Prospective object search in dogs: mixed evidence for knowledge of What and Where

We investigated whether two dogs that had been specially trained to retrieve objects by their names were able to integrate information about the identity (What) as well as the location (Where) of those objects so that they could plan their search accordingly. In a first study, two sets of objects were placed in two separate rooms and subjects were asked to retrieve the objects, one after the other. Both dogs remembered the identity of the objects as they reliably retrieved the correct objects. One of the dogs was also able to integrate information about the object’s location as he chose the correct location in which the object had been placed. Further investigation of the second dog’s behavior revealed that she followed a more stereotyped search strategy. Despite this variation in performance, this study provides evidence for the memory of What and Where in a domestic dog and shows the prospective use of such information in a search task

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

A Careful Look at Binding Site Reorganization in the even-skipped Enhancers of Drosophila and Sepsids

Organismic and Evolutionary Biolog

Interim data monitoring to enroll higher-risk participants in HIV prevention trials

<p>Abstract</p> <p>Background</p> <p>Lower-than-expected incidence of HIV undermines sample size calculations and compromises the power of a HIV prevention trial. We evaluated the effectiveness of interim monitoring of HIV infection rates and on-going modification of recruitment strategies to enroll women at higher risk of HIV in the Cellulose Sulfate Phase III study in Nigeria.</p> <p>Methods</p> <p>We analyzed prevalence and incidence of HIV and other sexually transmitted infections, demographic and sexual behavior characteristics aggregated over the treatment groups on a quarterly basis. The site investigators were advised on their recruitment strategies based on the findings of the interim analyses.</p> <p>Results</p> <p>A total of 3619 women were screened and 1644 enrolled at the Ikeja and Apapa clinics in Lagos, and at the Central and Peripheral clinics in Port Harcourt. Twelve months after study initiation, the overall incidence of HIV was less than one-third of the pre-study assumption, with rates of HIV that varied substantially between clinics. Due to the low prevalence and incidence rates of HIV, it was decided to close the Ikeja clinic in Lagos and to find new catchment areas in Port Harcourt. This strategy was associated with an almost two-fold increase in observed HIV incidence during the second year of the study.</p> <p>Conclusion</p> <p>Given the difficulties in estimating HIV incidence, a close monitoring of HIV prevalence and incidence rates during a trial is warranted. The on-going modification of recruitment strategies based on the regular analysis of HIV rates appeared to be an efficient method for targeting populations at greatest risk of HIV infection and increasing study power in the Nigeria trial.</p> <p>Trial Registration</p> <p>The trial was registered with the ClinicalTrials.gov registry under #NCT00120770 <url>http://clinicaltrials.gov/ct2/show/NCT00120770</url></p

Prevalence of transcription promoters within archaeal operons and coding sequences

Despite the knowledge of complex prokaryotic-transcription mechanisms, generalized rules, such as the simplified organization of genes into operons with well-defined promoters and terminators, have had a significant role in systems analysis of regulatory logic in both bacteria and archaea. Here, we have investigated the prevalence of alternate regulatory mechanisms through genome-wide characterization of transcript structures of ∼64% of all genes, including putative non-coding RNAs in Halobacterium salinarum NRC-1. Our integrative analysis of transcriptome dynamics and protein–DNA interaction data sets showed widespread environment-dependent modulation of operon architectures, transcription initiation and termination inside coding sequences, and extensive overlap in 3′ ends of transcripts for many convergently transcribed genes. A significant fraction of these alternate transcriptional events correlate to binding locations of 11 transcription factors and regulators (TFs) inside operons and annotated genes—events usually considered spurious or non-functional. Using experimental validation, we illustrate the prevalence of overlapping genomic signals in archaeal transcription, casting doubt on the general perception of rigid boundaries between coding sequences and regulatory elements

Challenges of one-year longitudinal follow-up of a prospective, observational cohort study using an anonymised database:Recommendations for trainee research collaboratives

Background: trainee research collaboratives (TRCs) have pioneered high quality, prospective ‘snap-shot’ surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates, and to identify factors associated with improved follow-up rates. Methods: in this multicentre study, patients undergoing major gastrointestinal surgery were prospectively identified and followed up at one-year following surgery for six clinical outcomes. The primary outcome for this report was the follow-up rate for mortality at 1 year. The secondary outcome was the data completeness rate in those patients who were followed-up. An electronic survey was disseminated to investigators to identify strategies associated with improved follow-up. Results: of the 173 centres that collected baseline data, 126 centres registered to participate in one-year follow-up. Overall 62.3% (3482/5585) of patients were followed-up at 1 year; in centres registered to collect one-year outcomes, the follow-up rate was 82.6% (3482/4213). There were no differences in sex, comorbidity, operative urgency, or 7-day postoperative AKI rate between patients who were lost to follow-up and those who were successfully followed-up. In centres registered to collect one-year follow-up outcomes, overall data completeness was 83.1%, with 57.9% (73/126) of centres having ≥95% data completeness. Factors associated with increased likelihood of achieving ≥95% data completeness were total number of patients to be followed-up (77.4% in centres with &lt; 15 patients, 59.0% with 15–29 patients, 51.4% with 30–59 patients, and 36.8% with &gt; 60 patients, p = 0.030), and central versus local storage of patient identifiers (72.5% vs 48.0%, respectively, p = 0.006). Conclusions: TRC methodology can be used to follow-up patients identified in prospective cohort studies at one-year. Follow-up rates are maximized by central storage of patient identifiers

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude