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Water droplet size variation has been established in the literature as an important variable that influences the behavior and characteristics of water in fuel emulsion. However, with the growing demand for sustainable aviation fuels (SAF), no data is available that shows how these fuels will affect the size of dispersed water droplets and their frequency distribution. To address this lack of knowledge, this study explores and presents experimental results on the characterization of dispersed water droplets in alternative fuels and Jet A-1 fuel under dynamic conditions. The alternative fuels comprised of two fully synthetic fuels, two fuels synthesized from bio-derived materials, and one bio-derived fuel. The data and statistics presented reveal that water droplet frequency and size distribution are sensitive to changes in fuel composition. Observations showed an evident transition of the droplet percentile over time in the cumulative frequency distribution; this could be attributed to droplet coalescence to form larger droplets. Mean droplet diameters between 3 and 6 μm were observed for all the fuels tested. With further analysis based on recommendations proposed in this work, the data may assist in providing insight to filter manufacturers.

Background MAT9001 is an omega‐3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA‐ethyl esters [EE]), EPA+DPA‐FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega‐3 levels following twice daily dosing, with meals, of EPA+DPA‐FFA and EPA‐EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. Methods and Results This open‐label, randomized, 2‐way crossover trial, with 28‐day treatment periods separated by ≥28‐day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150–499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA‐FFA and EPA‐EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively ( P =not significant). EPA+DPA‐FFA reduced least squares geometric mean high‐sensitivity C‐reactive protein by 5.8%; EPA‐EE increased high‐sensitivity C‐reactive protein by 8.5% ( P =0.034). EPA+DPA‐FFA increased least squares geometric mean plasma EPA, DPA, and total omega‐3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA‐EE of 692%, 140%, and 165% (all P P =0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. Conclusions EPA+DPA‐FFA raised plasma EPA, DPA, and total omega‐3 significantly more than did EPA‐EE. EPA+DPA‐FFA also reduced triglycerides and high‐sensitivity C‐reactive protein without increasing low‐density lipoprotein cholesterol. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04177680.

This study introduces spatially targeted decontamination using a synergistic combination of dielectric barrier discharge (DBD) flow actuation and ozone generation. Here, we relate the spatial distribution of local microbial decontaminations in an enclosure to that of local ozone concentrations caused by DBD ozone generation and flow actuation using two reactors with contrasting flow actuation, the Fan and Comb reactors, run at equal power of 1 ± 0.03 W for 3.5 min. Deviations in ozone concentrations and reductions of Escherichia coli on contaminated coupons over two planes were used to quantify the utilization capacity of the generated ozone to simultaneously disinfect regions of a surface placed in the planes. Results show that uniform ozone consumption by a contaminated target, i.e., targeted decontamination, lowers ozone requirements, exposure times, and reactor energy consumption for its disinfection. Furthermore, a significant positive correlation was found between local decontamination and ozone concentrations with Pearson’s correlation, ρ (34) = 0.64; p < 0.001. Simulated ozone distribution using an experiment integrated simulation method, governed by DBD reactor geometry induced flow actuation and ozone reaction rates, is also presented for predicting DBD actuated spatial decontamination distribution. Our study shows an innovative approach of applying DBD plasma reactors for decontamination using flow actuation and ozone generation to achieve targeted killing with maximized ozone utilization lowering overall ozone dosage requirements, energy requirements, and exposure times.

