Projecting international demand for and supply of protein feed.

Thesis (M.Sc.Agric.)-University of Natal, Pietermaritzburg, 2001.South African imports of protein feed (oilcake or meal) increased 210% from 1990 to 1998/1999. Over that same period local production increased by only 14% and imported protein feed now accounts for over 50% of local requirements at an estimated annual import cost of about R1 billion. Internationally, protein prices reached high levels in 1996/97 following increased Asian demand but then fell considerably in response to the Asian financial crisis and increased supply. The South African Protein Research Trust, who invest in research aimed at stimulating the local protein industry, are interested in the most likely long-term trends. Projections of world meal prices and local protein requirements under a variety of scenarios indicate the possible cost of future imports and the potential for local production. These can help strategists to make informed decisions when evaluating plans that impact on future production capacity. Two interactive spreadsheet models have been developed which estimate protein usage and price under various scenarios and thereby serve as a decision support system. The first model projects future world supply of and demand for oilcake and calculates equilibrium price and consumption using estimated price elasticities of demand and supply. Demand projections are driven by estimated population and income growth while supply is forecast based on past production trends. The model incorporates dynamic income elasticities of demand that decline with rising real incomes. Assuming a 3% annual growth in supply the model forecasts that real price for protein meal will remain relatively constant at 1999 prices to 2020. However, if supply increases linearly price is forecast to increase 22% by 2020. Developing Asia, notably China, accounts for most demand growth and projections are sensitive to income growth assumptions for China. A second model estimates South African consumption of oil cake to 2020 Novel features of the model include: the price of protein is endogenous as it is generated by the international model; it incorporates estimated rates of technological progress in livestock production, and predicts the resulting real price change and; use is made of declining income elasticities of demand. Population growth projections include the estimated effect of AIDS which could reduce population growth rates by killing adults and children and reducing fertility amongst women who are HIV positive. Total protein consumption in 2020 is projected at 1.54 million tons (a 24% increase from 2000) under low income growth and 1.96 million tons (a 58% increase from 2000) under high income growth. Declining broiler, egg and pork product prices (projected to decline in real terms because of expected technological advances) contribute to increasing protein usage even in the absence of significant real income growth rates. Population growth remains the most important demand driver and scenario analysis reveals that alternative population growth rates impact significantly on projections

Efficacy and cost-effectiveness of an outcall program to reduce carer burden and depression among carers of cancer patients (PROTECT) : rationale and design of a randomized controlled trial

Published: 6 January 2014BACKGROUND: Carers provide extended and often unrecognized support to people with cancer. The aim of this study is to test the hypothesis that excessive carer burden is modifiable through a telephone outcall intervention that includes supportive care, information and referral to appropriate psycho-social services. Secondary aims include estimation of changes in psychological health and quality of life. The study will determine whether the intervention reduces unmet needs among patient dyads. A formal economic program will also be conducted. METHODS/DESIGN: This study is a single-blind, multi-centre, randomized controlled trial to determine the efficacy and cost-efficacy of a telephone outcall program among carers of newly diagnosed cancer patients. A total of 230 carer/patient dyads will be recruited into the study; following written consent, carers will be randomly allocated to either the outcall intervention program (n = 115) or to a minimal outcall / attention control service (n = 115). Carer assessments will occur at baseline, at one and six months post-intervention. The primary outcome is change in carer burden; the secondary outcomes are change in carer depression, quality of life, health literacy and unmet needs. The trial patients will be assessed at baseline and one month post-intervention to determine depression levels and unmet needs. The economic analysis will include perspectives of both the health care sector and broader society and comprise a cost-consequences analysis where all outcomes will be compared to costs. DISCUSSION: This study will contribute to our understanding on the potential impact of a telephone outcall program on carer burden and provide new evidence on an approach for improving the wellbeing of carers.Patricia M Livingston, Richard H Osborne, Mari Botti, Cathy Mihalopoulos, Sean McGuigan, Leila Heckel, Kate Gunn, Jacquie Chirgwin, David M Ashley and Melinda William

Breeding Experience and the Heritability of Female Mate Choice in Collared Flycatchers

