Mining microsatellite markers from public expressed sequence tags databases for the study of threatened plants

Background Simple Sequence Repeats (SSRs) are widely used in population genetic studies but their classical development is costly and time-consuming. The ever-increasing available DNA datasets generated by high-throughput techniques offer an inexpensive alternative for SSRs discovery. Expressed Sequence Tags (ESTs) have been widely used as SSR source for plants of economic relevance but their application to non-model species is still modest. Methods Here, we explored the use of publicly available ESTs (GenBank at the National Center for Biotechnology Information-NCBI) for SSRs development in non-model plants, focusing on genera listed by the International Union for the Conservation of Nature (IUCN). We also search two model genera with fully annotated genomes for EST-SSRs, Arabidopsis and Oryza, and used them as controls for genome distribution analyses. Overall, we downloaded 16 031 555 sequences for 258 plant genera which were mined for SSRsand their primers with the help of QDD1. Genome distribution analyses in Oryza and Arabidopsis were done by blasting the sequences with SSR against the Oryza sativa and Arabidopsis thaliana reference genomes implemented in the Basal Local Alignment Tool (BLAST) of the NCBI website. Finally, we performed an empirical test to determine the performance of our EST-SSRs in a few individuals from four species of two eudicot genera, Trifolium and Centaurea. Results We explored a total of 14 498 726 EST sequences from the dbEST database (NCBI) in 257 plant genera from the IUCN Red List. We identify a very large number (17 102) of ready-to-test EST-SSRs in most plant genera (193) at no cost. Overall, dinucleotide and trinucleotide repeats were the prevalent types but the abundance of the various types of repeat differed between taxonomic groups. Control genomes revealed that trinucleotide repeats were mostly located in coding regions while dinucleotide repeats were largely associated with untranslated regions. Our results from the empirical test revealed considerable amplification success and transferability between congenerics. Conclusions The present work represents the first large-scale study developing SSRs by utilizing publicly accessible EST databases in threatened plants. Here we provide a very large number of ready-to-test EST-SSR (17 102) for 193 genera. The cross-species transferability suggests that the number of possible target species would be large. Since trinucleotide repeats are abundant and mainly linked to exons they might be useful in evolutionary and conservation studies. Altogether, our study highly supports the use of EST databases as an extremely affordable and fast alternative for SSR developing in threatened plants.

Five-year follow-up after catheter ablation of persistent atrial fibrillation using the stepwise approach and prognostic factors for success

BACKGROUND In the meantime, catheter ablation is widely used for the treatment of persistent atrial fibrillation (AF). There is a paucity of data about long-term outcomes. This study evaluates (1) 5-year single and multiple procedure success and (2) prognostic factors for arrhythmia recurrences after catheter ablation of persistent AF using the stepwise approach aiming at AF termination. METHODS AND RESULTS A total of 549 patients with persistent AF underwent de novo catheter ablation using the stepwise approach (2007-2009). A total of 493 patients were included (Holter ECGs ≥ every 6 months). Mean follow-up was 59 ± 16 months with 2.1 ± 1.1 procedures per patient. Single and multiple procedure success rates were 20.1% and 55.9%, respectively (80% off antiarrhythmic drug). Antiarrhythmic drug-free multiple procedure success was 46%. Long-term recurrences (n=171) were paroxysmal AF in 48 patients (28%) and persistent AF/atrial tachycardia in 123 patients (72%). Multivariable recurrent event analysis revealed the following factors favoring arrhythmia recurrence: failure to terminate AF during index procedure (hazard ratio [HR], 1.279; 95% confidence interval [CI], 1.093-1.497; P = 0.002), number of procedures (HR, 1.154; 95% CI, 1.051-1.267; P = 0.003), female sex (HR, 1.263; 95% CI, 1.027-1.553; P = 0.027), and the presence of structural heart disease (HR, 1.236; 95% CI, 1.003-1.524; P = 0.047). AF termination was correlated with a higher rate of consecutive procedures because of atrial tachycardia recurrences (P = 0.003; HR, 1.71; 95% CI, 1.20-2.43). CONCLUSIONS Catheter ablation of persistent AF using the stepwise approach provides limited long-term freedom of arrhythmias often requiring multiple procedures. AF termination, the number of procedures, sex, and the presence of structural heart disease correlate with outcome success. AF termination is associated with consecutive atrial tachycardia procedures.