Pumps, pressure drops across fittings, and flight operations (such as turning manoeuvres, take-off, and landing) are some of the many sources of turbulence mixing and shearing in aircraft fuel systems, therefore, making it an inevitable condition. Literature established that shearing conditions would influence the droplets and droplets size distribution in an oil/water emulsion. So, low intensity shearing conditions could be beneficial as it promotes droplets coalescence, which could be a driving force for a weak emulsion. However, to date no experimental data has shown the influence homogenising intensity and total water content has on dispersed water droplets size distribution in aviation fuel. Therefore, to expand knowledge of quantification of measurements of dispersed water droplets in aviation fuel, this study characterizes dispersed water droplets in aviation turbine fuel, varying available laboratory homogenising devices and water content. Results presented show that droplets count increases with water concentration and shearing effect. To provide more statistical evidence, kurtosis and skew values were calculated from the extrapolated data and compared with data from a hexanol/water mixture given that hexanol is likely to form a stable emulsion. Experimental results show that the higher the homogenising intensity the more stable the emulsion is likely to be with a higher kurtosis and skew value close to that for the hexanol/water mixture. Therefore, observations show that mild shearing conditions (high shear mixing in this case) could help promote droplets coalescence, leading to a better separation ability. Engineering and Physical Sciences Research Council (EPSRC): EP/N509127/1. Airbus Operations, Filton, Bristol (Reference ID: 1100152106), United Kingdom.

The contamination and behaviour of water in aircraft fuel systems remains a significant global research interest following several aircraft incidents. To engineer a solution to the problem of icing in jet fuel, it is crucial to precisely identify the conditions and features that may exacerbate this phenomenon. This review will aid prospective researchers to identify work that has been done and work that is yet to be available for future study. In this review, conclusive data integrating a wide range of literature and also providing an in-depth description of the factors that influence the behaviour of trace water, ice formation in jet fuels was carefully summarised. On investigational studies, it was discovered that to date, no work is available that studies the impact of sustainable jet fuel and its blends on ice formation, size and frequency distribution of dispersed water droplets in aircraft fuel systems. Findings from comparative studies also reveal that surfaces will have an essential role in the growth pattern of ice in aircraft fuel systems. Furthermore, findings show that supercooled water droplets with sizes greater than or equal to 5 µm can induce ice accretion. This review identified a common problem with the prominent methods of reporting results as a graphically fitted plot. Subsequently, it proposed that authors of any original technical work provide raw data as supplementary information to allow comprehensibility. The study further offers a system that could help manage the nature of ice in aircraft fuel tank systems—making it readily available and accessible.

Dielectric Barrier Discharge (DBD) based ozone therapy is an attractive non-thermal, additive-free and environment-friendly alternative to traditional food processing technologies. Its practical application is dependent on economical ozone generation and optimum ozone dosage. This study investigates the one-time and periodic application of a compact (48 cu. cm), lightweight (55 g), low power, low temperature, DBD ozone generator for treatment of spoilage inocula prepared from combinations of spoiled green beans, grape tomatoes, lettuce and strawberries. A one-time exposure of 126–136 ppm of average ozone concentration produced by the DBD generator over 3 min and 15 min resulted in at least 1 and 4 log reduction, respectively, in microbial colonies present in the spoilage inocula. Daily exposure of 128.7 ppm average ozone concentration over 3 min under similar conditions showed that inhibition through periodic exposure can successfully inhibit the growth of both bacteria and mold species with at least 5 log reduction of microbial colonies. Visual inspection of whole fruits and vegetables with similar 3-min daily exposure showed the potential of ozone therapy to at least double the shelf-life of food products. For the daily exposures, energy required by the DBD ozone generator was calculated as 0.39 $$\pm $$ ± 0.06 kJ/day.

Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.

Objective To examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting. Study Design All live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture. Results Of 12,622 births, 842 were admitted with suspected sepsis of whom 95% were 4–60 days old. Culture confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins, and extremely low resistance to Gentamicin and Amikacin was observed. Conclusion The bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship, and alternate modalities should be considered for the management or prevention of neonatal sepsis in India.

