Restricted dietary P supply to transition dairy cows has recently been reported to beneficially affect the Ca balance of periparturient cows. The objective of the present study was to determine ...whether this effect on the Ca balance can be reproduced when limiting the P-restricted feeding to the last 4 wk of gestation. A total of 30 dairy cows in late pregnancy were randomly assigned to a dry cow diet with either low or adequate P content (0.16 and 0.30% P in DM, respectively) to be fed in the 4 wk before expected calving. After calving, all cows received the same lactating cow ration with adequate P content (0.46% P in DM). Blood was collected daily from 4 d antepartum until calving, at calving (d 0), 6 and 12 h after calving (d +0.25 and d +0.5, respectively) and on days +1, +2, +3, +4 and +7 relative to calving. Blood gas analyses were conducted to determine the concentration of ionized Ca in whole blood (Ca2+), and plasma was assayed for concentrations of inorganic phosphorus (Pi), total calcium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25-(OH)2D3), and CrossLaps (CTX), a biomarker for bone resorption (Immunodiagnostic Systems GmbH). Repeated-measures ANOVA was conducted to study treatment, time, and lactation number effects. The mean Ca2+ in P-deprived cows remained above the threshold of 1.10 mmol/L throughout the study, and values were higher compared with cows on adequate P supply between d 0 and d +2 and on d +4. The Ca2+ differed between treatments at the sampling times d 0, d +0.25, d +0.5, d +2, and d +4. Plasma PTH and 1,25-(OH)2D3 did not differ between treatments, but P-deprived cows had greater CTX than cows with adequate P supply at d +1, d +2, and d +7. These results indicate that restricted dietary P supply to during the last 4 wk of the dry period improves the Ca homeostasis of these cows in the first days of lactation, an effect that seems to be primarily driven by increased bone tissue mobilization.
The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver ...oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort.
From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated.
In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control.
After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.
Phosphorus in bovine nutrition is under ongoing scrutiny because of concerns with excessive amounts of P excreted in manure contributing to environmental pollution. Feeding rations with excessive P ...content, however, still remains common practice, particularly during the transition period, as limited P supply in late gestation and early lactation is thought to present a risk for health and productivity of high-yielding dairy cows. The objectives of this study were to investigate the effect of restricted P supply during the last 4 wk of pregnancy on Ca and P homeostasis during the transition period in high-yielding dairy cows, and to identify possible effects on metabolism and productivity throughout the following lactation. Thirty late-pregnant multiparous dairy cows were randomly assigned to either a dry cow diet with low (LP) or adequate P (AP) content 0.16 and 0.30% P in dry matter (DM), respectively to be fed in the 4 wk before calving. After calving all cows received the same ration with adequate P content (0.46% P in DM). Blood, milk, and liver tissue samples were obtained during the dry period and the following lactation, DM intake (DMI), body weight, milk production, and disease occurrence were monitored. Plasma was assayed for the concentrations of P, Ca, Na, and K, metabolic parameters, and liver enzyme activities. Liver tissue was analyzed for mineral, triglyceride, cholesterol, and water contents. Repeated-measures ANOVA was used to identify treatment, time, and treatment × time interaction effects. Cows fed LP had lower plasma P concentrations (Pi) than AP cows during restricted P feeding, reaching a nadir of 1.1 mmol/L immediately before calving. After calving, plasma Pi of LP cows was at or above the level of AP cows and within the reference range for cattle. Symptoms assumed to be associated with hypophosphatemia were not observed, but plasma Ca was higher from 1 wk before to 1 wk after calving in LP cows, which was associated with a numerically lower incidence of clinical and subclinical hypocalcemia in LP cows. Both treatments had a similar 305-d milk yield (12,112 ± 1,298 kg for LP and 12,229 ± 1,758 kg for AP cows) and similar DMI. Plasma and liver tissue biochemical analysis did not reveal treatment effects on energy, protein, or lipid metabolism. The results reported here indicate that restricted dietary P supply during the dry period positively affected the Ca homeostasis of periparturient dairy cows but did not reveal negative effects on DMI, milk production, or metabolic activity in the following lactation. Restriction of P during the dry period was associated with hypophosphatemia antepartum but neither exacerbated postparturient hypophosphatemia, which is commonly observed in fresh cows, nor was associated with any clinical or subclinical indication of P deficiency in early lactation.
Abstract Introduction Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) ...other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. Methods 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10 Gy (BEDmax ). Results After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209 ± 67 Gy10 necessary for 90% TCP at 2 years with no prior chemotherapy, but 286 ± 78 Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2 years achievable with BEDmax of 157 ± 80 Gy10 or 80 ± 62 Gy10 with and without prior chemotherapy, respectively. Conclusions Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.
The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from ...colorectal cancer.
The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS.
Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC.
In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.
β-Adrenergic receptors (β-AR) are central to the overall regulation of cardiac function. From the first proposed receptor/transmitter concept to the latest clinical β-blocker trials β-AR have been ...shown to play an important role in cardiac disease and heart failure in particular. This study provides a historical perspective, reviews the latest discoveries and beliefs, and discusses the current clinical practices of β-AR and their modulation with their associated guanine-nucleotide regulatory protein/adenylylcyclasesignal transduction pathways.
