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Most cost-benefit analyses assume that the estimates of costs and benefits are more or less accurate and unbiased. But what if, in reality, estimates are highly inaccurate and biased? Then the assumption that cost-benefit analysis is a rational way to improve resource allocation would be a fallacy. Based on the largest dataset of its kind, we test the assumption that cost and benefit estimates of public investments are accurate and unbiased. We find this is not the case with overwhelming statistical significance. We document the extent of cost overruns, benefit shortfalls, and forecasting bias in public investments. We further assess whether such inaccuracies seriously distort effective resource allocation, which is found to be the case. We explain our findings in behavioral terms and explore their policy implications. Finally, we conclude that cost-benefit analysis of public investments stands in need of reform and we outline four steps to such reform., Comment: 25 pages, 1 table, 1 figure

Background The incidence of cardiovascular diseases and its associated complications have increased greatly in the past three decades. The purpose of this study was to evaluate the acute cardioprotective effects of Garcinia kola (GK) seed extract and Kolaviron (KV) and determine mechanisms of action involving RISK signalling pathways. Methods Male Wistar rats were used in this study. Hearts were excised and mounted on the Langendorff perfusion system. The control, group 1 was perfused with dimethyl sulfoxide (DMSO), group II with KV and group III with GK respectively. Western blot analyses were performed on frozen heart tissues. Results Isolated rat hearts perfused with KV and GK attenuated apoptotic pathways with significant reduction in p38 MAPK protein phosphorylation, as well as reduction in total caspase 3, cleaved caspase 3 (Asp 175) and PARP cleavage. KV and GK also down-regulated p-JNK1 (Tyr 185) and p-JNK 2 (Thr 183) protein expression at the 10 min reperfusion time ponit. Cardioprotection was achieved in part, by enhancement of the reperfusion injury signalling kinase (RISK) pathway; as evidenced by significant increases in protein expresion of Akt/PKB and p-Akt/PKB (Ser 473) in KV and GK respectively. Conclusions KV and GK supplementation led to significant increases in the expressions of survival proteins. It is noteworthy that both KV and GK supplementation offered cardioprotection in ischaemic/reperfusion injury rat heart model. In all, GK showed better cardioprotective effect that KV.

Cardiometabolic complications such as the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) are major causes of global morbidity and mortality. As sugar-sweetened beverages (SSBs) are implicated in this process, this study aimed to obtain greater mechanistic insights. Male Wistar rats (~200 g) were gavaged with a local SSB every day for a period of six months while the control group was gavaged with an iso-volumetric amount of water. Experimental dosages were calculated according to the surface area-to-volume ratio and were equivalent to 125 mL/day (in human terms). A proteomic analysis was performed on isolated liver samples and thereafter, markers of endoplasmic reticulum (ER) stress, antioxidant/oxidant capacity, calcium regulation, and mitochondrial functionality were assessed. These data show that SSB consumption resulted in (a) the induction of mild hepatic ER stress, (b) altered hepatic mitochondrial dynamics, and (c) perturbed calcium handling across mitochondria-associated ER membranes. Despite significant changes in markers of ER stress, the antioxidant response and calcium handling (proteomics data), the liver is able to initiate adaptive responses to counteract such stressors. However, the mitochondrial data showed increased fission and decreased fusion that may put the organism at risk for developing insulin resistance and T2DM in the longer term.

