Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons.Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT.Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin.Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.peer-reviewe

A retrospective case series on the usefulness of fractionated stereotactic radiotherapy for benign intracranial tumors

Introduction: Conventional radiation therapy has been progressively replaced by fractionated stereotactic radiotherapy (FSRT) and single fraction radiosurgery for dealing with benign intracranial lesions. Purpose of our study is to investigate the safety and efficacy of FSRT in a series of patients with benign intracranial tumors. Methods: 31 patients with benign intracranial lesions treated with FSRT between 2006 and 2014 were retrospectively reviewed. Indications for treatment included post-operative residual tumor growth or symptomatic exacerbation in patients in whom surgery was not indicated. A clinical and radiological outcome evaluation was performed. Univariate analysis was executed to identify predictors for post-treatment neurological function and radiological tumor control. Results: Median age was 62 years (range 22–82). The lesions treated included 20 meningiomas, 2 vestibular schwannomas, 7 pituitary adenomas, 1 craniopharyngioma, 1 jugular-tympanic paraganglioma. Median clinical target volume was 14.59 cm3 (range 0.43–159.06) and median planning treatment volume was 18.16 cm3 (range 0.81–217.24). Median total dose was 45 Gy (range 25–54), and median daily fraction 4 Gy (range 1.8–9). At a median follow-up of 78 and 50 months, respectively clinical and neuroradiological, no tumor had larger dimensions, and only one lesion changed in a way other than size determining a concomitant clinical worsening. Other three patients deteriorated without evidence of radiological progression. Conversely, 12 patients improved clinically. No significant predictor for post-treatment neurological function or radiological tumor control was found. Conclusion: FSRT may represent, when indicated, a safe and effective treatment modality for benign intracranial tumors, especially for large/irregular lesions. Keywords: Clinical outcome, Fractionated stereotactic radiotherapy, Intensity-modulated radiotherapy, Intracranial benign lesions, Tumor progression, Radiotherap

Geology of the historical Bodrogköz

Abstract The Bodrogköz is predominantly a flat area surrounded by the rivers Tisza, Bodrog and Latorica. The Hungarian-Slovakian border cuts it into two parts; consequently, the geologic data in the two countries are different in terms of scale and in approach. The authors harmonized the different data on the two sides and created a unified geologic database for the entire area. The Bodrogköz is part of the depression at the northeastern part of the Great Hungarian Plain. It is covered mostly by Quaternary formations but in the Slovakian part there are smaller outcrops of Permian formations and Miocene volcanics

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6–7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures

A database solution for the quantitative characterisation and comparison of deep-marine siliciclastic depositional systems

In sedimentological investigations, the ability to conduct comparative analyses between deep-marine depositional systems is hindered by the wide variety in methods of data collection, scales of observation, resolution, classification approaches and terminology. A relational database, the Deep-Marine Architecture Knowledge Store (DMAKS), has been developed to facilitate such analyses, through the integration of deep-marine sedimentological data collated to a common standard. DMAKS hosts data on siliciclastic deep-marine system boundary conditions, and on architectural and facies properties, including spatial, temporal and hierarchical relationships between units at multiple scales. DMAKS has been devised to include original and literature-derived data from studies of the modern sea-floor, and from ancient successions studied in the sub-surface and in outcrop. The database can be used as a research tool in both pure and applied science, allowing the quantitative characterisation of deep-marine systems. The ability to synthesise data from several case studies and to filter outputs on multiple parameters that describe the depositional systems and their controlling factors enables evaluation of the degree to which certain controls affect sedimentary architectures, thereby testing the validity of existing models. In applied contexts, DMAKS aids the selection and application of geological analogues to hydrocarbon reservoirs, and permits the development of predictive models of reservoir characteristics that account for geological uncertainty. To demonstrate the breadth of research applications, example outputs are presented on: (i) the characterisation of channel geometries, (ii) the hierarchical organisation of channelised and terminal deposits, (iii) temporal trends in the deposition of terminal lobes, (iv) scaling relationships between adjacent channel and levee architectural elements, (v) quantification of the likely occurrence of elements of different types as a function of the lateral distance away from an element of known type, (vi) proportions and transition statistics of facies in elements and beds, (vii) variability in net-to-gross ratios among element types