The effectiveness of antibiotics has been challenged by the increasing frequency of antimicrobial resistance (AMR), which has emerged as a major threat to global health. Despite its negative impact on the development of AMR, there are few effective strategies for reducing AMR in food-producing animals. Using whole-genome sequencing and comparative genomics of 36 multidrug-resistant (MDR) Escherichia coli strains isolated from beef cattle with no previous exposure to antibiotics, we obtained results suggesting that the occurrence of MDR E. coli also arises in animals with no antibiotic selective pressure. Extended-spectrum-β-lactamase-producing E. coli strains with enhanced virulence capacities for toxin production and adherence have evolved, which implies important ramifications for animal and human health. Gene exchanges by conjugative plasmids and insertion elements have driven widespread antibiotic resistance in clinically relevant pathogens. Phylogenetic relatedness of E. coli strains from various geographic locations and hosts, such as animals, environmental sources, and humans, suggests that transmission of MDR E. coli strains occurs intercontinentally without host barriers. IMPORTANCE Multidrug-resistant (MDR) Escherichia coli isolates pose global threats to public health due to the decreasing availability of treatment options. To better understand the characteristics of MDR E. coli isolated from food-producing animals with no antibiotic exposure, we employed genomic comparison, high-resolution phylogenetics, and functional characterization. Our findings highlight the potential capacity of MDR E. coli to cause severe disease and suggest that these strains are widespread intercontinentally. This study underlines the occurrence of MDR E. coli in food-producing animals raised without antibiotic use, which has alarming, critical ramifications within animal and human medical practice.

As part of establishing a gender surgery center at a pediatric academic hospital, we undertook a process of identifying key ethical, legal, and contextual issues through collaboration among clinical providers, review by hospital leadership, discussions with key staff and hospital support services, consultation with the hospital’s ethics committee, outreach to other institutions providing transgender health care, and meetings with hospital legal counsel. This process allowed the center to identify key issues, formulate approaches to resolving those issues, and develop policies and procedures addressing stakeholder concerns. Key issues identified during the process included the appropriateness of providing gender-affirming surgeries to adolescents and adults, given the hospital’s mission and emphasis on pediatric services; the need for education on the clinical basis for offered procedures; methods for obtaining adequate informed consent and assent; the lower and upper acceptable age limits for various procedures; the role of psychological assessments in determining surgical eligibility; the need for coordinated, multidisciplinary patient care; and the importance of addressing historical access inequities affecting transgender patients. The process also facilitated the development of policies addressing the identified issues, articulation of a guiding mission statement, institution of ongoing educational opportunities for hospital staff, beginning outreach to the community, and guidance as to future avenues of research and policy development. Given the sensitive nature of the center’s services and the significant clinical, ethical, and legal issues involved, we recommend such a process when a establishing a program for gender surgery in a pediatric institution.

Methicillin-resistant Staphylococcus aureus (MRSA) is currently the most commonly identified antibiotic-resistant pathogen in US hospitals. Resistance to methicillin is carried by SCCmec genetic elements. Multilocus sequence typing (MLST) covers internal fragments of seven housekeeping genes of S. aureus. In conjunction with mec typing, MLST has been used to create an international nomenclature for S. aureus. MLST sequence types with a single nucleotide polymorphism (SNP) considered distinct. In this work, relationships among MLST SNPs and methicillin/oxacillin resistance or susceptibility were studied, using a public data base, by means of cross-tabulation tests, multivariable (phylogenetic) logistic regression (LR), decision trees, rule bases, and random forests (RF). Model performances were assessed through multiple cross-validation. Hierarchical clustering of SNPs was also employed to analyze mutational covariation. The number of instances with a known methicillin (oxacillin) antibiogram result was 1526 (649), where 63% (54%) was resistant to methicillin (oxacillin). In univariable analysis, several MLST SNPs were found strongly associated with antibiotic resistance/susceptibility. A RF model predicted correctly the resistance/susceptibility to methicillin and oxacillin in 75% and 63% of cases (cross-validated). Results were similar for LR. Hierarchical clustering of the aforementioned SNPs yielded a high level of covariation both within the same and different genes; this suggests strong genetic linkage between SNPs of housekeeping genes and antibiotic resistant associated genes. This finding provides a basis for rapid identification of antibiotic resistant S. arues lineages using a small number of genomic markers. The number of sites could subsequently be increased moderately to increase the sensitivity and specificity of genotypic tests for resistance that do not rely on the direct detection of the resistance marker itself.

Ozone is a well-known disinfecting agent that is used as an alternative for chlorine in many applications, including water decontamination. However, the utility of ozone in water decontamination is limited by high electrical power consumption and expensive, bulky equipment associated with ozone generation. This study investigates the effectiveness of a lightweight, compact surface dielectric barrier discharge (SDBD) reactor as an ozone generator to inactivate Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) in an open water system. Experimental details are provided for ozone generation technique, mixing method, ozone concentrations in air and water, and input energy required to produce adequate ozone concentrations for bacterial inactivation in a contaminated, open water system. Specifically, an active plasma module (APM) reactor system of size 48 cubic centimeters, weighing 55 grams, with a maximum ozone yield of 68.6 g/KWh was used in atmospheric conditions as the source of ozone along with an air pump and a diffusion stone for mixing the ozone in water. Over 4-log reduction in P. aeruginosa concentration was achieved in 4 minutes with 0.1 mg/L ozone concentration in an open water system using 8.8 ± 1.48 J input energy. Also, over 5-log reduction in MRSA concentration was achieved in 2 minutes with 0.04 mg/L ozone concentration in an open water system using 4.4 ± 0.74 J input energy.

Summary Introduction A central ethical dilemma in management of the patient with a disorder of sex development (DSD) is the potential conflict between respect for the fundamental right of the child for physical and emotional integrity and self-determination, and the right of parents to serve as surrogate decision-makers and act in their child's best interest. Methods Over the past 2 years we have encountered three complex DSD cases on the spectrum of mixed gonadal dysgenesis to ovotesticular DSD in which gender assignment and therefore optimal surgical management was uncertain. All patients had mosaic karyotypes with Y chromosome, dysgenetic ovary and dysgenetic testis, a urogenital sinus, and prominent phallus. In all three cases a team approach was taken to assess functional potential and risks along either gender pathway and to develop a spectrum of treatment options for parental consideration, including: 1. masculinization with removal of dysgenetic ovary; 2. initial vaginoplasty but with retention of the phallus (±bilateral gonadectomy); 3. initial vaginoplasty with “burial” of corporal bodies (Pippi Salle procedure) (±bilateral gonadectomy); 4. full feminization: vaginoplasty and clitoroplasty (with bilateral gonadectomy); 5. no surgical intervention. Results In all three cases, after consideration of risks and benefits of all options, parents selected option 2: gonadectomy to eliminate tumor risk and vaginoplasty, taking advantage of the child's young age to exteriorize urinary and reproductive tracts to avoid incontinence and infection and supporting parental bias toward female gender, but preservation of phallic structures to ensure a male option should the patient later declare a male gender identity. Parents of the three patients were contacted post-operatively (at 7, 17, and 22 months) for follow-up. All (3/3) regarded their child's development and wellbeing positively, and their own decisions regarding gender assignment and surgical plan favorably. All (3/3) regarded the team advisory process as balanced and supportive. Conclusion In the setting of exposure of the neonatal brain to testosterone, vaginoplasty and phallic preservation afforded a balance between parental preferences and preservation of anatomic options, allowing potential reconstruction of male or female phenotype as gender identity is ascertained thereby respecting both parent and patient rights. Parents valued a spectrum of options, transparency, and the team decision-making process. Table . Patient characteristics. A B C Age at referral 14 months 23 months 6 weeks Karyotype 45,X/46,XY/47,XYY 45,X/46,XY 46XX/47XXY Gonads L Dysgenetic testis R Dysgenetic ovary L Dysgenetic testis R Dysgenetic ovary L Dysgenetic ovary R Dysgenetic testis Ductal structures Uterus R Fallopian tube Uterus L Fallopian tube Uterus UG sinus Mid confluence Low confluence Low confluence Phallus 4 × 1.5 cm 3 × 1 cm 2.7 × 1.3 cm Gender assignment Female Female Neutral

