Placental Transport of Zidovudine in the Rhesus Monkey

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey

A Nuclear DNA Perspective on Delineating Evolutionarily Significant Lineages in Polyploids: The Case of the Endangered Shortnose Sturgeon (Acipenser brevirostrum)

The shortnose sturgeon, Acipenser brevirostrum, oft considered a phylogenetic relic, is listed as an “endangered species threatened with extinction” in the US and “Vulnerable” on the IUCN Red List. Effective conservation of A. brevirostrum depends on understanding its diversity and evolutionary processes, yet challenges associated with the polyploid nature of its nuclear genome have heretofore limited population genetic analysis to maternally inherited haploid characters. We developed a suite of polysomic microsatellite DNA markers and characterized a sample of 561 shortnose sturgeon collected from major extant populations along the North American Atlantic coast. The 181 alleles observed at 11 loci were scored as binary loci and the data were subjected to multivariate ordination, Bayesian clustering, hierarchical partitioning of variance, and among-population distance metric tests. The methods uncovered moderately high levels of gene diversity suggesting population structuring across and within three metapopulations (Northeast, Mid-Atlantic, and Southeast) that encompass seven demographically discrete and evolutionarily distinct lineages. The predicted groups are consistent with previously described behavioral patterns, especially dispersal and migration, supporting the interpretation that A. brevirostrum exhibit adaptive differences based on watershed. Combined with results of prior genetic (mitochondrial DNA) and behavioral studies, the current work suggests that dispersal is an important factor in maintaining genetic diversity in A. brevirostrum and that the basic unit for conservation management is arguably the local population

Clinical Trials and Medical Care: Defining the Therapeutic Misconception

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment

Monogamy of entanglement and other correlations

It has been observed by numerous authors that a quantum system being entangled with another one limits its possible entanglement with a third system: this has been dubbed the "monogamous nature of entanglement". In this paper we present a simple identity which captures the trade-off between entanglement and classical correlation, which can be used to derive rigorous monogamy relations. We also prove various other trade-offs of a monogamy nature for other entanglement measures and secret and total correlation measures.Comment: 7 pages, revtex

Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren : A population-based record linkage cohort study

Data Availability: All health data are owned by the Information Services Division of NHS National Services Scotland (https://www.isdscotland.org), and all education data are owned by the ScotXed Unit, which is part of the Educational Analytical Services Division within the Learning and Justice Directorate of the Scottish Government (www2.gov.scot/Topics/Statistics/ScotXed). Interested researchers may apply at these sites for data access. Funding: The study was sponsored by Health Data Research UK (www.hdruk.ac.uk) (grant reference number MR/S003800/1) (MF) which is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome. There was additional funding from the Carnegie Trust for the Universities of Scotland (grant reference VAC007974) (EES) and an MRC Mental Health Data Pathfinder grant (grant reference MC_PC_17217) (MF, JPP, DK, SC).Peer reviewedPublisher PD

What Research Ethics Should Learn from Genomics and Society Research: Lessons from the ELSI Congress of 2011

Research on the ethical, legal, and social implications (ELSI) of human genomics has devoted significant attention to the research ethics issues that arise from genomic science as it moves through the translational process. Given the prominence of these issues in today's debates over the state of research ethics overall, these studies are well positioned to contribute important data, contextual considerations, and policy arguments to the wider research ethics community's deliberations, and ultimately to develop a research ethics that can help guide biomedicine's future. In this essay, we illustrate this thesis through an analytic summary of the research presented at the 2011 ELSI Congress, an international meeting of genomics and society researchers. We identify three pivotal factors currently shaping genomic research, its clinical translation, and its societal implications: (1) the increasingly blurred boundary between research and treatment; (2) uncertainty — that is, the indefinite, indeterminate, and incomplete nature of much genomic information and the challenges that arise from making meaning and use of it; and (3) the role of negotiations between multiple scientific and non-scientific stakeholders in setting the priorities for and direction of biomedical research, as it is increasingly conducted “in the public square.

Standard Cosmic Ray Energetics and Light Element Production

The recent observations of Be and B in metal poor stars has led to a reassessment of the origin of the light elements in the early Galaxy. At low it is metallicity ([O/H] < -1.75), it is necessary to introduce a production mechanism which is independent of the interstellar metallicity (primary). At higher metallicities, existing data might indicate that secondary production is dominant. In this paper, we focus on the secondary process, related to the standard Galactic cosmic rays, and we examine the cosmic ray energy requirements for both present and past epochs. We find the power input to maintain the present-day Galactic cosmic ray flux is about 1.5e41 erg/s = 5e50 erg/century. This implies that, if supernovae are the sites of cosmic ray acceleration, the fraction of explosion energy going to accelerated particles is about 30%, a value which we obtain consistently both from considering the present cosmic ray flux and confinement and from the present 9Be and 6Li abundances. Using the abundances of 9Be (and 6Li) in metal-poor halo stars, we extend the analysis to show the effect of the interstellar gas mass on the standard galactic cosmic ray energetic constraints on models of Li, Be, and B evolution. The efficiency of the beryllium production per erg may be enhanced in the past by a factor of about 10; thus the energetic requirement by itself cannot be used to rule out a secondary origin of light elements. Only a clear and undisputable observational determination of the O-Fe relation in the halo will discriminate between the two processes. (abridged)Comment: 24 pages, LaTeX, uses aastex macro

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928

Characteristics of maxillofacial injuries resulting from road traffic accidents – a 5 year review of the case records from Department of Maxillofacial Surgery in Katowice, Poland

BACKGROUND: In spite of employing numerous devices improving the safety in motor vehicles, traffic accidents are still among the main reasons of maxillofacial injuries. The maxillofacial injuries remain the serious clinical problem because of the specificity of this anatomical region. The knowledge of etiologic factors and mechanisms of injuries can be helpful in a satisfactory trauma prevention. The aim of this study was to find out the incidence and the pattern of maxillofacial injuries resulting from traffic accidents in the patients treated in the Department of Maxillofacial Surgery (Silesian Medical Academy in Katowice, Poland) from January 2001 to December 2005. METHODS: The material consisted of 1024 case records of patients with maxillofacial injuries treated in the Maxillofacial Surgery Department of Silesian Medical Academy. The detailed analysis was carried out on the case records of 198 patients in the age of 3 to 68 with maxillofacial injuries resulting from traffic accidents. On the basis of data from a history, examination on admission, consultations and radiological examinations, patients' age and gender, we obtained the information on a pattern of injury and detailed description of an accident (the date and the time of an accident, the role of the patient in an accident). RESULTS: The traffic accidents were the cause of 19,93% maxillofacial injuries in the analyzed period of time. Most of the patients had injuries to the soft tissues of the face (22,21%), followed by tooth and alveolar process injuries (20,71%) and mandibular fractures (18,69%). All the types of injuries were more common in men than in women. The majority of the patients were car drivers followed by car passengers, pedestrians, cyclists and motor cyclists. The peak age of the patients was between 18 to 25 years. The prevalent number of accidents resulting in injuries to this region took place in spring, especially between noon and 4 PM. CONCLUSION: Our results exhibit that road traffic accidents remain among the main reasons of maxillofacial injuries following the traumas resulting from assaults and interpersonal violence. This succession of etiologic factors is in accordance with the data from the most developed countries. The relatively high incidence of injuries resulting from traffic accidents indicates the necessity to reinforce legislation aimed to prevent road traffic crashes and thus to reduce maxillofacial injuries among children and adults