Depositional architecture of sand-attached and sand-detached channel-lobe transition zones on an exhumed stepped slope mapped over a 2500 km2 area

The geomorphology and seismic stratigraphy of deep-water clastic systems from slope valleys through channel-levee systems to basin-floor fans have been observed and described in modern and ancient sub surface examples around the world. However, the distribution of sedimentary facies, grain size, and small-scale architectural elements remains poorly constrained. Extensive exposures (>2500 km2) of four stacked deep-water composite sequences have been mapped from heterolithic channel-levee systems on the slope to sand-rich basin-floor deposits. The data set from Units C-F of the Fort Brown Formation in the Permian Laingsburg depocenter of South Africa permits a unique opportunity to document and compare their depositional architecture at a high resolution for tens of kilometers downdip. Isopach thickness maps indicate that compensational stacking across multiple stratigraphic scales occurs on the basin floor, whereas preferred axial pathways were present on the slope, leading to subvertical stacking patterns. Units C and D are sand-attached systems; slope valley systems are mapped to pass transitionally downslope through leveeconfined channels to lobe complexes over distances of >30 km. The slope valley fills of Units E and F, however, are separated from their downdip sand-rich lobe complexes by a thin, sand-poor tract several kilometers in length and are termed sand detached. Locally, this sand-poor tract is characterized by a distinctive facies association of thin-bedded turbidites with numerous scours mantled with rip-up clasts, and a top surface that includes megaflutes and remobilized sediments. This assemblage is interpreted to indicate a widespread area of sand bypass. This unique data set provides an exploration- scale insight and understanding of how different segments of a prograding slope evolved over time in terms of gradient, physiography, and hence the degree to which sand was stored or bypassed to the basin floor, and the evolution from sand-attached to sand-detached systems. The development of sand-detached systems suggests that a steeper gradient formed, possibly related to developing underlying structure, that led to the development of a stepped slope profile. The study highlights that updip stratigraphic trapping at reservoir scale can occur with minor bathymetric changes

Shelf-margin clinothem progradation, degradation and readjustment: Tanqua Depocentre, Karoo Basin (South Africa)

Degradation of basin-margin clinothems around the shelf-edge rollover zone may lead to the generation of conduits through which gravity flows transport sediment downslope. Many studies from seismic-reflection datasets show these features, but they lack small-scale (centimetre to metre) sedimentary and stratigraphic observations on process interactions. Exhumed basin-margin clinothems in the Tanqua depocentre (Karoo Basin) provide seismic-reflection-scale geometries and internal details of architecture with depositional dip and strike control. At the Geelhoek locality, clinothem parasequences comprise siltstone-rich offshore deposits overlain by heterolithic prodelta facies and sandstone-dominated deformed mouth bars. Three of these parasequences are truncated by a steep (6 to 22°), 100 m deep and 1.5 km wide asymmetrical composite erosion surface that delineates a shelf-edge canyon. The fill, from base to top comprises: (i) thick-bedded sandstone with intrabasinal clasts and multiple erosion surfaces; (ii) scour-based interbedded sandstone and siltstone with tractional structures; and (iii) inverse-graded to normal-graded siltstone beds. An overlying 55 m thick coarsening-upward parasequence fills the upper section of the canyon and extends across its interfluves. Younger parasequences display progressively shallower gradients during progradation and healing of the local accommodation. The incision surface resulted from initial oversteepening and high sediment supply triggering deformation and collapse at the shelf edge, enhanced by a relative sea-level fall that did not result in subaerial exposure of the shelf edge. Previous work identified an underlying highly incised, sandstone-rich shelf-edge rollover zone across-margin strike, suggesting that there was migration in the zone of shelf-edge to upper slope incision over time. This study provides an unusual example of clinothem degradation and re-adjustment with three-dimensional control in an exhumed basin margin succession. The work demonstrates that large-scale erosion surfaces can develop and migrate due to a combination of factors at the shelf-edge rollover zone, and proposes additional criteria to predict clinothem incision and differential sediment bypass in consistently progradational systems

