Automated in-silico detection of cell populations in flow cytometry readouts and its application to leukemia disease monitoring

BACKGROUND: Identification of minor cell populations, e.g. leukemic blasts within blood samples, has become increasingly important in therapeutic disease monitoring. Modern flow cytometers enable researchers to reliably measure six and more variables, describing cellular size, granularity and expression of cell-surface and intracellular proteins, for thousands of cells per second. Currently, analysis of cytometry readouts relies on visual inspection and manual gating of one- or two-dimensional projections of the data. This procedure, however, is labor-intensive and misses potential characteristic patterns in higher dimensions. RESULTS: Leukemic samples from patients with acute lymphoblastic leukemia at initial diagnosis and during induction therapy have been investigated by 4-color flow cytometry. We have utilized multivariate classification techniques, Support Vector Machines (SVM), to automate leukemic cell detection in cytometry. Classifiers were built on conventionally diagnosed training data. We assessed the detection accuracy on independent test data and analyzed marker expression of incongruently classified cells. SVM classification can recover manually gated leukemic cells with 99.78% sensitivity and 98.87% specificity. CONCLUSION: Multivariate classification techniques allow for automating cell population detection in cytometry readouts for diagnostic purposes. They potentially reduce time, costs and arbitrariness associated with these procedures. Due to their multivariate classification rules, they also allow for the reliable detection of small cell populations

Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease

Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcom

The shallow and deep western boundary circulation of the South Atlantic at 5-11°S

Repeated shipboard observation sections across the boundary flow off northeastern Brazil as well as acoustic Doppler current profiler (ADCP) and current-meter records from a moored boundary array deployed during 2000–04 near 11°S are analyzed here for both the northward warm water flow by the North Brazil Undercurrent (NBUC) above approximately 1100 m and the southward flow of North Atlantic Deep Water (NADW) underneath. At 5°S, the mean from nine sections yields an NBUC transport of 26.5 ± 3.7 Sv (Sv ≡ 106 m3 s−1) along the boundary; at 11°S the mean NBUC transport from five sections is 25.4 ± 7.4 Sv, confirming that the NBUC is already well developed at 11°S. At both latitudes a persistent offshore southward recirculation between 200- and 1100-m depth reduces the net northward warm water flow through the 5°S section (west of 31.5°W) to 22.1 ± 5.3 Sv and through the 11°S section to 21.7 ± 4.1 Sv (west of 32.0°W). The 4-yr-long NBUC transport time series from 11°S yields a seasonal cycle of 2.5 Sv amplitude with its northward maximum in July. Interannual NBUC transport variations are small, varying only by ±1.2 Sv during the four years, with no detectable trend. The southward flow of NADW within the deep western boundary current at 5°S is 25.5 ± 8.3 Sv with an offshore northward recirculation, yielding a nine-section mean of 20.3 ± 10.1 Sv west of 31.5°W. For Antarctic Bottom Water, a net northward flow of 4.4 ± 3.0 Sv is determined at 5°S. For the 11°S section, the moored array data show a pronounced energy maximum at 60–70-day period in the NADW depth range, which was identified in related work as deep eddies translating southward along the boundary. Based on a kinematic eddy model fit to the first half of the moored time series, the mean NADW transfer by the deep eddies at 11°S was estimated to be about 17 Sv. Given the large interannual variability of the deep near-boundary transport time series, which ranged from 14 to 24 Sv, the 11°S mean was considered to be not distinguishable from the mean at 5°

The zonal currents and transports at 35°W in the tropical Atlantic

The total of 13 existing cross-equatorial shipboard current profiling sections taken during the WOCE period between 1990 and 2002 along 35°W are used to determine the mean meridional structure of the zonal top-to-bottom circulation between the Brazilian coast, near 5°S, and 5°N and to estimate mean transports of the individual identified shallow, intermediate and deep current branches. One of the results is that, on the equator, a mean westward Equatorial Intermediate Current below the Equatorial Undercurrent exists

3He in the Bransfield Strait waters: indication for local injection from back-arc rifting

