Abstract Aim To assess the role of ipsilateral breast radiotherapy (IBR) in women with occult primary breast cancer presenting with axillary metastases (OPBC). Methods Patients with axillary nodal ...metastases and histological diagnosis of breast cancer without palpable, mammographic or ultrasonographic evidence of a breast primary were identified from a prospectively maintained single institution database. Imaging, surgery, radiotherapy, recurrence and survival data were collected. Patients whose breast cancer primary was detected on MRI (but occult on clinical examination and other imaging) were excluded from the analyses of IBR and outcome, but were included in other exploratory analyses. Results Fifty-five patients were included between 1975 and 2009. Median follow up was 68 months. Twenty patients had breast magnetic resonance imaging (MRI) in addition to other imaging. A primary breast cancer was detected in 7 of these 20. 48/55 patients had no detectable breast primary. 35/48 patients (73%) were treated with radiotherapy to the conserved breast, and 13/48 (27%) with observation. Patients who had IBR had better 5 year local recurrence free survival (LRFS) (84% versus 34%, p < 0.001), and relapse free survival (RFS) (64% versus 34%, p = 0.05), but no difference in overall survival (OS) (84% versus 85%, p = 0.2). There was no difference in 5 year LRFS (80% versus 90%: p = 0.3) between patients who received radiation of 50 Gy in 25 fractions versus ⩾60 Gy. Conclusion Patients with OPBC should be managed with IBR and breast conservation, or mastectomy. Our data suggest it is not necessary to irradiate the breast to more than 50 Gy in 25 fractions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We used transgenic mice in which the promoter sequence for connexin 43 linked to a lacZ reporter was expressed in neural crest but not myocardial cells to document the pattern of cardiac neural crest ...cells in the caudal pharyngeal arches and cardiac outflow tract. Expression of lacZ was strikingly similar to that of cardiac neural crest cells in quail–chick chimeras. By using this transgenic mouse line to compare cardiac neural crest involvement in cardiac outflow septation and aortic arch artery development in mouse and chick, we were able to note differences and similarities in their cardiovascular development. Similar to neural crest cells in the chick, lacZ-positive cells formed a sheath around the persisting aortic arch arteries, comprised the aorticopulmonary septation complex, were located at the site of final fusion of the conal cushions, and populated the cardiac ganglia. In quail–chick chimeras generated for this study, neural crest cells entered the outflow tract by two pathways, submyocardially and subendocardially. In the mouse only the subendocardial population of lacZ-positive cells could be seen as the cells entered the outflow tract. In addition lacZ-positive cells completely surrounded the aortic sac prior to septation, while in the chick, neural crest cells were scattered around the aortic sac with the bulk of cells distributed in the bridging portion of the aorticopulmonary septation complex. In the chick, submyocardial populations of neural crest cells assembled on opposite sides of the aortic sac and entered the conotruncal ridges. Even though the aortic sac in the mouse was initially surrounded by lacZ-positive cells, the two outflow vessels that resulted from its septation showed differential lacZ expression. The ascending aorta was invested by lacZ-positive cells while the pulmonary trunk was devoid of lacZ staining. In the chick, both of these vessels were invested by neural crest cells, but the cells arrived secondarily by displacement from the aortic arch arteries during vessel elongation. This may indicate a difference in derivation of the pulmonary trunk in the mouse or a difference in distribution of cardiac neural crest cells. An independent mouse neural crest marker is needed to confirm whether the differences are indeed due to species differences in cardiovascular and/or neural crest development. Nevertheless, with the differences noted, we believe that this mouse model faithfully represents the location of cardiac neural crest cells. The similarities in location of lacZ-expressing cells in the mouse to that of cardiac neural crest cells in the chick suggest that this mouse is a good model for studying mammalian cardiac neural crest and that the mammalian cardiac neural crest performs functions similar to those shown for chick.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a ...combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer.
A multifeature classifier was constructed to predict clinical outcomes using plasma-based genomic alterations detected in 120 genes and 772 lipidomic species as informative features in a cohort of 71 patients with mHSPC and 144 patients with mCRPC. Outcomes of interest were collected over 11 years of follow-up. These included in mHSPC state early failure of androgen-deprivation therapy (ADT) and exceptional responders to ADT; early death (poor prognosis) and long-term survivors in mCRPC state. The approach was to build binary classification models that identified discriminative candidates with optimal weights to predict outcomes. To achieve this, we built multi-omic feature-based classifiers using traditional machine learning (ML) methods, including logistic regression with sparse regularization, multi-kernel Gaussian process regression, and support vector machines.
The levels of specific ceramides (d18:1/14:0 and d18:1/17:0), and the presence of
mutations,
amplification, and
deletion were identified as the most crucial factors associated with clinical outcomes. Using ML models, the optimal multi-omics feature combination determined resulted in AUC scores of 0.751 for predicting mHSPC survival and 0.638 for predicting ADT failure; and in mCRPC state, 0.687 for prognostication and 0.727 for exceptional survival. The models were observed to be superior than using a limited candidate number of features for developing multi-omic prognostic and predictive signatures.
Using a ML approach that incorporates multiple omic features improves the prediction accuracy for metastatic prostate cancer outcomes significantly. Validation of these models will be needed in independent data sets in future.
