Radiomics for Predicting Lung Cancer Outcomes Following Radiotherapy: A Systematic Review.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Intestinal microbiota lipid metabolism varies across rainbow trout (Oncorhynchus mykiss) phylogeographic divide.

AIMS: This study focused on intestinal microbiome variation across the phylogeogrpahic divide of rainbow trout and its potential functional effects on ocean migration. METHODS AND RESULTS: Hindgut intestinal contents were analysed using the 16S V4 hypervariable ribosomal gene region. Core microbiome taxonomies and overall microbial diversity were identified across the species phylogeographic divide with increased diversity found in Eastern Cascade fish. To determine potential functional differences between groups PICRUSt metagenomics analysis was utilized, revealing significant enrichment of lipid and fatty acid metabolism genes in Western Cascade fish microbiomes. CONCLUSIONS: Decreased levels of intestinal microbial lipid metabolism in Eastern Cascade rainbow trout suggests increased lipid absorption in these fish given the consistent diets. Such absorption, and potential storage, would be an evolutionary benefit for increased migration distances experienced by Eastern Cascade fish. Core microbiome differences, and their functional associations, suggest evolutionary differences at the genetic level noticeably contribute to intestinal microbial community diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of genetic variation controlling intestinal microbiome diversity could have significant impacts on strain selection for rainbow trout aquaculture, especially given the consistent rearing conditions experienced in our sample populations likely result in differences in intramyocellular lipid storage.

Comparison of breast milk vitamin A concentration measured in fresh milk by a rapid field assay (the iCheck FLUORO) with standard measurement of stored milk by HPLC.

Availability of rapid, point-of-contact analytical methods would facilitate the use of breast milk vitamin A concentration (BMVA) to assess vitamin A (VA) status. We compared BMVA concentrations measured by high-performance liquid chromatography (HPLC) (the standard technique) with those by iCheck FLUORO, a new portable fluorometer that can rapidly quantify BMVA. Casual breast milk samples (n=154) were collected during a representative survey in Yaoundé and Douala, Cameroon. Milk fat and BMVA concentrations (by iCheck) were measured in fresh milk in the field. After storage at <-20 °C, BMVA concentrations were also measured by HPLC. BMVA values from the two methods were highly correlated (R(2)=0.72 for BMVA/l; R(2)=0.62 for BMVA/g fat, both P<0.0001). HPLC values were greater than iCheck values on average, and the difference increased with increasing BMVA. The iCheck FLUORO could be useful for monitoring fortification programs, but before-after surveys to assess change in BMVA concentrations should use one method consistently.

Acceptability of complementary foods and breads prepared from zinc-fortified cereal flours among young children and adults in Senegal.

We completed a series of studies to assess the acceptability of zinc-fortified, cereal-based complementary foods and zinc-fortified wheat breads. Young children and their caregivers completed acceptability tests with complementary foods fortified with iron only (60 mg iron as ferrous fumarate per kilogram cereal flour), or the same level of iron and zinc (240 mg zinc as zinc oxide per kilogram cereal flour), and the caregivers completed triangle taste tests to compare the same products. A separate group of adult participants completed acceptability tests with wheat breads fortified with iron and folic acid (15 mg iron as ferrous fumarate per kilogram flour and 1.5 mg folic acid per kilogram flour) or the same levels of iron-folic acid and 2 levels of zinc (63 mg zinc or 126 mg zinc as zinc oxide per kilogram flour). Finally, a threshold test was administered to another group of adult participants to compare nonfortified wheat bread to breads fortified with zinc in 80 mg increments ranging from 80 to 400 mg zinc as zinc oxide per kilogram flour. All products were acceptable when compared to non-zinc-fortified equivalents, and were well liked by the respective participants. For the triangle tests, caregivers were not able to detect significant differences between products. For threshold tests, adult participants detected differences in breads prepared from fortified wheat flour at 80 mg, 160 mg, and 320 mg zinc per kilogram flour, but not at 240 mg and 400 mg zinc per kilogram flour, respectively, when compared to nonfortified bread equivalents. Zinc fortification of cereal flours in the ranges of fortification that were tested does not adversely affect the acceptability of complementary foods and breads prepared from these flours. Practical Application: Fortification of staple food products is a low-cost approach to deliver additional micronutrients (including zinc) to large segments of a population. Determining the acceptability of products fortified with zinc is an important step in the development of zinc fortification programs.

Shared acquired genomic changes in zebrafish and human T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging clinical entity with high rates of induction failure and relapse. To discover the genetic changes occurring in T-ALL, and those contributing to relapse, we studied zebrafish (Danio rerio) T-ALL samples using array comparative genomic hybridization (aCGH). We performed aCGH on 17 T-ALLs from four zebrafish T-ALL models, and evaluated similarities between fish and humans by comparing all D. rerio genes with copy number aberrations (CNAs) with a cohort of 75 published human T-ALLs analyzed by aCGH. Within all D. rerio CNAs, we identified 893 genes with human homologues and found significant overlap (67%) with the human CNA dataset. In addition, when we restricted our analysis to primary T-ALLs (14 zebrafish and 61 human samples), 10 genes were recurrently altered in > 3 zebrafish cancers and ≥ 4 human cases, suggesting a conserved role for these loci in T-ALL transformation across species. We also conducted iterative allo-transplantation with three zebrafish malignancies. This technique selects for aggressive disease, resulting in shorter survival times in successive transplant rounds and modeling refractory and relapsed human T-ALL. Fifty-five percent of original CNAs were preserved after serial transplantation, demonstrating clonality between each primary and passaged leukemia. Cancers acquired an average of 34 new CNAs during passaging. Genes in these loci may underlie the enhanced malignant behavior of these neoplasias. We also compared genes from CNAs of passaged zebrafish malignancies with aCGH results from 50 human T-ALL patients who failed induction, relapsed or would eventually relapse. Again, many genes (88/164) were shared by both datasets. Further, nine recurrently altered genes in passaged D. rerio T-ALL were also found in multiple human T-ALL cases. These results suggest that zebrafish and human T-ALLs are similar at the genomic level, and are governed by factors that have persisted throughout evolution.

The time of day and the interval since previous meal are associated with plasma zinc concentrations and affect estimated risk of zinc deficiency in young children in Peru and Ecuador.

BACKGROUND/OBJECTIVES: Plasma zinc concentration is the preferred biomarker of zinc status, but the time of day and time since previous meals can modify the results. Measuring fasting plasma zinc concentration is not feasible among young children, so adjustments need to be developed for interpreting results. Our objective is to develop correction factors to adjust for the effects of time of day and interval since the previous meal when measuring plasma zinc concentrations of young children. SUBJECTS/METHODS: We measured plasma zinc concentrations among young Peruvian (n =297) and Ecuadorian (n=466) children, and constructed regression models adjusting for time of day, interval since previous meal and infections. RESULTS: Plasma zinc concentrations were positively related to the number of hours since the previous meal in the Peru trial (r =0.22, P<0.0001) and negatively related to the time of day of blood sampling in both Peru (r = -0.24, P<0.0001) and Ecuador (r = -0.18, P<0.001). In multivariate models, plasma zinc concentrations were ~2 µg per 100 ml less for each hour later in the morning when blood samples were collected, in both populations, and concentrations were ~1.0 µg per 100 ml greater for every hour since previous meal consumption in Peru. The percentage of children with low plasma zinc concentrations varied according to both these factors. CONCLUSIONS: The time of day and the interval since the preceding meal should be recorded when measuring plasma zinc concentration and incorporated into the statistical analysis and interpretation when assessing population zinc status.

Indoor carbon monoxide and PM2.5 concentrations by cooking fuels in Pakistan.

UNLABELLED: In developing countries biomass combustion is a frequently used source of domestic energy and may cause indoor air pollution. Carbon monoxide (CO)and particulate matter with an aerodynamic diameter of 2.5 lm or less (PM2.5)were measured in kitchens using wood or natural gas (NG) in a semi-rural community in Pakistan. Daytime CO and PM2.5 levels were measured for eight continuous hours in 51 wood and 44 NG users from December 2005 to April 2006. The laser photometer PM2.5 (Dustrak, TSI) was calibrated for field conditions and PM2.5 measurements were reduced by a factor of 2.77. CO was measured by an electrochemical monitor (Model T15v, Langan). The arithmetic mean for daytime CO concentration was 29.4 ppm in wood users; significantly higher than 7.5 ppm in NG users (P < 0.001). The arithmetic mean for daytime PM2.5 concentrations was 2.74 mg/m3 in wood users; significantly higher than 0.38 mg/m3 in NG users (P < 0.001). Higher peak levels of CO and PM2.5 were also observed in wood users. Time spent in the kitchen during fuel burning was significantly related to increasing CO and PM2.5 concentrations in wood users.These findings suggest that cooking with wood fuel may lead to hazardous concentrations of CO and PM2.5. PRACTICAL IMPLICATIONS: Biomass combustion is frequently used in developing countries for cooking. This study showed very high level of air pollution in kitchens using wood as the cooking fuel. Many people, especially women and children, are vulnerable to exposure to very high levels of air pollutants as they spend time in the kitchen during cooking hours.

Pharmacodynamics and pharmacokinetics of the novel thrombopoietin mimetic peptide RWJ-800088 in humans.

RWJ-800088 is a novel thrombopoietin mimetic peptide for the treatment of thrombocytopenia. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, and safety of ascending doses of RWJ-800088 administered as a single intravenous delivery in a double-blind, placebo-controlled study with five parallel groups of eight healthy human subjects each. Platelet counts and functionality, peripheral stem cells, drug concentrations, and routine laboratory parameters were measured frequently up to day 29, and antibody formation was measured up to days 56-72. At doses > or = 0.75 microg/kg of RWJ-800088, platelet levels showed dose-related elevation as compared to results with placebo. The pharmacokinetic profile was characterized for doses of 2.5 and 3.0 microg/kg, although the dose relationship could not be fully defined. The two highest doses of RWJ-800088 appeared to increase burst-forming units-erythroid and colony-forming unit counts, suggesting some effects on progenitor lineages. RWJ-800088 was well tolerated, with no evidence of antibody formation in this single-dose study. Additional patient studies are warranted to investigate the therapeutic use of this novel peptide.

Effects of bovine serum concentrate, with or without supplemental micronutrients, on the growth, morbidity, and micronutrient status of young children in a low-income, peri-urban Guatemalan community.

OBJECTIVE: To determine the effects of dietary supplements containing bovine serum concentrate (BSC, a source of immunoglobulins) and/or multiple micronutrients (MMN) on children's growth velocity, rates of common infections, and MN status. DESIGN: Randomized, controlled, community-based intervention trial. SETTING: Low-income, peri-urban Guatemalan community. SUBJECTS: Children aged 6-7 months initially. INTERVENTIONS: Children received one of four maize-based dietary supplements daily for 8 months, containing: (1) BSC, (2) whey protein concentrate (WPC, control group), (3) WPC+MMN, or (4) BSC+MMN. RESULTS: There were no significant differences in growth or rates of morbidity by treatment group. Children who received MMN had lower rates of anemia and (in the group that received WPC+MMN) less of a decline in serum ferritin than those who did not, but there were no differences in other biochemical indicators of MN status by treatment group. CONCLUSIONS: MMN supplementation reduced anemia and iron deficiency in this population, but the MMN content and source of protein in the supplements did not affect other indicators of MN status, growth or morbidity.

Use of androgenesis for estimating maternal and mitochondrial genome effects on development and oxygen consumption in rainbow trout, Oncorhynchus mykiss.

