Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma.

BACKGROUND: Prior studies characterized the association of molecular alterations with treatment-specific outcomes in KRAS-mutant (KRASMUT) lung adenocarcinoma (LUAD). Less is known about the prognostic role of molecular alterations and their associations with metastatic disease. PATIENTS AND METHODS: We analyzed clinicogenomic data from 1817 patients with KRASMUT LUAD sequenced at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC). Patients with metastatic (M1) and nonmetastatic (M0) disease were compared. Transcriptomic data from The Cancer Genome Atlas (TCGA) were investigated to characterize the biology of differential associations with clinical outcomes. Organ-specific metastasis was associated with overall survival (OS). RESULTS: KEAP1 (DFCI: OR = 2.3, q = 0.04; MSKCC: OR = 2.2, q = 0.00027) and SMARCA4 mutations (DFCI: OR = 2.5, q = 0.06; MSKCC: OR = 2.6, q = 0.0021) were enriched in M1 versus M0 tumors. On integrative modeling, NRF2 activation was the genomic feature most associated with OS. KEAP1 mutations were enriched in M1 versus M0 tumors independent of STK11 status (KEAP1MUT/STK11WT: DFCI OR = 3.0, P = 0.0064; MSKCC OR = 2.0, P = 0.041; KEAP1MUT/STK11MUT: DFCI OR = 2.3, P = 0.0063; MSKCC OR = 2.5, P = 3.6 × 10-05); STK11 mutations without KEAP1 loss were not associated with stage (KEAP1WT/STK11MUT: DFCI OR = 0.97, P = 1.0; MSKCC OR = 1.2, P = 0.33) or outcome. KEAP1/KRAS-mutated tumors with and without STK11 mutations exhibited high functional STK11 loss. The negative effects of KEAP1 were compounded in the presence of bone (HR = 2.3, P = 4.4 × 10-14) and negated in the presence of lymph node metastasis (HR = 1.0, P = 0.91). CONCLUSIONS: Mutations in KEAP1 and SMARCA4, but not STK11, were associated with metastatic disease and poor OS. Functional STK11 loss, however, may contribute to poor outcomes in KEAP1MUT tumors. Integrating molecular data with clinical and metastatic-site annotations can more accurately risk stratify patients.

Prevalence, severity and explanatory factors of tooth wear in Arab populations.

OBJECTIVES: The aim of this study was to assess the prevalence and severity of tooth wear and related risk indicators in six Arab countries. METHODS: This multicenter, multinational cross-sectional study was conducted among 2924 participants between the ages of 18-35 years old from six Arab countries. Calibrated dentists assessed tooth wear using the Basic Erosive Wear Examination Index (BEWE). Participants were also asked to complete a questionnaire that assessed their dietary and oral health habits. Each participant was identified by the sextant with the highest BEWE score in the upper and lower jaws. RESULTS: Odds ratios were estimated for correlates of tooth wear anterior and posterior regions. Oman had the highest prevalence of BEWE score 3 (N = 255 (60.2%)). Overall, the highest BEWE score 3 was observed on the incisal edge of the upper anterior teeth (N = 602 (20.6%)) and in the lower left posterior region (sextant 6) on the occlusal surface (N = 466 (15.9%)). Correlates of severe tooth wear in both regions were eating or drinking more than six times per day, age and education. Drinking soft drinks "once a day" was significantly associated with severe tooth wear in the posterior region (OR: 1.3, 95% CI:1.05, 1.6). Brushing teeth more than twice a day was inversely associated with tooth wear in the anterior region (OR:0.75, 95% CI: 0.57,0.97). CONCLUSION: The prevalence of tooth wear in Arab populations is relatively high, specific preventive and therapeutic measures should be developed to target people at higher risk of this condition. CLINICAL SIGNIFICANCE: Tooth wear is now regarded as a significant oral health problems, dentists should advise their patients about dietary and oral health habits that can lead to severe tooth wear.

Nutritional value and chemical composition of Sudanese millet-based fermented foods as affected by fermentation and method of preparation.

BACKGROUND: Although kissra and hulu-mur are well known millet-based foods in Sudan, the effect of fer- mentation and methods of preparation on their chemical compositions has not been thoroughly investigated. The aim of this study was to investigate the method of preparation and the composition of kisra, and hulu-mur. METHODS: The effect of fermentation and method of preparation on the composition, and mi- crobiological load were examined in millet flour during the preparation of Sudanese fermented foods (kisra & hulu-mur). RESULTS: A significant (P < 0.05) difference in the composition of millet flour and millet-based fermented foods was observed. Protein was significantly increased as a result of fermentation, while oil and carbo- hydrates were decreased. Most minerals increased significantly after the addition of spices to the hulu-mur batter. The total amino acid in millet flour (97.98 g 100 g-1 protein) was influenced by fermentation and preparation method, as it decreased to 86.09 and 88.7 g 100 g-1 protein, in millet batter and kisra, respectively. CONCLUSIONS: Kisra, and hulu-mur were found to have apparent dietary qualities, in spite of some compounds being lost during their production.

Nectar secretion dynamics of Ziziphus nummularia: A melliferous species of dry land ecosystems.

Nectar is used as raw material for the production of honey and as significant reward in the relationship between bees and plants during pollination. Therefore, it is important to investigate its abundance, dynamics and associated governing factors. Weather conditions are known to influence nectar production, and predicted climate changes may be responsible for future declining in total yield from beekeeping activities. We investigated nectar production as total soluble solids (TSS) of well-known species for honey production, Ziziphus nummularia in a hot-arid environment of Saudi Arabia. Data on nectar samples from bagged flowers of different stages during two blooming seasons, 2013 and 2015 were collected on weekly bases, and the data were correlated with weather conditions (temperature, relative humidity, and wind). A significant difference in TSS amount has been obtained, with 1-day old flowers displaying the higher content. TSS production was varied along the different day intervals, for both years, with a peak of production in the afternoon. In our results, nectar production was not correlated to temperature and wind, but was significantly negatively correlated with relative humidity. According to the current and future weather forecasting conditions, understanding of the relationship between weather conditions and nectar availability turned out to be important predictive information that may be interpreted into an economic projection of incomes from beekeeping activities.

Do implant overdentures improve dietary intake? A randomized clinical trial.

People wearing mandibular two-implant overdentures (IOD) chew food with less difficulty than those wearing conventional complete dentures (CD). However, there is still controversy over whether or not this results in better dietary intake. In this randomized clinical trials (RCT), the amounts of total dietary fiber (TDF), macronutrients, 9 micronutrients, and energy in diets consumed by persons with IOD and CD were compared. Male and female edentate patients ≥ 65 yrs (n = 255) were randomly divided into 2 groups and assigned to receive a maxillary CD and either a mandibular IOD or a CD. One year following prosthesis delivery, 217 participants (CD = 114, IOD = 103) reported the food and quantities they consumed to a registered dietician through a standard 24-hour dietary recall method. The mean and median values of TDF, macro- and micronutrients, and energy consumed by both groups were calculated and compared analytically. No significant between-group differences were found (ps > .05). Despite quality-of-life benefits from IODs, this adequately powered study reveals no evidence of nutritional advantages for independently living medically healthy edentate elders wearing two-implant mandibular overdentures over those wearing conventional complete dentures in their dietary intake at one year following prosthesis delivery.

Prediction of User's Web-Browsing Behavior: Application of Markov Model.

Web prediction is a classification problem in which we attempt to predict the next set of Web pages that a user may visit based on the knowledge of the previously visited pages. Predicting user's behavior while serving the Internet can be applied effectively in various critical applications. Such application has traditional tradeoffs between modeling complexity and prediction accuracy. In this paper, we analyze and study Markov model and all- Kth Markov model in Web prediction. We propose a new modified Markov model to alleviate the issue of scalability in the number of paths. In addition, we present a new two-tier prediction framework that creates an example classifier EC, based on the training examples and the generated classifiers. We show that such framework can improve the prediction time without compromising prediction accuracy. We have used standard benchmark data sets to analyze, compare, and demonstrate the effectiveness of our techniques using variations of Markov models and association rule mining. Our experiments show the effectiveness of our modified Markov model in reducing the number of paths without compromising accuracy. Additionally, the results support our analysis conclusions that accuracy improves with higher orders of all- Kth model.

Implant overdentures and nutrition: a randomized controlled trial.

We conducted a randomized clinical trial to determine whether providing simple mandibular implant overdentures (IODs) to elderly individuals would give them a significantly better nutritional profile than those who receive complete dentures (CDs). Two hundred fifty-five edentate patients > 65 yrs were randomly assigned to receive maxillary CDs and mandibular IODs (n = 128) or CDs (n = 127). Six-month and one-year post-treatment outcomes were blood plasma levels of homocysteine (tHcy), vitamin B12, vitamin B6, albumin, serum folate, and C-reactive protein concentrations, as well as dietary intake. The association between treatment and tHcy levels was not statistically significant. A decline of folate from baseline values in both study groups, as well as those of vitamins B6 and B12 and albumin, was observed. Significant between-group differences were detected in food preparation and in the individuals' ability to chew a variety of foods. This study suggests that implant overdentures do not have a more positive effect on the nutritional state of elderly edentate individuals at 6 and 12 mos post-treatment than new complete dentures. However, those wearing IODs are significantly more likely to take in their nutrients through fresh, whole fruits and vegetables.

The effectiveness of 2-implant overdentures - a pragmatic international multicentre study.

The purpose of this multicentre observational study was to determine patient satisfaction with either conventional dentures or mandibular 2-implant overdentures in a 'real world' setting. Two hundred and three edentulous patients (mean age 68·8 ± 10·4 years) were recruited at eight centres located in North America, South America and Europe. The patients were provided with new mandibular conventional dentures or implant overdentures supported by two implants and ball attachments. At baseline and at 6 months post-treatment, they rated their satisfaction with their mandibular prostheses on 100-mm visual analogue scale questionnaires. One hundred and two (50·2%) participants had valid baseline and 6-month satisfaction data. Although both groups reported improvements, the implant overdenture group reported significantly higher ratings of overall satisfaction, comfort, stability, ability to speak and ability to chew. These results suggest that edentulous patients who choose mandibular implant overdentures have significantly greater improvements in satisfaction, despite their relatively higher cost, than those who choose new conventional dentures.

Caries prevalence and intra-oral pattern among young children in Ajman.

OBJECTIVE: To describe the prevalence and intra-oral pattern of caries among young children in Ajman, UAE. METHODS: A one-stage cluster sampling was used to randomly select children aged 5 or 6 years old who were enrolled in public or private schools in Ajman. Clinical examinations for dental caries were conducted by a single examiner using WHO criteria. RESULTS: The total number of children sampled was 1297, of whom 1036 (79.9%) were dentally examined. The prevalence of caries (defined as dmft > 0) in 5- and 6-year-olds was 72.9% (95% CI, 61.8, 83.9) and 80.0% (95% CI, 76.0, 84.4) respectively, with mean dmft scores of 4.0 (sd, 4.1) and 4.9 (sd, 4.3) respectively (P < 0.05). The teeth most frequently affected by caries were mandibular second molars (38.6% of those on the left, and 36.9% of those on the right) and the least affected were mandibular central incisors (2.1% and 2.0% respectively). The prevalence of bilateral molar caries (that is, contralateral teeth both affected) was relatively high, being 29.7% for mandibular second molars and 28.3% for mandibular first molars. CONCLUSIONS: Dental caries prevalence and severity in 5- and 6-year-olds in Ajman were high, with the lower molars and upper central incisors most commonly affected by caries. There is an urgent need for oral health programs targeted at the treatment and prevention of dental caries in these children.

