Procedural sedation in children continues to be a problem in the emergency department (ED). Midazolam is the first water-soluble benzodiazepine and it has been widely used for procedural sedation in pediatric patients.The aim of this study was evaluation of clinical safety and effectiveness of intramuscular Midazolam for pediatric sedation in the ED setting.We performed a self-controlled clinical trial on 30 children who referred to the Baqiyatallah Hospital ED between 2009 and 2010. They received intramuscular Midazolam 0.3 mg/kg for procedural sedation and then they were followed for sedative effectiveness and safety. Vital signs and O2 saturation were also observed. The findings were compared using SPSS ver. 16 software.The mean age was 5.50 ± 2.70 years, the mean weight was 19.50 ± 6.63 kilograms and 16 patients (53.3%) were females. The most common adverse effect was euphoria (66.66%) and vertigo (6.7%); 27.7% did not show any side effects. There was an overall complication rate of 72.3%. The vital signs including heart rate, respiratory rate, systolic and diastolic blood pressure and O2 saturation decreased significantly during sedation .Midazolam is an effective and relatively safe sedative for pediatric patients in the ED. The patient should be observed closely and monitored for psychological and hemodynamic side effects. Procedural sedation in children continues to be a problem in the emergency department (ED). Midazolam is a benzodiazepine that has been widely used for procedural sedation in adults . VariousThe aim of this study was evaluation of clinical safety and effectiveness of intramuscular midazolam for pediatric sedation.We conducted a before-after clinical trial on a highly selective group of 30 children between 2 and 12 years-old. The children who presented to the ED of the Baqiyatallah Hospital between 2009 and 2010 were enrolled. The patients that met the inclusion criteria received intramuscular midazolam 0.3 mg/kg, before imaging (CT-Scan or magnetic resonance imaging). Midazolam was administrated at least 30 minutes before beginning the procedure. Sedation, irritability and cooperation scores were followed every 15 minutes during the first hour after receiving the drug. Five stages for sedation were assessed ..2 saturation were observed during the sedation. The findings were analyzed by using t-test, Chi-square and repeated measure ANOVA SPSS ver. 16; and P value < 0.05 was considered statistically significant. This study was approved by ethics committee of our university and the parents filled an informed consent before enrollment.Also, the vital signs and OThe mean age was 5.50 ± 2.70 years, the mean weight was 19.50 ± 6.63 Kg and 16 patients (53.3%) were female. All of the patients were sedated completely after the first dose. The trend of sedation staging progressed to deep sleep; irritability progressed to complete calmness . These t2 saturation at first was 97.50 ± 1.30 that at the last check changed to 96.33 ± 1.68. The trend of O2 saturation changes during sedation had significant decreases . None of the children suffered hypoxemia (O2 saturation under 90%). The mean RR at the onset was 22.23 ± 6.54 ; at the last visit it changed to 18.80 ± 4.81. Also the mean of HR at the onset was 112.46 ± 14.82 and at the last visit it changed to 103.90 ± 14.57. The trends of RR and HR changes had significant decreases . Moreover, the trends of systolic and diastolic BP changes also had significant decreases .The mean OThere was an overall side effect rate of 72.3%. The most common was euphoria (66.66%) followed by vertigo (6.7%); 27.7% did not present any side effects. All of the adverse effects resolved by observation only.Effectiveness of midazolam compared closely to other routine sedative agents such as propofol, fentanyl and ketamine , 6. MidaPsychological side effects such as hallucination and agitation have been commonly reported for benzodiazepines but euphoria with this high incidence has been reported rarely. One reason for this high incidence might be race -9. Previ


Cumulative effect of the three positive loci was measured by the genetic risk score (GRS), showing a significant relationship with the risk of obesity (Ptrend < 0.001). The OR of obesity increased to 21.38 (95% CI = 21.19–21.55) among the 10q11.22 deletion carriers who had meat-based diets, indicating prominent multiplicative interaction (MI) between deletions of 10q11.22 and preference for a meat-based diet. Simultaneous deletions of 5q13.2 and duplications of 6q14.1 had significant MI with a preference for salty foods. Our results suggested that CNVs may contribute to the genetic susceptibility of childhood obesity, and the CNV-diet interactions modulate the risk of obesity.Copy number variants (CNVs) have been implicated as an important genetic marker of obesity, and gene-environment interaction has been found to modulate risk of obesity. To evaluate the associations between CNVs and childhood obesity, as well as the interactions between CNVs and dietary behaviors, we recruited 534 obese children and 508 controls from six cities in China and six candidate CNVs were screened through published genome-wide studies (GWAS) on childhood obesity. We found three loci  to be significantly associated with obesity after false discovery rate (FDR) correction (all the  Obesity is a concerning public health issue within modern society, and childhood obesity has become a global epidemic . The preet al. [et al. also detected copy number changes at 10q11.22 in European children [Inheritance or genetic variations are crucial contributors to obesity, with high body mass index (BMI) heritability (0.47 to 0.90) estimated from twin studies . Copy nuet al. . Later, et al. . A meta-et al. . Two subet al. ,15. Anotet al. . Jarick children .et al. reported that the PRDX3 gene was associated with obesity in subjects with high dietary fat intake, but not in subjects with low dietary fat intake [Besides genetic factors, dietary behaviors play a vital role in obesity ,20. Recet intake . An intet intake . Such evThe aims of the present study were to examine the associations of candidate obesity-related common CNVs in obese Han Chinese children and further explore the biological interactions of candidate CNVs and dietary behaviors.The subjects were recruited from a cross-sectional study on metabolic syndrome of children and adolescents throughout six Chinese cities  in 2010. A total of 1042 unrelated individuals (534 obese children and 508 non-obese samples) aged 7–17 were finally included in the study. Subject recruitment has been described in detail elsewhere . The obeAnthropometric measurements and epidemiologic investigation has been described previously . In brieet al. [et al. were selected for this study [P values of under 0.005 from case-control discovery samples. Thirteen loci were sent to be designed via Multiplex AccuCopy™ Kit ; they were 11q11, 1p31.1, 4q32.1, 3q21.3, 4q25, 5q13.2, 15q13.2, 10q11.22(1), 2p22.1, 10q11.22(2), 17q21.31, 1q21.1 and 6q14.1. Six loci were successfully designed for the CNV assay in one panel  on childhood obesity compiled prior to December 2011; three GWASs and two aCGH studies were published ,14,16,27et al.  focused is study . Two CNVanel see .® assay, a technology of multiple competitive real-time Polymerase Chain Reaction (PCR) developed by Genesky BioTech  [One and a half milliliters fasting whole blood samples were collected and frozen at −40 °C for subsequent DNA extraction. The TOYOBO MagExtractor Genomic DNA Purification Kit  was used to extract DNA from whole blood. DNA concentration and purity were measured by Nano drop 2000 (Thermo Scientific) and DNA was stored at −80 °C. Qualified DNA was used to detect the copy number changes utilizing AccuCopy, China) . In briet-test for normally distributed variables, Mann-U Whitney test for non-normally distributed variables and χ2 test for categorical variables were utilized to examine the differences between obese and non-obese subjects. The standardized data of Chinese children was not available, so the WHO 2007 growth reference was used to calculate the age- and sex-specific BMI z-scores in order to exclude the effects of age and sex [P values of deletions or duplications for the risk of obesity were computed via logistic regression adjusted for gender and age, using a normal CNV state (two copies) as reference. The same analysis was done when using the suggested age and gender specific cut-off of BMI by the International Obesity Task Force (IOTF) to assess obesity status [p-values were further adjusted by false discovery rate (FDR) using R software (version 2.15.3). Covariance analysis was used to evaluate the BMI z-score and WHtR difference between different copy number states of the positive loci using sex and age as covariates. For multiple comparisons, the least significant difference (LSD) test was used. Genetic risk score (GRS) was calculated as the number of the CNV risk alleles of the three positive loci on obesity, and chi-square trend test was performed to evaluate the dose response association between the GRS and the risk of obesity.All statistical analyses were performed using SPSS version 19.0 . Participants with missing CNV genotype data were excluded from the analysis. Normality of distribution of continuous variables was evaluated by Kolmogorov-Smirnov test. The quantitative data were described as means ± standard deviations (SD) for normally distributed variables, and median (lower quartile–upper quartile) for non-normally distributed data. Independent  and sex . Odds ray status . The p-vversus normal, duplication vs. normal) between dietary behaviors were calculated separately. Next, interaction terms were added to a multivariate logistic regression model to examine effects of MI, adjusted for sex and age. The bootstrap method with 1000 re-sampling was used to estimate the odds ratio and a 95% confidence interval of the logistic regression to reduce small sample bias. AP (attributable proportion due to interaction) and its 95% CI were calculated to evaluate the proportion of the risk of obesity due to interactions between candidate CNV loci and dietary behaviors [A multiplicative model of interaction was used to assess interactions between candidate CNV loci and dietary behaviors. As the effects ranging from deletions to duplications of the same loci were not necessarily linear, the interactions of different CNV states . Approximately 23.5% of the obese children preferred a meat-based diet compared to 11.0% of the normal weight children (p <0.001). A significantly higher percentage of cases than controls preferred salty foods . No significant difference in preference for sweet food was observed. Subjects who preferred salty food and a meat-based diet had a significantly increased risk of obesity.Five obese and ten non-obese children failed in the genotyping assay and thus were excluded in the analysis. The clinical characteristics of the remaining 529 obese children and 498 non-obese children were summarized in p < 0.05). The significance persisted in all the three loci after multiple corrections by FDR. The deletion of 10q11.22 was closely associated with an increased risk of childhood obesity . Similar results were observed for 4q25 . In addition, the three CNV loci showed consistent results when the obese definition of the IOTF was applied: the deletions of 11q11 and 10q11.2 were significantly associated with obesity after FDR correction (both p < 0.05) and 4q25 showed marginal significance, with a p-value of 0.06 , and 11q11 showed marginal significance with the two indexes .Furthermore, the association analysis of the three positive loci showed consistent results on obesity-related index, BMI and WHtR . Deletiop for trend = 2.92 × 10−4) . The ORs of each group were calculated using the group with GRS equal to 0 as reference (OR = 1). The ORs of the subjects with GRS equal to 1, 2 and 3 increased to 1.16 (95% CI = 0.86–1.57), 4.13 (95% CI = 1.67–10.23) and 10.45 (95% CI = 1.33–82.25), respectively. Significant dose-response relationship was observed between GRS and the risk of obesity ( × 10−4) . The risThe duplications of 6q14.1 showed a marginal association with preference for sweet foods. No significant association was observed between other CNV loci and dietary behaviors .Interestingly, three CNV loci  showed significant MI with dietary behaviors , and the AP being 0.76 (95% CI = 0.46–1.06) b. MI betIn the present study, we comprehensively evaluated 6 obesity-related CNV loci in childhood obesity of Han Chinese. We confirmed that CNVs at 10q11.22, 4q25 and 11q11 were associated with childhood obesity. Furthermore, significant interactions between 10q11.22, 5q13.2 and 6q14.1 and diet preferences were observed.p = 9.1 × 10−4). One study on Chinese population also detected that deletions at PPYR1 were significantly associated with higher BMI [PPYR1 in 536 Chinese obese individuals and 263 healthy controls [PPYR1 is the most interesting gene in the region. PPYR1, also termed neuropeptide Y receptor Y4 (NPY4R), is one of the receptors of pancreatic polypeptide (PP). A series of studies have found that PP was associated with reduced food intake and lowered body weight [PPYR1; PPYR1 knockout mice had no response to PP injections [The deletions of 10q11.22 (CNV_4) demonstrated a highly significant association with the risk of childhood obesity in our study  with preference for sweet foods. This may be partly due to PP release stimulated by glucose consumption. These results may help explain how genetic factors responded to diet and are intricately involved in the pathophysiologic development of obesity, i.e., how gene-diet interactions operate on a cellular level.Interestingly, the interaction between deletion of 10q11.22 and dietary behaviors had prominent effects on the risk of obesity, especially the interaction with a preference for meat-based diets. The calculated AP for dietary pattern was almost 1, meaning that approximately 100% of the risk was due to the interaction. Although this might, to some extent, be due to the limited sample size of our study, it indicated strong interactivity between dietary patterns and 10q11.22 in obesity. Such strong interactions might be due to the regulation PP production. It has been well studied that protein and dietary fat can stimulate PP secretion, and glucose can also lead to a minor increase in PP levels . Regularp = 0.004). Little is known about the biological function of this region. There may reside some long-range regulators such as enhancers or repressors. CNVs may exert their effects on the causative gene that the distance can be as far as 1 Mb away [et al. found that the duplication of the region was associated with obesity, whereas little is known about the region itself [4q25 is a gene desert region, and deletions of CNV 4q25 conferred a highest risk of childhood obesity in our analysis . The cumulative effect is highly significant with a In conclusion, our results provide support for the role of CNVs in the risk of childhood obesity, which is modified by lifestyle factors. The present study successfully replicated three obesity-related loci 10q11.22, 4q25 and 11q11 in Han Chinese children. A strong cumulative effect of these loci on the risk of obesity was noted. Furthermore, we observed strong MI between CNVs and dietary behaviors. Our findings highlight the importance of the interplay between genotypes and lifestyle factors. The full elucidation of complex interactions between genes and lifestyle factors may help establish public guidelines for the general population and have great implications on public health systems worldwide.


To determine whether the plasma concentration of high sensitive Troponin T (TnThs) correlates with the initial echocardiographic ejection fraction (EF) in patients with sepsis. Analyze whether the TnThs acts as a biomarker and independent determinant factor of myocardial dysfunction in these patients.We performed a prospective observational study with a cohort of 60 septic patients admitted to the ICU. Demographic data, severity scales, organ failure and doses of noradrenalin were registered. TnThs analysis was performed at baseline and in the first 24 hours a transthoracic echocardiography was performed to assess the ejection fraction (Simpson), once a correct resuscitation had been performed. Patients were monitored until hospital discharge. The statistical analysis was aimed to show whether biomarker TnThs acts as an early myocardial dysfunction biomarker in patients with sepsis and if it is an independent determinant factor of myocardial dysfunction. A bivariate analysis was performed using non-parametric tests and multiple logistic regression with the aim of obtaining a model adjusted to severity. Statistical significance if p < 0.05.Of the 60 studied patients, 65% were men, with a mean age 63.9 ± 13.2 years. APACHE II was 16.8 ± 7.5 points, SAPS II 38.3 ± 15.7 points and an initial SOFA of 6.8 ± 2.8 points. Mortality to 28 days was 23.3%. The most frequent source of sepsis was abdominal (38.3%), followed by respiratory (23.3%). 36.7% of patients had initial myocardial dysfunction (EF < 50%) and TnThs values were positive (> 15 ng / L) in 76.6%.The correlation between the quantitative levels of initial TnThs and doses of noradrenaline was positive and statistically significant, with p = 0.0001. There was also a significant correlation, in this case negative, between the quantitative levels of initial TnThs and the initial EF (p = 0.04). The multiple logistic regression model adjusted for APACHE II showed that the TnThs  was an independent determinant of myocardial dysfunction in this model.The TnThs is a suitable biomarker for detecting myocardial dysfunction and correlates well with the initial EF and doses of noradrenalin. In a multiple logistic regression model adjusted by severity, TnThs behaves as an independent determinant factor of myocardial dysfunction in patients with sepsis.


Those prefectures were mainly located along two belts: one from northeast China to Sichuan province, the other from Shanghai to Guangxi province. Our study demonstrates the deterioration in urban air quality and its potential impacts on its surrounding areas in China. We hope that the results presented here will encourage different approaches to urbanization to mitigate the negative impact caused by urban air pollution, both in China and other rapidly developing countries.The negative impacts of rapid urbanization in developing countries have led to a deterioration in urban air quality, which brings increasing negative impact to its surrounding areas (e.g. in China). However, to date there has been rare quantitative estimation of the urban air pollution to its surrounding areas in China.We thus evaluated the impact of air pollution on the surrounding environment under rapid urbanization in Chinese prefectures during 1999 – 2011. We found that: (1) the urban environment generated increasing negative impact on the surrounding areas, and the PM To monitoring PM2.5 concentration changes, the monitoring networks have been well established in many developed countries, but fewer in developing countries which were suffering severe PM2.5 pollution72.5 concentrations were introduced for large-scale air quality analysis.China’s rapid urban and economic development over a short period has not only led to better living standard, but also caused severe environmental pollution, particularly air pollution, in urbanized regions12tter PM2. has beca2.5 concentration records suggest that PM2.5 concentrations are higher in many regions of China than in other countries, particularly in urban areas92.5 concentrations in Chinese cities, or the impact of urbanization on PM2.5 concentrations2.5 concentration data3http://www.gov.cn/zwgk/2013-09/12/content_2486773.htm) and to accomplish the new-type urbanization plan. Therefore, the objectives of this study were to examine the changes in PM2.5 concentration differences between urban and surrounding areas, and suggest better air quality controls to policy makers in China.Remote sensing and modeling derived PM2.5 concentration in the urban areas . The prefectural averaged 3 in 1999, but was increased to 4.09 μg/m3 in 2011. The amount of prefectures with PM6 in 2011.2 = 0.8864, P < 0.05). The trend with more 0.4 μg/m3•year was obtained at cities with more than 300 km2, however, the trend with less than 0.4 μg/m3•year was obtained at cities with less than 100 km2.Urban size influenced The spatial pattern of  to the  . Only 42ond belt .Urbanization can both positive and negative impact on rapid developing countries. Accelerating urbanization is considered important for economic development in China2.5 were also observed mainly along the east China plain area3Urbanization and its environmental impact experiencing different spatial patterns, suggested various urbanization and environmental protection policies should be considered and taken in different areas of China. China’s current urbanization has mainly occurred in eastern and central China, with less than half the nation’s land supporting more than 90% of the population152.5 concentration on the surrounding areas  products92.5 concentrations were estimated from the combination of MODIS and Multi-angle Imaging SpectroRadiometer (MISR) AOD with aerosol vertical profiles and scattering properties92.5 concentration dataset had a spatial resolution of 10 km as three years moving average from 1999 to 20112.5 concentration’s dynamichttp://fizz.phys.dal.ca/~atmos/martin/). We used a subset of the global PM2.5 concentration dataset that covered China from 1999 to 2011.The PMhttp://ngcc.sbsm.gov.cn/).Urban distribution with a spatial resolution of 1 km was used to identify urban from non-urban areas in 2000 and 20102.5 concentration in the urban/non-urban areas  on areas surrounding Chinese cities. Sci. Rep.5, 12467; doi: 10.1038/srep12467 (2015).


