Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

CoDaPack. An Excel and Visual Basic based software of compositional data analysis. Current version and discussion form upcoming versions

In the eighties, John Aitchison (1986) developed a new methodological approach for the statistical analysis of compositional data. This new methodology was implemented in Basic routines grouped under the name CODA and later NEWCODA inMatlab (Aitchison, 1997). After that, several other authors have published extensions to this methodology: Marín-Fernández and others (2000), Barceló-Vidal and others (2001), Pawlowsky-Glahn and Egozcue (2001, 2002) and Egozcue and others (2003). (...)

Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection.

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.

Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.

BACKGROUND In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use. METHODS This was a retrospective observational study (May 2007 to April 2010) of PTC-assessed drugs. The variables measured to describe the committee's activity were number of drugs assessed per year and number of drugs included in any of these settings: without restrictions, with criteria for use, and not included in formulary. These drugs were also analyzed by therapeutic group. To assess the degree of compliance of prescriptions, a score was calculated to determine whether prescriptions for bevacizumab, cetuximab, trastuzumab, and bortezomib were issued in accordance with PTC drug use criteria. RESULTS The PTC received requests for inclusion of 40 drugs, of which 32 were included in the hospital formulary (80.0%). Criteria for use were established for 28 (87.5%) of the drugs included. In total, 293 patients were treated with the four cancer drugs in eight different therapeutic indications. The average prescription compliance scores were as follows: bevacizumab, 83% for metastatic colorectal cancer, 100% for metastatic breast cancer, and 82.3% for non-small-cell lung cancer; cetuximab, 62.0% for colorectal cancer and 50% for head and neck cancer; trastuzumab, 95.1% for early breast cancer and 82.4% for metastatic breast cancer; and bortezomib, 63.7% for multiple myeloma. CONCLUSION The degree of compliance with criteria for use of cancer drugs was reasonably high. PTC functions need to be changed so that they can carry out more innovative tasks, such as monitoring conditions for drug use.

Adverse selection, moral hazard, and outlier payment policy

In this article, we analyze the rationale for introducing outlier payments into a prospective payment system for hospitals under adverse selection and moral hazard. The payer has only two instruments: a fixed price for patients whose treatment cost is below a threshold and a cost-sharing rule for outlier patients. We show that a fixed-price policy is optimal when the hospital is sufficiently benevolent. When the hospital is weakly benevolent, a mixed policy solving a trade-off between rent extraction, efficiency, and dumping deterrence must be preferred. We show how the optimal combination of fixed price and partially cost-based payment depends on the degree of benevolence of the hospital, the social cost of public funds, and the distribution of patients severity. [Authors]

Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla.

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMRGlc ) in excess of those in oxygen (CMRO2 ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, reporting a wide range of changes in brain lactate from 20% to 250%. The present study reports functional magnetic resonance spectroscopy measurements at 7 Tesla using the enhanced sensitivity to study a small cohort (n = 6). Small increases in lactate (19% ± 4%, P < 0.05) and glutamate (4% ± 1%, P < 0.001) were seen within the first 2 min of activation. With the exception of glucose (12% ± 5%, P < 0.001), no other metabolite concentration changes beyond experimental error were significantly observed. Therefore, the present study confirms that lactate and glutamate changes during physiological stimulation are small (i.e. below 20%) and shows that the increased sensitivity allows reproduction of previous results with fewer subjects. In addition, the initial rate of glutamate and lactate concentration increases implies an increase in CMRO2 that is slightly below that of CMRGlc during the first 1-2 min of activation.

Enhanced Model Selection for motion segmentation

In this paper a novel rank estimation technique for trajectories motion segmentation within the Local Subspace Affinity (LSA) framework is presented. This technique, called Enhanced Model Selection (EMS), is based on the relationship between the estimated rank of the trajectory matrix and the affinity matrix built by LSA. The results on synthetic and real data show that without any a priori knowledge, EMS automatically provides an accurate and robust rank estimation, improving the accuracy of the final motion segmentation

Electoral competition through issue selection

Politics must tackle multiple issues at once. In a first-best world, political competition constrains parties to prioritize issues according to the voters' true concerns. In the real world, the opposite also happens: parties manipulate voter priorities by emphasizing issues selectively during the political campaign. This phenomenon, known as priming, should allow parties to pay less attention to the issues that they intend to mute. We develop a model of endogenous issue ownership in which two vote-seeking parties (i) invest to attract voters with "better" policy proposals and (ii) choose a communication campaign to focus voter attention on specific issues. We identify novel feedbacks between communication and investment. In particular, we find that stronger priming effects can backfire by constraining parties to invest more resources in all issues, including the ones they would otherwise intend to mute. We also identify under which conditions parties prefer to focus on their "historical issues" or to engage in issue stealing. Typically, the latter happens when priming effects are strong, and historical reputations differentiates parties less.

The Impact of advice on women's and men's selection into competition

We conduct a laboratory experiment to study how advice affects the gender gap in the entry into a real-effort tournament. Our experiment is motivated by the concerns raised by approaching the gender gap through affirmative action. Advice is given by subjects who have already had some experience with the participation decision. We show that advice improves the entry decision of subjects, in that forgone earnings due to wrong entry decisions go significantly down. This is mainly driven by significantly increased entry of strong performing women, who also become significantly more confident, and reduced entry of weak performing men.

Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol.

BACKGROUND Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course. METHODS/DESIGN The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis. DISCUSSION This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia. TRIAL REGISTRATION Current Controlled Trials ISRCTN01897462.

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis.

Visual management of sags and incidents gathered in distribution substations for power quality management

Monitor a distribution network implies working with a huge amount of data coining from the different elements that interact in the network. This paper presents a visualization tool that simplifies the task of searching the database for useful information applicable to fault management or preventive maintenance of the network

Visual loss after orthopedic procedures.

Perioperative visual loss (PVL) is a very rare and unpredictable complication of surgery performed at distance from the visual pathways, mostly after spine or cardiac procedures. We report 6 consecutive patients with PVL after routine orthopedic procedures (osteosynthesis for complex fracture of the femur [2], total hip arthroplasty [2], hip prosthesis arthroplasty [1], bilateral simultaneous total knee arthroplasty [1]) and reviewed the literature on the subject. An ischemic optic neuropathy was diagnosed in all cases, and visual loss was bilateral in 5 of 6 patients. Partial visual improvement occurred in only 3 of 11 eyes. No specific therapy is available for PVL. Postoperative visual disturbances should prompt without delay an ophthalmic evaluation because emergent correction of anemia, systemic hypotension, or hypovolemia might improve visual prognosis of PVL.

Positioning an underwater vehicle through image mosaicking

Mosaics have been commonly used as visual maps for undersea exploration and navigation. The position and orientation of an underwater vehicle can be calculated by integrating the apparent motion of the images which form the mosaic. A feature-based mosaicking method is proposed in this paper. The creation of the mosaic is accomplished in four stages: feature selection and matching, detection of points describing the dominant motion, homography computation and mosaic construction. In this work we demonstrate that the use of color and textures as discriminative properties of the image can improve, to a large extent, the accuracy of the constructed mosaic. The system is able to provide 3D metric information concerning the vehicle motion using the knowledge of the intrinsic parameters of the camera while integrating the measurements of an ultrasonic sensor. The experimental results of real images have been tested on the GARBI underwater vehicle