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of healthcare-associated infections (HAIs), significantly contributing to morbidity and mortality of hospitalized patients. Infants in the neonatal intensive care unit (NICU) are at increased risk for infection and colonization with MRSA, often resulting in poor outcomes and long-term sequelae.1 MRSA in the NICU may be acquired from colonized parents, healthcare workers (HCWs), and other neonates.2,3 The CDC estimates that ~50% of MRSA infections for patients 3–89 days old are hospital-onset cases.4 Community reservoirs have been implicated in the introduction of MRSA into NICUs by increasing colonization prevalence among patients and visitors.5 However, identifying reservoirs and tracking the source of implicated strains has proven difficult, resulting in the persistence of transmission despite aggressive control measures.6–8 Limitations in genotyping techniques available in clinical practice may hinder the investigation of MRSA outbreaks in healthcare settings.8 Genotyping is an indispensable component of epidemic detection and investigation because it discriminates among genetically similar strains for the identification of epidemiologically important isolates. Pulsed-field gel electrophoresis (PFGE), spa typing, antibiograms, and multilocus sequence typing (MLST) are commonly employed to investigate MRSA transmission. However, these methods may not be optimal, as the unit of categorization (eg, PFGE type, spa type, MLST profile) can encompass broad genetic and epidemiological diversity,6,8 making it difficult to differentiate sporadic from epidemic cases,9–14 particularly when a prevalent strain type is commonly identified. MRSA PFGE-typed USA300 is an important pathogen in community and healthcare settings. In the United States, these strains were historically associated with community-associated (CA) infections acquired outside of hospitals. However, in many healthcare facilities, including those in our study area, CA-MRSA strains are displacing healthcare-associated (HA) strains as a cause of HAIs. The increasing prevalence of USA300 emphasizes the need for advanced typing methods in clinical practice. Recently, phylogenetic analysis of whole-genome sequencing (WGS) data has provided the resolution to discriminate between closely related isolates of bacterial pathogens through comparison of single nucleotide polymorphisms (SNPs).15,16 As a result, epidemiologically important isolates may be identified among a sample that appears homogenous when analyzed using conventional genotyping methods. WGS technology is often not readily available to investigators of outbreaks in the healthcare setting.15,17–19 Epidemiological linkages between patients may then be spuriously attributed and transmission sources obscured, leading to ineffective interventions and uninterrupted transmission. We sought to determine whether phylogenetic analysis of SNPs would facilitate identification of the source of MRSA transmission amid a putative NICU outbreak, compared to the initial investigation that utilized traditional genotyping. We considered multiple typing methods including maximum likelihood (ML) and Bayesian phylogenetic analysis of SNP data. Epidemiological and phylogenetic data were covisualized to illustrate the temporal and genetic relationships among cases, allowing for assessment of patient-to-patient transmission events. We demonstrate how this approach would have enhanced the investigation, ruling out several sporadic cases of MRSA and potentially augmenting infection control interventions.

Currently, there are only limited data available on rates of major diagnostic categories of illnesses among Haitian children. We have established a cohort of 1,245 students attending schools run by the Christianville Foundation in the Gressier/Leogane region of Haiti, for whom our group provides primary medical care. Among 1,357 clinic visits during the 2012-2013 academic year, the main disease categories (with rates per 1,000 child years of observation) included acute respiratory infection (ARI) (385.6 cases/1,000 child years of observation), gastrointestinal complaints (277.8 cases/1,000 child years), febrile illness (235.0 cases/1,000 child years), and skin infections (151.7 cases/1,000 child years). The most common diarrheal pathogen was enteroaggregative Escherichia coli (present in 17% of children with diarrhea); Vibrio cholerae O1 and norovirus were the next most common. Our data highlight the importance of better defining etiologies for ARI and febrile illnesses and continuing problems of diarrheal illness in this region, including mild cases of cholera, which would not have been diagnosed without laboratory screening.

A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.

