) is often poor. It is important to establish an accurate prognosis as soon as possible after the insult to guide management. Clinical assessment is not reliable and ancillary investigations, particularly imaging and EEG, are needed to understand the severity of brain injury and the likely outcome. METHODS: We undertook a retrospective study of 39 patients on an intensive therapy unit (ITU) with HIBI who were referred for MRI. The patients were seen consecutively >57 months. HIBI was due to a variety of insults causing cardiac arrest, hypoperfusion or isolated hypoxia. RESULTS: The outcome was poor, 29 patients died, 7 were left severely disabled and only 3 made a good recovery. Characteristic imaging changes were seen on MRI. These included extensive changes in the cortex and the deep grey matter present on diffusion-weighted imaging (DWI) and T2-weighted imaging within 6 days of the insult. In other patients, different patterns of involvement of the cortex and basal ganglia occurred. There was no significant difference in the outcome or imaging appearances according to aetiology. A poor prognosis was consistently associated with a non- or poorly responsive EEG rhythm and the presence of periodic generalized phenomena with a very low-voltage background activity. CONCLUSION: In this retrospective study of patients with HIBI, MRI and EEG provided valuable information concerning prognosis.

Outcomes of critically ill patients with cirrhosis admitted to intensive care: an important perspective from the non-transplant setting.

BACKGROUND: Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care. AIMS: To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets. METHODS: A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated. RESULTS: Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43-59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8-11], Model for End-Stage Liver Disease (MELD) 18 [12-24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13-22]. CONCLUSIONS: Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs.