Price Transmission in the Swedish Pork Chain: Asymmetric non linear ARDL

Agribusiness, Livestock Production/Industries,

The Market for Tractors in the EU: Price Differences and Convergence. Factor Markets Working Documents No. 35, February 2013

This study evaluates the degree of segmentation of the market for agricultural machinery and equipment in the EU. We focus on agricultural tractors, the most common and biggest investment in machinery and equipment in the agricultural sector. By using country price data for individual tractor models, we test the law of one price, i.e. the existence of a common price for tractors across EU member states. We find that significant price differences exist, yet unlike most other studies we find that large price deviations are penalised within a short time. The study also shows that transport costs are an important source of price differences, as domestic production leads to lower prices on the domestic market and as price convergence is negatively correlated with distance. Finally, price differences should not solely be understood from a geographical perspective, as evidence supports the idea that farmers’ buying power is significant in explaining price differences within countries

PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer:current status and future perspectives

Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)—provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer (64)Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome

Laster som investering - Är summan av lasterna konstant?

Abstract Laster som investering – Är summan av lasterna konstant? Nationalekonomiska Institutionen, Lund, 2009 Ämne och problemställning Genom att undersöka hur väl laster står emot nedgång på marknaden, samt hur väl en portfölj bestående av laster kan minimera osystematisk risk, skall den huvudsakliga frågeställningen besvaras. Hur kan investering i tillgångar kategoriserade som laster ge en välpresterande portfölj, och finns det någon sanning i uttrycket att summan av lasterna är konstant? Syfte Vårt huvudsakliga syfte med den här uppsatsen är att med hjälp av kvantitativ analys av historisk data undersöka prestation för branscher och portföljer med innehåll av tillgångar i form av laster. Viktiga teorier Studien utgår till stor del från modern porföljvalsteori och har sin utgångspunkt i hur en rationell investerare kan diversifiera sin portfölj för att optimera dess avkastning. Metod Detta är en undersökning av historiska data med slutsatser dragna genom nationalekonomisk teoretisk analys av branschindex. En deduktiv och kvantitativ metod användes under studiens gång. Innehåll Första delen behandlar branschindexens prestation individuellt och i förhållande till varandra och marknaden. Andra delen behandlar samvariation mellan branscherna och den tredje delen fokuserar på portföljanalys. I varje del görs analys dels för hela tidsperioden dels beroende på marknadsläge. Resultat Sett över hela perioden har samtliga lastindex haft en bättre medelavkastning jämfört med världsindex vilket till stor del har skett med en förhöjd standardavvikelse. Vid konstruktion av portföljer minskas däremot den osystematiska risken och den likviktade och minsta variansportföljen visar på högre avkastning och en lägre risk jämfört med världsindex. Samvariationsanalysen visar låga korrelationer, lastindexen emellan och gentemot världsindex, detsamma gäller för de två portföljerna. Detta tyder på att portföljerna och indexen följer marknaden till viss del men något tydligt utbyte branscherna sinsemellan kan inte visas. Slutsats Studiens problemställning besvaras med att en portfölj av laster viktad enligt minsta varianskriteriet ger en välpresterande portfölj som historiskt sett gett bättre avkastning till lägre risk jämfört med marknadsportföljen. Vidare ser man ett mer stabilt uppförande hos portföljen under lågkonjunktur och en tendens till låga korrelationer undersökta branscher sinsemellan vilket till viss del dock ej fullt ut understödjer påståendet: summan av lasterna är konstant

Improved PET imaging of uPAR expression using new (64)Cu-labeled cross-bridged peptide ligands:comparative in vitro and in vivo studies