Methicillin Resistant Staphylococcus aureus (MRSA) cause pneumonia and empyema thoraces. TLR9 activation provides protection against bacterial infections and Heme oxygenase-1 (HO-1) is known to enhance host innate immunity against bacterial infections. However, it is still unclear whether HO-1 regulates TLR-9 expression in the pleura and modulates the host innate defenses during MRSA empyema. In order to determine if HO-1 regulates host innate immune functions via modulating TLR expression, in MRSA empyema, HO-1+/+ and HO-1-/- mouse pleural mesothelial cells (PMCs) were infected with MRSA (1:10, MOI) in the presence or absence of Cobalt Protoporphyrin (CoPP) and Zinc Protoporphyrin (ZnPP) or CORM-2 (a Carbon monoxide donor) and the expression of mTLR9 and mBD14 was assessed by RT-PCR. In vivo, HO-1+/+ and HO-1-/- mice were inoculated with MRSA (5x106 CFU) intra-pleurally and host bacterial load was measured by CFU, and TLR9 expression in the pleura was determined by histochemical-immunostaining. We noticed MRSA inducing differential expression of TLR9 in HO-1+/+ and HO-1 -/- PMCs. In MRSA infected HO-1+/+ PMCs, TLR1, TLR4, and TLR9 expression was several fold higher than MRSA infected HO-1-/- PMCs. Particularly TLR9 expression was very low in MRSA infected HO-1-/- PMCs both in vivo and in vitro. Bacterial clearance was significantly higher in HO-1+/+ PMCs than compared to HO-1-/- PMCs in vitro, and blocking TLR9 activation diminished MRSA clearance significantly. In addition, HO-1-/- mice were unable to clear the MRSA bacterial load in vivo. MRSA induced TLR9 and mBD14 expression was significantly high in HO-1+/+ PMCs and it was dependent on HO-1 activity. Our findings suggest that HO-1 by modulating TLR9 expression in PMCs promotes pleural innate immunity in MRSA empyema.

We inventoried non-surface water sources in the Leogane and Gressier region of Haiti (approximately 270 km(2)) in 2012 and 2013 and screened water from 345 sites for fecal coliforms and Vibrio cholerae. An international organization/non-governmental organization responsible for construction could be identified for only 56% of water points evaluated. Sixteen percent of water points were non-functional at any given time; 37% had evidence of fecal contamination, with spatial clustering of contaminated sites. Among improved water sources (76% of sites), 24.6% had fecal coliforms versus 80.9% in unimproved sources. Fecal contamination levels increased significantly from 36% to 51% immediately after the passage of Tropical Storm Sandy in October of 2012, with a return to 34% contamination in March of 2013. Long-term sustainability of potable water delivery at a regional scale requires ongoing assessment of water quality, functionality, and development of community-based management schemes supported by a national plan for the management of potable water.

In 2010 a magnitude 7.0 earthquake struck Haiti, severely damaging the drinking and waste water infrastructure and leaving millions homeless. Compounding this problem, the introduction of Vibrio cholera resulted in a massive cholera outbreak that infected over 700,000 people and threatened the safety of Haiti’s drinking water. To mitigate this public health crisis, non-government organizations installed thousands of wells to provide communities with safe drinking water. However, despite increased access, Haiti currently lacks the monitoring capacity to assure the microbial safety of any of its water resources. For these reasons, this study was designed to assess the feasibility of using a simple, low cost method to detect indicators of fecal contamination of drinking water that could be implemented at the community level. Water samples from 358 sources of drinking water in the Léogâne flood basin were screened with a commercially available hydrogen sulfide test and a standard membrane method for the enumeration of thermotolerant coliforms. When compared with the gold standard method, the hydrogen sulfide test had a sensitivity of 65% and a specificity of 93%. While the sensitivity of the assay increased at higher fecal coliform concentrations, it never exceeded 88%, even with fecal coliform concentrations greater than 100 colony forming units per 100 milliliters. While its simplicity makes the hydrogen sulfide test attractive for assessing water quality in low resource settings, the low sensitivity raises concerns about its use as the sole indicator of the presence or absence of fecal coliforms in individual or community water sources.