For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10−10). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available.The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1  and genetic score 2 . For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10 Accounting for 2% of all malignancies, kidney cancer has become one of the most important health problems worldwide, with an estimated 270,000 new cases and 116,000 deaths every year. [Besides the environmental risk factors , inherited risk has been considered as one of the most important risk factors of RCC. Risks of sporadic RCC will increase more than two folds if individuals have a first-degree relative with RCC. , 3 ThereIn this study, we evaluated whether genetic scores based on RCC risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risk of RCC in Chinese population.−8) was significantly associated with ccRCC in Chinese population (Table 2=0.58) which might bring duplication efforts to the model if we would include both of them.Baseline characteristics of the study population were summarized in Table on Table . Combinion Table . Two gen−13. Table −11). The likelihood of RCC for individual who had low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively . It remained significant when adjusting for age (P=1.49×10−18). Individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively  the relatively small sample size of the study might challenge the power of our statistics even we have significant association results. Larger studies are needed to provide external validation and further evaluation between genetic scores and RCC. (2) The cutoff values used in this study were subjective by just using <0.8, 0.8-1.2, ≥1.2 or quartiles. However, we believed that they would be easier to understand. A genetic score of 0.8 means the risk for RCC of an individual is below average population risks, while a genetic score of 1.2 means the risk for RCC is higher than average. Efforts should be devoted to evaluate the clinical application of genetic scores.In conclusion, Genetic score can reveal personal inherited risk of RCC, especially when family history is not available. Further investigation in large scale studies will be necessary to evaluate its potential application.All patients with ccRCC (346 cases) were recruited from our institute  from 2010 to 2014. A total of 1,130 health people from community populations in Shanghai were included as control group. The inclusion/exclusion criteria and the characteristics of the population from case and control groups were described reported in the previous studies. , 12 BrieIn the previous study, we evaluated all established or potential RCC risk-associated SNPs from published Caucasian/African-American based genome-wide association study (GWAS) in Chinese population (the SNPs which were significantly associated with ccRCC in the previous study were summarized in Table Blood Samples were collected from each study population. Whole-genome DNA was extracted using Puregene DNA Purification Kit (for case group) and Qiagen QIAamp DNA Blood Mini Kit (for control group). SNPs genotyping were performed using MassARRY iPLEX system  at Fudan University, Shanghai, China. Four subjects and four negative controls (water samples) were duplicated in the 384-well panel for quality control. All the control samples were previously performed GWAS by using Illumina Human OmniExpress Bead Chips. SNPs were imputed by using IMPUTE 2.2.2 program based on haplotype data from the 1000 Genomes Project CHB+JPT population , because these SNPs were not included in the GWAS chip. All assays were performed in blinded fashion.All the SNPs were evaluated for Hardy-Weinberg equilibrium. The association between SNPs and ccRCC were analyzed by logistic regression, or Fisher's exact test if the allele frequency of SNP was lower than 5%. The analysis was performed by using PLINK 1.09 with 2-tailed P values of 0.005 (after Bonferroni correction P=0.05/10).2, carrying one risk allele=OR, not carrying risk allele=1); (3) the relative risk to average risk level in Chinese population was calculated based on genotypic OR and genotype frequency (HapMap CHB population data); (3) the genetic score was calculated by multiplying relative risk of each SNPs based on different genotype of each individual : (1) the allelic OR for each SNP was obtained from our studies based on Chinese population; (2) the genotypic OR was calculated assuming a multiplicative model of allelic OR  and Mann-Whitney U-test  were used to evaluate the differences of variables between groups. Chi-square trend tests and ROC analyses were used to analyze the prediction ability of genetic scores. These statistic analyses were performed by using SPSS 19.0. In this part, two-tailed P values of 0.05 were considered significant.


In the absence of an internationally recognised biomarker of treatment response in HAM/TSP, the HAM/TSP clinial trial study group chose improvement of 10 meter time walk (TW) as the primary outcome measure for the HAMLET-P trial.To define the minimum change in TW required for an observed treatment effect to be detectable and important. To calculate the sample size required for 90% power to detect this difference.Prospectively collected TW (seconds/10m) of HAM/TSP patients from the four countries were submitted to two biostatisticians (Japan+UK). Analysis of covariance and log transformed TW were used.Matched TW data (baseline+6 months) were available for a total of 76 patients. Mean  TW were 23.46  at baseline, 24.85  at 6 months. Mean  log10m TW were 2.89  at baseline, 2.91  at 6 months. The estimated SD of log10m TW after adjustment for the baseline measurement was 0.26. With 30 participants/group, we have 90% power to detect a difference of ±0.21. This corresponds to a ratio of 0.81 or 1.23, so we could detect a decrease in time of 19% or an increase of 23%. With power 80% we could detect a difference of -15% or +18%.Prospectively collected longitudinal data on TW is useful in measuring inter- and intra- patient variability of this clinical efficacy marker. To power HAMLET-P at 90%, a minimum of 30 patients are needed in each arm, to be increased by 3-5 patients/arm to cover for 10-15% estimated trial drop-out rate.


Background. Little is known about precancerous cervical lesion (PCCL), the precursor of cervical cancer among Human Immunodeficiency (HIV) infected women in a postconflict setting of Northern Uganda. Objective. To establish factors associated with PCCL among HIV infected women above thirty years of age in a postconflict setting of Northern Uganda. Method. This retrospective cohort study used electronic data from 995 HIV-positive women that attended cervical cancer screening during June 2014 and December 2015. Data on social, sexual, obstetric, and gynecological factors was analyzed at 95% confidence level. Multivariate analysis determined factors independently associated with positive PCCL. Probability value less than 5% was considered significant. Results. Prevalence of PCCL was 3.0% : 2.0–4.3). A positive PCCL was significantly associated with absence of sexually transmitted diseases (STDs) during clinic visits : 0.09–0.64; P = 0.004) and first pregnancy before the age of 20 years . Conclusion. The prevalence of PCCL was low in the postconflict setting of Northern Uganda. HIV-positive women presenting with STDs and those with first pregnancy before the age of 20 years were at increased risk of PCCL. Cancer of the cervix is a leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected women . It usuaSeveral epidemiological studies linked PCCL to multiple sexual partners, inception of sex at early age, cigarette smoking, and nutritional deficiencies . MeanwhiCurrent evidence on risk factors for PCCL pertains to the general population of HIV-positive women from stable settings. The application of such findings to make conclusions and interventions among HIV-positive women in unstable settings and among HIV-positive women aged thirty years and above is limiting. In this study, we established factors associated with PCCL among HIV-positive women above thirty years of age attending cervical cancer screening in a postconflict setting of Northern Uganda.This was a retrospective cohort study that used secondary data collected from HIV-positive women attending cervical cancer screening at the AIDS (Acquired Immune Deficiency Syndrome) Support Organization (TASO), Gulu HIV Clinic .The study cohort comprised of HIV-positive women screened for cervical cancer between June 2014 and December 2015. During the screening, data are collected on sociodemographic, sexual, behavioral, obstetric, and sexually transmitted infections (STIs) using a standardized cervical cancer screening form of Uganda's Ministry of Health. In the HIV clinic, HIV-positive women 15 years and older consent to undergo pelvic examination using a sterile speculum by a trained nurse or midwife. The initial screening technique is Visual Inspection with Acetic Acid (VIA) reported as positive, negative, and uncertain for PCCL. All VIA positive cases undergo colposcopy to confirm PCCL.All cervical screening data are entered in EPIINFO (TM) version 3.4.7. We simply obtained these data, cleaned and exported to Stata version 12  for statistical analysis. We analyzed data on 995 HIV-positive women . The outWe stated sensitivity, specificity, PPV, and NPV with corresponding 95% confidence intervals (CI).We summarized numerical data in frequencies, percentages, means with standard deviations (SD), and medians with interquartile ranges (IQR). The prevalence of PCCL was determined by dividing the number of positive colposcopy tests by the entire sample size, expressed in percentage.t-test was used for testing association between the outcome variable and numerical independent variable. Chi-squared, Fisher's exact, and Student's t-test probability values  less than 20% were considered statistically significant for univariate analysis. Meanwhile, P values less than 5% at univariable analysis together with clinically relevant variables were considered statistically significant for multivariable analysis using binary logistic regression. Results of binary logistic regression were stated in odds ratios with 95% CI and P values.The association between the outcome variable and categorical independent variables was assessed using the Chi-squared test for larger cell counts  and Fisher's exact test for smaller cell counts (less than five). Student's Ethical approval to use the cervical cancer data was sought from the Ethics and Research Committee of TASO Gulu. All clients had written informed consent at enrollment into HIV chronic care. All TASO clients are identified by unique registration numbers to ensure anonymity, secrecy, privacy, and confidentiality of information.The mean age of the 995 women is 40.0 years (SD = 8.2). Among 741 women aged 30–44 years, 21 (2.8%) had PCCL and 720 (97.2%) had no PCCL. Among 222 women in the age group of 45–59 years, 215 (96.9%) had no PCCL and 7 (3.2%) had PCCL. For the age group of 60–70 years, out of 32 women, 30 (93.8%) had no PCCL and 2 (6.3%) had PCCL.Of 25 women that had their first sexual intercourse before start of menstruation, none (0.0%) had PCCL. 11 (1.8%) out of 622 women that had their first sexual intercourse after start of menstruation had PCCL and 611 (98.2%) had no PCCL. Of 881 women that had less than or equal to five lifetime sexual partners, 29 (3.3%) had PCCL while 852 (96.7%) had no PCCL. On the other hand, of 46 women that had more than five lifetime sexual partners, 1 (2.2%) had PCCL while 45 (97.8%) had no PCCL.859 women had less than or equal to five sexual partners preceding their clinic visit, of which 26 (3.0%) had PCCL and 833 (97.0%) had no PCCL. On the contrary, among eight women that had more than five sexual partners preceding the clinic visit, 1 (12.5%) had PCCL while 7 (87.5%) had no PCCL. Of 315 women that experienced first menstrual cycle before or at the age of 14 years, 7 (2.2%) had PCCL and 308 (97.8%) had no PCCL. Equally, among 372 women that experienced their first menstrual cycle after the age of 14 years, 7 (1.9%) had PCCL while 365 (%98.1) had no PCCL. Of 46 women that had menopause before the age of 55 years, only 1 (2.2%) had PCCL and 45 (97.8%) had no PCCL.Three women (100.0%) had menopause after the age of 55 years and all had no PCCL. 20 (3.7%) out of 545 women that had ever got pregnant for less or exactly five times had PCCL. In contrast, 10 (2.3%) out of 427 women that had ever got pregnant for more than five times had PCCL and the 417 (97.7%) had no PCCL. 26 (3.5%) out of 739 women that had less than or equal to five live births had PCCL and 713 (96.5%) had no PCCL. Four (1.8%) out of 224 women that had more than five live births had PCCL while 220 (98.2%) had no PCCL .63 (6.3%) out of 995 women tested positive for PCCL with VIA. By colposcopy, 28 out of the 63 cases  were confirmed as PCCL-positive cases. The sensitivity of the test was 93.3% (95% CI: 77.9–99.2), specificity was 96.4% (95% CI: 95.0–97.5), PPV was 44.3% (95% CI: 36.2–52.8), and NPV was 99.8% (99.2–99.9). The prevalence of PCCL was therefore 3.0% (95% CI: 2.0–4.3) .http://dx.doi.org/10.1155/2016/5473681). 111 (11.2%) reported vaginal itching, of which 5 (4.5%) had PCCL and 106 (95.5%) had no PCCL. 854 (85.2%) had no vaginal itching, of which 25 (2.9%) had PCCL and 829 (97.1%) had no PCCL. 48 (5.2%) reported pain during sexual intercourse or during urination, of which 1 (2.1%) had PCCL and 47 (97.9%) had no PCCL.Our study participants presented to the HIV clinic cervical cancer screening with sexually transmitted disease (STD) symptoms and concerns  that reported no pain during sex or urination, 28 (3.2%) had PCCL and 848 (96.8%) had no PCCL.P = 0.021), first pregnancy before or after the age of 20 years , and the mean parity  were significantly associated with PCCL. The average number of sexual partners in the previous month  and the number of lifetime sexual partners  were considered as clinically relevant variables for PCCL.In bivariate analysis, presenting to the HIV clinic with an STD  = 1; P = 0.027). On the other hand, women that had their first pregnancy before the age of 20 years were over two times more likely to have PCCL compared to women that had had their first pregnancy after the age of 20 years . Also, for every 1-unit increase in parity, the odds of PCCL reduced by 17% . In addition, for every 1-unit increase in the number of lifetime sexual partners, the odds of PCCL increased too .In univariable analysis, three factors  were statistically significantly associated with PCCL. Women that had no STD during HIV clinic visits were 65% less likely to have PCCL compared to those that had an STD (unadjusted odds ratio (uOR) = 0.35; 95% CI: 0.14–0.89; P = 0.004). Also, women that had their first pregnancy at or before the age of 20 years had lower adjusted odds of PCCL compared to those that had had their first pregnancy after the age of 20 years . Increase in parity , the number of sexual partners in the preceding month of clinic visit , and the number of lifetime sexual partners  were not associated with PCCL  and clinically relevant variables , multivariate analysis  indicateith PCCL .This study determined factors associated with PCCL among HIV-positive women attending chronic care at TASO Gulu. The prevalence of PCCL was 3.0% (95% CI: 2.0–4.2). Compared to previous studies , 14, thiIn this study, the prevalence of PCCL was 2.8% among HIV-positive women aged 30–44 years, 3.2% among 45–59-year-olds, and 6.3% among 60–70-year-olds. The prevalence of PCCL increased with increasing age. Old age is known to increase the risk of PCCL according to previous literature , 17. CerOur study indicated that women that had their first pregnancy before the age of 20 years were at increased risk of PCCL. This implies that early pregnancy and early sex is a risk factor for PCCL. Our result confirms the results of previous study in Spain and Columbia that found over fourfold higher risk of cervical cancer among women with history of early (before the age of 16 years) sexual intercourse . Sexual Women that presented with sexually transmitted diseases (STDs) syndromes such as lower abdominal pain and abnormal and foul smelling vaginal discharges at the HIV clinic were at increased risk of having PCCL. Abnormal vaginal discharge is not a known symptom or concern suggestive of PCCL other than occasional abnormal bleeding but is an important reason for seeking medical care . AbnormaLiterature indicates that as the number of children born to a women increases, the chances of developing cervical cancer increase too . In thisOur study is the first in Uganda to determine the magnitude of PCCL among HIV-positive women aged 30 years and older in a postconflict setting of Northern Uganda. It highlighted low prevalence of PCCL. The main factors associated with this prevalence were having STDs and first pregnancy before the age of 20 years. We recommend that current HIV prevention interventions should focus on reducing early sexual practices among HIV-positive adolescents to protect them from PCCL. In clinical practice, healthcare providers  should routinely evaluate women presenting with STDs for PCCL or cervical cancer.Although the present study is limited by lack of data on ART and socioeconomic variables, it has set the benchmark for future research on PCCL among HIV-positive older women (aged thirty years and older). The interpretations of this study should hence recognize these limitations.Symptoms and concerns reported by study participants during cervical cancer screening.


Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth's grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients n = 28 (60.9%) were well differentiated, n = 15 (32.6%) were moderately differentiated, and only n = 3 (6.5%) were poorly differentiated. All n = 46 cases of OSCC were positive for EP3 receptor antibody, n = 14 (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, n = 17 (37%) cases showed moderate intensity, and n = 15 (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study. Globally, oral cancer is the eighth most common cause of cancer-related deaths, but in spite of this fact most of the people are unaware of its presence . SquamouOSCC arises from various molecular pathways that progress from the mutual effects of susceptibility and vulnerability to environmental carcinogens. These carcinogens are snuff, chemical carcinogens, alcohol, microorganisms, and ultraviolet or ionizing radiation. Damage to genes and chromosomes may occur due to prolonged exposure to these carcinogens .For decades, no change in mortality rate has been observed. Even with advancements in surgery and radiotherapy, mortality still is very high with a 5-year survival rate of only 50% . CurrentAmong the prostanoids, the E-type PGs, particularly PGE2 derived from arachidonic acid, are produced in the body. PGE2 is found in most animal species and exhibits the multipurpose actions. There are four different receptors labelled EP1, EP2, EP3, and EP4 for the E-type PGs . The proμm thick, paraffin embedded sections were cut and mounted on glass slides and sections were stained with haematoxylin and eosin stain and examined by light microscope. Anneroth's histological grading system had been used to grade OSCC cases on H&E staining [After informed consent, biopsy specimens from 46 patients having undergone various diagnostic and/or surgical resection procedures for OSCC were acquired from Maxillofacial Surgical Department of NID, Multan. Sociodemographic information  was obtained along with relevant clinical, laboratory, and radiological information. To confirm the diagnosis 5 staining .μm thick sections were cut from all specimens and mounted on positively charged glass slides. Sections were deparaffinized in xylene and rehydrated in graded ethyl alcohol, followed by immersion in citrate buffer solution of pH 6.0, and were put in the microwave oven before staining procedures. For immunostaining, Universal Kit (Lab Vision) employing the streptavidin biotin system was used to carry out the peroxidase-antiperoxidase method of immunohistochemistry staining. Sections were then incubated with a primary polyclonal anti-EP3 receptor antibody  and DAB chromogen was applied to the sections followed by counterstaining with haematoxylin [About 4 atoxylin .t-test. A difference of P < 0.05 was considered to be significant. The present study was certified by the Ethical Review Committee and Advanced Studies and Research Board of University of Health Sciences Lahore.The intensity and proportion of positive tumour cells of the EP3 immunohistochemical staining were evaluated using a light microscope. The intensity of cytoplasmic staining was graded from 0 to 3  and the tumour was also scored according to the proportion of positive tumour cells  , 16. Then = 36). In the present study male to female ratio was found to be 1.4 : 1  while in females the age range was 25 to 95 years (mean age 51.68 ± 15.61). This data shows that age of incidence was similar in both genders; however, most of the patients were in the range of 40 to 70 years of age ( 1.4 : 1 .n = 9 (47%) cases were located on tongue while in males only n = 4 (14.8%) cases were located on tongue. When t-test was applied to observe the statistical relation it was significant (P = 0.01)  cases, fungating mass in 8 (17.4%) cases, and plaque-like lesion in 3 (6.5%) cases. Regarding the site of involvement of oral cavity, the occurrence of OSCC was found significantly higher on buccal mucosa where 23 (50%) cases were present. There were 13 (28.3%) cases that involved the tongue . When site of specimen was corelated with gender, the most number of cases in both genders were located on buccal mucosa but in females  = 0.01) .A total of 60.9% were well differentiated (WD) Figures , 32.6% wAmong 46 cases of OSCC, 31 cases had attached nontumorous epithelium. Out of these 31 cases of OSCC with attached epithelium, 11 23.9%) had strong intensity (Score +3) of EP3 antibody staining, 17 (37%) had moderate intensity (Score +2) of antibody staining, and only 3 6.5%) cases had weak intensity (Score +1) of EP3 antibody staining  cases had strong intensity (+3) of anti-EP3 antibody staining in tumour tissue, 17 (37%) cases showed moderate intensity (+2), and 15 (32.6%) cases showed weak intensity (+1) .P = 0.486). The statistical relation between intensity of antibody staining and histological grade of OSCC was insignificant (n = 3 (6.5%) while the number of cases showing weak intensity in tumorous tissue was n = 15 (32.6%) in the present study .The number of cases showing weak intensity EP3 antibody in adjacent epithelium was  Figures  and 16. As already stated above that a total of 31 cases had attached nontumorous epithelium, 11 (23.9%) cases had 76–100% (Score +4) positive epithelial cells for EP3 antibody, 11 (23.9%) cases had 51–75% (Score +3) positive epithelial cells, 26–50% (Score +2) epithelial cells were positive in 8 (17.4%) cases, and only 1 (2.2%) had 11–25% (Score +1) positive epithelial cells.Among 46 cases of OSCC, 15 (32.6%) cases had 76–100% (Score +4) positive tumour cells for EP3 antibody, 21 (45.7%) cases had 51–75% (Score +3) positive tumour cells, and 10 (21.7%) cases had 26–50% (Score +2) positive tumour cells .t-test to observe the