Heritability in mate preferences is assumed by models of sexual selection, and preference evolution may contribute to adaptation to changing environments. However, mate preference is difficult to measure in natural populations as detailed data on mate availability and mate sampling are usually missing. Often the only available information is the ornamentation of the actual mate. The single long-term quantitative genetic study of a wild population found low heritability in female mate ornamentation in Swedish collared flycatchers. One potentially important cause of low heritability in mate ornamentation at the population level is reduced mate preference expression among inexperienced individuals.Applying animal model analyses to 21 years of data from a Hungarian collared flycatcher population, we found that additive genetic variance was 50 percent and significant for ornament expression in males, but less than 5 percent and non-significant for mate ornamentation treated as a female trait. Female breeding experience predicted breeding date and clutch size, but mate ornamentation and its variance components were unrelated to experience. Although we detected significant area and year effects on mate ornamentation, more than 85 percent of variance in this trait remained unexplained. Moreover, the effects of area and year on mate ornamentation were also highly positively correlated between inexperienced and experienced females, thereby acting to remove difference between the two groups.The low heritability of mate ornamentation was apparently not explained by the presence of inexperienced individuals. Our results further indicate that the expression of mate ornamentation is dominated by temporal and spatial constraints and unmeasured background factors. Future studies should reduce unexplained variance or use alternative measures of mate preference. The heritability of mate preference in the wild remains a principal but unresolved question in evolutionary ecology

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Diagnostic utility of Cerebrospinal fluid biomarkers in Irish subjects with cognitive impairment

Background CSF biomarkers have been recently implemented in Ireland for clinical use in subjects with cognitive impairment with several sites performing the CSF extraction and a single national reference laboratory carrying out the assay. To-date, there are no published data on their clinical utility for the differential diagnosis of Alzheimer’s disease (AD) in Irish subjects. Methods Retrospective cross-sectional study. Descriptive statistics were calculated for basic demographics and CSF biomarker results (Aβ42, total-tau (ttau), phosphorylated-tau (ptau), neurofilament light chain (NfL), analysed with currently available commercial kits), in a cohort of subjects with mild cognitive impairment (MCI), AD dementia, and controls. Single (Aβ42, ttau, ptau, NfL) and composite biomarkers (Aβ42/ptau ratio) receiver operating characteristics (ROC) curves were also calculated for the differential diagnosis of AD and controls. Results The sample comprised 93 subjects (46% males): 28 MCI (68±8.6 years, MMSE 26.7±2.4), 33 AD (67±9.4 years), MMSE 22±3.6) and 32 controls (65±8.1 years, MMSE 29.2±0.6). Aβ42 was lower in AD (388±146pg/ml) than in controls (736pg/ml, p<.001). Ttau and ptau levels were higher in AD (710±345pg/ml, 97±42pg/ml) than in controls (241±82pg/ml, 49±12pg/ml, p<.001). NfL levels (n=69) were highest in subjects with AD (1619±1100pg/ml) as compared with MCI (1100±750pg/ml) and controls (459±123pg/ml). 22/28 MCI had amnestic (single or multi-domain) phenotypes. 13/22 amnestic MCI and 2/6 non-amnestic MCI subjects had Aβ42 values lower than 500pg/ml. In the sample, ttau and ptau were correlated with each other (r=0.92), age (r=0.27, r=0.26) and MMSE (r=-0.6, r=-0.59) whereas NfL correlated with ptau (r=0.37), Aβ42(r= -0.39) and MMSE (r=-0.44). Diagnostic accuracy of CSF biomarkers for differentiating between AD and controls was higher for composite biomarkers (AUC Aβ42/ptau 0.957) as compared with individual biomarkers (AUC Aβ42 0.914, AUC ttau 0.932, AUC ptau 0.896). Interestingly, NfL outperformed individual core CSF biomarkers in differentiating between AD and controls (AUC 0.960). Conclusions CSF biomarkers performed well in Irish subjects in differentiating subjects with dementia due to AD from controls and can be used for assessing underlying AD pathology in MCI subjects. Composite biomarkers behave better for clinical diagnostic purposes than single CSF biomarkers. NfL showed promising results, outperforming any other single biomarker