Living in the twilight zone:A qualitative study on the experiences of patients with advanced cancer obtaining long-term response to immunotherapy or targeted therapy

Purpose The introduction of immunotherapy and targeted therapy has drastically improved the life expectancy of patients with advanced cancer. Despite improved survival, obtaining long-term response can be highly distressing and comes with uncertainties that affect several life domains. The aim of this study is to gain a deeper understanding of long-term responders’ lived experiences with obtaining long-term response to immunotherapy or targeted therapy. Methods We conducted an exploratory qualitative study using thematic data analysis. Semi-structured in-depth interviews were conducted with 17 patients with advanced melanoma or lung cancer who had a confirmed response to or long-term stable disease while on immunotherapy or targeted therapy. Results Long-term responders are living in a twilight zone, where they neither feel like a patient, nor feel healthy. This impacts their self-image, interactions with their social environment, and feelings of uncertainty. Due to their uncertain life perspective, long-term responders are going back and forth between hope and despair, while they are longing for their ‘old’ life, several barriers, such as protective behavior of the social environment, force them to adjust to a life with cancer. Conclusion Long-term responders are facing many challenges, such as searching for a renewed identity, dealing with ongoing uncertainty, and having to adapt to a new normal. This emphasizes the importance of providing this new patient group with tailored information and support

Balancing end-to-end budgets of the Georges Bank ecosystem

Author Posting. © Elsevier, 2007. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 74 (2007): 423-448, doi:10.1016/j.pocean.2007.05.003.Oceanographic regimes on the continental shelf display a great range in the time scales of physical exchange, biochemical processes and trophic transfers. The close surface-to-seabed physical coupling at intermediate scales of weeks to months means that the open ocean simplification to a purely pelagic food web is inadequate. Top-down trophic depictions, starting from the fish populations, are insufficient to constrain a system involving extensive nutrient recycling at lower trophic levels and subject to physical forcing as well as fishing. These pelagic-benthic interactions are found on all continental shelves but are particularly important on the relatively shallow Georges Bank in the northwest Atlantic. We have generated budgets for the lower food web for three physical regimes (well mixed, transitional and stratified) and for three seasons (spring, summer and fall/winter). The calculations show that vertical mixing and lateral exchange between the three regimes are important for zooplankton production as well as for nutrient input. Benthic suspension feeders are an additional critical pathway for transfers to higher trophic levels. Estimates of production by mesozooplankton, benthic suspension feeders and deposit feeders, derived primarily from data collected during the GLOBEC years of 1995-1999, provide input to an upper food web. Diets of commercial fish populations are used to calculate food requirements in three fish categories, planktivores, benthivores and piscivores, for four decades, 1963-2002, between which there were major changes in the fish communities. Comparisons of inputs from the lower web with fish energetic requirements for plankton and benthos indicate that we obtained reasonable agreement for the last three decades, 1973 to 2002. However, for the first decade, the fish food requirements were significantly less than the inputs. This decade, 1963-1972, corresponds to a period characterized by a strong Labrador Current and lower nitrate levels at the shelf edge, demonstrating how strong bottom-up physical forcing may determine overall fish yields.The research was done under the aegis of the U.S.-GLOBEC Northwest Atlantic Georges Bank Study, a program sponsored jointly by the U.S. National Science Foundation and the U.S. National Oceanic and Atmospheric Administration. We acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele), NSF awards OCE0217399 (D.J. Gifford), OCE0217122 (J.J. Bisagni) and OCE0217257 (M.E. Sieracki). W.T. Stockhausen was supported by the NOAA Sponsored Coastal Ocean Research Program

ANOVA-principal component analysis and ANOVA-simultaneous component analysis: a comparison.

ANOVA-simultaneous component analysis (ASCA) is a recently developed tool to analyze multivariate data. In this paper, we enhance the explorative capability of ASCA by introducing a projection of the observations on the principal component subspace to visualize the variation among the measurements. We compare the significance of experimental effects for ASCA and ANOVA-principal component analysis (PCA), a similar tool to explore multivariate data, by using permutation tests. Furthermore, we quantify the quality of the loadings estimate obtained with ASCA and compare this with the loadings estimate obtained with ANOVA-PCA

Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia

BACKGROUND: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia. METHODS: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers. RESULTS: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor. CONCLUSIONS: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway

X-ray diffraction studies of potassium dihydrogen phosphate (KDP) crystal surfaces

We have studied the surface atomic structure of KDP crystals using X-ray scattering. These crystals were grown from an aqueous solution and we have done measurements both ex situ and in situ. The ex situ measurements were performed in vacuum or in air. In order to be able to do in situ measurements, we designed and built a crystal growth chamber which is compatible with X-ray diffraction experiments. The atomic arrangement of the two naturally existing faces of KDP has been determined. Preliminary results are presented of measurements performed during growth. Furthermore, the influence of metal impurities on the atomic structure of the growing interface is examined