statistical relation between histological grade and proportion of positive tumour cells for EP3 antibody, it was found to be insignificant (P = 0.843). It was also insignificant when it was applied to find the relation between proportion of positive adjacent epithelial and tumour cells for EP3 antibody (P = 0.213).When we applied P = 0.486). A total of 31 cases had attached nontumorous epithelium, 54.8% showing (+2) intensity score, 35.4% cases showing (+4) proportion score for EP3 antibody  and +3 (45.6%); similarly 46.6% of MD exhibited +1 and +3, while 66% of each of PD tumours demonstrates +2 and +3 of intensity and proportion score, respectively. So most cases of well differentiated OSCC (71%) showed moderate to strong intensity of staining  cases were present followed by 13 (28.3%) cases that involved the tongue . A study by Tahir et al. on OSCC reported results which were similar to the present study regarding the site of involvement. The most frequent location of OSCC in that study was also buccal mucosa 32.4%) (slightly higher in the present study which was 50%) followed by tongue (21.6%); this value is also comparable to the present study (28.3%) . Many st% (slightP = 0.049). This is comparable to another study carried out in Pakistan in the recent past in which the most common clinical presentation of OSCC was a nonhealing indurated ulcer (51.4%) and it was also significantly common on the buccal mucosa (P = 0.001) [Tumours can grow to a size that exceeds its blood supply, leading to tumour necrosis and ulceration. In the present study the most frequent presenting symptom was ulcerating lesion on buccal mucosa (= 0.001) . Another= 0.001) .P = 0.042). This finding suggests that as the squamous epithelial cell becomes less differentiated it loses its ability to express prostanoid EP3 receptors. This was also observed during the histological examination of OSCC cases stained with EP3 antibody: as the squamous cell is more differentiated it shows more intense staining and as the cell gradually loses its differentiation, it also loses its property to express prostanoid EP3 receptors and the intensity of staining with EP3 antibody becomes weak. When we applied Fisher's exact test to observe the statistical relation between intensity of antibody staining and histological grade of OSCC, it was found to be insignificant (P = 0.486), because overall intensity of staining was randomly distributed among different grades of OSCC.In the current study out of 46 cases, lymphovascular invasion was found in 33 (71.7%) while 13 cases showed no lymphovascular invasion. In another study carried out in Japan Nomura et al. reported 57.5% lymphovascular invasion in cases of OSCC, which is slightly lower than the present study . In the A similar study carried out in Brazil by Ryott et al. reported that 94% of cases of OSCC were positive for EP3 receptor antibody and most of the cases in that study were of moderately differentiated histological grade . While iKnowledge of the molecular mechanisms underlying dysregulated growth and progression of OSCC may provide a rational basis for exploring new treatment modalities and can prove valuable in the development of new molecular therapies and targeting tools. Since PGE2 is likely to pile up at high levels in the tumour microenvironment and can be produced by the action of the COX-2 expressed in both cancer and stromal cells , PGE2 maTo our knowledge no such documented immunohistochemical study elaborating the role of prostanoid receptor EP3 in OSCC has been carried in Pakistan or any other South Asian country so there is a lack of data comparison in this aspect. Further studies on large sample size are now needed to elucidate the underlying molecular and genetic mechanisms to assess the tumour related effects of PGE2 and its receptors in vivo. This area of future research undoubtedly will further improve our understanding of carcinogenesis of OSCC and the role played by EP3 receptors and prostaglandin E2.Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors . However


Vaccine preventable diseases account for about 17% of deaths among children below five years in Kenya. Immunization is one the most cost-effective ways of reducing child mortality and morbidity worldwide. In Kenya, national full vaccination coverage today stands at above 80%. However there continue to be pockets of low full vaccination coverage like the catchment area of Alupe Sub-District Hospital which pose a threat to the rest of the country.This was a case-control study at Alupe Sub-District Hospital, Western Kenya. Sixty one (61) cases and 122 controls were sampled from the facility maternal and child health register by systematic random sampling and traced to their households. Cases were defined as children 12-23 months resident in Kenya who received at least one infant vaccine at the facility but were not fully vaccinated at the time of the study, while controls were children 12-23 months who were fully vaccinated by the time of the study. Pretested structured questionnaires were used for data collection. Data entry and analysis was done using Epi-Info 3.5.4 statistical software.Independent determinants of infant vaccination completion were the child's age < 18 months (AOR 4.2(1.8-9.6), p < 0.01), maternal age < 25 years (AOR 2.5(1.1-5.0), p = 0.03), maternal tetanus toxoid vaccination status < 2 TT doses (AOR 2.5(1.2-5.4), p < 0.02) and late receipt of BCG [AOR 3.2(1.4-7.3), p = 0.005).Strategies to increase full vaccination should target young mothers especially during antenatal period. In Africa, the mortality rate in children less than 5 years is 119/1000 live births and in Kenya it is 74/1000 live births . The couThe study was conducted at Alupe Sub district hospital in Alupe division of Teso South sub-county, Busia County. The division serves as the main catchment area of Alupe Sub-District Hospital within Kenya. However, the facility also serves the neighbouring Amukura division in Teso North sub county, Busia Sub County in Kenya and the neighbouring Busia district in Uganda. The hospital is a level 4 facility with a catchment population of 40,000. It offers both out-patient and in-patient services. It is currently linked to two community health units. The population served is multi-ethnic though Teso is the predominant ethnic group. Most people are Christians. The majority of the population lives below the national poverty line of KShs 3000 per month. Teso South is a border district with a poverty rate above 60% compared to the national average of 45.9%. National poverty line for Kenya is $ 1.25 per person per day at 2005 purchasing power parity. Literacy rate as per Kenya Integrated Household Budget Survey (2005/06) was 76% with males at 84.2% and females at 68.1%. The predominant religion is Christianity, though Islam is also present as are traditional African religions. The sex ratio is 98 males for 100 females. Children 0-14 years account for 47.5% of the population. Orphan hood was estimated at 10.2% for either one or both parents. 45.9% of the population lives more than 5 kilometers away from the nearest health facility. The average household size is 5.9 members. More than half (57%) of household heads are married in monogamous unions, 23% in polygamous unions, 15% are widowed and 0.3% has never married. Two thirds (66.5%) of households were male led and 33.5% female led. Latrine coverage is above 99% although more than 58.2% of households share latrines. More than 60% of households have access to safe drinking water although about half have to walk more than 30 minutes to access it . Busia CStudy population: children who received at least one infant vaccine at Alupe SDH during the period 1st September 2011 to 31st August 2012 were studied.Study design: a 1:2 un-matched case-control study design was employed. Two comparison groups, cases and controls, were selected based on a predefined outcome case definition. Two controls were selected for each case to increase the power of the study. Different exposure variables were analyzed against outcome and measures of association were computed to determine significant determinants of full vaccination status in children 12-23 months resident in Kenya that had received at least one infant vaccine at Alupe SDH. The age range was chosen in line with WHO recommendations for immunization coverage surveys for countries where the final primary vaccination was measles at 9 months , likely to have to have younger fathers [OR 0.5(0.3-1.0)p = 0.04] and younger mothers [OR 0.4(0.2-0.8)p = 0.01]. However they were similar with respect to card availability [OR 0.7(0.1-4.6)], sex [OR 1.3(0.7-2.5)p = 0.43] and birth order .Cases were similar to controls in respect of all household and socioeconomic determinants of immunization reported in other studies , Table 3Delayed receipt of birth OPV and BCG were the only significant access factors associated with full immunization coverage . DistancThe statistically significant health system factors/indicators were delayed receipt of OPV3 (OR 3.0(1.5-6.3) p = 0.02) and failure by the mother to receive (= > ) 2 doses of antenatal tetanus toxoid (OR 3.2(1.6-6.5) < 0.01’> p < 0.01) . There wVariables with p = < 0.1 from bivariate analysis included in the model were child age group, maternal age group, paternal marital status, timely birth OPV, timely BCG, timely OPV3, (= > ) 2 doses of maternal tetanus toxoid, receipt of immunization IEC from CHWs and receipt of immunization IEC from friends. Only four factors remained statistically significant after unconditional logistic regression as shown in .Younger children were less likely to be fully immunized at 12 months probably reflecting fewer chances for immunization. This could also arise due to a recent period of poor immunization services such as healthcare workers strikes as occurred in Kenya in November-December 2013 , 15. TheHealth system utilization was a significant determinant of full immunization as indicated by age-appropriate coverage with OPV 3, DPT 3 and measles. Owino and colleaguesworking in a slum area in Nairobi, Kenya found that health system utilization remained low in spite of excellent access to immunization services . DeliverChildren resident in Uganda were not included in the study due to administrative reasons. This could have introduced information bias. Case findings efforts of the present study traced 38/61(62%) from the original sample and the control finding efforts traced 85/122(70%). Through key informant interviews with the community leaders, the missed children were noted to reside on the Ugandan side of the border. It was noted also that the parents of these children register them as Kenyan residents because the health facility charges non-Kenyan residents more to access charged services. This unexpectedly high number of non-residents may have biased our study. This is a special population that needs study.The main determinants of full immunization were child's age (12-17 months), maternal age (= < 25 years), timely receipt of birth OPV and receipt of at least 2 doses of neonatal tetanus toxoid by the mother. Physical distance, socioeconomic and household factors were not significant determinants of full vaccination as reported in many studies in similar settings. Strategies to increase full immunization should aim at increasing the frequency of ANC attendance to at least twice per pregnancy, ensuring comprehensive IEC to the whole community with special focus to younger mothers, early initiation of the vaccination schedule and improving health system performance. CHWs and peer education through friends may be an important addition to traditional modes of immunization IEC for mothers.


