The genome of melon (Cucumis melo L.).

We report the genome sequence of melon, an important horticultural crop worldwide. We assembled 375 Mb of the double-haploid line DHL92, representing 83.3% of the estimated melon genome. We predicted 27,427 protein-coding genes, which we analyzed by reconstructing 22,218 phylogenetic trees, allowing mapping of the orthology and paralogy relationships of sequenced plant genomes. We observed the absence of recent whole-genome duplications in the melon lineage since the ancient eudicot triplication, and our data suggest that transposon amplification may in part explain the increased size of the melon genome compared with the close relative cucumber. A low number of nucleotide-binding site-leucine-rich repeat disease resistance genes were annotated, suggesting the existence of specific defense mechanisms in this species. The DHL92 genome was compared with that of its parental lines allowing the quantification of sequence variability in the species. The use of the genome sequence in future investigations will facilitate the understanding of evolution of cucurbits and the improvement of breeding strategies.

Helicobacter pylori genome evolution during human infection.

High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals=3-16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27-232 isolated SNPs and 16-441 imported clusters of polymorphisms resulting from recombination. Imports (mean length=394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.

Cross-cultural validation of the desire for information about prescribed medicines scale.

OBJECTIVES: It is the overall aim of this study to validate an existing scale to measure patients' desire for information about their medicines in the geographically and culturally disparate context of the USA. Specific objectives are to determine the psychometric properties of the previously validated Extent of Information Desired (EID) and Perceived Utility of Medicines (PUM) scales and to describe the complexities inherent to cross-cultural validation. METHODS: The setting was a culturally diverse tri-county (Palm Beach, Broward and Miami Dade counties) area of South Florida. The research design was cross-sectional and descriptive; data were gathered from respondents using a facilitator-administered survey instrument. KEY FINDINGS: The overall reliability of the survey was 0.669 using Cronbach's alpha. When EID and PUM survey statements were analysed alone, internal consistency was 0.692 and 0.545 respectively. The association between scores and select demographic variables were analysed and no correlation was found. The previously validated scale (UK) was not reliable in the complex cultural population of Florida. CONCLUSIONS: Instruments demonstrating reliability in one country are not immediately replicable in other countries, even if the same language is spoken. Caution needs to be taken when interpreting the findings from studies using instruments designed in cultural contexts dissimilar from those in which the have been developed originally.

Economic burden of spinal muscular atrophy in the United States: a contemporary assessment.

Aims: To estimate healthcare resource utilization (HRU) and costs among patients with spinal muscular atrophy (SMA) type 1 (SMA1) in real-world practice, overall and among patients treated with nusinersen. As a secondary objective, HRU and costs were estimated among patients with other SMA types (i.e. 2, 3, or 4 combined), overall and among patients treated with nusinersen.Materials and methods: Patients with SMA were identified from the Symphony Health's Integrated Dataverse (IDV) open claims database (September 1, 2016-August 31, 2018) and were classified into four cohorts based on SMA type and nusinersen treatment (i.e. SMA1, SMA1 nusinersen, other SMA, and other SMA nusinersen cohorts). The index date was the date of the first SMA diagnosis after December 23, 2016 or, for nusinersen cohorts, the date of nusinersen initiation. The study period spanned from the index date to the earlier among the end of clinical activity or data availability.Results: Patients in the SMA1 (n = 349) and SMA1 nusinersen (n = 45) cohorts experienced an average of 59.4 and 56.6 days with medical visits per-patient-per-year (PPPY), respectively, including 14.1 and 4.6 inpatient days. Excluding nusinersen-related costs, total mean healthcare costs were $137,627 and $92,618 PPPY in the SMA1 and SMA1 nusinersen cohorts, respectively. Mean nusinersen-related costs were $191,909 per-patient-per-month (PPPM) for the first 3 months post-initiation (i.e. loading phase) and $36,882 PPPM thereafter (i.e. maintenance phase). HRU and costs were also substantial among patients in the other SMA (n = 5,728) and other SMA nusinersen (n = 404) cohorts, with an average of 44.5 and 63.7 days with medical visits PPPY and total mean healthcare costs (excluding nusinersen-related costs) of $49,175 and $76,371 PPPY, respectively.Limitations: The database may contain inaccuracies or omissions in diagnoses, procedures, or costs, and does not capture medical services outside of the IDV network.Conclusions: HRU and healthcare costs were substantial in patients with SMA, including in nusinersen-treated patients.