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian children.

We determined the seroprevalence of hepatitis A virus antibodies (HAV Ab) among 296 Egyptian children aged 2.5-18 years of different social classes to ascertain whether to give HAV vaccine early in life or to leave children to acquire natural immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant increase in the seroprevalence of HAV Ab with higher age and lower social class; in children aged < 6 years, 72.7% of high and 19.0% of low social class were seronegative for HAV Ab. A national vaccination programme for HAV is not a priority. We recommend vaccination against hepatitis A for high social class children at the preschool period without testing for HAV. Vaccination for middle social class children can be done, but only after testing for HAV.

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian children

We determined the seroprevalence of hepatitis A virus antibodies [HAV Ab] among 296 Egyptian children aged 2.5-18 years of different social classes to ascertain whether to give HAV vaccine early in life or to leave children to acquire natural immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant increase in the seroprevalence of HAV Ab with higher age and lower social class; in children aged < 6 years, 72.7% of high and 19.0% of low social class were seronegative for HAV Ab. A national vaccination programme for HAV is not a priority. We recommend vaccination against hepatitis A for high social class children at the preschool period without testing for HAV. Vaccination for middle social class children can be done, but only after testing for HAV

Measuring the effect of intra-oral implant rehabilitation on health-related quality of life in a randomized controlled clinical trial.

The importance of assessing the impact of treatments for chronic conditions on an individual's quality of life has been well-established. In this randomized clinical trial, oral-health-related quality of life, measured with the Oral Health Impact Profile (OHIP), was compared between two groups of edentulous patients. One group (n = 54) received mandibular implant-supported overdentures, and the other group (n = 48) received conventional dentures. Assessments were performed pre-treatment and two months after the prostheses were delivered. The multivariate model showed that implant treatment was significantly associated with lower post-treatment OHIP scores (p = 0.0002), indicating a better quality of life. In addition, pretreatment OHIP scores, treatment allocation, age, sex, and marital status explained 31% of the variation in post-treatment OHIP scores (F = 0.0001). These results suggest that implant treatment provides significant short-term improvement over conventional treatment in oral-health-related quality of life.

Determinants of patients' treatment preferences in a clinical trial.

Several researchers have suggested that patients' preferences for a particular form of treatment should be taken into account in clinical trials. Preferences may influence the outcome of treatment, especially in trials when patients cannot be blinded to the type of treatment received and the outcome is based on patients' evaluations of therapy. Participants in this study were 136 edentulous patients who took part in a randomised controlled clinical trial comparing two types of treatments for edentulism: conventional dentures and implant-supported prostheses. Prior to receiving treatment, subjects were required to complete a questionnaire regarding their satisfaction with their present prostheses. In addition, they were asked to indicate which treatment they would prefer if given a choice. The objective of this study was to determine whether there are important differences among study participants between patients who have a treatment preference and those who do not. The effects of satisfaction with pre-treatment prostheses, age, gender and level of education on preferences were examined. Level of satisfaction with the original dentures and level of education were significant predictors of preference. Compared to subjects who rated their satisfaction with their current condition as 'low', the odds ratios associated with having a preference for implant treatment were 0.31 (95% CI: 0.09 to 0.96) for subjects who rated their prostheses in the 'medium' range and 0.11 (95% CI: 0.03 to 0.41) for those who rated in the 'high' range. In addition, subjects with high levels of education were significantly less likely to have a preference for either conventional or implant treatments (OR = 0.18, 95% CI: 0.02 to 0.77 and OR = 0.20, 95% CI: 0.05 to 0.76, respectively) compared to those with low education. Neither age nor gender was a significant predictor of preference. We suggest that study designs which incorporate patients' preferences must take into account possible differences between preference groups that might confound the relationship between preference and the outcome of interest.

Measuring patient satisfaction with mandibular prostheses.