Background: Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis.Objectives: The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals.Materials and Methods: In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida. Morphology on cornmeal agar, germ tube formation and growth at 45°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method.Results: In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of ≤8 μg/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at ≥8 μg/mL.Conclusions: This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards. The colonization of Candida species  and resistance to routine used antifungals among hospitalized patients in ICUs and NICUs can be a challenge for clinicians and patients. Candida species are the commonest fungal infections agents and several studies showed that there are an increasing in candidiasis during the last several decades (Candida species in urinary system (candiduria) is one of the most important challenges for patients, clinicians and laboratory workers. Candiduria is a common finding in patients with multiple predisposing factors such as, diabetes mellitus, indwelling urinary catheters, antimicrobials and corticosteroids users  than terms (10%). decades -3. In ad decades . The preds users -9. In adds users -12. Physds users ,13. Colota et al  have belCandida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were increased during 2-3 last decades  were calculated.In the present study 298 specimens including; 98 blood, 100 urines and 100 swabs from oral cavity were taken from infants and children hospitalized in NICUs and ICUs, Aboozar, Sina and Imam Khomeini hospitals, Ahvaz Jundishapur University of Medical Sciences. Two to 5 mL of venous blood were sampled and injected into blood culture media . All cultured media were incubated at 37ºC for 1 week and examined daily. After 3, 5 and 7 days, 10 µL of culture media were transferred to CHROMagar Candida  and incubated at 37°C for 2-3 days. All media were examined for colored colonies of C. albicans, C. glabrata, and C. tropicalis were produced green, pink and blue colored colonies, respectively. In addition morphology on cornmeal agar  supplemented with 1% Tween 80, germ tube formation and growth at 45°C were confirmed isolates. All isolated strains subcultured on slants of Sabouraud dextrose agar, SDA  and stored at room temperature until use.Initial detection was done according to the coloration colonies on CHROMagar Candida culture medium. In the present study, amphotericin B, fluconazole and terbinafine antifungals were used for the susceptibility tests using microdilution method according to Clinical and Laboratory Standards Institute (CLSI) protocol .The research followed the tenets of the Declaration of Helsinki. Informed consents were obtained. All patients took part in this study voluntary. The research was approved by ethical committee of Ahvaz Jundishapur University of Medical Sciences (ethic code: ajums.REC.1392.172).In the present study the frequency of candiduria and theirs causative agents among both case and control were calculated and tabulated.All data were analyzed by SPSS 15 . Values were shown as the percent frequency.Candida species including; 15 (44.1%) cases males and 19 (55.9%) cases females. As C. albicans 24 (61.5%) followed by Candida species 7 (18%), C. glabrata 5 (12.9%), and C. tropicalis 3 (7.6%). Our study shows that 18 (46.1%) of samples yielded more than 50 colonies per each swab  males and 9 (42.9%) females  followed by C. glabrata 5 (20%), Candida species 3 (12%), and C. tropicalis 1 (4%). Polymicrobial growth in urine cultures was identified in three cases. C. albicans , followed by C. glabrata , C. tropicalis  and Candida species .Our study shows that 21% of urines samples were yielded  females . TotallyIn the present study all blood cultures were negative for fungal growth.Candida species including C. albicans (40 isolates), C. glabrata (10 isolates), C. tropicalis (4 isolates) and Candida species (10 isolates) were examined against 3 systemic antifungal drugs . Amphotericine B were inhibited the growth of tested isolates at the rage of 0.5 – ≥8 µg/mL. The most of the isolates (32.8%) had MIC = 4 µg/mL, whereas MIC for only 9 (14.1%) of isolates was more than 8 µg/mL  of were sensitive to antifungal at the concentration of 0.0625 µg/mL. Our results indicated that both non-albicans species, C. glabrata and C. tropicalis isolates were more resistant to fluconazole than C. albicans.The range of MICs to fluconazole of the 64 isolates was from 0.03125 to 64 μg/mL . In addiCandida, especially non-albicans species. As shown in Our results described that terbinafine has no valuable effect against different species of Candida colonization, 57.5% and 71.4% was reported in ICU patients by Jain et al  was the most commonly isolated organism in candiduric patients in ICU and NICU followed by C. glabrata (20%), C. tropicalis (4%) and Candida species (12%). Our results agreed with Said et al  was observed  were sensitive to fluconazole at the concentration of ≤8 μg/mL, whereas 14 (21.9%) of isolates had a MIC ≥64 μg/mL and dose dependent (16-32 μg/mL) were only detected at 5 (7.8%) isolates. The MIC 50 and MIC 90 of these isolates were 0.25 and 0.0625 μg/mL, respectively. Similar to previous reports, resistance to fluconazole was found among non-albicans species such as C. glabrata and C. tropicalis . As a results, hospitalized patients in critical wards need to major attention for a better control for infections. On the other hand, due to the different susceptibility antifungals results against Candida species, the present study showed the need to identify candida recovered from candiduria.It is concluded that In the present study only hospitalized neonates and children in ICUs and NICUs were sampled and all obtained data correlated to these groups of patients. In addition, the duration of stay in both wards in hospital was ignored, as a results the sampled patients have different length of hospital stay.We are thankful Jundishapur Infectious and Tropical Diseases Research Centre for supporting this study.AZM developed the original idea and the protocol, and edited final manuscript, and is guarantor. ARM contributed to the development of the protocol and edited draft manuscript. MN contributed to the isolation, identification and susceptibility tests and data analysis. MT and SM contributed to present patients for sampling. All authors read and signed final draft.The authors declared no competing interests.This study was an MSc thesis (Mojgan Navid) supported by a grant (No. 92133) from the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.


GY reached 5.6 and 5.8 t/ha under WW in the LPSpop and the DTPpop, respectively. Under DS, grain yield was reduced by 65% (LPSpop) to 59% (DTPpop) relative to WW. GY was strongly associated with the normalized vegetative index  across environmental conditions and with an early flowering under drought stressed conditions (r ranging from -0.18 to -0.25) indicative of the importance of early vigor and drought escape for GY. Out of the 105 detected QTL, 53 were overdominant indicative of strong heterosis. For 14 out of 18 detected vigor QTL, as well as for eight flowering time QTL the trait increasing allele was derived from CML491. Collocations of early vigor QTL with QTL for stay green , the number of ears per plant  and GY , reinforce the importance of the observed correlations. LOD scores for early vigor QTL in these bins ranged from 2.2 to 11.25 explaining 4.6 (additivity: +0.28) to 19.9% (additivity: +0.49) of the observed phenotypic variance. A strong flowering QTL was detected in bin 2.06 across populations and environmental conditions explaining 26–31.3% of the observed phenotypic variation . Improving drought tolerance while at the same time maintaining yield potential could be achieved by combining alleles conferring early vigor from the recurrent parent with alleles advancing flowering from the donor. Additionally bin 8.06 (DTPpop) harbored a QTL for GY under WW (additivity: 0.27 t/ha) and DS (additivity: 0.58 t/ha). R2 ranged from 0  to 26.54%  for NDVI, 18.6  to 42.45%  for anthesis and from 0  to 24.83%  for GY. Lines out-yielding the best check by 32.5%  to 60%  for all population-by-irrigation treatment combination  identified are immediately available for the use by breeders.We aimed to identify quantitative trait loci (QTL) for secondary traits related to grain yield (GY) in two BC On a global scale more than 800 million people suffer from energy and/or protein deficiencies. As maize accounts for a high percentage of total cereal production, the successful and continuous production of maize is key to global food security . DroughtIn order to cope with anticipated climate change it is indispensable to develop drought tolerant maize. To cope with dry environmental conditions plants have developed different strategies : escape In order to maintain grain yield and selection gains high in the future it is necessary to identify new secondary traits associated with grain yield. A desirable secondary trait should be genetically correlated with grain yield, exhibit adequate genetic variability, record moderate to high heritability, easy and economical to measure in the field, lend itself for reliable assessments with individual plants or in small plots and have no yield penalty in non-stressed environments , 17. TwoEarly vigor is especially important since it was shown  that witMarker assisted selection using QTL has the potential to increase the efficiency of traditional breeding strategies for improvement of varieties . The resAs a result of cost and technical feasibility many studies carried out in the past 5 years have rarely used more than several hundred markers molecular markers (SNPs). As a result the confidence interval surrounding a QTL is usually large, making it difficult to precisely locate a QTLs position or use in marker assisted selection. New technologies like next generation sequencing have made the fast, low cost and reliable identification of thousands of molecular markers possible. A next-generation molecular marker discovery approach called genotyping by sequencing (GBS), has been proposed to increase the availability of thousands of SNP molecular markers evenly distributed throughout the genome , 34. Usi1F2:3 backcross QTL populations (ABQTL), which were developed by crossing an elite line (CML491) with two advanced donors for drought tolerance [Many studies carried out in the past have limited value for breeding for various reasons: Evaluation of recombinant inbred lines  with little predictive value of testcross performance; use of a limited number of populations not allowing the validation of QTL across genetic backgrounds; use of marker densities too low to map QTL with a sufficiently high genetic resolution; strong focus on only grain yield under drought, thereby neglecting secondary traits. In the current study, we propose to address all of these points. We used two BColerance , testcroolerance . The useolerance , enablin1F2:3 populations under well-watered and drought stressed conditions.The objectives of the current study were to identify i) secondary traits associated with grain yield; ii) QTL for secondary traits and grain yield in two related BCAll trials of this study were carried out in agreement with landowners  owning the land used for these trials. Crop management (agronomy) did not have any adverse effects on the natural environment. Crop management treatment (well-watered vs drought stressed) did not have any adverse effect on land outside the trial area.1F2:3 populations, LPSpop and DTPpop, were developed with two drought tolerant lines DTPWC9-F104-5-4-1-1-B-B (DTPWC9F104) and La Posta Sequia C7-F64-2-6-2-1-B-B (LPSC7F64), respectively. Inbred line DTPWC9F104 was derived from Family 104 of the Drought Tolerant Population White (DTPW) Cycle 9, a tropical population developed at CIMMYT. DTPW consists of germplasm coming from Corn Belt experimental hybrids and unimproved landraces which performed well under drought conditions at altitudes below 1800 meters. The first step was the formation of DTP1 which consisted of 14 drought tolerant sources. Four cycles of half sib recurrent selection were made under drought stressed conditions. The DTP1C5 population was crossed with 25 other drought-tolerant sources to form DTP2. From cycle 0 to 3, improvement was carried out using half sib recurrent selection without drought performance evaluation, from cycle 4 to 9, using full sib recurrent selection under drought stressed conditions. Selection for white kernel was made in cycles 8 and 9 [Two connected BC 8 and 9 . DiffereThe second inbred line donor, LPSC7F64, is traced to the La Posta Sequia Population. The La Posta Sequia Population is a white dent, Tuxpeño-related synthetic, well adapted to the lowland tropics. Full sib recurrent selection was carried out under drought conditions from cycle 0 to cycle 7.http://apps.cimmyt.org). 