RESTORE: A Prospective Multinational Registry of Patients with Genetically Confirmed Spinal Muscular Atrophy - Rationale and Study Design.

BACKGROUND: Dramatic improvements in spinal muscular atrophy (SMA) treatment have changed the prognosis for patients with this disease, leading to important new questions. Gathering representative, real-world data about the long-term efficacy and safety of emerging SMA interventions is essential to document their impact on patients and caregivers. OBJECTIVES: This registry will assess outcomes in patients with genetically confirmed SMA and provide information on the effectiveness and long-term safety of approved and emerging treatments. DESIGN AND METHODS: RESTORE is a prospective, multicenter, multinational observational registry. Patients will be managed according to usual clinical practice. Both newly recruitedSMAtreatment centers and sites involved in existing SMA registries, including iSMAC, Treat-NMD, French SMA Assistance Publique- Hôpitaux de Paris (AP-HP), Cure-SMA, SMArtCARE, will be eligible to participate; de novo; sites already participating in another registry may be included via consortium agreements. Data from patients enrolled in partnering registries will be shared with the RESTORE Registry and data for newly diagnosed patients will be added upon enrollment. Patients will be enrolled over a 5-year period and followed for 15 years or until death. Assessments will include SMA history and treatment, pulmonary, nutritional, and motor milestones, healthcare resource utilization, work productivity, activity impairment, adverse events, quality of life, caregiver burden, and survival.Status:Recruitment started in September 2018. As of January 3, 2020, 64 patients were enrolled at 25 participating sites. CONCLUSIONS: The RESTORE Registry has begun recruiting recently diagnosed patients with genetically confirmed SMA, enabling assessment of both short- and long-term patient outcomes.

The Genome Sequencer FLX System--longer reads, more applications, straight forward bioinformatics and more complete data sets.

The Genome Sequencer FLX System (GS FLX), powered by 454 Sequencing, is a next-generation DNA sequencing technology featuring a unique mix of long reads, exceptional accuracy, and ultra-high throughput. It has been proven to be the most versatile of all currently available next-generation sequencing technologies, supporting many high-profile studies in over seven applications categories. GS FLX users have pursued innovative research in de novo sequencing, re-sequencing of whole genomes and target DNA regions, metagenomics, and RNA analysis. 454 Sequencing is a powerful tool for human genetics research, having recently re-sequenced the genome of an individual human, currently re-sequencing the complete human exome and targeted genomic regions using the NimbleGen sequence capture process, and detected low-frequency somatic mutations linked to cancer.

The uses and benefits of cluster analysis in pharmacy research.

PURPOSE: Cluster analysis (CA) refers to a set of analytic procedures that reduce complex multivariate data into smaller subsets or groups. Compared with other data reduction methods, such as factor analysis, CA yields groupings that are based on the similarity of whole cases, as opposed to the individual variables that comprise those cases. CA represents a valuable analytic tool for the health sciences, and may be used to devise patient or consumer profiles, or in the development of classification systems or taxonomies. CA has become a more widely used analytic tool because before the advent of personal computers with high processing power, CA methods were too complex to be time efficient. Yet in the past few decades, interest in and the applied use of CA have advanced considerably. CA tools are now integrated into most popular statistical software packages and are therefore more accessible. METHODS: The authors provide a discussion of CA that seeks to introduce the various methods, issues, and considerations to the researcher who is largely unfamiliar with CA. A conceptual understanding of CA is guided through breaking down CA into a series of steps and issues to consider including composition of the dataset, selection of variables, decisions about standardizing variables, selecting a measure of association, selecting a clustering method, determining the number of clusters, and interpretation. RESULTS/CONCLUSIONS: Because the range of CA methods is diverse, and because the steps within each method are so varied, an attempt to offer a complete "how-to" process in a single article is imprudent. Rather, the novice reader will be able to use this article as a starting point for conducting his or her own particular CA study.