Aims Although there is evidence linking sugar-sweetened beverage (SSB) intake with the development of cardio-metabolic diseases, the underlying mechanisms remain unclear. The current study therefore evaluated the effects of SSB consumption by establishing a unique in-house in vivo experimental model. Main methods Male Wistar rats were divided into two groups: a) one consuming a popular local SSB (SSB- Jive), and b) a control group (Control-water) for a period of three and six months (n = 6 per group), respectively. Rats were gavaged on a daily basis with an experimental dosage amounting to half a glass per day (in human terms) (SSB vs. water). Cardiac function was assessed at baseline (echocardiography) and following ex vivo ischemia-reperfusion of the isolated perfused working rat heart. Oral glucose tolerance tests and mitochondrial respiratory analyses were also performed. In addition, the role of non-oxidative glucose pathways (NOGPs), i.e. the polyol pathway, hexosamine biosynthetic pathway (HBP) and PKC were assessed. Key findings These data show that SSB intake: a) resulted in increased weight gain, but did not elicit major effects in terms of insulin resistance and cardiac function after three and six months, respectively; b) triggered myocardial NOGP activation after three months with a reversion after six months; and c) resulted in some impairment in mitochondrial respiratory capacity in response to fatty acid substrate supply after six months. Significance SSB intake did not result in cardiac dysfunction or insulin resistance. However, early changes at the molecular level may increase risk in the longer term.

This paper constructs a number of possible core measures of inflation using singular spectrum analysis (SSA). Annual changes in monthly inflation are decomposed into its trend, oscillatory and noise components in order to develop an understanding of the trend and cyclicality in South African headline inflation. Three cyclical components with differing amplitude and frequency are identified. The trend and cyclical components of inflation are found to be a good approximation of core inflation, the inertial part of inflation. These core measures are compared with other candidate core measures based on the properties of a good core inflation measure. Generally, the SSA measures outperform commonly used measures of core inflation based on both in- and out-of-sample performance.

In a recent paper [1] we introduced the Fuzzy Bayesian Learning (FBL) paradigm where expert opinions can be encoded in the form of fuzzy rule bases and the hyper-parameters of the fuzzy sets can be learned from data using a Bayesian approach. The present paper extends this work for selecting the most appropriate rule base among a set of competing alternatives, which best explains the data, by calculating the model evidence or marginal likelihood. We explain why this is an attractive alternative over simply minimizing a mean squared error metric of prediction and show the validity of the proposition using synthetic examples and a real world case study in the financial services sector., 6 pages, 1 page appendix

Daunorubicin (DNR) and doxorubicin (DOX) are two of the most effective anthracycline drugs known for the treatment of systemic neoplasms and solid tumors. However, their clinical use is hampered due to profound cardiotoxicity. The mechanism by which DNR injures the heart remains to be fully elucidated. Recent reports have indicated that DOX activates ubiquitin proteasome-mediated degradation of specific transcription factors; however, no reports exist on the effect of DNR on the E3 ubiquitin ligases, MURF-1 (muscle ring finger 1) and MAFbx (muscle atrophy F-box). The aim of this study was to investigate the effect of DNR treatment on the protein and organelle degradation systems in the heart and to elucidate some of the signalling mechanisms involved. Adult rats were divided into two groups where one group received six intraperitoneal injections of 2 mg/kg DNR on alternate days and the other group received saline injections as control. Hearts were excised and perfused on a working heart system the day after the last injection and freeze-clamped for biochemical analysis. DNR treatment significantly attenuated cardiac function and increased apoptosis in the heart. DNR-induced cardiac cytotoxicity was associated with upregulation of the E3 ligases, MURF-1 and MAFbx and also caused significant increases in two markers of autophagy, beclin-1 and LC3. These changes observed in the heart were also associated with attenuation of the phosphoinositide 3-kinase/Akt signalling pathway.

AW was supported by the Norwegian Women’s PublicHealth Association and University of Bergen. AKJ wassupported by grants from the Bergen Medical Foundationand Bergen Heart Foundation, University of Bergen,Norway. AKJ and JvR were supported with funding fromThe Norwegian Cen tre for International Cooperation inHigher Education (SIU) (NUFU Supplementing Activities)for movement of scientific personnel from South Africa to Norway.

