Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials.

PURPOSE: Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis. MATERIALS AND METHODS: We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors. RESULTS: Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes. CONCLUSION: In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Reevaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials.

BACKGROUND: Disease-free survival (DFS) with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival (OS) with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence in patients who received adjuvant FOLFOX. Hence, reevaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. METHODS: Individual patient data from 9 randomized studies conducted between 1998 and 2009 were included; 3 trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (RWLS2) and Copula bivariate (RCopula2) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. RESULTS: Data from a total of 18 396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (T1-3 and N1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high or deficient mismatch repair tumors. Trial-level correlation between 3-year DFS and 5-year OS remained strong (RWLS2 = 0.82, 95% CI = 0.67 to 0.98; RCopula2 = 0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. CONCLUSIONS: Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database.

BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials.

PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.

Deep learning for prediction of colorectal cancer outcome: a discovery and validation study.

BACKGROUND: Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. METHODS: More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. FINDINGS: 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72-5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07-4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. INTERPRETATION: A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes. FUNDING: The Research Council of Norway.

3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT.

BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894).

Patients diagnosed with bowel cancer are likely to have surgery to remove the tumour. Patients diagnosed with a more advanced stage of the disease are then likely to be offered what is known as adjuvant chemotherapy ­ chemotherapy to kill any cancer cells that have already spread but cannot be seen. Adjuvant chemotherapy is usually given over 6 months using two medicines known as oxaliplatin and fluoropyrimidine. This chemotherapy has side effects of diarrhoea, nausea and vomiting, and it reduces the numbers of cells in the blood. It can also damage nerves, which causes discomfort, numbness and tingling; in some cases, this can go on for years. These side effects are more likely to develop with longer treatment. This study looked at whether or not shortening the time over which patients were given oxaliplatin and fluoropyrimidine chemotherapy reduced its effectiveness. In this large study of over 6000 patients, half of the patients were allocated by chance to be treated for 3 months and the other half to be treated for 6 months. Reducing the time that patients had chemotherapy from 6 months to 3 months did not make the treatment less effective. When patients treated with chemotherapy over 3 months were compared with those treated over 6 months, 77% of patients in both groups were well with no detectable disease 3 years after surgery. Patients were less likely to get side effects with 3-month chemotherapy. In particular, the chance of persistent long-term nerve damage was lower, resulting in patients with 3-month chemotherapy having better health-related quality of life. Overall, the study showed that 3-month adjuvant chemotherapy for patients with bowel cancer is as effective as 6-month adjuvant chemotherapy and causes fewer side effects.

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.

BACKGROUND: Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS: We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS: After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS: Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).

The determinants of dietary diversity and nutrition: ethnonutrition knowledge of local people in the East Usambara Mountains, Tanzania.

BACKGROUND: Diet and nutrition-related behaviours are embedded in cultural and environmental contexts: adoption of new knowledge depends on how easily it can be integrated into existing knowledge systems. As dietary diversity promotion becomes an increasingly common component of nutrition education, understanding local nutrition knowledge systems and local concepts about dietary diversity is essential to formulate efficient messages. METHODS: This paper draws on in-depth qualitative ethnographic research conducted in small-scale agricultural communities in Tanzania. Data were collected using interviews, focus group discussions and participant observation in the East Usambara Mountains, an area that is home primarily to the Shambaa and Bondei ethnic groups, but has a long history of ethnic diversity and ethnic intermixing. RESULTS: The data showed a high degree of consensus among participants who reported that dietary diversity is important because it maintains and enhances appetite across days, months and seasons. Local people reported that sufficient cash resources, agrobiodiversity, heterogeneity within the landscape, and livelihood diversity all supported their ability to consume a varied diet and achieve good nutritional status. Other variables affecting diet and dietary diversity included seasonality, household size, and gender. CONCLUSIONS: The results suggest that dietary diversity was perceived as something all people, both rich and poor, could achieve. There was significant overlap between local and scientific understandings of dietary diversity, suggesting that novel information on the importance of dietary diversity promoted through education will likely be easily integrated into the existing knowledge systems.

Comparison of Phytochemicals and Antioxidant Capacity in Three Bean Varieties Grown in Central Malawi.

The aims of the current work were: (1) to study the influence of variety and geographical production area on the total phenolic content, total anthocyanin content, total flavonoid content, total carotenoid content and antioxidant activity in bean varieties (Dimeta, Napirira and Nanyati) from different growing areas in central Malawi, and (2) to evaluate the possibility of establishing a classification based on the geographical areas of the growing regions. A total of 47 bean samples were collected from Makowe, Mphathi, Chuma-Chitsala and Khulungira Zone. These four locations were segregated based on altitude, latitude and longitude. Principal component and hierarchical cluster analysis were used to distinguish and classify among these samples. Significant differences (P < 0.05) in total phenolic content (2.92-4.97 mg/g), total anthocyanin content (14.52-152.31 µg/g), total flavonoid content (2.01-6.38 mg/g) and oxygen radical absorbance capacity (16.75-24.51 µmol/g) were found among the different sampled villages, showing a significant effect of the producing region on these parameters. The beans in Makowe had lower polyphenols than in other locations. Results of principal component analysis indicate that phytochemicals and antioxidant capacity could serve as parameters to establish a bean classification according to the geographical area of production.

Provitamin A potential of landrace orange maize variety (Zea mays L.) grown in different geographical locations of central Malawi.

The provitamin A potential of landrace orange maize from different locations (A, B, C and D) of central Malawi has been evaluated. Physicochemical compositions, color, total carotenoid content (TCC), carotenoid profiles, and oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging activity as antioxidant capacities of maize were determined. Color values of orange maize had correlations with ß-cryptoxanthin (r>0.36). TCC of white and orange maize averaged 2.12 and 59.5 mg/kg, respectively. Lutein was the most abundant carotenoid (47.8%) in orange maize, followed by zeaxanthin (24.2%), ß-carotene (16.4%) and ß-cryptoxanthin (11.6%). Location D showed the highest levels of lutein, zeaxanthin and antioxidant capacity. Provitamin A content of orange maize met the target level (15 µg/g) of biofortification. Retinol activity equivalent (RAE) from ß-cryptoxanthin and ß-carotene in orange maize averaged 81.73 µg/100g. In conclusion, orange maize has the potential to be a natural source of provitamin A.

Non-nematode-derived double-stranded RNAs induce profound phenotypic changes in Meloidogyne incognita and Globodera pallida infective juveniles.

Nine non-nematode-derived double-stranded RNAs (dsRNAs), designed for use as controls in RNA interference (RNAi) screens of neuropeptide targets, were found to induce aberrant phenotypes and an unexpected inhibitory effect on motility of root knot nematode Meloidogyne incognita J2s following 24h soaks in 0.1 mg/ml dsRNA; a simple soaking procedure which we have found to elicit profound knockdown of neuronal targets in Globodera pallida J2s. We have established that this inhibitory phenomenon is both time- and concentration-dependent, as shorter 4h soaks in 0.1 mg/ml dsRNA had no negative impact on M. incognita J2 stage worms, yet a 10-fold increase in concentration to 1 mg/ml for the same 4h time period had an even greater qualitative and quantitative impact on worm phenotype and motility. Further, a 10-fold increase of J2s soaked in 0.1 mg/ml dsRNA did not significantly alter the observed phenotypic aberration, which suggests that dsRNA uptake of the soaked J2s is not saturated under these conditions. This phenomenon was not initially observed in potato cyst nematode G. pallida J2s, which displayed no aberrant phenotype, or diminution of migratory activity in response to the same 0.1 mg/ml dsRNA 24h soaks. However, a 10-fold increase in dsRNA to 1mg/ml was found to elicit comparable irregularity of phenotype and inhibition of motility in G. pallida, to that initially observed in M. incognita following a 24h soak in 0.1 mg/ml dsRNA. Again, a 10-fold increase in the number of G. pallida J2s soaked in the same volume of 1 mg/ml dsRNA preparation did not significantly affect the observed phenotypic deviation. We do not observe any global impact on transcript abundance in either M. incognita or G. pallida J2s following 0.1 mg/ml dsRNA soaks, as revealed by reverse transcriptase-PCR and quantitative PCR data. This study aims to raise awareness of a phenomenon which we observe consistently and which we believe signifies a more expansive deficiency in our knowledge and understanding of the variables inherent to RNAi-based investigation.

Intergenerational participatory discussion groups foster knowledge exchange to improve child nutrition and food security in northern Malawi.

This article assesses the effectiveness of a participatory, intergenerational, dialogue approach in addressing gender and generational conflicts related to both child nutrition and agriculture. Analysis of 46 interviews and 3 focus groups with smallholder farmers in rural agrarian communities with high rates of child malnutrition in northern Malawi suggested that participatory discussion can lead to positive change, including increasing child feeding frequency and dietary diversity. An intergenerational, transformative, and holistic approach to nutrition education which integrates agricultural and gender issues can effectively address sensitive conflicts within households and communities that affect child nutrition, and come up with local solutions.