Cognitive services provided by pharmacists: is the public willing to pay for them?

OBJECTIVES: The primary objective of this study was to determine if the respondents were willing to pay out-of-pocket for specific pharmacist medication therapy management services and patient education services. Secondary objectives were to determine the extent to which the respondents were willing to pay for these services based on percentage of out-of-pocket payment and to differentiate willingness to pay among demographics (age, gender, income). DESIGN: A cross-sectional study. SETTING: Three cities in Florida. PARTICIPANTS: Individuals volunteering to complete a survey instrument. MAIN OUTCOME MEASURES: Participants were asked if they would be willing to pay for certain services based on the proportion of payment that would be out-of-pocket. "Willingness to pay" was measured on a five-point Likert scale. The payment scale of 0%, 20%, and 100% was used to mirror other medical and professional expenses and comparable insurance coverage for those services. RESULTS: The majority of the sample population, 70%, was willing to pay 20% out-of-pocket for pharmacist cognitive services. Income and age versus willingness to pay 20% varied from 64% to 78% and 50% to 79%, respectively. Males were slightly less willing to pay 20% than females, 68% versus 71%. CONCLUSION: Respondent's willingness to pay for pharmacist cognitive services appeared to be correlated with insurance coverage and out-of-pocket expense and inversely proportional to the amount of out-of-pocket expense to the patient. Of those willing to use pharmacist cognitive services, 47% of the sample were willing to pay 100% out-of-pocket for pharmacist cognitive services, 70% were willing to pay a copay of 20%, and 85% were willing to use these services if insurance paid 100% of the cost.

Toward a new era in sequencing.

Sequencing is a powerful tool that helps scientists in gaining new insights in many areas of medicine and biology. The electrophoresis-based Sanger method is currently the most popular sequencing technology and was the foundation stone of the human genome project. With the Sanger technique it became possible to sequence not only complete genomes, but also fragments of genomes. Nowadays, this standard method is very close to reach its limits.

Prevalence of and interest in unionization among staff pharmacists.

BACKGROUND: Although the propensity for staff pharmacists to join a labor union has never been high, conditions in the profession and workplace have changed over the last decade. Some of these changes may result in staff pharmacists joining a labor union, as well as increased interest in staff pharmacists who are currently not union members to join. OBJECTIVES: The objectives of this study were to (1) assess the degree of union membership among staff pharmacists in 6 states, (2) compare the practice settings, work activities and conditions, compensation, and demographic characteristics between union and nonunion staff pharmacists, (3) assess the level of interest in joining a union among nonunion staff pharmacists, and (4) compare the practice settings, work activities and working conditions, wages and benefits, and demographic characteristics between nonunion staff pharmacists interested in joining a union and nonunion staff pharmacists who were not interested in joining a union. METHODS: A biennial pharmacist compensation study was conducted in 6 states (Florida, Iowa, Illinois, Minnesota, Tennessee, Wisconsin) in late 2003. Randomly selected pharmacists were mailed a self-administered questionnaire asking about their practice setting, work activities and conditions, wages and benefits, and demographic characteristics. Respondents were also asked to indicate current membership in a union and, if not a member, their desire to unionize their workplace. RESULTS: Compensation and unionization data were provided by 2,180 respondents (27% usable response rate), of which 1,226 (56%) were staff pharmacists. Eight percent of the staff pharmacists were union members, whereas 18% of nonunion members would vote to unionize their workplace. There were few statistically significant differences between union and nonunion staff pharmacists regarding work activities, working conditions, and hourly wages. However, the benefits provided to union staff pharmacists differed from those provided to nonunion staff pharmacists in several ways. Union staff pharmacists were younger than their nonunion counterparts (40.9 vs 44.5 years, P=.01), yet had worked for their current employers a longer time (11.1 vs 7.3 years, P=.03). Nonunion staff pharmacists interested in joining a union differed from those who would not by practice location and setting, working conditions, and benefits. CONCLUSIONS: Although the union membership rate among staff pharmacists is relatively low, there are geographic and practice areas where membership rates are higher. Differences in work activities, working conditions, wages, and benefits were noted between union and nonunion staff pharmacists as well as between those who would join a union and those who would not. These differences merit further investigation, especially with respect to evaluating the effectiveness of unions and identifying factors that may lead nonunionized staff pharmacists to join a union.

Examining gender salary disparities: an analysis of the 2003 multistate salary survey.

BACKGROUND: Pharmacist salary and wage surveys have been conducted at the state and national level for more than 20 years; however, it is not known to what extent, if any, wage disparities due to gender still exist. OBJECTIVES: The overall objective of this study was to determine if wage disparities exist among male and female pharmacists at the multistate and individual state level for each of 6 states studied. A secondary objective was to explore the effect of various demographic variables on the hourly wages of pharmacists. METHODS: Data were collected from 1,688 pharmacists in 6 states during 2003 using a cross-sectional descriptive survey design. A multiple regression analysis on hourly wage testing the effects of state of practice, practice setting, position, terminal degree, and years in practice was conducted. Subsequent multiple regression analyses were conducted individually for each of the 6 states to test the effects of the above variables on hourly wage for both male and female pharmacists, followed by state-level analyses for male and female pharmacists, respectively. RESULTS: For the pooled data, all variables were found to be significant predictors of hourly wage, except for earning a PharmD degree without a residency or graduate degree. Gender was not a significant predictor of wage disparities in the state-level analyses. Position was the only significant predictor of wage disparities in all states (except Tennessee) such that pharmacists in management positions make significantly higher salaries than those in staff positions. CONCLUSIONS: The results of these analyses suggest that wage disparities due to gender do not exist at the state level for the 6 states surveyed, when controlling for practice setting, position, terminal degree, and years in practice. The larger number of men in management positions may explain lower wages for female pharmacists.

Methodological challenges surrounding direct-to-consumer advertising research--the measurement conundrum.

OBJECTIVES: Numerous studies have focused on the impact of direct-to-consumer (DTC) prescription drug advertising on consumer behavior and health outcomes. These studies have used various approaches to assess exposure to prescription drug advertising and to measure the subsequent effects of such advertisements. The objectives of this article are to (1) discuss measurement challenges involved in DTC advertising research, (2) summarize measurement approaches commonly identified in the literature, and (3) discuss contamination, time to action, and endogeneity as specific problems in measurement design and application. METHODS: We conducted a review of the professional literature to identify illustrative approaches to advertising measurement. Specifically, our review of the literature focused on measurement of DTC advertising exposure and effect. We used the hierarchy-of-effects model to guide our discussion of processing and communication effects. Other effects were characterized as target audience action, sales, market share, and profit. RESULTS: Overall, existing studies have used a variety of approaches to measure advertising exposure and effect, yet the ability of measures to produce a valid and reliable understanding of the effects of DTC advertising can be improved. Our review provides a framework for conceptualizing DTC measurement, and can be used to identify gaps in the literature not sufficiently addressed by existing measures. CONCLUSIONS: Researchers should continue to explore correlations between exposure and effect of DTC advertising, but are obliged to improve and validate measurement in this area.

A retrospective cohort study of economic outcomes and adherence to monotherapy with metformin, pioglitazone, or a sulfonylurea among patients with type 2 diabetes mellitus in the United States from 2003 to 2005.

OBJECTIVES: The aims of this study were to compare all-cause total health care costs and diabetes mellitus (DM)-specific health care costs between patients who were adherent or nonadherent to monotherapy with metformin, pioglitazone, or a sulfonylurea and to examine whether cost differences varied among patients using these oral antidiabetic drugs. METHODS: This was a retrospective cohort study using data from the MEDSTAT MarketScan Research Databases. Patients aged 18 to 90 years who were continuously insured between 2003 and 2005 and had > or =2 outpatient claims or > or =1 inpatient claim with a diagnosis of DM (International Classification of Diseases, Ninth Revision, Clinical Modification code 250.xx) in 2003 were eligible for the study. To be part of the final sample, patients had to fill > or =2 prescriptions for metformin, pioglitazone, or a sulfonylurea during 2003, including > or =1 prescription during the last 3 months of the year. Patients were not eligible if they were taking polytherapy or a combination drug. All eligible patients were followed in 2004 and 2005. Adherence was calculated for each year using a medication possession ratio, and was dichotomized at > or =80% as either adherent or nonadherent. Annual all-cause health care costs and diabetes-specific costs were estimated using generalized linear models, adjusting for demographic characteristics, insurance, and comorbid conditions. RESULTS: A total of 108,592 patients who met the inclusion criteria were identified. Their mean age was 63 years; 49.8% (54,037/108,592) were women. More pioglitazone users resided in the north-central or south regions (81.3% [9364/11,520]) compared with metformin (62.4% [32,550/52,156]) or sulfonylurea (62.6% [28,105/44,916]) users (P < 0.001). Mean comorbidity scores were higher in the sulfonylurea (1.78) and pioglitazone (1.69) group than in the metformin group (1.45) (P < 0.001). Mean adherence ranged from 61.3% to 73.8% during the 2 years of follow-up. After adjustment, all-cause health care costs were $12,412 annually among adherent patients and $13,258 among nonadherent patients (difference, $846 [95% CI, $747 to $945]). Diabetes-related health care costs were $2230 annually among adherent patients and $2284 among nonadherent patients (difference, $55 [95% CI, $33 to $77]). In specific monotherapy groups, adjusted annual all-cause health care costs were $336 higher (95% CI, $216 to $456) for nonadherent metformin users, $1140 higher (95% CI, $793 to $1486) for nonadherent pioglitazone users, and $1509 higher (95% CI, $1339 to $1679) for nonadherent sulfonylurea users compared with adherent users. Compared with metformin users, sulfonylurea and pioglitazone users had greater adherence-related differences in all-cause health care costs (P < 0.05). There was no significant difference in diabetes-specific total costs between nonadherent and adherent patients taking metformin (difference, $6; 95% CI, -$31 to $20). Patients who were nonadherent to sulfonylureas had $271 higher (95% CI, $235 to $307) diabetes-specific costs per year than patients who were adherent to sulfonylureas. Patients who were nonadherent to pioglitazone had $433 lower (95% CI, -$516 to -$350) diabetes-specific costs per year than patients who were adherent to pioglitazone. CONCLUSIONS: Adherence with metformin, pioglitazone, or a sulfonylurea was associated with overall cost reductions in the patients studied, but these cost reductions varied by monotherapy. Adherence to sulfonylureas or pioglitazone was associated with greater total cost reductions than was adherence to metformin. Health systems that commit resources to improving interventions may be able to achieve a return on investment if adherence to oral antidiabetic agents can be improved.

The role of the mentor in retaining junior pharmacy faculty members.