Edible oils form an essential part of the modern diet. These oils play a role as an energy source, and provide the diet with many beneficial micronutrients. Although a popular conception may be that fat should be avoided, certain edible oils as a dietary supplement may play an important role in the improvement of cardiovascular health. CVD has become one of the leading causes of death worldwide. Dietary supplementation with different oils may have beneficial effects on cardiovascular health. While olive oil and sunflower-seed oil are known to reduce serum cholesterol, fish oil has become well known for reducing potentially fatal cardiac arrhythmias. Recently, red palm oil research has shown beneficial effects on cardiac recovery from ischaemia–reperfusion injury. It is clear that dietary supplementation with edible oils may play a vital role in reducing the mortality rate due to heart disease. The specific benefits and disadvantages of these oils should, however, be explored in greater depth. The present review will attempt to identify the benefits and shortcomings of four popular edible oils, namely olive oil, sunflower-seed oil, fish oil and palm oil. Additionally the present review will aim to reveal potential areas of research which could further enhance our understanding of the effects of edible oils on cardiovascular health.

Objective: The study was designed to investigate the ameliorative effect of Kolaviron (KV) on ischemic/reperfusion injury in experimental animal models. Materials and Methods: Male Wistar rats were randomly divided into two groups: Group 1 received corn oil as a vehicle and rats in Group 2 were administered KV at 200 mg/kg for 4 weeks. The rats were fed with rat standard chow pellet and water administered ad libitum. After 4 weeks of KV administration, hearts were excised and mounted on the working heart perfusion system. Western blot analysis for protein expression was carried out on frozen heart samples. Results: There was significant (P < 0.05) reduction in the activity of catalase, superoxide dismutase, and glutathione peroxidase with concomitant reduction in oxygen radical absorbance capacity in ischemic rat heart of control compared to group pre-treated with KV, respectively. Similarly, intracellular reactive oxygen species and malondialdehyde were significantly elevated in control compared to KV pre-treated rats. KV significantly increased total Akt/protein kinase B (PKB), phosphorylated Akt/PKB at serine 473 and also caused a significant reduction in p38 mitogen-activated protein kinase, Caspase 3, and cleaved poly adenosine diphosphate ribose polymerase. Conclusion: Taken together, KV offered significant cardioprotection via free radical scavenging activity and upregulation of pro-survival pathway.

This paper constructs a number of possible core measures of annual inflation using Singular Spectrum Analysis (SSA). Annual inflation is decomposed into its trend, oscillating and noise components in order to develop an understanding of the trend and cyclicality in South African headline inflation. Five cyclical components are identified with differing amplitude and frequency. The trend and cyclical components of inflation are found to be a good approximation of core inflation, the inertial part of inflation. These core measures are compared to other candidate core measures based on the properties of a good core inflation measure. Generally, the SSA measures outperform commonly use measures of core inflation.

Background and Aims The effect of red palm oil (RPO) supplementation on infarct size after ischaemia/reperfusion in a cholesterol enriched diet-induced hyperlipidemic animal model has not been reported. Previous studies reported results on the effect of RPO in a normal diet, whilst evidence of protection has been linked to improved functional recovery, prosurvival kinase, anti-apoptosis and NO-cGMP. Therefore, we aimed to investigate the effects of dietary RPO supplementation in a cholesterol-enriched diet-induced hyperlipidemic rat model and to investigate the involvement of matrix metalloproteinase 2 (MMP2) inhibition as a possible mechanism of protection. Materials and Methods Male Wistar rats were fed either a standard rat chow diet (Norm) or a 2% cholesterol-enriched diet (Chol) for nine weeks. Additionally, two more groups received the same treatment, however, at the week 4, diet was supplemented with RPO for the last five weeks (Norm+RPO and Chol+RPO), respectively. After the feeding period hearts were isolated, perfused according to Langendorff and subjected to 30 minutes of normothermic global ischaemia followed by two hours of reperfusion. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining at the end of reperfusion. Results Cholesterol-enriched diet increased myocardial infarct size from 23.5 ± 3.0% to 37.2 ± 3.6% (p < 0.05) when compared to normal diet. RPO supplementation significantly reduced infarct size either in Norm+RPO or in Chol+RPO (to 9.2 ± 1.0% and 26.9 ± 3.0%), respectively. Infarct size in Chol+RPO was comparable to the Norm group. MMP2 activity before ischaemia was significantly reduced in the Chol+RPO group when compared to the Chol group. However, the MMP2 activity of the hearts of the RPO fed rats was significantly increased when compared to the normal diet group after ischaemia. Conclusions For the first time it was shown that dietary RPO supplementation attenuated the increased susceptibility of the hearts in cholesterol fed rats to ischaemia/reperfusion injury. This was shown by reduced infarct size. For the first time we also show that red palm oil supplementation altered pre-ischaemic levels of MMP-2, which may indicate that myocardial MMP2 may be implicated as a possible role player in RPO mediated protection against ischaemia/reperfusion injury in hearts of cholesterol supplemented rats.

