Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers

To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers.

First middle-atmospheric zonal wind profile measurements with a new ground-based microwave Doppler-spectro-radiometer

We report on the wind radiometer WIRA, a new ground-based microwave Doppler-spectro-radiometer specifically designed for the measurement of middle-atmospheric horizontal wind by observing ozone emission spectra at 142.17504 GHz. Currently, wind speeds in five levels between 30 and 79 km can be retrieved which makes WIRA the first instrument able to continuously measure horizontal wind in this altitude range. For an integration time of one day the measurement error on each level lies at around 25 m s−1. With a planned upgrade this value is expected to be reduced by a factor of 2 in the near future. On the altitude levels where our measurement can be compared to wind data from the European Centre for Medium-Range Weather Forecasts (ECMWF) very good agreement in the long-term statistics as well as in short time structures with a duration of a few days has been found. WIRA uses a passive double sideband heterodyne receiver together with a digital Fourier transform spectrometer for the data acquisition. A big advantage of the radiometric approach is that such instruments can also operate under adverse weather conditions and thus provide a continuous time series for the given location. The optics enables the instrument to scan a wide range of azimuth angles including the directions east, west, north, and south for zonal and meridional wind measurements. The design of the radiometer is fairly compact and its calibration does not rely on liquid nitrogen which makes it transportable and suitable for campaign use. WIRA is conceived in a way that it can be operated remotely and does hardly require any maintenance. In the present paper, a description of the instrument is given, and the techniques used for the wind retrieval based on the determination of the Doppler shift of the measured atmospheric ozone emission spectra are outlined. Their reliability was tested using Monte Carlo simulations. Finally, a time series of 11 months of zonal wind measurements over Bern (46°57′ N, 7°26′ E) is presented and compared to ECMWF wind data.

Soft tissue profile changes following mandibular advancement and setback surgery an average of 12 years postoperatively

PURPOSE: The aim of this study was to assess long-term changes in position of soft tissue landmarks following mandibular advancement and setback surgery. MATERIALS AND METHODS: Twenty-seven patients (14 women, 13 men; mean age, 36 years) who had undergone either mandibular advancement (15 patients) or setback surgery (12 patients), were available for a long-term follow-up an average of 12 years postoperatively. In all of these cases, lateral cephalometric radiographs taken immediately before operation, at 1 week, 14 months, and 12 years postoperatively, were studied. RESULTS: During the 14 months postoperatively, soft tissue chin and mentolabial fold followed its underlying hard tissue in all patients. A continuous skeletal relapse was observable 12 years after mandibular advancement, but soft tissue chin moved more in an anterior direction. After mandibular setback, soft and hard tissue landmarks remained almost unchanged. Over the entire observation period, a thickening of soft tissue at pogonion was generally seen, and particularly a thickening of the whole chin in the setback group. All patients showed a significant lengthening and thinning of the upper lip. In all except 2 males, the patient's body weight increased markedly. CONCLUSION: In contrast to the immediate postoperative stage, soft tissue changes observed an average of 12 years after the primary operation do not directly follow the movements of the underlying skeletal structure. The soft tissue profile changes observed over such a long term seem to be influenced not only by the underlying skeletal structure but also by other factors such as weight gain and aging process.

Estimation of vertical groundwater fluxes into a streambed through continuous temperature profile monitoring and the relationship of groundwater fluxes to coaster brook trout spawning habitat