Helium data from the waters of the Bransfield Strait, the southern Drake Passage and the northwestern shelf of the Weddell Sea are presented. The 3He profiles from the eastern and central basins of the Bransfield Strait show maxima (δ3He ≈ 7%) below the sill depths that separate the strait from the surrounding open ocean. The 3He excess is interpreted as a local injection of a 3He-rich helium component into the deep waters of the Bransfield Strait from backarc rifting. Tritiogenic 3He and excess 3He from mixing with Circumpolar Deep Water are excluded as possible sources. The estimated 3He/4He ratio of the injected helium component (2.4–5.0 × 10−6) is less than that of pure mantle helium and may contain radiogenic helium from continental crustal material which underlies the Bransfield Strait

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences

BACKGROUND: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy. PATIENTS AND METHODS: For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used. RESULTS AND DISCUSSION: Bony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10–12 minutes, which can be further reduced by streamlining the different steps. CONCLUSION: The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable

Remodeling of metabolism and inflammation by exercise ameliorates tumor-associated anemia

A considerable number of patients with cancer suffer from anemia, which has detrimental effects on quality of life and survival. The mechanisms underlying tumor-associated anemia are multifactorial and poorly understood. Therefore, we aimed at systematically assessing the patho-etiology of tumor-associated anemia in mice. We demonstrate that reduced red blood cell (RBC) survival rather than altered erythropoiesis is driving the development of anemia. The tumor-induced inflammatory and metabolic remodeling affect RBC integrity and augment splenic phagocyte activity promoting erythrophagocytosis. Exercise training normalizes these tumor-associated abnormal metabolic profiles and inflammation and thereby ameliorates anemia, in part, by promoting RBC survival. Fatigue was prevented in exercising tumor-bearing mice. Thus, exercise has the unique potential to substantially modulate metabolism and inflammation and thereby counteracts pathological remodeling of these parameters by the tumor microenvironment. Translation of this finding to patients with cancer could have a major impact on quality of life and potentially survival

Beschäftigungsformen

Inhalt: C Beschäftigungsformen; C.I Einführung und Resümee; C.II Entwicklung und Struktur der Beschäftigungsverhältnisse; C.III Teilzeitbeschäftigung; C.IV Zeitarbeit und Befristungen; C.V Beschäftigungsformen im europäischen Vergleich; Literatur zu Kapitel C

Convection above the Labrador continental slope

The Labrador Sea is one of the few regions of the World Ocean where deep convection takes place. Several moorings across the Labrador continental slope just north of Hamilton Bank show that convection does take place within the Labrador Current. Mixing above the lower Labrador slope is facilitated by the onshore along-isopycnal intrusions of low-potential-vorticity eddies that weaken the stratification, combined with baroclinic instability that sustains slanted mixing while restratifying the water column through horizontal fluxes. Above the shelf break, the Irminger seawater core is displaced onshore while the stratification weakens with the increase in isopycnal slope. The change in stratification is partially due to the onshore shift of the “classical” Labrador Current, baroclinic instability, and possibly slantwise convection

Long-term trends of temperature, salinity, density and transient tracers in the Central Greenland Sea

We present long-term observations of temperature, salinity, tritium/3He, chlorofluorocarbon-11 (CFC 11), and chlorofluorocarbon-12 (CFC 12) for the central Greenland Gyre. The time series span the periods between 1952 and 1994 (temperature), 1981 and 1994 (salinity), 1972 and 1994 (tritium/3He), and 1982 and 1994 (CFCs). The correlation between hydrographic and transient tracer data indicates that low temperatures in the deep water in the early 1950s and between 1960 and 1980 reflect periods of higher deep water formation rates whereas periods of increasing temperatures in the late 1950s and between 1980 and 1994 are related to low deep water formation rates. However, the transient tracer observations obtained in the 1980s and early 1990s indicate that even during periods of low deep water formation, some water from the upper water column contributed to deep water formation between 1980 and 1994. In 1994, the deep water reached temperatures and salinities of −1.149 °C and 34.899, respectively, and no longer fits most of the classical definitions of Greenland Sea Deep Water (−1.29°C< Θ < −1.0°C, 34.88<S<34.90). The temperature increase in the water column between 200 and 2000 m depth between 1980 and 1994 corresponds to an average heating rate of about 5 Wm−2 over this period, resulting in a decrease in density. The 13-year warming could be balanced by intensive cooling in two winters. The surface salinity steadily increased from 34.50 in 1991 to 34.85 in 1994