175 and 220 BC1F2:3families were developed from DTPWC9F104 and LPSC7F64, respectively.The recurrent parent CML491, is an elite inbred line which is used as male in composition of three way hybrids released by CIMMYT. CML491 is a late tropical white, quality protein maize , dent inhttp://apps.cimmyt.org). Hybrids CML312/CML444, SC-Malawi/CML444 and SC-Malawi/H16 were included in both trials as reference hybrids. CML444 and H16 are lines widely used in hybrids deployed in drought prone areas in sub-Saharan Africa.CML503 was used as the tester. CML503 is a lowland tropical, late/intermediate, white dent inbred line belonging to heterotic group B which has a good specific combining ability with CML491 , were conducted in Mexico during the winter cycle of 2012, 2013 and 2014. Experiments were carried out in Autlan , Iguala , Obregon , Tlatizapan  and Agua Fria .2. Plots were hand-planted with two seeds per hill and thinned to one plant per hill three weeks after planting. Trials were drip-irrigated. Fertilizers, insecticides and herbicides were applied as needed.For each environment, the experimental design was an alpha-lattice  replicated twice in each environment at a block size of 5. Plots were 4.5 m long and 1 row wide at a row spacing of 0.75 m and an interplant spacing of 0.2 m resulting in a planting density of 6.66 plants/m2 was applied five days after the mean male flowering date of each trial to ensure proper grain filling. Four environments TL12A, IG14A, TL14A and AF14A were used as well-watered environments during which evapotranspirated water was fully replaced through weekly irrigations. Soil moisture content was measured at 10, 20, 30, 40, 60 and 100 cm soil depth three times weekly using Delta-t PR2/6 soil moisture probes  to schedule irrigations in the drought stress treatment.Drought stress was induced in TL13A, IG13A, AUT13A, OB13A, IG14A and TL14A. Water deficit was induced by withholding irrigation two weeks (~190 GDD) before flowering. An additional irrigation of 20 l/ mRNIR is the reflectance of near infrared wavelength, and RRed is the reflectance of red wavelength. NDVI illustrates the part of red wavelength which is absorbed by the plant.A set of traits have been measured for each plot, throughout the cropping cycle at different stages of development. Two, four, five and six weeks after planting the normalized differential vegetative index (NDVI) was measured using an RT-505 Greenseeker . NDVI measurements were taken by running the sensor in the middle of each plot at a height of 80 cm above the canopy. NDVI was calculated according to the following equation:At flowering, anthesis (AD) and silking date (SD) were recorded when 50% of plants within a plot were shedding pollen, and growing silks respectively. The anthesis silking interval (ASI) was calculated as the difference between male and female flowering. Four and six weeks after flowering senescence was measured visually using a scale ranging from 1 (no senescence) to 9 (complete senescence) to approximate stay green. The area under the curve (AUC) for NDVI and senescence was calculated by integrating a polynomial function of second degree fitted to individual measurements taken before (for NDVI) or after flowering (for senescence). Grain yield (GY) was calculated based on dry shelled grain yield and is reported at 12% moisture.hmlk is the trait value of the hth genotype  for the lth environment , the mth replication (m = 2); μ the overall mean, ah the main effect of the genotype, Eml the effect of the environment, ahEml the genotype-by-environment interaction, r(Eml) the replication within environment effect and r(Eml)δk the effect of blocks within replicates within environments and the random error term εmhlk. All factors were set as random factors. Best linear unbiased predictors (BLUP) of genotypes, variance components, and broad sense heritability were obtained. Since physiological mechanisms conveying grain yield are expected to be different under well-watered and drought stressed treatments, data for both irrigation treatments were analyzed separately.The mixed effect linear model used for the analysis of phenotypic data measured in multilocation trials was:Variance components were estimated by restricted maximum likelihood (REML) and heritability as the relationship between genetic and phenotypic variance, according to the formula:y is the vector of the response variable, G the matrix of variance covariance of the random effects, Z′ the design matrix for random effects in the model, V estimated variance of y, 1 a vector of ones and μ the overall mean, the only fixed parameter in the model. For grain yield, anthesis date was included as covariate in the model. Correlations were calculated using BLUPs of the different genotypes using a linear fixed model. Genetic correlations between traits were estimated with a method described previously [BLUPs for genotypes effects are shrinkage predictors that were obtained as:eviously .www.panzea.org). This collection includes genotypes of more than 60,000 maize samples. In this study, we focused on the subset of two bi-parental populations, and imputed GBS data was used for further linkage map construction and QTL mapping analyses. Initially, 955,690 SNPs evenly distributed on maize chromosomes were called for each line; 955,120 of them were assigned to chromosomes 1–10, and 570 of them could not be anchored to any of the 10 maize chromosomes. Saturated linkage maps were constructed in QTL IciMapping version 3.2 for each of the bi-parental populations for further QTL mapping analyses, 1,266 and 1,457 SNPs were finally filtered and selected to construct the linkage map in DTPpop and LPSpop, respectively (methods on selecting reliable SNPs and constructing linkage map haven’t been published yet). In the DTPpop, the total length of the linkage map was 1956.92 cM with an average marker density of 1.55 cM. In the LPSpop, the total length of the linkage map was 1813.78 cM with an average marker density of 1.24 cM.For all the maize testcrosses phenotyped in this study, leaf samples bulked from 12 plants of each line were used for DNA extraction with a CTAB procedure , 40. DNA2 represent the total phenotypic variance explained by all QTL detected for individual traits.Inclusive composite interval mapping was used in ICIMv3.2 . 214 and2 = 0.52) and from 5.32 to 6.43 t/ha in the DTPpop  and the LPSpop (h2 = 0.36), respectively. Flowering time reflected in the IQR for days to silking ranged from 84.78 to 87.68 in DTPpop (h2 = 0.85) and 85.51 to 88.92 in the LPSpop (h2 = 0.52) population. Flowering was delayed by 7.92 and 3.81 days under drought stressed conditions compared to well-watered conditions in the DTPpop (h2 = 0.68) and the LPSpop (h2 = 0.68), respectively. Under well-watered conditions the ASI was generally longer in the DTPpop compared to the LPSpop as indicated by an IQR ranging from 1.38 to 1.83 d for the DTPpop (h2 = 0.45) compared to -0.4 to -0.25 d for the LPSpop (h2 = 0.11). Under drought stressed conditions the differences between populations were not as significant in the DTPpop (h2 = 0.35) relative to the LPSpop (h2 = 0.5) since IQR for ASI ranged from 4.58 to 4.82 d in the DTPpop and from 3.13 to 3.41 d for the LPSpop. The DTPpop also showed greater vigor than the LPSpop indicated by higher NDVI values measured before flowering: the IQR for NDVI under well-watered conditions for the DTPpop ranged from 19.61 to 20.84 (h2 = 0.87) and from 13.74 to 14.8 for the LPSpop (h2 = 0.72). Under drought stressed conditions it ranged from 13.76 to 15.57 for the DTPpop (h2 = 0.63) and 12.63 to 13.75 for the LPSpop (h2 = 0.71). The DTPpop on average showed greater plant height: The IQR for the DTPpop (h2 = 0.83) under well-watered conditions ranged from 201.75 to 212.74 and from 183.36 to 188.18 for the LPSpop (h2 = 0.46) while under drought stress it ranged from 161.64 to 163.61 in the DTPpop (h2 = 0.42) and from 161.23 to 163.72 in the LPSpop (h2 = 0.38). A differential pattern between both populations was measured for visual senescence after flowering. While the DTPpop showed better stay green relative to the LPSpop four weeks after flowering under both conditions the pattern was reversed six weeks after flowering: Under well-watered conditions, IQR for SEN increased from 46.43–50.74 (h2 = 0.44) after flowering to 63.97–68.29 six weeks (h2 = 0.41) after flowering in the DTPpop. Meanwhile under drought stressed conditions senescence had increased as indicated by IQR ranging from 50.76–53.05 (h2 = 0.53) to 120.06–122.07 (h2 = 0.25) at four and six weeks after flowering. At the same time the IQR for SEN increased from 55.3–62.975.02–76.5 four weeks after flowering (h2 = 0.27) to 57.47–69.2 six weeks (h2 = 0.35) after flowering under well-watered conditions and from 65.5–73.49 (h2 = 0.28) to 109.5–123.58 (h2 = 0.42) under drought stressed conditions in the LPSpop. EPP was generally higher for the LPSpop relative to the DTPpop across irrigation treatments: EPP ranged from 1.01 to 1.03 (h2 = 0.35) in the DTPpop and from 1.07–1.09 in the LPSpop (h2 = 0.20) under well-watered conditions and from 0.77–0.78 for the DTPpop (h2 = 0.26) and 0.87–0.89 in the LPSpop (h2 = 0.21) under drought stressed conditions.The LPSpop and DTPpop were evaluated for grain yield, anthesis, silking, ASI, NDVI, PHT and senescence under well-watered (WW) and drought stressed (DS) conditions. Under well-watered conditions, the interquartile range (IQR) for GY ranged from 5.29 to 6.09 t/ha in the LPSpop (hA negative (r = -0.31) genetic correlation under drought stressed conditions and a positive correlation  with potential effects on stay green  and EPP (DS) was found in bin 6.04. Vigor QTL (measured as NDVI) with potential effects on stay green (SEN6) were detected in bins 8.01 and 2.07 in the DTPpop. Another collocation for stay green  was found in the DTPpop in bin 1.11.In the LPSpop six QTL were found for EPP, grain yield, and NDVI, four for anthesis and senescence, nine for PHT and two for ASI with LOD scores ranging from 2.02  to 17.2  at a PVE of 3.78 and 26.02%, respectively. In the DTPpop four