We hypothesized that the spatial distribution of groundwater inflows through river bottom sediments is a critical factor associated with the selection of coaster brook trout (a life history variant of Salvelinus fontinalis,) spawning sites. An 80-m reach of the Salmon Trout River, in the Huron Mountains of the upper peninsula of Michigan, was selected to test the hypothesis based on long-term documentation of coaster brook trout spawning at this site. Throughout this site, the river is relatively similar along its length with regard to stream channel and substrate features. A monitoring well system consisting of an array of 27 wells was installed to measure subsurface temperatures underneath the riverbed over a 13-month period. The monitoring well locations were separated into areas where spawning has and has not been observed. Over 200,000 total temperature measurements were collected from 5 depths within each of the 27 monitoring wells. Temperatures within the substrate at the spawning area were generally cooler and less variable than river temperatures. Substrate temperatures in the non-spawning area were generally warmer, more variable, and closely tracked temporal variations in river temperatures. Temperature data were inverted to obtain subsurface groundwater velocities using a numerical approximation of the heat transfer equation. Approximately 45,000 estimates of groundwater velocities were obtained. Estimated velocities in the spawning and non-spawning areas confirmed that groundwater velocities in the spawning area were primarily in the upward direction, and were generally greater in magnitude than velocities in the non-spawning area. In the non-spawning area there was a greater occurrence of velocities in the downward direction, and velocity estimates were generally lesser in magnitude than in the spawning area. Both the temperature and velocity results confirm the hypothesis that spawning sites correspond to areas of significant groundwater influx to the river bed.

The Equilibrium Relations of Nickel Sulfide with Copper and Sodium Sulfides

The equilibrium relations of many of the metallic sulfides have long been a source of scientific and commer­cial interest, of particular interest, are the sulfides of nickel and copper, since the economic recovery of both of these useful metals, from their ores, involves the formation of a sulfide at some stage of the operations.

Early- and long-term intravascular ultrasound and angiographic findings after bioabsorbable magnesium stent implantation in human coronary arteries

OBJECTIVES: This study aimed to evaluate the degradation rate and long-term vascular responses to the absorbable metal stent (AMS). BACKGROUND: The AMS demonstrated feasibility and safety at 4 months in human coronary arteries. METHODS: The PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting) was a prospective, multicenter clinical trial of 63 patients with coronary artery disease who underwent AMS implantation. Angiography and intravascular ultrasound (IVUS) were conducted immediately after AMS deployment and at 4 months. Eight patients who did not require repeat revascularization at 4 months underwent late angiographic and IVUS follow-up from 12 to 28 months. RESULTS: The AMS was well-expanded upon deployment without immediate recoil. The major contributors for restenosis as detected by IVUS at 4 months were: decrease of external elastic membrane volume (42%), extra-stent neointima (13%), and intra-stent neointima (45%). From 4 months to late follow-up, paired IVUS analysis demonstrated complete stent degradation with durability of the 4-month IVUS indexes. The neointima was reduced by 3.6 +/- 5.2 mm(3), with an increase in the stent cross sectional area of 0.5 +/- 1.0 mm(2) (p = NS). The median in-stent minimal lumen diameter was increased from 1.87 to 2.17 mm at long-term follow-up. The median angiographic late loss was reduced from 0.62 to 0.40 mm by quantitative coronary angiography from 4 months to late follow-up. CONCLUSIONS: Intravascular ultrasound imaging supports the safety profile of AMS with degradation at 4 months and maintains durability of the results without any early or late adverse findings. Slower degradation is warranted to provide sufficient radial force to improve long-term patency rates of the AMS.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

BACKGROUND We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. METHODS In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. RESULTS Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). CONCLUSIONS Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Clinical performance of a sutureless aortic bioprosthesis: five-year results of the 3f Enable long-term follow-up study.

OBJECTIVE Sutureless valves are designed to facilitate surgical implantation, including less-invasive techniques in aortic valve replacement, by maintaining surgical precision of implantation compared with transcatheter techniques. Long-term clinical experience with sutureless valves is lacking. We report the 5-year follow-up results of an international, prospective, multicenter study evaluating the clinical performance and safety of the 3f Enable valve (Medtronic Inc, Minneapolis, Minn). METHODS Between March 2007 and December 2009, 141 patients (54 male; mean age, 76.1±5.7 years) undergoing aortic valve replacement with the 3f Enable valve were enrolled in 10 European sites. The mean follow-up was 2.76 years (range, 2 days to 5.1 years; total, 388.7 patient-years). Echocardiographic valvular hemodynamic and morphologic analyses were performed by an independent core laboratory. RESULTS The mean systolic gradient was 10.4±4.4 mm Hg at discharge and 7.7±4.1 mm Hg at 5 years. The mean effective orifice area was 1.7±0.5 cm2 at discharge and 1.6±0.2 cm2 at 5 years. Freedom from all-cause and valve-related mortality was 87.6%±2.9% and 96.8%±1.6% at 1 year (113 patients at risk) and 77.0%±7.5% and 93.8%±4.8% at 5 years (24 patients at risk), respectively. Six patients underwent reoperation (4 because of major paravalvular leakage and 2 because of endocarditis). Freedom from reoperation was 95.4%±1.9% at 1 year and 95.4%±6.1% at 5 years. No structural valve deterioration occurred during the follow-up period. CONCLUSIONS The sutureless 3f Enable valve represents a safe and effective treatment for aortic valve stenosis, providing an excellent hemodynamic profile. This study represents the longest follow-up study for a sutureless bioprosthesis. Sutureless valves may become an option for all patients with indicated biological aortic valve replacement.

