509 research outputs found
Depreciation, Deterioration and Obsolescence when there is Embodied or Disembodied Technical Change
The paper considers how to measure capital in a model where technical progress is either embodied in new units of capital or it is "disembodied" and simply causes the price of capital services to fall. The disembodied case is considered in sections 2-4. Sections 2 and 3 set out standard vintage capital aggregation models when there is no embodied technical progress. Section 4 discusses disembodied obsolescence in more detail. Section 5 introduces new (more efficient) models of the capital good so that technical progress is embodied in the new models. Section 6 shows how the parameters in the Jorgenson model of capital services could be estimated by statistical agencies if their investment surveys covered sales and retirements of used assets as well as purchases of new assets. Section 7 concludes.Aggregation of Capital, embodiment of technical progress, depreciation, deterioration, obsolescence, index number theory
Energy, Obsolescence, and the Productivity Slowdown
The growth rate of output per worker in the U.S. declined sharply during the 1970's. A leading explanation of this phenomenon holds that the dramatic rise in energy prices during the 1970's caused a significant portion of the U.S. capital stock to become obsolete. This led to a decline in effective capital input which, in turn, caused a reduction in the reduction in the growth rate of output per worker. This paper examines a key prediction of this hypothesis. If there is a significant link between energy and capital obsolescence, it should be revealed in the market price of used capital: if rising energy costs did in fact render older, energy-inefficient capital obsolete, prospective buyers should have reduced the price that they were willing to pay for that capital. An examination of the market for used capital before and after the energy price shocks should thus reveal the presence and magnitude of the obsolescence effect. We have carried out this examination for four types of used machine tools and five types of construction equipment. We did not find a general reduction in the price of used equipment after the energy price shocks. Indeed, the price of used construction equipment - the more energy intensive of our two types of capital - tended to increase after 1973. We thus conclude that our data do not support the obsolescence explanation of the productivity of slowdown.
The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer
Regulation by hypoxia may underlie the expression of vascular endothelial growth factor in bladder cancer. We have compared the distribution of vascular endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor mRNA was analysed by in situ hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The relationship of microvessels to the distribution of CA IX was determined. In a separate series of 49 superficial tumours, CA IX immunostaining was compared with clinico-pathological outcome. In superficial and invasive disease there was overlap in the expression of vascular endothelial growth factor and CA IX, CA IX being more widespread. Both were expressed predominantly on the luminal surface, and surrounding areas of necrosis (invasive tumours). Expression of both factors was greater in superficial disease. Expression was absent within ∼80 μm of microvessels. Unlike vascular endothelial growth factor, CA IX did not predict outcome in superficial disease. Differential responses to reoxygenation provide one explanation: vascular endothelial growth factor mRNA declined rapidly, while CA IX expression was sustained for >72 h. Expression of vascular endothelial growth factor mRNA in bladder tumours is consistent with hypoxic regulation and suggests differential regulation in superficial vs invasive disease. The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator
The SPX domain of the yeast low-affinity phosphate transporter Pho90 regulates transport activity
Yeast has two phosphate-uptake systems that complement each other: the high-affinity transporters (Pho84 and Pho89) are active under phosphate starvation, whereas Pho87 and Pho90 are low-affinity transporters that function when phosphate is abundant. Here, we report new regulatory functions of the amino-terminal SPX domain of Pho87 and Pho90. By studying truncated versions of Pho87 and Pho90, we show that the SPX domain limits the phosphate-uptake velocity, suppresses phosphate efflux and affects the regulation of the phosphate signal transduction pathway. Furthermore, split-ubiquitin assays and co-immunoprecipitation suggest that the SPX domain of both Pho90 and Pho87 interacts physically with the regulatory protein Spl2. This work suggests that the SPX domain inhibits low-affinity phosphate transport through a physical interaction with Spl2
Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma
Hypoxia and pH influence gene expression in tumours, and it is becoming increasingly clear that the pattern of genes expressed by a tumour determines its growth and survival characteristics. Hypoxia-inducible factor-1 (HIF-1) is a key mediator of the cellular response to hypoxia and high HIF-1 expression has been identified as a poor prognostic factor in tumours. Recently, we identified the tumour-associated carbonic anhydrases (CA), CA9 and CA12 as hypoxia-inducible in tumour cell lines. Furthermore, we identified CA IX to be a poor prognostic factor in breast cancer. The aim of this study was to assess the prognostic significance of CA XII. CA XII expression was studied by immunohistochemistry in a series of 103 cases of invasive breast cancer and any association with recognised prognostic factors or relation with the outcome was examined. CA XII expression was present in 77 out of 103 (75%) cases and was associated with lower grade (P=0.001), positive estrogen receptor status (P<0.001), and negative epidermal growth factor receptor status (P<0.001). Furthermore, although CA XII expression was associated with an absence of necrosis (P<0.001), expression of CA XII in some high-grade tumours was induced in regions directly adjacent to morphological necrosis. Additionally, using univariate analysis, CA XII positive tumours were associated with a lower relapse rate (P=0.04) and a better overall survival (P=0.01). In conclusion, CA XII expression is influenced both by factors related to differentiation and hypoxia in breast cancer in vivo and CA XII expression is associated with a better prognosis in an unselected series of invasive breast carcinoma patients
Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials.
Abstract Purpose To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design Proxima A (NCT02479386) and Proxima B (NCT02399072) were global, prospective, non-interventional, observational clinical trials. Participants Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N=295). Patients in Proxima B had GA with no CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n=168); or GA with no CNV in the study eye, without CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n=32). Methods Changes in visual function and imaging/anatomic parameters were evaluated over time using a Mixed Model for Repeated Measurement (MMRM) accounting for key baseline characteristics. Main Outcome Measures Pre-specified endpoints included change in GA area from baseline, best corrected visual acuity (BCVA) score assessed by ETDRS, and BCVA under low-luminance conditions (LLVA). Results At 24 months, the adjusted mean (standard error; SE) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). GA progression was greater in patients with baseline non-subfoveal (vs. subfoveal) GA lesions, and tended to increase as baseline low-luminance deficit increased (Proxima A; Proxima B, all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (SE) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months: −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in the Proxima B fellow eye CNV cohort, −11.48 (3.39) and −8.37 (3.02) in the Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline
Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene
Gene expression analysis was performed on a human renal cancer cell line (786-0) with mutated VHL gene and a transfectant with wild-type VHL to analyse genes regulated by VHL and to compare with the gene programme regulated by hypoxia. There was a highly significant concordance of the global gene response to hypoxia and genes suppressed by VHL. Cyclin D1 was the most highly inducible transcript and 14-3-3 epsilon was downregulated. There were some genes regulated by VHL but not hypoxia in the renal cell line, suggesting a VHL role independent of hypoxia. However in nonrenal cell lines they were hypoxia regulated. These included several new pathways regulated by hypoxia, including RNase 6PL, collagen type 1 alpha 1, integrin alpha 5, ferritin light polypeptide, JM4 protein, transgelin and L1 cell adhesion molecule. These were not found in a recent SAGE analysis of the same cell line. Hypoxia induced downregulation of Cyclin D1 in nonrenal cells via an HIF independent pathway. The selective regulation of Cyclin D1 by hypoxia in renal cells may therefore contribute to the tissue selectivity of VHL mutation
Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data
BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO).
SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses.
RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P \u3c 0.001).
CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO
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Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.
To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria
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