Three-year outcomes of Straumann Bone Level SLActive dental implants in daily dental practice: a prospective non-interventional study

OBJECTIVE The aim of this investigation was to evaluate the performance of Straumann Bone Level SLActive implants in various clinical situations in daily dental practice for up to 3 years. METHOD AND MATERIALS This was a prospective, multicenter, non-interventional study in which implants were placed within approved indications in any situation deemed suitable by the treating clinician. No implant placement or loading protocol was specified, and implants were placed according to the routine treatment protocols at each participating center. RESULTS In this analysis, data were available from 342 implants in 233 patients in three countries (USA, Canada, and Switzerland). One or two implants were placed in the majority of patients (70.8% and 19.3%, respectively), mostly in the maxilla (71.3%); almost half (47.7%) were placed in the esthetic zone. Implant placement after 4 to > 16 weeks of healing was preferred in Switzerland (92.0%), while 42.0% of implants were placed immediately in the USA and Canada. A flapless procedure was performed in 25.2% of cases in the USA and Canada, compared to 0.5% in Switzerland. Cumulative implant survival and success rates after 3 years were 97.5% and 93.5%, respectively. CONCLUSION Straumann Bone Level Implants can achieve favorable outcomes and high survival rates after 3 years in daily dental practice. The survival and success rates were comparable with those achieved in formal controlled clinical trials.

Prognostic markers in lentigo maligna patients treated with imiquimod cream: A long-term follow-up study.

BACKGROUND More data are needed to define factors that predict long-term success after imiquimod therapy for lentigo maligna (LM). OBJECTIVE We sought to determine the demographic, clinical, and histologic prognostic markers of relapse-free survival in patients with LM who were treated with imiquimod. METHODS This was a single-arm, open-label, nonrandomized, prospective study. RESULTS Eighty-nine patients with histologically confirmed LM and a median follow-up time of 4.8 years after imiquimod treatment were included in our study. Sixteen patients (18%) relapsed. Statistically significant indicators of an increased risk of local recurrence included: the total number of melanocytes, the number of basal and suprabasal melanocytes and the number of pagetoid spreading melanocytes. LIMITATIONS Our study was a single-center, nonrandomized study. CONCLUSION An assessment of different melanocyte fractions in the diagnostic baseline biopsy specimen may help to predict the response of LM to imiquimod therapy.

Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice

PURPOSE Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. METHODS We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b(+) seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. RESULTS We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b(+) mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we still recorded light responses from C3H/HeOu retinal ganglion cells until the age of 24 weeks. These results show that genetic background plays an important role in the rd1 mouse pathology. CONCLUSIONS Analogous to human RP, the mouse genetic background strongly influences the rd1 phenotype. Thus, different rd1 mouse lines may follow different timelines of retinal degeneration, making exact knowledge of genetic background imperative in all studies that use rd1 models.

Evaluation of the success of medical management for presumptive thoracolumbar intervertebral disk herniation in dogs.

OBJECTIVE To determine the success of medical management of presumptive thoracolumbar disk herniation in dogs and the variables associated with treatment outcome. STUDY DESIGN Retrospective case series. ANIMALS Dogs (n=223) with presumptive thoracolumbar disk herniation. METHODS Medical records from 2 clinics were used to identify affected dogs, and owners were mailed a questionnaire about success of therapy, recurrence of clinical signs, and quality of life (QOL) as interpreted by the owner. Signalment, duration and degree of neurologic dysfunction, and medication administration were determined from medical records. RESULTS Eighty-three percent of dogs (185/223) were ambulatory at initial evaluation. Successful treatment was reported for 54.7% of dogs, with 30.9% having recurrence of clinical signs and 14.4% classified as therapeutic failures. From bivariable logistic regression, glucocorticoid administration was negatively associated with success (P=.008; odds ratio [OR]=.48) and QOL scores (P=.004; OR=.48). The duration of cage rest was not significantly associated with success or QOL. Nonambulatory dogs were more likely to have lower QOL scores (P=.01; OR=2.34). CONCLUSIONS Medical management can lead to an acceptable outcome in many dogs with presumptive thoracolumbar disk herniation. Cage rest duration does not seem to affect outcome and glucocorticoids may negatively impact success and QOL. The conclusions in this report should be interpreted cautiously because of the retrospective data collection and the use of client self-administered questionnaire follow-up. CLINICAL RELEVANCE These results provide an insight into the success of medical management for presumptive thoracolumbar disk herniation in dogs and may allow for refinement of treatment protocols.

Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin.

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥800 000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.

Complex syntax in autistic spectrum disorders: A study with relative clauses

Background The few studies that have evaluated syntax in autism spectrum disorder (ASD) have yielded conflicting findings: some suggest that once matched on mental age, ASD and typically developing controls do not differ for grammar, while others report that morphosyntactic deficits are independent of cognitive skills in ASD. There is a need for a better understanding of syntax in ASD and its relation to, or dissociation from, nonverbal abilities. Aims Syntax in ASD was assessed by evaluating subject and object relative clause comprehension in adolescents and adults diagnosed with ASD with a performance IQ within the normal range, and with or without a history of language delay. Methods & Procedures Twenty-eight participants with ASD (mean age 21.8) and 28 age-matched controls (mean age 22.07) were required to point to a character designated by relative clauses that varied in syntactic complexity. Outcomes & Results Scores indicate that participants with ASD regardless of the language development history perform significantly worse than age-matched controls with object relative clauses. In addition, participants with ASD with a history of language delay (diagnosed with high-functioning autism in the DSM-IV-TR) perform worse on subject relatives than ASD participants without language delay (diagnosed with Asperger syndrome in the DSM-IV-TR), suggesting that these two groups do not have equivalent linguistic abilities. Performance IQ has a positive impact on the success of the task for the population with ASD. Conclusions & Implications This study reveals subtle grammatical difficulties remaining in adult individuals with ASD within normal IQ range as compared with age-matched peers. Even in the absence of a history of language delay in childhood, the results suggest that a slight deficit may nevertheless be present and go undetected by standardized language assessments. Both groups with and without language delay have a similar global performance on relative clause comprehension; however, the study also indicates that the participants with reported language delay show more difficulty with subject relatives than the participants without language delay, suggesting the presence of differences in linguistic abilities between these subgroups of ASD.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874.

A retrospective analysis of factors influencing the success of autotransplanted posterior teeth

BACKGROUND Survival and success rates of tooth transplantations even after long follow-up periods have been shown to be very high. Nevertheless, it is important to analyse factors potentially influencing these rates. The aim of this study was to assess the influence on success of potential factors. METHODS The research was based on a retrospective analysis of clinical and radiological data from a sample of 59 subjects (75 transplanted teeth). The follow-up period varied from 0.44 to 12.28 years (mean 3.95 years). Success rates were calculated and depicted with Kaplan-Meier plots. Log-rank tests were used to analyse the effect of root development stage, apex width, the use of enamel matrix proteins or the surgeon on success of transplantations. RESULTS Results for success of premolar transplantations were comparable with already published data, while molars performed worse than shown in other studies. The surgeon performing the transplantation (p = 0.001) and tooth type (p ≤ 0.001) were significantly associated with transplantation success. Use of enamel matrix proteins (p = 0.10), root development stage (p = 0.13), the recipient area (p = 0.48) and apex width (p = 0.59) were not significantly associated with success. CONCLUSIONS Molar transplantations were not as successful as premolar transplantations; however, success rates varied greatly depending on the surgeon's experience. The use of enamel matrix proteins as well as root development stage, the recipient area and apex width did not show significant associations with success of tooth transplantations.

Comparative Study of Digital Rights Management Systems for Music and Text Files

Digital Rights Management Systems (DRMS) are seen by content providers as the appropriate tool to, on the one hand, fight piracy and, on the other hand, monetize their assets. Although these systems claim to be very powerful and include multiple protection technologies, there is a lack of understanding about how such systems are currently being implemented and used by content providers. The aim of this paper is twofold. First, it provides a theoretical basis through which we present shortly the seven core protection technologies of a DRMS. Second, this paper provides empirical evidence that the seven protection technologies outlined in the first section of this paper are the most commonly used technologies. It further evaluates to what extent these technologies are being used within the music and print industry. It concludes that the three main Technologies are encryption, password, and payment systems. However, there are some industry differences: the number of protection technologies used, the requirements for a DRMS, the required investment, or the perceived success of DRMS in fighting piracy.