QTL were identified for anthesis and grain yield, three for SEN, two for PHT and one for NDVI and EPP each with LOD scores ranging from 2.17  to 12.9  at PVE of 17.1% and 31.28%, respectively .2) explained by all QTL (excluding overdominant QTL) for a single trait ranged from 5.2 (ASI) to 36.6% (PHT) in the LPSpop and from 0 (NDVI4) to 28.2% (Anthesis) in the DTPpop (2 ranged from 5.2 (SEN6) to 42.5% (Anthesis) in the LPSpop and from 0 (NDVI) to 23.8% (Anthesis) in the DTPpop. Low R2 can be explained by low heritability for certain traits (e.g. ASI) or the genetic control of a trait by multiple QTL with small effects, that could not be detected in this study, when low R2 coincided with high heritability .Under well-watered conditions variation , flowering time (bin 2.06) and grain yield (8.06) deserve further attention for validation and potential use in marker assisted selection based on high PVE, identification across populations and/ or environmental conditions and their strong association with grain yield .The collocation of QTL for NDVI (WW), PHT (WW), GY (WW) and EPP (DS) in the LPSpop in bin 5.04 suggests that this locus has concomitant effects on vigor and grain yield under well-watered conditions and EPP under drought stressed conditions. While the allele increasing vigor  and grain yield (0.29 t/ha) under well-watered conditions was derived from CML491, the allele increasing EPP by 0.0018 under drought stressed conditions was derived from LPSC7F64. It is worth noting that the QTL for NDVI explained 5.5%, while the QTL for grain yield explained 18.6% of the observed phenotypic variation.Potential effects of a chromosomal region on vigor, stay-green and EPP were detected in bin 2.02 where a QTL for NDVI detected under drought stressed conditions collocated with a QTL for EPP and two QTL for senescence under well-watered conditions. The allele derived from CML491 increased vigor , while the allele derived from LPSC7F64 increased EPP by 0.01. The allele derived from LPSC7F64 equally reduced senescence by 0.51 and 0.78. LOD scores for the QTL for EPP reached 4.02 explaining 8.64% of the observed phenotypic variance.Bin 5.02 harbored two QTL for NDVI and EPP under drought stress in the LPSpop. The allele derived from CML491 increased NDVI and EPP by 0.49 and 0.01, respectively indicative of a common genetic control. LOD scores and PVE for the QTL for NDVI reached 11.25 and 19.9%, respectively.The vigor QTL (PHT DS) detected under drought in bin 2.05 collocated with two QTL for EPP and anthesis under well-watered conditions. The allele derived from CML491 increased PHT by 0.65 cm and delayed flowering by 0.31 d, while the allele derived from LPSC7F64 increased EPP by 0.01; QTL for EPP and time to flowering had LOD scores of 12.6 and 7.89 explaining 20.27% and 14.87% of the observed phenotypic variance.A vigor QTL (PHT WW) in bin 2.07 measured under well-watered conditions collocated with a QTL for senescence under drought stress and a QTL for grain yield under well-watered conditions in the DTPpop. Similar to PHT (+0.27 cm), grain yield was increased by the allele derived from CML491 by 0.3 t/ha, while the allele derived from DTPWC9F104 reduced senescence by 4.99 explaining 23.65% of the observed phenotypic variance. It should be noted that an overdominant QTL for NDVI was detected in the same bin under well-watered conditions, further emphasizing the importance of this locus for the genetic control of vigor.In the DTPpop, bin 8.06 harbored a constitutive QTL for grain yield (independent of early vigor) under well-watered and drought stressed conditions with potential interest for marker assisted selection. The allele derived from DTPWC9F104 increased grain yield by 0.58 t/ha under drought stressed conditions while the allele derived from CML491 increased grain yield by 0.27 t/ha under well-watered conditions. Both QTL explained 7.8 and 7.5% of the observed phenotypic variance.Two strong anthesis QTL mapped to bin 2.06 in the DTPpop and the LPSpop under well-watered and drought stressed conditions. QTL had LOD scores of 12.9 and 17.1 explaining 31.2% and 26% of the phenotypic variation observed. Similar to the other six anthesis QTL, the allele derived from CML491 delayed flowering by 0.14 d and 0.58 d in the DTPpop and the LPSpop, respectively.Grain yield in the DTPpop and LPSpop was significantly affected by factors, genotype, irrigation treatment and the genotype-by-environment interaction (data not shown). As a result the ranking of genotypes changed across irrigation treatments . In all 1F2:3backcross populations under well-watered and drought stressed conditions. Averaged across locations mean grain yield reached 5.6 t/ha and 5.8 t/ha under well-watered conditions in the LPSpop and the DTPpop, respectively. Drought stress reduced grain yield by 60–65% relative to the non-stressed control, indicating that measured grain yield can be attributed to drought tolerance as suggested previously [1F2:3 backcross population structure. It is not clear to what extent overdominant QTL detected may be masking additive/partially dominant QTL with less strong effects, as the inbred line populations were not evaluated phenotypically in the current study.In the current study we aimed to identify QTL for secondary traits associated with grain yield in two BCeviously , but thaIn contrast to most other studies carried out under drought stressed conditions , 45, 46 A secondary trait suitable for selection should be fast, easy and cheap to measure, have a high heritability (if possible higher than grain yield) and a strong association with grain yield . One suc2, while traits in question should at the same time be associated with grain yield. Based on these considerations seven chromosomal segments located in bins 2.02, 2.05, 2.06, 2.07, 5.02, 5.04 and 8.06 should be further investigated for their potential use in breeding  and gl*-N681A (glossyN681A). The d*-dwarf candidate6 gene determines plant development mediated by gibberellic acid, bv1 determines internode length while gl*-N681A determines leaf width. It is therefore conceivable that individual effects or interactions among these genes may explain QTL detected for NDVI and plant height.The importance of the vigor QTL in bin 5.04 for the control of PHT, NDVI and assimilate partitioning is further emphasized by the collocation with QTL for grain yield in studies carried out , 53, 54 The QTL identified under drought for vigor and EPP in bin 5.02 collocated with QTL for grain yield identified by several authors under well-watered , 26 and Nec*-t. Nec*-t is responsible for stress induced reduction of chloroplasts and chlorophyll [The importance of QTL for early vigor under drought stressed conditions and EPP and stay-green (2 x SEN) under well-watered conditions detected in bin 2.02 is highlighted by the collocation observed with a QTL for kernel number, SPAD  and graiorophyll  potentiaHcf1 and spt1. Hcf has been shown to affect the NADP+ oxireductase resulting in efficient electron transport in photosynthesis and radiation use efficiency [Spt1 has been shown to affect leaf chlorophyll content and general vigor. It is therefore likely that individual or combined action of hcf1 and/or spt1 affect leaf chlorophyll content, photosynthesis and resulting vigor under drought stressed conditions as well as assimilate partitioning to the growing ear under well-watered and drought stressed conditions as indicated by the observed collocations.The QTL for vigor detected under drought and for EPP under well-watered conditions in bin 2.05 collocated with QTL for quantum efficiency of photosystem II  and leafficiency . Spt1 haCBF3 like transcription factor [CBF3 like transcription factors have been shown to increase growth and development under low temperatures and drought and modulate the sugar metabolism in the plant [The importance of the vigor QTL detected under well-watered conditions in bin 2.07 is highlighted by the collocations with QTL for the hundred kernel weight and grain yield under well-watered , 29 and n factor . In arabhe plant .sps1) as suggested previously [Sps1 regulates sucrose synthesis and determines the partitioning of sucrose for export and storage. PVE and LOD for this QTL are not as high as typically expected for marker assisted selection but the presence across multiple environments and populations make this chromosomal segment highly interesting for further investigation.The grain yield QTL detected under well-watered and drought stressed conditions in the DTPpop in bin 8.06 collocated with QTL detected for grain yield in previous studies under well-watered , 26, 52,rf8) discovered earlier [rf8 is responsible for pollen fertility and potentially accounts for the identified QTL.Two strong flowering time QTL mapped to bin 2.06 in the DTPpop and the LPSpop under well-watered and drought stressed conditions respectively. A potential candidate gene underlying the observed collocations is restorer fertility 8  into the elite inbred line (CML491) using marker assisted selection. Overall, allele origin for specific traits was not exclusive under either condition indicating that additive effects of alleles from both parents were complementing each other and increasing grain yield under well-watered and drought stressed conditions. Within the seven chromosomal segments  with potential utility  for breeders, six beneficial alleles were derived from the donor parents while 12 alleles were derived from the recurrent parent. Vigor (NDVI/PHT) was generally increased by alleles derived from CML491, EPP was increased by alleles derived from both parents in both irrigation treatments, while senescence was reduced by the allele derived from the donor under well-watered conditions. At the same time flowering time was consistently delayed by the allele derived from CML491. Alleles with beneficial effects on grain yield (and traits associated with grain yield) being derived from both parents does not come as a surprise since the release of a CIMMYT maize line (CML) typically implies selection for beneficial agronomic traits, vigor, disease tolerance and a certain level of drought tolerance. At the same time the improved performance of LPSC7F64 and DTPWF104 under drought partially relies on drought escape as a result of earlier flowering [1F2:3 population since the genome of entries included in the current study only consisted of 25% derived from the donor. On the one hand high marker density used in this study allowed us to identify lines having ‘genetic target areas’ while at the same time reducing linkage drag. On the other hand using two BC1F2:3 populations (25% donor genome only) with a limited amount of entries  would have a had reduced genetic and phenotypic variation compared to traditionally used mapping populations [Using two linked BClowering  explainiulations , 31 makiThe key to improved drought tolerance while at the same time maintaining yield potential in germplasm developed/discovered here, is to combine alleles conferring early vigor from the recurrent parent and alleles from the donor conferring earlier flowering. Good early vigor would allow for a rapid establishment, weed suppression, a deep rooting system and resulting improved water homeostasis under drought stressed conditions. Earlier flowering would allow plants to partially escape drought under environmental conditions with terminal drought  whereas 1F2:3 backcross populations is that germplasm generated is likely to outperform parents and potentially current check hybrids [An advantage using BC hybrids . Best of