Femtosecond mega-electron-volt electron microdiffraction.

To understand and control the basic functions of physical, chemical and biological processes from micron to nano-meter scale, an instrument capable of visualizing transient structural changes of inhomogeneous materials with atomic spatial and temporal resolutions, is required. One such technique is femtosecond electron microdiffraction, in which a short electron pulse with femtosecond-scale duration is focused into a micron-scale spot and used to obtain diffraction images to resolve ultrafast structural dynamics over a localized crystalline domain. In this letter, we report the experimental demonstration of time-resolved mega-electron-volt electron microdiffraction which achieves a 5 µm root-mean-square (rms) beam size on the sample and a 110 fs rms temporal resolution. Using pulses of 10k electrons at 4.2 MeV energy with a normalized emittance 3 nm-rad, we obtained high quality diffraction from a single 10 µm paraffin (C44H90) crystal. The phonon softening mode in optical-pumped polycrystalline Bi was also time-resolved, demonstrating the temporal resolution limits of the instrument. This new characterization capability will open many research opportunities in material and biological sciences.

Participation in activities and secondary health complications among persons aging with traumatic spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe participation in activities and explore the relationship with secondary complications among persons aging with a traumatic spinal cord injury (SCI). SETTING: A regional SCI outpatient center in Sweden. METHODS: Data were collected through a phone survey, which included 10 activities from the instrument PARTS/M-v3 (PARTicipation Survey/Mobility version-3) together with data from the participants' medical records. Cross-tabulation and χ2 were used for data analysis. RESULTS: In this study, 121 persons matched the inclusion criteria and the final study sample comprised 73 participants (60% response rate): 55 men and 18 women. Mean age was 63.7±9.4 years, and mean time since injury was 36.3±9.2 years. Regardless of duration of SCI, all 73 participated in dressing, bathing and leisure activities. Women reported better health than men. Particularly for those who lived 36-55 years after injury; increasing pain, fatigue, spasticity and decreased muscle strength were negatively affecting participation in activities, especially exercise and active recreation. Additionally, a need to save strength/energy was also a reason for not participating in the activities. Perceived future support and concerns in relation to personal assistance, assistive devices and rehabilitation was also reported. CONCLUSION: Increasing secondary health complications and a need to save strength/energy influenced participation in activities. Laws and/or governmental policies regarding personal assistance and assistive devices did not always support participation in activities. Interventions should aim to create a balance among activities in everyday life.

Speckle-based x-ray phase-contrast and dark-field imaging with a laboratory source.

We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.

X-ray phase contrast with injected gas for tumor microangiography.

We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas-tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research.

Comparison of two x-ray phase-contrast imaging methods with a microfocus source.

We present a comparison for high-resolution imaging with a laboratory source between grating-based (GBI) and propagation-based (PBI) x-ray phase-contrast imaging. The comparison is done through simulations and experiments using a liquid-metal-jet x-ray microfocus source. Radiation doses required for detection in projection images are simulated as a function of the diameter of a cylindrical sample. Using monochromatic radiation, simulations show a lower dose requirement for PBI for small object features and a lower dose for GBI for larger object features. Using polychromatic radiation, such as that from a laboratory microfocus source, experiments and simulations show a lower dose requirement for PBI for a large range of feature sizes. Tested on a biological sample, GBI shows higher noise levels than PBI, but its advantage of quantitative refractive index reconstruction for multi-material samples becomes apparent.

X-ray phase-contrast CO(2) angiography for sub-10 µm vessel imaging.

X-ray in-line phase contrast has recently been combined with CO(2) angiography for high-resolution small-animal vascular imaging at low radiation dose. In this paper we further investigate the potential and limitations of this method and demonstrate observation of vessels down to 8 µm in diameter, considerably smaller than the 60 µm previously reported. Our in-line phase-contrast imaging system is based on a liquid-metal-jet-anode x-ray source and utilizes free-space propagation to convert phase shifts, caused by refractive index variations, into intensity differences. Enhanced refractive index variations are obtained through injection of CO(2) gas into the vascular system to replace the blood. We show rat-kidney images with blood vessels down to 27 µm in diameter and mouse-ear images with vessels down to 8 µm. The minimum size of observable blood vessels is found to be limited by the penetration of gas into the vascular system and the signal-to-noise ratio, i.e. the allowed dose. The diameters of vessels being gas-filled depend on the gas pressure and follow a simple model based on surface tension. A theoretical signal-to-noise comparison shows that this method requires 1000 times less radiation dose than conventional iodine-based absorption contrast for observing sub-50 µm vessels.