With the acceleration of urbanization, there are continually huge increases in internal population migration from rural areas to metropolitan areas in China that have resulted in not only required work forces to propel the economy, but also in a new social phenomenon—children being left behind in rural areas. The issue of children left behind in rural areas—either in the care of uneducated and incapable grandparents, relatives, neighbors, or alone when their parents go to metropolitan areas to work has become a severe social problem. Through investigating the current conditions of the left-behind children (LBC) in China, this study attempts to discover some of the negative effects that have resulted, particularly on the education of LBC. Based on the empirical study of population mobility and formal education, and left-behindness and family education, practical solutions to the problems that surround the issue of LBC’s education are presented in this study. Included are also measures that must be carried out by governments, schools, parents and local communities. The specific initiatives for the establishment of education programmes particularly tailored to the needs of LBC are proposed. A goal of this paper is to find the effective solutions that might also be useful for the migration population in the other developing countries that have the similar issue.

Dielectric barrier discharge (DBD) devices are known ozone generators. Authors have previously demonstrated a DBD surface plasma source, operating in air at atmospheric pressure, to achieve killing of vegetative cells in 2–3min and sterilization in 20min (bacterial spores). The aim of this paper is to examine the role of the ozone in surface DBD plasma sterilization. The role of ozone in plasma killing is examined by a) characterizing the rate of production/decay of ozone during DBD plasma generation, b) studying the effect of exposing bacteria (Escherichia coli) solely to the ozone thus produced. Our results indicate that while ozone plays a major role, the energy flux delivered to the electrodes is also crucial in the process of plasma sterilization.

Vibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6th and 7th pandemic lineages, and diverge from “modern” cholera strains around 1548 C.E. [95% HPD: 1532–1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ.

Third-generation cephalosporins are an important class of antibiotics that are widely used in treatment of serious Gram-negative bacterial infections. In this study, we report the isolation of bacteria resistant to the third-generation cephalosporin cefotaxime from cattle with no previous cefotaxime antibiotic exposure. The prevalence of cefotaxime-resistant bacteria was examined by a combination of culture based and molecular typing methods in beef cattle (n = 1341) from 8 herds located in North Central Florida. The overall prevalence of cefotaxime-resistant bacteria was 15.8% (95% CI: 13.9, 17.8), varied between farms, and ranged from 5.2% to 100%. A subset of isolates (n = 23) was further characterized for the cefotaxime minimum inhibitory concentration (MIC) and antibiotic susceptibility against 10 different antibiotics, sequencing of nine β- lactamase genes, and species identification by 16S rRNA sequencing. Most of the bacterial isolates were resistant to cefotaxime (concentrations, > 64 μg/mL) and showed high levels of multi-drug resistance. Full length 16S rRNA sequences (~1300 bp) revealed that most of the isolates were not primary human or animal pathogens; rather were more typical of commensal, soil, or other environmental origin. Six extended spectrum β-lactamase (ESBL) genes identical to those in clinical human isolates were identified. Our study highlights the potential for carriage of cefotaxime resistance (including “human” ESBL genes) by the bacterial flora of food animals with no history of cefotaxime antibiotic exposure. A better understanding of the origin and transmission of resistance genes in these pre-harvest settings will be critical to development of strategies to prevent the spread of antimicrobial resistant microorganisms to hospitals and communities.

Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N1 = 112, N2 = 62; controls, N = 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR = 8.10, P = 1.10 × 10−11) and low risk with the LMP7-Q/Q genotype (OR = 0.10, P = 5.97 × 10−13). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-γ stimulation of colon carcinoma cell lines (N = 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t½ ≈ 7 minutes) compared with LMP7-Q (t½ ≈ 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-γ stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (

Structure guided optimization of a series of nonpeptidic alkyl amine renin inhibitors allowed the rational incorporation of additional polar functionality. Replacement of the cyclohexylmethyl group occupying the S1 pocket with a (R)-(tetrahydropyran-3-yl)methyl group and utilization of a different attachment point led to the identification of clinical candidate 9. This compound demonstrated excellent selectivity over related and unrelated off-targets, >15% oral bioavailability in three species, oral efficacy in a double transgenic rat model of hypertension, and good exposure in humans.