The correlation between uPAR expression, cancer cell invasion and metastases is now well-established and has prompted the development of a number of uPAR PET imaging agents, which could potentially identify cancer patients with invasive and metastatic lesions. In the present study, we synthesized and characterized two new cross-bridged (64)Cu-labeled peptide conjugates for PET imaging of uPAR and performed a head-to-head comparison with the corresponding and more conventionally used DOTA conjugate. Based on in-source laser-induced reduction of chelated Cu(II) to Cu(I), we now demonstrate the following ranking with respect to the chemical inertness of their complexed Cu ions: DOTA-AE105 << CB-TE2A-AE105 < CB-TE2A-PA-AE105, which is correlated to their corresponding demetallation rate. No penalty in the uPAR receptor binding affinity of the targeting peptide was encountered by conjugation to either of the macrobicyclic chelators (IC(50) ~ 5-10 nM) and high yields and radiochemical purities (>95%) were achieved in all cases by incubation at 95ºC. In vivo, they display identical tumor uptake after 1h, but differ significantly after 22 hrs, where the DOTA-AE105 uptake remains surprisingly high. Importantly, the more stable of the new uPAR PET tracers, (64)Cu-CB-TE2A-PA-AE105, exhibits a significantly reduced liver uptake compared to (64)Cu-DOTA-AE105 as well as (64)Cu-CB-TE2A-AE105, (p<0.0001), emphasizing that our new in vitro stability measurements by mass spectrometry predicts in vivo stability in mice. Specificity of the best performing ligand, (64)Cu-CB-TE2A-PA-AE105 was finally confirmed in vivo using a non-binding (64)Cu-labeled peptide as control ((64)Cu-CB-TE2A-PA-AE105(mut)). This control PET-tracer revealed significantly reduced tumor uptake (p<0.0001), but identical hepatic uptake compared to its active counterpart ((64)Cu-CB-TE2A-PA-AE105) after 1h. In conclusion, our new approach using in-source laser-induced reduction of Cu(II)-chelated PET-ligands provides useful information, which are predictive for the tracer stability in vivo in mice. Furthermore, the increased stability of our new macrobicyclic (64)Cu-CB-TE2A-PA-AE105 PET ligand is paralleled by an excellent imaging contrast during non-invasive PET scanning of uPAR expression in preclinical mouse cancer models. The translational promises displayed by this PET-tracer for future clinical cancer patient management remains, however, to be investigated

Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial

Introduction: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Methods and analysis: Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years. The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. Ethics and dissemination: The study will be conducted under International Conference on Harmonisation – Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications

Dosimetry of ⁶⁴Cu-DOTA-AE105, a PET tracer for uPAR imaging

Abstract64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105.MethodsFive mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE.ResultsHuman estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918mSv/MBq) followed by the liver (0.0815mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02–0.04mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation.ConclusionFavorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of 64Cu-DOTA-AE105

Good validity in the Norwegian Knee Ligament Register: assessment of data quality for key variables in primary and revision cruciate ligament reconstructions from 2004 to 2013

Background: The Norwegian Knee Ligament Register was founded in 2004 to provide representative and reliable data on cruciate ligament surgery. The aim of this study was to evaluate the validity of key variables in the Norwegian Knee Ligament Register to reveal and prevent systematic errors or incompleteness, which can lead to biased reports and study conclusions. Method: We included a stratified cluster sample of 83 patients that had undergone both primary and revision anterior cruciate ligament surgery. A total of 166 medical records were reviewed and compared with their corresponding data in the database of the Norwegian Knee Ligament Register. We assessed the validity of a selection of key variables using medical records as a reference standard to compute the positive predictive values of the register data for the variables. Results: The positive predictive values for the variables of primary and revision surgery ranged from 92 to 100% and from 39 to 100% with a mean positive predictive value of 99% and 88% respectively. Data on intraoperative findings and surgical details had high positive predictive values, ranging from 91 to 100% for both primary and revision surgery. The positive predictive value for the variable “date of injury” was 92% for primary surgeries but only 39% for revision surgeries. The positive predictive value for “activity at the time of injury” was 99% for primary surgeries and 52% for revisions. Conclusion: Overall, the data quality of the key variables examined in the Norwegian Knee Ligament Register was high, making the register a valid source for research.publishedVersio