X-ray phase contrast for CO2 microangiography.

We demonstrate a laboratory method for imaging small blood vessels using x-ray propagation-based phase-contrast imaging and carbon dioxide (CO(2)) gas as a contrast agent. The limited radiation dose in combination with CO(2) being clinically acceptable makes the method promising for small-diameter vascular visualization. We investigate the possibilities and limitations of the method for small-animal angiography and compare it with conventional absorption-based x-ray angiography. Photon noise in absorption-contrast imaging prevents visualization of blood vessels narrower than 50 µm at the highest radiation doses compatible with living animals, whereas our simulations and experiments indicate the possibility of visualizing 20 µm vessels at radiation doses as low as 100 mGy. Experimental computed tomography of excised rat kidney shows blood vessels of diameters down to 60 µm with improved image quality compared to absorption-based methods. With our present prototype x-ray source, the acquisition time for a tomographic dataset is approximately 1 h, which is long compared to the 1-20 min common for absorption-contrast micro-CT systems. Further development of the liquid-metal-jet microfocus x-ray sources used here and high-resolution x-ray detectors shows promise to reduce exposure times and make this high-resolution method practical for imaging of living animals.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

A 24 keV liquid-metal-jet x-ray source for biomedical applications.

We present a high-brightness 24-keV electron-impact microfocus x-ray source based on continuous operation of a heated liquid-indium/gallium-jet anode. The 30-70 W electron beam is magnetically focused onto the jet, producing a circular 7-13 µm full width half maximum x-ray spot. The measured spectral brightness at the 24.2 keV In K(α) line is 3 × 10(9) photons∕(s × mm(2) × mrad(2) × 0.1% BW) at 30 W electron-beam power. The high photon energy compared to existing liquid-metal-jet sources increases the penetration depth and allows imaging of thicker samples. The applicability of the source in the biomedical field is demonstrated by high-resolution imaging of a mammography phantom and a phase-contrast angiography phantom.

Bio fuel ash in a road construction: impact on soil solution chemistry.

Limited natural resources and landfill space, as well as increasing amounts of ash produced from incineration of bio fuel and municipal solid waste, have created a demand for useful applications of ash, of which road construction is one application. Along national road 90, situated about 20 km west of Sollefteå in the middle of Sweden, an experiment road was constructed with a 40 cm bio fuel ash layer. The environmental impact of the ash layer was evaluated from soil solutions obtained by centrifugation of soil samples taken on four occasions during 2001-2003. Soil samples were taken in the ash layer, below the ash layer at two depths in the road and in the ditch. In the soil solutions, pH, conductivity, dissolved organic carbon (DOC) and the total concentration of cations (metals) and anions were determined. Two years after the application of the ash layers in the test road, the concentrations in the ash layer of K, SO4, Zn, and Hg had increased significantly while the concentration of Se, Mo and Cd had decreased significantly. Below the ash layer in the road an initial increase of pH was observed and the concentrations of K, SO4, Se, Mo and Cd increased significantly, while the concentrations of Cu and Hg decreased significantly in the road and also in the ditch. Cd was the element showing a potential risk of contamination of the groundwater. The concentrations of Ca in the ash layer indicated an ongoing hardening, which is important for the leaching rate and the strength of the road construction.

Controlling mechanisms of aluminium in soil solution--an evaluation of 180 podzolic forest soils.

To monitor the level of soil acidification in the county of Värmland in the middle west of Sweden 180 podzolic forest soils were investigated. Soil solutions from four horizons were obtained by centrifugation and the soil was sampled for a determination of the exchangeable pool by extraction. The concentrations of inorganic Al and its fraction of the total Al in solution were greater in the south of the county (up to 50%). The factors influencing the total Al and free inorganic Al3+ in the soil solutions were evaluated. Saturation indices (SI) for five different mineral phases were calculated but none implied equilibrium conditions. The relationships between pAl3+ and pH (in the pH range 4-6.2) gave slopes of about 1, which indicated that ion exchange/complexation reactions may be important for determining the Al3+ concentration in the B and C horizons. In the E horizon solutions complexation with soluble organic acids seemed to be the major factor which influenced the Al3+ activity. The influence of organic matter on Al solubility was supported by partial least square (PLS) regressions.