The American Association of Colleges of Pharmacy (AACP) has identified faculty retention as a top concern since 76 colleges of pharmacy reported a total of 406 vacant and/or lost positions in the 2004-2005 academic year. Since today's junior faculty members are tomorrow's leaders in pharmacy education, retention of quality faculty members is critical to our future. Mentoring is one effective method of retaining faculty members and decreasing workplace stress, especially in the area of scholarship. However, in the last decade, the disproportionate increase of junior faculty members to the number of senior faculty members employed has resulted in a major limitation of the dyad (mentor and protégé) mentoring process. One effective method of overcoming this limitation is the use of the triad mentoring model (organization, mentor, and protégé). Colleges of pharmacy that consider adopting this triad model will likely promote an environment that nurtures relationships, resulting in job satisfaction, and thereby leading to retention of junior faculty members.

Comparing the T scores from bone sonometer measurements in Hispanic and non-Hispanic white women.

UNLABELLED: Ethnicity is an important risk factor for the development of osteoporosis. Non-Hispanic white or Asian women are commonly considered at higher risk than other ethnicities. Hispanics in the U.S. are of Mexican, Caribbean, Central American, or South American descent. Conclusive data on the relative risk of osteoporosis in Hispanic women based upon heritage within the Hispanic population are not available. OBJECTIVE: To investigate whether Hispanic white women are at a significantly lower risk than non- Hispanic whites for the development of osteoporosis. METHODS: Cross-sectional study. SETTING: Community health screenings. PARTICIPANTS: Hispanic and non-Hispanic white women. INTERVENTION: Bone density measurements of the non-dominant heel. Descriptive statistics and inferential statistics including regression analyses were performed using SPSS 14.0. MAIN OUTCOMES MEASURE: T scores. RESULTS: Overall, measurements were obtained from 352 women (209 Hispanic & 143 non-Hispanic white) ranging in age from 55-97 years old. The mean T score obtained for Hispanic women was - 1.194 and -1.280 for non-Hispanic white women. The correlation between the obtained T score and age was negative (r = -0.36, p<0.01), reflecting bone loss with increasing age. Regression analysis using age and ethnicity showed that ethnicity was a non-significant contributor to the best-fit regression line (t=0.60, p=0.55). CONCLUSION: This study indicates that Hispanic white women may be at comparable risk of developing osteoporosis as non-Hispanic white women.

The role of reflective practice in pharmacy.

CONTEXT: There has been a considerable paradigm shift from a product-centred focus towards a patient-centered focus in pharmacy. Pharmaceutical care practice (Cipolle et al., 1998) can be seen as the latest proposal to transform the profession as mandated by most major professional associations in pharmacy. Pharmaceutical care is an innovative way of practicing pharmacy that has the potential to make drug-therapy safer, more effective, and more convenient for the patient. Even though pharmacists' time spent on customer communication has increased over time (Savage, 1999), this alone will not be sufficient to bring about a paradigm shift in view of what the pharmacist actually does to provide quality patient care. It appears equally important to reflect on how pharmacists practice pharmacy. METHODS/OBJECTIVES: It is the aim of this discussion paper to argue for the importance of linking education and practice as a core part of the teaching of pharmaceutical care. CONCLUSION: In order for pharmacists to partake in truly interdisciplinary health care teams and the profession of pharmacy to demonstrate its unique and indispensable contribution to quality health care, pharmacy curricula would teach toward reflective practice, be problem-based, be positioned in collaborative teams, and have an outside (authentic) focus.

Illuminating the evolutionary history of chlamydiae.

Chlamydiae are the major cause of preventable blindness and sexually transmitted disease. Genome analysis of a chlamydia-related symbiont of free-living amoebae revealed that it is twice as large as any of the pathogenic chlamydiae and had few signs of recent lateral gene acquisition. We showed that about 700 million years ago the last common ancestor of pathogenic and symbiotic chlamydiae was already adapted to intracellular survival in early eukaryotes and contained many virulence factors found in modern pathogenic chlamydiae, including a type III secretion system. Ancient chlamydiae appear to be the originators of mechanisms for the exploitation of eukaryotic cells.