Chromosome set manipulation was used to produce rainbow trout, Oncorhynchus mykiss, with identical nuclear backgrounds, but different maternal backgrounds to determine mitochondrial effects on development rate and oxygen consumption. Significant differences in development rate and oxygen consumption were observed between groups from different females. Development rates ranged from a mean of 317.97 degree days ( degrees d) to 335.25 degrees d in progeny from different females. Mean oxygen consumption rates ranged from 3.31 micromol O2 g(-1) wet mass h(-1) to 9.66 micromol O2 g(-1) wet mass h(-1). Oxygen consumption and development rate analysis revealed the two slowest developing groups had the highest oxygen consumption rates. Development rate differences between second generation clonal females indicate that mitochondrial genomes play a significant role on early development and are comparable to development rate differences between clonal lines of rainbow trout. These results indicate that selection for mitochondrial genomes could increase growth rates and possibly food conversion ratios in aquaculture species.

The Food Marketing Institute and the National Council of Chain Restaurants: animal welfare and the retail food industry in the United States of America.

In order to achieve real change, there must be a motivating force and all the stakeholders need to be involved. This is the premise of the animal welfare programme developed for the food retail, wholesale and chain restaurant industries in the United States of America (USA) by the Food Marketing Institute (FMI) and the National Council of Chain Restaurants (NCCR). This paper outlines a collaborative process that retailers and producers in the USA are using to enhance the care and welfare of animals in commercial food production. Although the efforts of the FMI and the NCCR are still underway, the process provides one example of how different parts of the food production system can work together to achieve positive change.

A consolidated linkage map for rainbow trout (Oncorhynchus mykiss).

Androgenetic doubled haploid progeny produced from a cross between the Oregon State University and Arlee clonal rainbow trout (Oncorhynchus mykiss) lines, used for a previous published rainbow trout map, were used to update the map with the addition of more amplified fragment length polymorphic (AFLP) markers, microsatellites, type I and allozyme markers. We have added more than 900 markers, bringing the total number to 1359 genetic markers and the sex phenotype including 799 EcoRI AFLPs, 174 PstI AFLPs, 226 microsatellites, 72 VNTR, 38 SINE markers, 29 known genes, 12 minisatellites, five RAPDs, and four allozymes. Thirty major linkage groups were identified. Synteny of linkage groups in our map with the outcrossed microsatellite map has been established for all except one linkage group in this doubled haploid cross. Putative homeologous relationships among linkage groups, resulting from the autotetraploid nature of the salmonid genome, have been revealed based on the placement of duplicated microsatellites and type I loci.

Multiple micronutrient supplementation increases the growth of Mexican infants.

BACKGROUND: The role of single micronutrient deficiencies in the etiology of growth retardation has recently gained attention. However, because multiple micronutrient deficiencies are common in children in developing countries, it is possible that more than one micronutrient may limit growth and, hence, the correction of a single deficiency may not be enough to improve growth substantially. OBJECTIVE: The objective was to evaluate the effect of multiple micronutrient supplementation on the growth of children aged 8-14 mo whose diets were poor in several micronutrients. DESIGN: Children were randomly assigned to 1 of 2 groups. One group received a multiple micronutrient supplement containing the recommended dietary allowance (RDA) or 1.5 times the RDA of vitamins A, D, E, K, C, B-1, B-6, B-12, riboflavin, niacin, biotin, folic acid, and pantothenic acid, and iron, zinc, iodine, copper, manganese, and selenium. The other group received a placebo. Supplements were administered 6 d/wk for an average of 12.2 mo. Body length was measured at baseline and monthly thereafter until the end of supplementation. RESULTS: Supplemented infants initially aged <12 mo had significantly greater length gains than did the placebo group, with a difference of 8.2 mm (length-for-age z score: 0.3) at the end of supplementation. In contrast, differences in length gains between the supplemented and placebo groups initially aged > or =12 mo were not significant. CONCLUSIONS: Micronutrient deficiencies limited the growth of the Mexican infants studied. Improving micronutrient intakes should be a component of interventions to promote growth in infants living in settings where micronutrient intakes are inadequate.

Identifying populations at risk of zinc deficiency: the use of supplementation trials.

Zinc supplementation trials assessing the response of growth and immunity have assisted in identifying populations at risk of zinc deficiency and the factors that contribute. A recent trial in Ethiopia demonstrated a high risk of zinc deficiency among young children, particularly among those who were stunted.