Aluminium speciation in forest soil solution--modelling the contribution of low molecular weight organic acids.

The concentrations of Al bound to identified low molecular weight organic acids (LMWOAs), phosphate and humic compounds in soil solutions (O1, O2, E, B1 and B2 horizons) from Fennoscandinavian coniferous forest soils were calculated. Two models were evaluated: WHAM (Winderemere Humic Aqueous Model) and a model treating the natural organic acids as monoprotic. The WHAM model was calibrated to find an average charge balance of unity, and then used for Al speciation. This was achieved considering approximately 80% of the natural fulvic acid to be 'active'. For the monoprotic model, constants obtained from previous fitting of soil solution data were used and the model was calibrated using acid/base titrations. The modelling confirms that the low molecular weight acids are important complex formers, binding on average 11-42% (O), 19-20% (E), and 0-30% (B) of the total Al in solution depending on the model used. The monoprotic model yielded higher concentrations than WHAM. Both models predicted that the major part of Al in solution was organically complexed to humic substances and LMWOAs, which was consistent with analytical values of 'quickly reacting' Al (monomenc inorganic forms; 12-14% of Al(tot) on average in the E and B1 solutions). Both models could predict the magnitude of the analytical values (RMSD = 4-5 microM). On average the WHAM model showed a better fit for the E horizon solutions and the monoprotic model for the upper B horizon. The pH dependence of the low molecular weight fraction of Al was modelled in the pH range 3-5.5 for a 'typical' O1 and E solution assuming no other changes in soil solution composition. The extrapolation showed that the models had a different pH dependence. The concentration of Al bound to LMWOAs in WHAM decreased with higher pH while the opposite was seen for the monoprotic model. Also the influence of the concentration of total Al in solution was modelled. The models showed similar trends but for the 'typical' O1 horizon sample the monoprotic model yielded higher concentrations of Al bound to LMWOAs than WHAM.

Determination of low molecular weight organic acids in soil solution by HPLC.

An HPLC method employing an ion exclusion column was developed for the determination of low molecular weight organic acids in soil solution. The method includes extensive sample pretreatment using ultrafiltration and cation exchange. The method showed linear calibration graphs (r>0.99) and the limits of detection in the range 0.1-26 muM. The recovery of eleven added acids ranged from 89 to 102%. Soil solutions of five horizons of a podzolised soil were analysed. The results showed that these compounds made up 1-3% of the dissolved organic carbon and 0-14% of the acidity. Identification of the major acids was also carried out by capillary zone electrophoresis.

Central venous thrombosis after cardiac operations in children.

To evaluate the incidence, mortality, late outcome, and cause of central venous thrombosis after pediatric heart operations and other operations performed with cardiopulmonary bypass, we identified patients with postoperative central venous thrombosis during a 10-year period at a single pediatric hospital. There had been 1591 open heart (with bypass) and 1086 closed heart (no bypass) procedures and 13 operations with cardiopulmonary bypass for extracardiac indications. There were 20 patients with central venous thrombosis, yielding incidences of 1.1% and 0.2% after cardiopulmonary bypass and after closed heart operations, respectively. When neonates were compared with older children (1 to 119 months of age) undergoing heart procedures, a tenfold increase (5.8% vs 0.6%) (p < 0.001) in the incidence of central venous thrombosis was observed. The mortality was eight of 20 (40%). Central venous thrombosis contributed to seven deaths and it was a direct cause of one death. Ten patients were reinvestigated 5 to 108 months after central venous thrombosis. The outcome of surgery was excellent in eight. Two had residual thrombosis, but this was not hemodynamically significant to the cardiorespiratory condition of the patients. During or preceding thrombosis, low levels of antithrombin III and/or protein C and high levels of the plasminogen activator inhibitor were observed in five of the patients. A congenital thrombotic risk factor, "resistance to activated protein C," was found in two of 12 tested patients with central venous thrombosis (17%). In conclusion, central venous thrombosis, especially in neonates, is an important cause of morbidity and mortality after cardiac operations. The cause is multifactorial, with contributions from multiple acquired thrombophilic coagulation abnormalities, and resistance to activated protein C may act as a risk factor for thrombosis already during neonatal period.

Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation.

Cardiotoxicity is a potential adverse effect of anthracycline (A) therapy. Radiotherapy (XRT) may also cause a variety of cardiac complications. The purpose of the present study was to evaluate these cardiac side-effects in children and adolescents treated for cancer. We assessed the cardiac status of 91 patients, divided into three groups: Group A (n = 53) had anthracyclines at a mean cumulative dose of 410 mg/m2, group A+XRT (n = 26) had both chest irradiation (XRT) and A (mean 360 mg/m2), and group XRT (n = 12) had XRT alone. The patients differed from the controls in both systolic and diastolic indices of myocardial function. In echocardiography, the left ventricular (LV) contractility was abnormal in 32% in group A, in 50% in group A+XRT, and in 8% in group XRT. In radionuclide cineangiography, the LV ejection fraction was subnormal in 19% in group A, in 24% in group A+XRT, and in 1 patient in group XRT. A higher cumulative dose of A predicted decreased contractility. Treatment with A and/or XRT often leads to cardiotoxicity. Although in most cases this cardiotoxicity seems to be mild and subclinical, the long-term clinical sequelae merit further evaluation.

Bleeding and use of blood products after heart operations in infants.

Recent studies have suggested that postoperative bleeding is decreased in pediatric heart operations if fresh whole blood instead of blood component therapy is used for postoperative transfusions. Because this is in contrast to our practice to use whole blood for only the priming of the cardiopulmonary bypass circuit and then to use blood components for additional transfusion requirements, it was our interest to analyze the bleeding complications and the use of blood products after heart operations in infants. The patient records of the 73 infants operated on in 1992 were reviewed. The chest tube drainage varied from 3 to 51 ml/kg per 6 hours (mean 10 ml/kg) and it did not correlate with any of the tested clinical or laboratory parameters. One infant underwent reoperation because of surgical bleeding. Disseminated intravascular coagulation developed in another patient. Sixty-eight patients (93%) needed red blood cell supplementation. Sixty-eight percent of patients between 1 month and 1 year old could be treated without any other postoperative transfusion except for red blood cell supplementation. In contrast, in the neonates, platelet concentrates or fresh frozen plasma, or both, were used in 61% of the patients. In addition to the known immaturity of the hemostatic system, the increased need for platelet concentrates in the neonates was attributed to longer cardiopulmonary bypass time, deeper hypothermia in association with circulatory arrest, larger dosages of heparin, and more extensive plasma dilution during cardiopulmonary bypass. In conclusion, a low rate of bleeding complications and acceptably low general blood loss can be achieved postoperatively with blood component therapy.

Effects of bone marrow transplantation on myocardial function in children.

Of 41 pediatric patients currently alive after total body irradiation (TBI) and bone marrow transplantation (BMT), 30 (allogeneic 20, autologous 10) participated in the study. Pre-transplant therapy included high-dose cyclophosphamide (CY) and TBI (n = 12), high-dose CY alone (n = 4), high-dose Ara C and TBI (n = 5), cisplatinum, high-dose melphalan, VP-16 and TBI (n = 9). Acute cardiotoxicity was suggested by a > 15% decrease in the QRS voltage sum of the limb leads in all patients. Late cardiotoxicity was evaluated 0.5-10 years (median 5 years) post-transplant by ECG, chest radiograph, radionuclide cineangiography (RNCA) and echocardiography (ECHO). Six patients had a persistent decrease in the QRS amplitudes. They were all asymptomatic but had abnormal systolic function at the time of the study. BMT patients differed from their controls in the mean values of both the systolic and diastolic indices of myocardial function shown by RNCA and ECHO. Treatment was associated with decreased myocardial contractility. Isovolumic relaxation time and deceleration time were longer in BMT patients than in controls. Myocardial damage seemed to be worst after CY while high-dose Ara C was tolerated best. We conclude that both acute and late cardiotoxicity may occur after BMT, calling for long-term cardiac follow-up.