"My One Regret...": The Case for Cultural Immersion in Study Abroad Programs

Study abroad has been an established institution in US universities for almost a century, and hundreds of thousands of students travel to all corners of the world every year. While many list some degree of cultural immersion as a main goal, most students have a difficult time achieving this. Drawing from interviews with twenty-five UConn undergraduates that studied abroad, this study attempts to identify factors that hold students back from cultural encounters. The study also discusses the 'success stories' of undergrads that made significant connections abroad, and highlights the factors that can lead to this (e.g., homestays, jobs, internships).

Conceptualizing Success in Therapeutic Wilderness Experiences: The Creation and Maintenance of Instructor-Participant Relationships

Researchers have noted that relationships created between instructors and clients in therapeutic wilderness experiences are unique (Russell, 2003; Russell & Phillips-Miller, 2001; Sklar, Anderson, & Autry, 2007; Taniguchi et al., 2009), but little research has been done to explore these relationships. The present study is an investigation of how instructors build and maintain relationships with participants, conceptualize these relationships, and define success in these tasks. Nine instructors from a wilderness program for at-risk youth participated in interviews. Data were analyzed using a line-by-line coding technique. Results of this study add to existing research on wilderness therapy and therapeutic wilderness experiences, provide models of successful instructing, and guide programs and instructors in the services they provide to their participants.

Digital repository implementation: a toolbox for streamlined success

Purpose – The purpose of this paper is to describe the tools and strategies that were employed by C/W MARS to successfully develop and implement the Digital Treasures digital repository. Design/methodology/approach – This paper outlines the planning and subsequent technical issues that arise when implementing a digitization project on the scale of the large, multi-type, automated library network. Workflow solutions addressed include synchronous online metadata record submissions from multiple library sources and the delivery of collection-level use statistics to participating library administrators. The importance of standards-based descriptive metadata and the role of project collaboration are also discussed. Findings – From the time of its initial planning, the Digital Treasures repository was fully implemented in six months. The discernable and statistically quantified online discovery and access of actual digital objects greatly assisted libraries unsure of their own staffing costs/benefits to join the repository. Originality/value – This case study may serve as a possible example of initial planning, workflow and final implementation strategies for new repositories in both the general and library consortium environment. Keywords – Digital repositories, Library networks, Data management. Paper type – Case study

A focused ethnographic study of women in recovery from alcohol abuse

Alcohol abuse and its related problems are among the most pervasive health and social concerns in the United States (U.S.) today. Women are especially vulnerable to the physical and social devastation of alcohol abuse. Yet, although there is extensive research about alcohol drinking patterns, treatment strategies, and early recovery, there is little information about the factors that facilitate successfully sustained abstinence in women. The purpose of this study was to examine and describe the common factors to successful recovery from alcohol abuse among women and to place these factors within both the context of their social networks and the larger social environment. This study draws from the population of New Mexico, where alcohol-related deaths are the highest of any state in the U.S. and the leading cause of death for individuals under the age of 65 years. The study was a focused ethnography of women who had successfully maintained long-term recovery from alcohol abuse. As an ethnographic study, data collection included participant observation, in-depth interviews with 21 women, and the collection of historical and current culturally relevant data. A purposive sampling plan was used to maximize the selection of participants who had used traditional and non-traditional approaches to recovery. As such, the analysis of the success narratives revealed two distinct findings: the first that women used several different trajectories to achieve long-term recovery. Three trajectory typologies were identified from the success narratives and labeled, A.A. as ceremony, A.A. as grounding, and Recovery as self-management. ^ However, within each of these trajectories, variations in successful recovery were seen. The second major finding was that all women articulated an overarching theme of connections as an indispensable aspect of sustained recovery. The success narratives demonstrated the powerful role that connections played in their long-term recovery and the analysis distinguished two unifying concepts of connections—those that focused beyond self (spirituality, social support, and pets) and those that focused toward self (self-nurturance, agency, and identity). This discussion will focus on the implications for clinical practice related to both women who are still actively abusing alcohol and for those who are successfully maintaining long-term recovery. ^