Inherited Variation at MC1R and Histological Characteristics of Primary Melanoma

Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype.     

Gastrointestinal Symptoms and Helicobacter pylori Infection in School-Age Children Residing in Porto Torres, Sardinia, Italy

Background: Helicobacter pylori infection is typically acquired in childhood, and following the acute event, it is thought that most infections remain asymptomatic. H. pylori has been suggested to protect against diarrhea in childhood. Aim: To examine the role of H. pylori in gastrointestinal symptoms in children. Materials and Methods: A cross‐sectional sero‐epidemiologic study was conducted in Porto Torres, Sardinia, Italy. Demographic information, socioeconomic factors, and the frequency of upper gastrointestinal symptoms during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn, halitosis, slow digestion, belching, and weight loss) were evaluated by a questionnaire. H. pylori status was determined by ELISA. Results: Approximately 95% (N = 1741) of school children between the age of 6 and 15 years from Porto Torres participated. The sero‐prevalence of H. pylori infection was 13.3% (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting (odds ratio (OR) = 2.2 (95% CI = 1.2–5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3–2.8)) were each significantly associated with H. pylori infection, and these associations remained significant after controlling for other study variables. There was no significant association between H. pylori and abdominal pain or heartburn (p > .25). Conclusions: The study does not support either a role of H. pylori infection in abdominal pain in children or a protective role against diarrheal illnesses or nausea/vomiting.     

Assessing the structural complexity of manufacturing systems configurations

Modern manufacturing systems are increasingly required to be flexible and adaptable to changing market demands, which adds to their structural and operational complexity. One of the major challenges at the early design stages is to select a manufacturing system configuration that both satisfies the production functional requirements and is easy to operate and manage. A new metric for assessing the structural complexity of manufacturing system configurations is presented in this paper. The proposed complexity metric incorporates the quantity of information using an entropy approach. It accounts for the complexity inherent in the various modules in the manufacturing system through the use of an index derived from a newly developed manufacturing systems classification code. The code captures the effect of various component types and technologies used in a manufacturing system on the system’s structural complexity. The presented metric would be helpful in selecting the least complex manufacturing system configuration that meets the requirements. An engine cylinder head production system is used to illustrate the application of the proposed methodology in comparing feasible but different manufacturing system configurations capable of producing the cylinder head based on their structurally inherent complexity.     

A prospective study for the association of Helicobacter pylori infection to a multidimensional measure for recurrent abdominal pain in children

BACKGROUND: There is a controversial association between Helicobacter pylori infection and recurrent abdominal pain (RAP) in childhood and inconsistent information on specific symptomatology of the infection. AIMS: To examine the prevalence of H. pylori infection among children with RAP compared to asymptomatic children. METHODS: Two prospective studies were conducted. The first study enrolled 223 children diagnosed with RAP from two pediatric gastroenterology clinics in Houston, Texas. Children were qualified if they were identified by their physician as having RAP. A new multidimensional measure for RAP (MM-RAP) consisting of four scales (pain intensity scale, symptoms scale, disability scale, and satisfaction scale) was administered to each child/parent. The second study enrolled 330 asymptomatic children from the same community who did not have any upper gastrointestinal symptoms. Symptomatic and asymptomatic children underwent (13)C-urea breath testing. RESULTS: In the first study, the prevalence of H. pylori in children with RAP was 11% and fell with age from 20% at age < or = 5 years to 7% for children > 10 years (OR = 2.7, 95% CI = 0.7-11.2). There was no association between the mother's educational level and H. pylori prevalence; (12% among children whose mothers completed college versus 11% among those who had elementary school, p = .8). No relationship was found between H. pylori and mean scores of the RAP scales. In the second study, the prevalence of H. pylori in asymptomatic children was 17% and increased with age from 11% for children < or = 5 years to 40% for children > 10 years (OR = 5.4, 95% CI = 2.0-13.8). The mother's educational level was inversely correlated with H. pylori (OR = 3.0, 95% CI = 2.2-6.1, p < .01). CONCLUSIONS: The epidemiologic patterns of H. pylori infection differed significantly between symptomatic and asymptomatic children. Younger children suffering from RAP are more likely to be infected with H. pylori than older children with the same complaint, suggesting that early acquisition may manifest in symptoms that lead to clinic visits.     

Intravenous Delivery of Targeted Liposomes to Amyloid-β Pathology in APP/PSEN1 Transgenic Mice

Extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles constitute the major neuropathological hallmarks of Alzheimer’s disease (AD). It is now apparent that parenchymal Aβ plaque deposition precedes behavioral signs of disease by several years. The development of agents that can target these plaques may be useful as diagnostic or therapeutic tools. In this study, we synthesized an Aβ-targeted lipid conjugate, incorporated it in stealth liposomal nanoparticles and tested their ability to bind amyloid plaque deposits in an AD mouse model. The results show that the particles maintain binding profiles to synthetic Aβ aggregates comparable to the free ligand, and selectively bind Aβ plaque deposits in brain tissue sections of an AD mouse model (APP/PSEN1 transgenic mice) with high efficiency. When administered intravenously, these long circulating nanoparticles appear to cross the blood-brain barrier and bind to Aβ plaque deposits, labeling parenchymal amyloid deposits and vascular amyloid characteristic of cerebral amyloid angiopathy.     

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

Background

The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries.

Methods and Findings

We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30–100%) and 81% (range 26–100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22–99%) and 60% (range 19–100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44–100%) of infants were tested for HIV and 11% (range 3–18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis.

Conclusion

The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed.     

Genomic in situ hybridization in plants with small genomes is feasible and elucidates the chromosomal parentage in interspecific Arabidopsis hybrids.

Genomic in situ hybridization (GISH) is a useful tool to analyse natural polyploids, hybrid plants, and their backcross progenies as to their origin, genomic composition, and intergenomic rearrangements. However, in angiosperms with very small genomes (<0.6 pg/1 C), often only heterochromatic regions were found to be labeled. We have modified the GISH technique to label entire mitotic and meiotic chromosomes of Arabidopsis thaliana (2n = 10) and closely related species with very small genomes by using high concentrations of DNA (7.5-15 microg per probe per slide) or 5 microg of probe and long hybridization times (>60 h). According to our GISH data, Cardaminopsis carpatica (2n = 16) is most likely the diploid ancestor of the autotetraploid Arabidopsis arenosa (2n = 32). Furthermore, within the allotetraploid species Arabidopsis suecica (2n = 26), it was possible to elucidate the origin of chromosomes contributed by the parental species A. thaliana and A. arenosa for a specimen with 2n = 26 or a deviating chromosome number.     

Flexible and reconfigurable manufacturing systems paradigms

Reconfigurable Manufacturing System (RMS) is a new manufacturing systems paradigm that aims at achieving cost-effective and rapid system changes, as needed and when needed, by incorporating principles of modularity, integrability, flexibility, scalability, convertibility, and diagnosability. RMS promises customized flexibility on demand in a short time, while Flexible Manufacturing Systems (FMSs) provides generalized flexibility designed for the anticipated variations and built-in a priori. The characteristics of the two paradigms are outlined and compared. The concept of manufacturing system life cycle is presented. The main types of flexibility in manufacturing systems are discussed and contrasted with the various reconfiguration aspects including hard (physical) and soft (logical) reconfiguration. The types of changeability and transformability of manufacturing systems, their components as well as factories, are presented along with their enablers and compared with flexibility and reconfigurability. The importance of having harmonized human-machine manufacturing systems is highlighted and the role of people in the various manufacturing paradigms and how this varies in pursuit of productivity are illustrated. Finally, the industrial and research challenges presented by these manufacturing paradigms are discussed.