Trajectories of psychological adaptation to marital breakup after a long-term marriage

While the negative effects of divorce on well-being are well documented in research literature, the large individual differences in psychological adaptation over time are still not well understood. This is especially the case for marital breakup after long-term marriage, which is still a neglected research topic. Against this background, the aim of the present contribution is to shed light on the various trajectories of psychological adaptation to marital breakup after a long-term relationship. Data stem from a longitudinal survey study, which is part of the Swiss National Centre of Competence in Research ‘LIVES – Overcoming vulnerability: life course perspectives’ (funded by the Swiss National Science Foundation). Our analyses are based on results of an exploratory latent profile analysis performed at the first assessment in 2012 among 308 divorced participants aged 45 – 65 years, who divorced after an average of 25 years of marriage (Perrig-Chiello, Hutchison, & Morselli, 2014). Five different groups regarding psychological adaptation to marital breakup (i.e. life satisfaction, depression, hopelessness, subjective health, and mourning) were identified. They were composed of two larger groups of individuals that adapted quite well or very well (“average copers”, n=151 and “resilients”, n=90) and of three smaller groups with major difficulties to adjust to the new situation (“vulnerables”, n= 18; “malcontens”, n= 37 and “resigned ones”, n=12). Clusters differed statistically significant regarding personality variables, time since separation, current relationship status, and financial situation. In the present contribution, we want to investigate the course of adaptation of the five classes two years later by using latent transition analysis. Furthermore, we aim to examine which variables in terms of personality, relationship status, variables of the context of the separation and socio-demographic variables are crucial for change or stability in levels of adaptation in the different classes. The evaluation of the trajectories of adaptation to this critical life event and the identification of variables that enhance the adaptation over time is essential for developing more differentiated measures in counselling as well as intervention techniques in clinical and social services.

A Late-glacial and Holocene record of climatic change from a Swiss peat humification profile

Colorimetric measurements of alkaline extracts from two Swiss peat cores have provided a complete 14500-year-long record of peat humification, a proxy of effective precipitation. Peat from the cold Younger Dryas (11050–9550 cal. bc) was well preserved despite low levels of precipitation. A particularly dry period, peaking at c. 7100 cal. bc, is indicated by well-decomposed peat. Peat from c. 6750–4250 cal. bc shows a low degree of decomposition, indicating a wet bog surface despite relatively warm temperatures and therefore indicating high levels of precipitation. A sharp transition to higher levels of decomposition c. 4450–3750 cal. bc indicates a major transition to a drier bog surface. Subsequently, peat humification generally decreases towards the end of the deeper profile (c. cal. ad 1050), indicating a gradual return to wetter conditions. This gradual decrease is punctuated by periods of particularly low humification which appear to be due to shifts to higher levels of effective precipitation from c. 2500 to 1350 cal. bc, c. 1050 to 550 cal. bc, centered around 150 cal. bc, and from c. cal. ad 550 onwards. Anthropogenic influences appear to have affected peat humification at the site at least since the Middle Ages. This study indicates that humification in colder regions/time periods could be more affected by temperature than precipitation and vice versa.