The discovery in the chick embryo that a specific region of the neural crest, termed the cardiac neural crest, is essential for septation of the cardiac outflow tract and for aortic arch artery ...development has led to the classification of a whole series of human cardiac defects as neural crest-associated. Recently, several mouse genetic models have been effectively employed to yield new insights into the relationship between cardiac neural crest and structural heart development. In all the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects of the heart alone, and there are obvious signs of severe cardiac dysfunction. The evidence indicates that poor viability is from impaired cardiac excitation-contraction coupling and contractile function at the myocyte level. The continued study of experimental and genetically defined models with neural crest-associated heart defects will prove useful in identifying the common pathways by which the neural crest contributes to normal heart development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Magnesium hydride nanoparticles were synthesized within a carbon aerogel (CA) scaffold using a dibutylmagnesium precursor. The synthesis reaction was tracked using small-angle X-ray scattering (SAXS) ...to analyze the structural evolution during MgH2 formation. The CA/MgH2 composite was also investigated using X-ray diffraction (XRD) and transmission electron microscopy (TEM) to provide a better representation of the physical system. The CA has a large quantity of 2 nm pores as shown by nitrogen adsorption data. Both SAXS and TEM investigations confirm that MgH2 does form within the 2 nm pores but XRD proves that there is also a significant quantity of larger MgH2 particles within the system. Variations between hydrogen desorption isotherms from the CA/MgH2 composite and bulk MgH2 are detected that are indicative of changes in the decomposition properties of the small fraction of 2 nm MgH2 nanoparticles within the CA/MgH2 composite, changes which match theoretical predictions.
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IJS, KILJ, NUK, PNG, UL, UM
'I appointed Mary Gaudron to the High Court of Australia because I knew her to have a keen mind and a good heart: two very important attributes for a judge.' Robert J. Hawke, Prime Minister of ...Australia 1983-1991.
Johne's disease (JD) is a widespread and economically important chronic inflammatory disease of the small intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Although ...there are several techniques available for diagnosis of JD, their sensitivity is questionable. New proteome profiling methods, such as serum/plasma protein fingerprinting by 2-Dimensional Fluorescence Difference Gel Electrophoresis (2D-DIGE), may therefore be useful for identifying novel protein biomarkers of MAP infection. In this study, plasma samples were collected from 380 Holstein cows and screened for the presence of MAP infection using the M.pt. Johne's antibody Kit (IDEXX). Five negative (MAP-), and 5 strongly positive (MAP+) cows were selected for proteomic analysis. Highly abundant proteins were depleted from the plasma samples using the ProteoMiner technology (Bio-Rad) to enhance the resolution of low abundance proteins. Plasma samples from MAP-, MAP+, and a pooled internal control were labelled with different fluorescent dyes and separated based on their isoelectrical point (IP) and then their molecular weight. Gel images of the fluorescent plasma protein maps were acquired using a Typhoon scanner and analyzed using the DeCyder software. Proteins that were differentially expressed were excised from the gels, trypsin digested, and subjected to MS/MS analysis for identification. Six proteins were identified as being up-regulated at least 2-fold in MAP+ cows including: transferrin, gelsolin isoforms α & β (actin binding protein - ABP), complement subcomponent C1r, complement component C3, amine oxidase - copper containing 3 (AOC3), and coagulation factor II (thrombin) (p<0.05). Two proteins that were down-regulated approximately 2-fold in the MAP+ cows included coagulation factor XIII -B polypeptide (COAFXIII), and fibrinogen γ chain (FGG) and its precursor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The late-Glacial/Holocene transition in the North Atlantic-European sectors has long been known to be a period of rapid climate change. There is, however, a continued need for acquiring and ...developing paleoclimate archives spanning this interval from continental settings. Here we report on a lacustrine (Fayetteville Green Lake) isotope record sampled at a 10-year resolution from the NE USA over the late-Glacial/Holocene interval (14,600-8000 cal year BP). Based on prior isotopic and hydrologic research from Green Lake, the delta super(18)O sub((calcite)) values predominantly reflect winter moisture source and thus winter atmospheric patterns. Furthermore, we use historic (AD 1948-1980) winter circulation data and delta super(18)O sub((calcite)) values from varved sediments to examine the relationship between the circumpolar vortex latitude and isotopes which results in a strong (r = -0.79; r super(2) = 0.63) negative relationship. Using the linear regression from the isotope-vortex relationship, we model the winter vortex latitude for the late-Glacial/Holocene transition over the NE USA. In addition, we identify an interval from 11,600 to 10,300 cal year BP (the post-Younger Dryas climate interval) wherein the mean winter vortex over the NE USA was expanded by ~6 degree latitude (~36.1 degree N; i.e., ~630 km) from its mean historic position between AD 1948-1998 (~41.8 degree N). Renewal of more vigorous thermohaline circulation following the Younger Dryas cold event may have forced the post-Younger Dryas climate interval. Increased poleward heat transport due to an active oceanic conveyor would have strengthened the thermal contrast between the NE USA and the North Atlantic thereby enhancing atmospheric pressure gradients and firmly establishing the semi-permanent winter trough over the NE USA. Consequently, storms tracked more frequently up the east coast of the United States from the Gulf of Mexico and Atlantic regions delivering precipitation with relatively high delta super(18)O values to the NE USA. Alternatively, the relative dominance of seasonal precipitation may have changed resulting in less total winter precipitation (low delta super(18)O) causing lake waters to become relatively enriched in high delta super(18)O summer precipitation. Both hypotheses are good candidates for testing by global circulation modeling (GCM). The termination of the post-YD interval at 10,300 cal year BP and the beginning of the Holocene was likely forced by a gradual decrease in thermohaline circulation and poleward heat transport as freshwater input from melting of high-latitude ice sheets increased.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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