Structure based design led directly to 1,3-oxazinan-2-one 9a with an IC(50) of 42 nM against 11β-HSD1 in vitro. Optimization of 9a for improved in vitro enzymatic and cellular potency afforded 25f with IC(50) values of 0.8 nM for the enzyme and 2.5 nM in adipocytes. In addition, 25f has 94% oral bioavailability in rat and >1000× selectivity over 11β-HSD2. In mice, 25f was distributed to the target tissues, liver, and adipose, and in cynomolgus monkeys a 10 mg/kg oral dose reduced cortisol production by 85% following a cortisone challenge.

O-antigen biosynthetic ( wbf ) regions for Vibrio cholerae serogroups O5, O8, and O108 were isolated and sequenced. Sequences were compared to those of other published V. cholerae O-antigen regions. These wbf regions showed a high degree of heterogeneity both in gene content and in gene order. Genes identified frequently showed greater similarities to polysaccharide biosynthesis genes from species other than V. cholerae . Our results demonstrate the plasticity of O-antigen genes in V. cholerae , the diversity of the genetic pool from which they are drawn, and the likelihood that new pandemic serogroups will emerge.

Plasmid-mediated AmpC-producing Escherichia coli and Klebsiella pneumoniae have been associated with poor clinical outcomes, but they are not readily identified in hospital microbiology laboratories. We tested 753 gram-negative bloodstream isolates for AmpC by using the EDTA disk test and the modified Hodge test (n = 172) and the modified Hodge test alone (n = 581). The 30-day mortality for the AmpC group was 9% (2/23) and was 6% (3/51) for the control group. The clinical response was similar: afebrile on day 2 (AmpC group, 16/23 [70%]; control group, 32/45 [71%]) and on day 4 (AmpC group, 19/22 [86%]; control group, 37/44 [84%]). Patients with isolates in the AmpC group were more likely to be in an intensive care unit at the time of the positive blood culture (P = .01) and more likely to be intubated (P = .05) than patients with isolates in the control group. Effective antibiotic treatment within the first 48 hours was given to 47 (92%) of 51 patients with isolates in the control group but to only 14 (61%) of 23 patients with isolates in the AmpC group (P = .001). The modified Hodge test and the EDTA disk test did not identify patients at risk for a poor outcome from AmpC-producing bacterial infections.

Staphylococcus aureus is a common cause of infections that has undergone rapid global spread over recent decades. Formal phylogeographic methods have not yet been applied to the molecular epidemiology of bacterial pathogens because the limited genetic diversity of data sets based on individual genes usually results in poor phylogenetic resolution. Here, we investigated a whole-genome single nucleotide polymorphism (SNP) data set of health care-associated Methicillin-resistant S. aureus sequence type 239 (HA-MRSA ST239) strains, which we analyzed using Markov spatial models that incorporate geographical sampling distributions. The reconstructed timescale indicated a temporal origin of this strain shortly after the introduction of Methicillin, followed by global pandemic spread. The estimate of the temporal origin was robust to the molecular clock, coalescent prior, full/intergenic/synonymous SNP inclusion, and correction for excluded invariant site patterns. Finally, phylogeographic analyses statistically supported the role of human movement in the global dissemination of HA-MRSA ST239, although it was unable to conclusively resolve the location of the root. This study demonstrates that bacterial genomes can indeed contain sufficient evolutionary information to elucidate the temporal and spatial dynamics of transmission. Future applications of this approach to other bacterial strains may provide valuable epidemiological insights that may justify the cost of genome-wide typing.