Effects of exclusive breastfeeding for four versus six months on maternal nutritional status and infant motor development: results of two randomized trials in Honduras.

To examine whether the duration of exclusive breastfeeding affects maternal nutrition or infant motor development, we examined data from two studies in Honduras: the first with 141 infants of low-income primiparous women and the second with 119 term, low birth weight infants. In both studies, infants were exclusively breastfed for 4 mo and then randomly assigned to continue exclusive breastfeeding (EBF) until 6 mo or to receive high-quality, hygienic solid foods (SF) in addition to breast milk between 4 and 6 mo. Maternal weight loss between 4 and 6 mo was significantly greater in the exclusive breastfeeding group (EBF) group than in the group(s) given solid foods (SF) in study 1 (-0.7 +/- 1.5 versus -0.1 +/- 1.7 kg, P < 0.05) but not in study 2. The estimated average additional nutritional burden of continuing to exclusively breastfeed until 6 mo was small, representing only 0.1-6.0% of the recommended dietary allowance for energy, vitamin A, calcium and iron. Women in the EBF group were more likely to be amenorrheic at 6 mo than women in the SF group, which conserves nutrients such as iron. In both studies, few women (10-11%) were thin (body mass index <19 kg/m(2)), so the additional weight loss in the EBF group in study 1 was unlikely to have been detrimental. Infants in the EBF group crawled sooner (both studies) and were more likely to be walking by 12 mo (study 1) than infants in the SF group. Taken together with our previous findings, these results indicate that the advantages of exclusive breastfeeding during this interval appear to outweigh any potential disadvantages in this setting.

Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA.

BACKGROUND: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. OBJECTIVE: We assessed iron absorption from porridges prepared from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. DESIGN: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. RESULTS: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P<0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron. CONCLUSION: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Exclusively breastfed, low birthweight term infants do not need supplemental water.

UNLABELLED: Breast milk intake, urine volume and urine-specific gravity (USG) of exclusively breastfed, low birthweight (LBW) term male infants in Honduras were measured during 8-h periods at 2 (n = 59) and 8 (n = 68) wk of age. Ambient temperature was 22-36 degrees C and relative humidity was 37-86%. Maximum USG ranged from 1.001 to 1.012, all within normal limits. CONCLUSIONS: We conclude that supplemental water is not required for exclusively breastfed, LBW term infants, even in hot conditions.

Predictors of growth from 1 to 18 months among breast-fed Ghanaian infants.

OBJECTIVE: To examine factors associated with the physical growth of breast-fed Ghanaian infants during the first 18 months of life. DESIGN: A community-based longitudinal study. SETTING: The study was carried out in Techiman, a district capital and major food trading center in the Brong Ahafo region of Ghana. SUBJECTS: One-month old infants (n=216) with birth weight >/= 2.5 kg were recruited from Maternal and Child Health Centers. METHOD: From 6 to 12 months, infants were provided with one of four types of nutritionally enhanced complementary foods. Anthropometric assessments were completed monthly from 1 to 12 months and every other month from 12 to 18 months. Information was collected on household characteristics, morbidity from common infections and dietary intakes. Blood samples were collected at 6 and 12 months to assess iron, zinc, riboflavin and vitamin A status. Multiple regression analysis was used to examine factors associated with growth during the age intervals of 1-6, 4-6, 6-12 and 12-18 months as well as size attained at 12 and 18 months. RESULTS: Prevalence of diarrhea and fever were negatively associated with growth during the first year of life. No significant relationship was found between respiratory illness (defined as cough or purulent nasal discharge) and growth. With the exception of dietary zinc intake, dietary variables were generally not significantly associated with growth. Maternal education was positively associated with growth during most of the age intervals. CONCLUSION: These findings suggest that interventions to reduce morbidity and improve the education of girls may benefit children's growth in this population. SPONSORSHIP: Nestle Foundation; Rockefeller Foundation African Dissertation Internship Award; Fulbright Scholarship. European Journal of Clinical Nutrition (2000) 54, 41-49