Architecture and morphodynamics of subcritical sediment waves in an ancient channel–lobe transition zone

In modern systems, submarine channel–lobe transition zones show a well‐documented assemblage of depositional and erosional bedforms. In contrast, the stratigraphic record of channel–lobe transition zones is poorly constrained, because preservation potential is low and criteria have not been established to identify depositional bedforms in these settings. Several locations from an exhumed fine‐grained base of slope system (Unit B, Laingsburg depocentre, Karoo Basin, South Africa) show exceptional preservation of sandstone beds with distinctive morphologies and internal facies distributions. The regional stratigraphic context, lack of a basal confining surface, wave‐like morphology in dip section, size and facies characteristics support an interpretation of subcritical sediment waves within a channel–lobe transition zone setting. Some sediment waves show steep (10 to 25°) unevenly spaced (10 to 100 m) internal truncation surfaces that are dominantly upstream‐facing, which suggests significant spatio‐temporal fluctuations in flow character. Their architecture indicates that individual sediment wave beds accrete upstream, in which each swell initiates individually. Lateral switching of the flow core is invoked to explain the sporadic upstream‐facing truncation surfaces, and complex facies distributions vertically within each sediment wave. Variations in bedform character are related to the axial to marginal positions within a channel–lobe transition zone. The depositional processes documented do not correspond with known bedform development under supercritical conditions. The proposed process model departs from established mechanisms of sediment wave formation by emphasising the evidence for subcritical rather than supercritical conditions, and highlights the significance of lateral and temporal variability in flow dynamics and resulting depositional architecture

Disconnected submarine lobes as a record of stepped slope evolution over multiple sea-level cycles

The effects of abrupt changes in slope angle and orientation on turbidity current behavior have been investigated in numerous physical and numerical experiments and examined in outcrop, subsurface, and modern systems. However, the long-term impact of subtle and evolving seabed topography on the stratigraphic architecture of deep-water systems requires fine-scale observations and extensive 3-D constraints. This study focuses on the Permian Laingsburg and Fort Brown formations, where multiple large sand-rich systems (Units A–F) have been mapped from entrenched slope valleys, through channel-levee systems, to basin-floor lobe complexes over a 2500 km2 area. Here, we investigate three thinner (typically <5 m in thickness) and less extensive sand-rich packages, Units A/B, B/C, and D/E, between the large-scale systems. Typically, these sand-rich units are sharp-based and topped, and contain scours and mudstone clast conglomerates that indicate deposition from high-energy turbidity currents. The mapped thickness and facies distribution suggest a lobate form. These distinctive units were deposited in similar spatial positions within the basin-fill and suggest similar accommodation patterns on the slope and basin floor prior to the larger systems (B, C, and E). Stratigraphically, these thin units represent the first sand deposition following ­major periods of shut-down in sediment supply, and are interpreted as marking a partial re-establishment of sand delivery pathways creating “disconnected lobes” that are fed mainly by flows sourced from failures on the shelf and upper slope rather than major feeder channel-levee systems. Thickness and facies patterns throughout the deep-water stratigraphy suggest seabed topography was present early in the basin formation and maintained persistently in a similar area to ultimately form a stepped slope profile. The stepped slope profile evolved through three key stages of development: Phase 1, where sediment supply exceeds deformation rate (likely caused by differential subsidence); Phase 2, where sediment supply is on average equal to deformation rate; and Phase 3, where deformation rate outpaces sediment supply. This study demonstrates that smaller systems are a sensitive record of evolving seabed topography and they can consequently be used to recreate more accurate paleotopographic profiles