OBJECTIVES: Previous research has shown that patients' evaluations of their prostheses correlate poorly with the clinicians' assessments, as well as with intraoral anatomic factors. It has been recommended that researchers conduct more studies that use patient satisfaction as the primary outcome measure in treatment evaluation and that more attention be paid to understanding exactly what measures of patient satisfaction represent. In this study, the relationship between patients' ratings of general satisfaction and their perceptions of different aspects of mandibular prostheses is investigated. METHODS: One hundred and twenty subjects applied to participate in a randomized controlled clinical trial comparing two types of mandibular prostheses: conventional dentures and implant prostheses. At baseline, they were asked to rate on 100 mm visual analog scales (VAS) factors that edentulous patients indicated were important to them. These included comfort, ability to chew, stability, esthetics, ability to speak and ease of cleaning of their conventional dentures. Subjects were also asked to rate their general satisfaction with their dentures. In addition, they selected the one quality of their denture that they considered to be most important. RESULTS: Multiple regression methods revealed that gender, as well as patients' ratings of comfort, stability, esthetics, ability to chew and ability to speak with their prostheses contributed significantly to general satisfaction (F<0.0001). Furthermore, 89% of the variation in ratings of general satisfaction was explained by these factors. In addition, patients who considered ability to chew as the most important factor associated with their dentures rated their general satisfaction significantly higher than the other subjects (P=0.0003). CONCLUSION: Patient satisfaction with conventional dental prostheses is highly dependent on gender, and the appearance and functionality of the appliance. The combined effect of these factors explained most of the variation in the satisfaction ratings.

The impact of patient preference on the design and interpretation of clinical trials.

Research on several health problems shows that patients and health care providers do not use the same criteria to evaluate the effectiveness of treatment and often disagree on the severity of symptoms. When the disease is chronic and the main aim of treatment is to improve quality of life, we argue that variables rated as important by patients should be used as outcomes in clinical trials, and that in most cases these need to be measured from subjects' self-reports. In many non-pharmacological randomized clinical trials, the subjects cannot be blinded to treatment. Furthermore, many of them will probably have a preference for a particular treatment option. It has been proposed that emotional responses following assignment of treatments, which may or may not be preferred, will strongly influence the outcome, especially when it is based on self-reports of treatment satisfaction. Because of this concern, some investigators have suggested alternative study designs that incorporate preference. Brewin & Bradley (Br Med J 1989; 299 [6694]:313-5) have proposed allocating subjects to treatment methods according to their preferences, and randomizing those individuals with no preference. To determine the influence of preference on treatment outcome, they recommend comparing results from the preference group with those of the randomized group. However, we have found that there are clear differences in level of education and in the pre-treatment state between individuals with preferences and those with no strong preferences. Therefore, we believe that the design proposed by Wennberg et al. (Ann N Y Acad Sci 1993;703:52-62) is more appropriate. In it, subjects are randomly allocated to a preference trial (subjects choose their treatment) or to a randomized trial (random allocation to treatment). Between-trial comparisons can then be used to determine the influence of preference on outcome. This will lead to better evaluation of treatment efficacy and allow better estimates of the true effectiveness to be made.

Isotopic and hydrogeochemical evaluation of groundwater at Qusier-Safaga area, eastern desert, Egypt.

The groundwater resources of the El-Qusier-Safaga area on the Red Sea coastal zone have still to be utilised fully for social and economic development. In the present study, an inventory of recharge sources and quality of groundwater in different water bearing formations is made to assist in management of these vital resources. From a hydrochemical point of view, the origin of salinity in the five investigated aquifers are mainly dissolution of terrestrial minerals, leaching of soilsvia floods or ion exchanges processes. Stable isotope data clarify the interaction between different aquifers and indicate that the source of recharge is mainly meteoric water originating from palaeowater of the Pleistocene pluvial period, and from local precipitation as well as some marine water. Evaluation of the groundwater quality for domestic, irrigation and industrial purposes is discussed.