Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival

The role of fibrocytes in fibrotic diseases of the lungs and heart

Fibrosis is the end result of a complex series of events that follow tissue injury and inflammation. Pathophysiologic fibrosis results in permanent scar formation, and can impair organ function. Fibrocytes are circulating, bone-marrow-derived progenitor cells that traffic from the bone marrow to the injured organ via the bloodstream, where they differentiate into fibroblasts and myofibroblasts, and play a pivotal role in both physiologic and aberrant fibrosis. In this review, we focus on the contribution of fibrocytes to fibrotic diseases of the lungs and the heart, including interstitial lung diseases, asthma, pulmonary hypertension, atherosclerosis and ischemic cardiomyopathy

Coupled-channels effects in elastic scattering and near-barrier fusion induced by weakly bound nuclei and exotic halo nuclei

The influence on fusion of coupling to the breakup process is investigated for reactions where at least one of the colliding nuclei has a sufficiently low binding energy for breakup to become an important process. Elastic scattering, excitation functions for sub-and near-barrier fusion cross sections, and breakup yields are analyzed for $^{6,7}$Li+$^{59}$Co. Continuum-Discretized Coupled-Channels (CDCC) calculations describe well the data at and above the barrier. Elastic scattering with $^{6}$Li (as compared to $^{7}$Li) indicates the significant role of breakup for weakly bound projectiles. A study of $^{4,6}$He induced fusion reactions with a three-body CDCC method for the $^6$He halo nucleus is presented. The relative importance of breakup and bound-state structure effects on total fusion is discussed.Comment: 29 pages, 9 figure

Changes in fire intensity have carry-over effects on plant responses after the next fire in southern California chaparral

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Regulation of gastric epithelial cell homeostasis by gastrin and bone morphogenetic protein signaling

We reported that transgenic expression of the bone morphogenetic protein (BMP) signaling inhibitor noggin in the mouse stomach, leads to parietal‐cell (PC) loss, expansion of transitional cells expressing markers of both mucus neck and zymogenic lineages, and to activation of proliferative mechanisms. Because these cellular changes were associated with increased levels of the hormone gastrin, we investigated if gastrin mediates the expression of the phenotypic changes of the noggin transgenic mice (NogTG mice). Three‐month‐old NogTG mice were crossed to gastrin‐deficient (GasKO mice) to generate NogTG;GasKO mice. Morphology of the corpus of wild type, NogTG, GasKO, and NogTG;GasKO mice was analyzed by H&E staining. Distribution of PCs and zymogenic cells (ZCs) was analyzed by immunostaining for the H+/K+‐ATPase and intrinsic factor (IF). Expression of the H+/K+‐ATPase and IF genes and proteins were measured by QRT‐PCR and western blots. Cell proliferation was assessed by immunostaining for proliferating cell nuclear antigen. The corpus of the NogTG;GasKO mice displayed a marked reduction in the number of PCs and ZCs in comparison to NogTG mice. Further, cellular proliferation was significantly lower in NogTG;GasKO mice, than in the NogTG mice. Thus, gastrin mediates the increase in gastric epithelial cell proliferation induced by inhibition of BMP signaling in vivo. Moreover, gastrin and BMP signaling exert cooperative effects on the maturation and differentiation of both the zymogenic and PC lineages. These findings contribute to a better understanding of the factors involved in the control of gastric epithelial cell homeostasis.We investigated the role of gastrin and BMP signaling in the regulation of gastric epithelial homeostasis by crossing mice expressing the BMP inhibitor noggin in the stomach (NogTG mice) to gastrin‐deficient mice (GasKO mice). Analysis of these animals indicates that gastrin mediates the increase in gastric epithelial cell proliferation induced by inhibition of BMP signaling in vivo. Moreover, gastrin and BMP signaling exert cooperative effects on the maturation and differentiation of both the zymogenic and parietal‐cell lineages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113157/1/phy212501.pd

Taste assessment for paediatric drug Development: A comparison of bitterness taste aversion in children versus Naïve and expert young adult assessors

Medicines for children often taste bitter, presenting a significant challenge to treatment compliance. However, most studies on paediatric drug development rely on adult volunteers for sensory research, and the level of expertise required from these assessors is unclear. This study aimed to address this gap by investigating perceived bitterness aversion to taste strips impregnated with different concentrations of quinine hydrochloride in 439 school-aged children. Expert (n = 26) and naïve (n = 65) young adult assessors evaluated quinine solutions as well as taste strips, for methodological bridging purposes. All assessors differentiated the aversiveness of the taste strips in a dose dependent manner. Younger children aged 4–8 years had difficulty discriminating higher bitter concentrations, whereas pre-adolescents 9–11 years and naive adults showed better discrimination at the top of the scale. Naive assessors showed similar bitter perception as children. However, the results were slightly different between strips and solution in adults. These findings highlight the key role that adult panels can play in paediatric formulation development. Taste strips show promise as a safe and pragmatic tool for sensory pharmaceutical evaluations, though further studies are warranted to establish the relationship between age and hedonic taste perception using compounds with diverse physicochemical and sensory qualities

Simultaneous Optical Model Analyses of Elastic Scattering, Breakup, and Fusion Cross Section Data for the 6^{6}He + 209^{209}Bi System at Near-Coulomb-Barrier Energies

Based on an approach recently proposed by us, simultaneous $\chi^{2}$-analyses are performed for elastic scattering, direct reaction (DR) and fusion cross sections data for the $^{6}$He+$^{209}$Bi system at near-Coulomb-barrier energies to determine the parameters of the polarization potential consisting of DR and fusion parts. We show that the data are well reproduced by the resultant potential, which also satisfies the proper dispersion relation. A discussion is given of the nature of the threshold anomaly seen in the potential