Background and Aims Recent studies have shown that dietary red palm oil (RPO) supplementation improves functional recovery following ischaemia/reperfusion in isolated hearts. The main aim of this study was to investigate the effects of dietary RPO supplementation on myocardial infarct size after ischaemia/reperfusion injury. The effects of dietary RPO supplementation on matrix metalloproteinase-2 (MMP2) activation and PKB/Akt phosphorylation were also investigated. Materials and methods Male Wistar rats were divided into three groups and fed a standard rat chow diet (SRC), a SRC supplemented with RPO, or a SRC supplemented with sunflower oil (SFO), for a five week period, respectively. After the feeding period, hearts were excised and perfused on a Langendorff perfusion apparatus. Hearts were subjected to thirty minutes of normothermic global ischaemia and two hours of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Coronary effluent was collected for the first ten minutes of reperfusion in order to measure MMP2 activity by gelatin zymography. Results Dietary RPO-supplementation decreased myocardial infarct size significantly when compared to the SRC-group and the SFO-supplemented group (9.1 ± 1.0% versus 30.2 ± 3.9% and 27.1 ± 2.4% respectively). Both dietary RPO- and SFO-supplementation were able to decrease MMP2 activity when compared to the SRC fed group. PKB/Akt phosphorylation (Thr 308) was found to be significantly higher in the dietary RPO supplemented group when compared to the SFO supplemented group at 10 minutes into reperfusion. There was, however, no significant changes observed in ERK phosphorylation. Conclusions Dietary RPO-supplementation was found to be more effective than SFO-supplementation in reducing myocardial infarct size after ischaemia/reperfusion injury. Both dietary RPO and SFO were able to reduce MMP2 activity, which suggests that MMP2 activity does not play a major role in protection offered by RPO. PKB/Akt phosphorylation may, however, be involved in RPO mediated protection.

High-cholesterol diets alter myocardial and vascular NO-cGMP signaling and have been implicated in ischaemic/reperfusion injury. We investigated the effects of dietary red palm oil (RPO) containing fatty acids, carotonoids, tocopherols and tocotrienols on myocardial ischaemic tolerance and NO-cGMP pathway function in the rat. Wistar rats were fed a standard rat chow±RPO, or a standard rat chow+cholesterol±RPO diet. Myocardial mechanical function and NO-cGMP signaling pathway intermediates were determined before, during and after 25 min ischaemia. RPO-supplementation improved aortic output recovery and increased myocardial ischaemic cGMP concentrations. Simulated ischaemia (hypoxia) increased cardiomyocyte nitric oxide levels in the two RPO supplemented groups, but not in control non-supplemented groups. RPO supplementation also increased hypoxic nitric oxide levels in the control diet fed, but not the cholesterol fed rats. These data suggest that dietary RPO may improve myocardial ischaemic tolerance by increasing bioavailability of NO and improving NO-cGMP signaling in the heart.

This technique describes a method for making maxillofacial prostheses with tissue undercuts that allows trial closure for esthetic characterization. The finish line is placed on the external eyelid to facilitate final trimming of the prosthesis.