Exercise responses in patients with congenital heart disease after Fontan repair: patterns and determinants of performance.

After a Fontan repair for congenital heart disease, 42 patients underwent graded supine bicycle exercise tests at levels relevant to normal daily activities. Results were compared with those of 28 age-matched normal control subjects. At rest, the cardiac index, stroke index and systolic blood pressure were comparable in both groups, but increases with exercise were smaller in the patients with a Fontan circulation. The heart rate at rest was higher in the Fontan group, but this difference disappeared as soon as exercise started. To determine whether there are limitations intrinsic to the Fontan circulation at these levels of exercise, the 10 best performers were compared with 10 age-matched control subjects; no differences were found in cardiac index, stroke index, heart rate or blood pressure at any exercise level. Analysis of the determinants of cardiac output showed that at the other end of the spectrum poor performance after a Fontan operation did not result from inadequate levels of heart rate, but from an inability to increase or maintain stroke volume. Multivariate analysis demonstrated that impairment of ventricular contractility, only when severe, predicted limited performance. There was no evidence of increased afterload, particularly in the poor performers. Therefore, ventricular filling, which is determined primarily by the pulmonary vascular bed, appears to be a major determinant of functional result after a Fontan repair.

The natural and "unnatural" history of congenitally corrected transposition.

The data available on 111 patients with congenitally corrected transposition and 2 adequate ventricles managed over the 20-year period to 1988 were reviewed retrospectively. The ages of survivors ranged from 1 to 58 years (median 20) and all but 10 had additional anatomic abnormalities. Tricuspid valve abnormalities were more prevalent in patients symptomatic with heart failure (26 of 43 patients) than those whose main problem was cyanosis (11 of 52 patients); all dysplastic or Ebstein valves were at least moderately incompetent. Intracardiac repair of the lesion was attempted in 51 patients with 11 early deaths; in multivariate models, the risk factors for early death or a bad early outcome or poor result 6 months later related to poor preoperative symptomatic status (especially from heart failure), impaired right ventricular function, heart block and younger age at surgery. Patients with more than mild preoperative tricuspid regurgitation whose valves were not replaced did very poorly. Thus, patients symptomatic from heart failure should probably be repaired early in the natural history of the disease, before the systemic right ventricles dilate. By contrast, the course of patients who were predominantly cyanosed was more stable in early childhood and their surgical outcome was less compromised by poor preoperative symptomatic status; their intracardiac repair can probably be delayed until symptoms become unacceptable.

Impact of Fontan operation on left ventricular size and contractility in tricuspid atresia.

Left ventricular dimensions and contractility were determined by echocardiography in 33 patients with tricuspid atresia in 1985 and again in 1988. Eight patients remained palliated throughout the 3-year period; neither the left ventricular end-diastolic diameter (153 +/- 15% of normal vs. 157 +/- 19%, p = NS) nor a load-independent index of contractility (rate-corrected velocity of shortening [VCFc]/end-systolic meridional stress [ESSM]) changed. Eleven patients underwent a Fontan operation during the study and were reevaluated at least 6 months after surgery; left ventricular dimension decreased (130 +/- 15% vs. 114 +/- 19%, p less than 0.001), and the contractility index VCFc/ESSM improved (p less than 0.05). Fourteen patients had undergone a Fontan operation 0.9-9.5 years (mean, 4.2 years) before initial examination in 1985. Over the 3-year period, left ventricular dimensions did not change (121 +/- 17% vs. 118 +/- 11%, p = NS), but the contractility index showed significant improvement (p less than 0.01). Eight additional patients were studied just before and after a Fontan operation to examine the early effects of surgery. Left ventricular dimensions decreased from 130 +/- 14% to 100 +/- 13% by 10 days p less than 0.001) with no further change at 2 months. An inappropriate degree of ventricular hypertrophy was observed in only the early postoperative period. Successful Fontan repair results in rapid reduction of left ventricular size, followed by regression of hypertrophy to a normal mass-to-volume ratio. Operating at more favorable dimensions and loading conditions results in an early increase in left ventricular contractility, which further improves in the medium term follow-up.