Results are presented for a Hubble Space Telescope Advanced Camera for Surveys high-resolution imaging campaign of 90 white dwarfs with known or suspected low-mass stellar and substellar companions. ...Of the 72 targets that remain candidate and confirmed white dwarfs with near-infrared excess, 43 are spatially resolved into two or more components, and a total of 12 systems are potentially triples. For 68 systems where a comparison is possible, 50% have significant photometric distance mismatches between their white dwarf and M dwarf components, suggesting that white dwarf parameters derived spectroscopically are often biased due to the cool companion. Interestingly, 9 of the 30 binaries known to have emission lines are found to be visual pairs and hence widely separated, indicating an intrinsically active cool star and not irradiation from the white dwarf. There is a possible, slight deficit of earlier spectral types (bluer colors) among the spatially unresolved companions, exactly the opposite of expectations if significant mass is transferred to the companion during the common envelope phase. Using the best available distance estimates, the low-mass companions to white dwarfs exhibit a bimodal distribution in projected separation. This result supports the hypothesis that during the giant phases of the white dwarf progenitor, any unevolved companions either migrate inward to short periods of hours to days, or outward to periods of hundreds to thousands of years. No intermediate projected separations of a few to several AU are found among these pairs. However, a few double M dwarfs (within triples) are spatially resolved in this range, empirically demonstrating that such separations were readily detectable among the binaries with white dwarfs. A straightforward and testable prediction emerges: all spatially unresolved, low-mass stellar and substellar companions to white dwarfs should be in short-period orbits. This result has implications for substellar companion and planetary orbital evolution during the post-main-sequence lifetime of their stellar hosts.
Purpose Chronic pelvic pain syndrome is a debilitating disease which often has a major impact on quality of life. A significant number of patients do not respond to conservative treatment and often ...no good alternative can be offered except radical surgery. Sacral neuromodulation is a well established therapy for patients with lower urinary tract dysfunction. This therapy has also been suggested to be useful in the treatment of chronic pelvic pain. Although currently no Food and Drug Administration approval exists for this indication, several studies have demonstrated promising results. We provide an overview of the published literature on sacral neuromodulation as a treatment for chronic pelvic pain. Materials and Methods A PubMed® search was performed to identify articles in English from 1990 to February 2010 reporting treatment of pelvic pain with sacral neuromodulation. In addition, the current definitions of pelvic pain syndromes and the mechanisms of action are discussed. Results A total of 12 relevant articles were identified. Of these articles 10 mainly addressed the efficacy of sacral neuromodulation in patients with interstitial cystitis/bladder pain. The percentage of patients who responded to test stimulation was reported between 51% and 77%. Of the 10 articles 7 reported treatment outcome after implantation. The duration of followup ranged between 5 and 87 months. The mean reduction in pain scores was reported between 40% and 72%. The reoperation rate ranged between 27% and 50% after long-term followup. Two articles included patients with miscellaneous urogenital pain syndromes. The success rates after implantation ranged from 60% to 77% with followup ranging between 19 and 36 months. Conclusions Currently there is insufficient evidence to determine the role of sacral neuromodulation in the treatment of chronic pelvic pain. Larger prospective trials with long-term evaluation are required to determine the ultimate efficacy of this treatment.
Many X-ray binaries remain undetected in the mid-infrared, a regime where emission from their compact jets is likely to dominate. Here, we report the detection of the black hole binary GX 339-4 with ...the Wide-field Infrared Survey Explorer (WISE) during a very bright, hard accretion state in 2010. Combined with a rich contemporaneous multiwavelength data set, clear spectral curvature is found in the infrared, associated with the peak flux density expected from the compact jet. An optically thin slope of ~ --0.7 and a jet radiative power of >6 X 1035 erg s--1 (d/8 kpc)2 are measured. A ~24 hr WISE light curve shows dramatic variations in mid-infrared spectral slope on timescales at least as short as the satellite orbital period ~95 minutes. There is also significant change during one pair of observations spaced by only 11 s. These variations imply that the spectral break associated with the transition from self-absorbed to optically thin jet synchrotron radiation must be varying across the full wavelength range of ~3-22 Delta *mm that WISE is sensitive to, and more. Based on four-band simultaneous mid-infrared detections, the break is constrained to frequencies of 4.6+3.5 -- 2.0 X 1013 Hz in at least two epochs of observation, consistent with a magnetic field B 1.5(? 0.8) X 104 G assuming a single-zone synchrotron emission region. The observed variability implies that either B or the size of the acceleration zone above the jet base is being modulated by factors of ~10 on relatively short timescales.
Supernova fallback disks around neutron stars have been suspected to influence the evolution of the diverse neutron star populations. Slowly rotating neutron stars are the most promising places to ...find such disks. Searching for the cold and warm debris of old fallback disks, we carried out Herschel PACS (70 mum, 160 mum) and Spitzer IRAC (3.6 mum, 4.5 mum) observations of eight slowly rotating (P approximate3-11 s) nearby (< 1 kpc) isolated neutron stars. Herschel detected 160 mum emission (>5sigma) at locations consistent with the positions of the neutron stars RX J0806.4-4123 and RX J2143.0+0654. No other significant infrared emission was detected from the eight neutron stars. We estimate probabilities of 63%, 33%, and 3% that, respectively, none, one, or both Herschel PACS 160 mum detections are unrelated excess sources due to background source confusion or an interstellar cirrus. If the 160 mum emission is indeed related to cold (10-22 K) dust around the neutron stars, this dust is absorbing and re-emitting ~10% to ~20% of the neutron stars' X-rays. Such high efficiencies would be at least three orders of magnitude larger than the efficiencies of debris disks around nondegenerate stars. While thin dusty disks around the neutron stars can be excluded as counterparts of the 160 mum emission, dusty asteroid belts constitute a viable option.
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