First continuous ground-based observations of long period oscillations in strato-/mesospheric wind profiles

Direct measurements of middle-atmospheric wind oscillations with periods between 5 and 50 days in the altitude range between mid-stratosphere (5 hPa) and upper mesosphere (0.02 hPa) have been made using a novel ground-based Doppler wind radiometer. The oscillations were not inferred from measurements of tracers, as the radiometer offers the unique capability of near-continuous horizontal wind profile measurements. Observations from four campaigns at high, mid and low latitudes with an average duration of 10 months have been analyzed. The dominant oscillation has mostly been found to lie in the extra-long period range (20–40 days), while the well-known atmospheric normal modes around 5, 10 and 16 days have also been observed. Comparisons of our results with ECMWF operational analysis model data revealed remarkably good agreement below 0.3 hPa but discrepancies above.

Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

OBJECTIVE To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. MATERIALS AND METHODS Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique and M1 extraction, and 15 untreated asymmetrical Class II adolescents (4 boys, 11 girls; mean age, 12.2 years; SD, 1.3 years) were examined in this study. Cephalometric analysis and PAR assessment were carried out before treatment (T1), after treatment (T2), and on average 2.5 years posttreatment (T3) for the treatment group, and at similar time points and average follow-up of 1.8 years for the controls. RESULTS The adjusted analysis indicated that the maxillary incisors were 2.3 mm more retracted in relation to A-Pog between T1 and T3 (β  =  2.31; 95% CI; 0.76, 3.87), whereas the mandibular incisors were 1.3 mm more protracted (β  =  1.34; 95% CI; 0.09, 2.59), and 5.9° more proclined to the mandibular plane (β  =  5.92; 95% CI; 1.43, 10.41) compared with controls. The lower lip appeared 1.4 mm more protrusive relative to the subnasale-soft tissue-Pog line throughout the observation period in the treated adolescents (β  =  1.43; 95% CI; 0.18, 2.67). There was a significant PAR score reduction over the entire follow-up period in the molar extraction group (β  =  -6.73; 95% CI; -10.7, -2.7). At T2, 65% of the subjects had maxillary midlines perfectly aligned with the face. CONCLUSIONS Unilateral M1 extraction in asymmetrical Class II cases may lead to favorable occlusal outcomes in the long term without harming the midline esthetics and soft tissue profile.

Behavioral risk profile of marathon runners

Although long distance running clearly has benefits--as witnessed by its popularity--it also has risks of injury and death. Little is known, however, about the prevalence of potentially dangerous training habits in long distance runners, although anecdotal information suggests that many runners have erroneous beliefs about risks and benefits of marathon running. We conducted a cross-sectional survey to estimate the prevalence of 19 potentially dangerous training habits (risky behaviors) among marathon runners. A 66-item self-administered questionnaire was mailed to a stratified random sample of runners who finished of the 1992 Houston-Tenneco Marathon and were 21-71 years of age. Responses were obtained from 508 runners (83%) with approximately equal representation in four age-gender groups: men $<$40 years, men $\ge$40 years, women $<$40 years, and women $\ge$40 years.^ Prevalences of risky behaviors were high. 50% or more ran in dangerously hot and humid conditions, did not cool down or stretch after running, did not wear proper running gear, or ran when injured or ill; 25-49% did not warm up, ran on dangerous surfaces, did not drink sufficient water during training, increased weekly mileage too quickly, and ran during lightning storms; 10-24% ran daily, ran in areas with high pollution, ran in the same direction as traffic, did hard runs frequently, ran more than 60 miles per week, or ran against the advice of a physician.^ Positive associations were found between the practice of risky behaviors and self-reported prevalence of musculoskeletal injuries, heat-related injuries, noncompliance with recommendations for preventive health examinations, and noncompliance with positive health habits.^ These results indicate that many marathon runners engage in training habits that may increase risk of substantial injury or illness. Further studies are needed to explore the association of risky training behaviors on the incidence of injuries, and to determine reasons for noncompliance with recommendations from sports medicine specialists. ^

Pollen record and age determination of a sediment profile from Frengstadsetra, Norway

Innerdalen was once a mountain valley (ca. 780 m a.s.l.) with birch forests, bogs and several summer farms. Today it is a 6.5 km**2 artifical lake. In 1980 and 1981 archaeological and palynological investigations were carried out due to the hydroelectric power plans. Radiocarbon dated pollen diagrams from 9 different localities in Innerdalen provide information on a mountain environment which has been exploited to varying degrees by human groups for thousands of years. In the Birch Zone, ca. 9500-8500 years B.P., the deglaciated surface is vegetated by the normal sequence of pioneering species, first show-bed communities, then shrub/dwarf-shrub communities, and finally a birch forest community. In the Pine Zone, ca. 8500-7500 years B.P., the mixed Birch-Pine forest which prevailed at the end of the Birch Zone is replaced by a dense pine forest. The tree limit was higher than it is today. In the Alder Zone, ca. 7500-4000 years B.P., the newly arrived alder gradually succeeded pine, particularily on good soils. This alder forest has a modem analog in the pre-alpine gray alder forests in Norway. In the last part of the Alder Zone, ca. 6000-4000 years B.P., elm and hazel are nominally present on particularily rich soils, marking the edaphic and climatic optimum in Innerdalen. During this time the first evidence of human impact on the vegetation is apparent in the pollen diagrams. At both Sætersetra in the south of the valley and Liabekken in the north, forest clearance and the development of grazed grass meadows is documented, and human impact continues until the present. The Herb Zone, ca. 4000 years B.P. to 1600 A.D., is characterized by the rapid decline of alder. The forest is increasingly open, and bog formation is initiated. The sub-alpine belt of birch forest is established, probably due to the shift to a cooler, moister climate. Human activity can also have influenced the vegetational changes, although at 4 of the localities human activity also is first apparent after the alder decline. Some localities show measurably less human impact on the vegetation ca. 2600-2000 years B.P. Grazing intensity increases ca. 2000 years B.P. At the end of the Herb Zone rye and barley pollen is registered at Sætersetra and Flonan, indicating contact between the grazing activities of Innerdal and grain cultivation activities outside the valley. The Spruce Zone, ca. 1600 A.D. to the present, does not begin synchronously since the presence of long-distance transported spruce pollen at a locality is entirely dependent on the density of the vegetation ie. degree of human impact. The youngest spruce rise is ca. 1500 A.D. at Røstvangen, when summerfarming is initiated. Summerfarming activities in Innerdal produce an increasingly open landscape. Rye and barley pollen at several localities may indicate limited local cultivation, but is more likely long-distance transport via humans and domesticated animals from cultivated areas outside Innerdalen.

Mineral and oxygen isotopic compositions in a profile through the altered lower oceanic crust, ODP Hole 176-735B

ODP Hole 735B located on the Southwest Indian Ridge at 57°E is an in situ sampled long, continuous section of lower oceanic crust. Oxygen isotope compositions of constituent minerals of Leg 176 gabbros have been measured by UV-laser oxygen isotope microprobe. Together with existing data from Leg 118, a complete oxygen isotope profile through the lower oceanic crust has been obtained. Most clinopyroxenes and olivines have normal mantle values of ~5.5 per mil and ~5.2 per mil, respectively, while plagioclases show slight d18O enrichment relative to its mantle value of 6.1per mil. Down-hole variations of Hole 735B gabbro indicate a downward decreasing d18O profile, with a kink at a depth of about 800 m below sea floor. Above this depth, gabbros are depleted in 18O relative to unaltered basalts, while below ~800 m they show nearly unmodified d18O values. Abundant seawater penetration appears to be limited to the upper part of the lower crust at ODP site 735 (~800 m into the gabbroic layer and ~2-2.5 km into the oceanic crust from the top of pillow basalts). Mass balance calculations show that the lower crust formed under this ultra-slow-spreading ridge has an average d18O value of 5.5 per mil. The whole crust at Site 735 has an overall 18O enrichment with d18O values of 6.0 per mil to 7.8 per mil, depending on the possible variation of the d18O values of the upper pillow basalts and sheeted dykes. The apparent difference in oxygen isotope compositions of ocean crusts formed with different spreading rates has important implications on the buffering of ocean water over geological time, as well as on the oxygen recycling between crust and mantle through subduction. The difference of seawater penetration between fast- and slow-spreading ridges could be related to their particular magmatic-tectonic history during the formation and aging of the crust. However, more analyses on continuous sections through oceanic and ophiolitic crust in different tectonic settings are required to derive any predictive models.