Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection

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Estrogen-inducible and liver-specific expression of the chicken very low density apolipoprotein II gene locus in transgenic mice.

We have examined the chicken Very Low Density Apolipoprotein II (apoVLDL II) gene locus in transgenic mice. A DNA fragment composed of the transcribed region, 16 kb of 5' flanking and 400 bp of 3' flanking sequences contained all the information sufficient for estrogen-inducible, liver-specific expression of the apoVLDL II gene. The far-upstream region contains a Negative Regulating Element coinciding with a DNaseI-hypersensitive site at -11 kb. In transgenic mice, the NRE at -11 kb is used for downregulating the expression to a lower maximum level. The NRE might be used for modulating apoVLDL II gene expression, and may be involved in the rapid shut-down of the expression after hormone removal

Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1

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A new rhynchocephalian from the late jurassic of Germany with a dentition that is unique amongst tetrapods.

Rhynchocephalians, the sister group of squamates (lizards and snakes), are only represented by the single genus Sphenodon today. This taxon is often considered to represent a very conservative lineage. However, rhynchocephalians were common during the late Triassic to latest Jurassic periods, but rapidly declined afterwards, which is generally attributed to their supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide important new information on the evolutionary history of the group. A new fossil relative of Sphenodon from the latest Jurassic of southern Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is unique amongst tetrapods. The dentition of this taxon consists of massive, continuously growing tooth plates, probably indicating a crushing dentition, thus representing a previously unknown trophic adaptation in rhynchocephalians. The evolution of the extraordinary dentition of Oenosaurus from the already highly specialized Zahnanlage generally present in derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of these animals. Together with other lines of evidence, this seriously casts doubts on the assumption that rhynchocephalians are a conservative and adaptively inferior lineage. Furthermore, the new taxon underlines the high morphological and ecological diversity of rhynchocephalians in the latest Jurassic of Europe, just before the decline of this lineage on this continent. Thus, selection pressure by radiating squamates or Mesozoic mammals alone might not be sufficient to explain the demise of the clade in the Late Mesozoic, and climate change in the course of the fragmentation of the supercontinent of Pangaea might have played a major role

The use of a pre-operative scoring system for the prediction of phacoemulsification case difficulty and the selection of appropriate cases to be performed by trainees

Background: To establish whether a previously validated scoring system (Habib) for the prediction of risk or likelihood of posterior capsule rupture during phacoemulsification surgery could be used to: 1. Predict the difficulty of a phacoemulsification case, and 2. Select appropriate phacoemulsification cases for trainees. Methods: The study sample was consecutive phacoemulsification cases undertaken by senior surgeons at a single ophthalmic unit over a three-week period (170 cases). Each case was scored using a potential difficulty scoring system. Immediately post-operatively, each case was given two scores by the operating surgeon (who was masked with regard to the potential complication score). The first score indicated the perceived difficulty of the case, and the second score, the degree of experience that they thought a trainee would require in order to have performed the same case without complication. Results: Using Cuzick's non-parametric test for trend, there was evidence for a trend of increasing perceived difficulty with increasing potential difficulty score (p = 0.05), and of increasing experience required with increasing potential difficulty score (p < 0.001) Conclusion: The authors advocate that Habib's potential difficulty scoring system can be used to inform the surgeon of the likely difficulty of a phacoemulsification case and to aid selection of appropriate cases for trainees prior to surgery

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy

HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

BACKGROUND: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. METHODS AND FINDINGS: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. CONCLUSIONS: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention

Cranio-spinal migration of a metallic clip placed during arteriovenous malformation resection - A case report, review of the literature, and management strategies

<p>Abstract</p> <p>Background</p> <p>Microclip placement during AVM resection is generally accepted to be a safe practice in neurosurgery. Here, we describe an unusual complication involving cranio-spinal clip migration discovered five years after the initial AVM surgery.</p> <p>Case Presentation</p> <p>A 53-year-old man underwent resection of a superior vermian AVM that required the placement of two microclips during the procedure. Five years after surgery, the patient suffered from descending sensory radiculopathy that resolved spontaneously. The workup revealed cranio-spinal migration of one of the previously placed microclips.</p> <p>Conclusions</p> <p>AVM clip migration is a rare phenomenon; however, the diagnosis should be entertained in patients with posterior fossa instrumentation who suffer from unusual neurologic symptoms.</p

The mortality rates and the space-time patterns of John Snow’s cholera epidemic map

Background Snow’s work on the Broad Street map is widely known as a pioneering example of spatial epidemiology. It lacks, however, two significant attributes required in contemporary analyses of disease incidence: population at risk and the progression of the epidemic over time. Despite this has been repeatedly suggested in the literature, no systematic investigation of these two aspects was previously carried out. Using a series of historical documents, this study constructs own data to revisit Snow’s study to examine the mortality rate at each street location and the space-time pattern of the cholera outbreak. Methods This study brings together records from a series of historical documents, and prepares own data on the estimated number of residents at each house location as well as the space-time data of the victims, and these are processed in GIS to facilitate the spatial-temporal analysis. Mortality rates and the space-time pattern in the victims’ records are explored using Kernel Density Estimation and network-based Scan Statistic, a recently developed method that detects significant concentrations of records such as the date and place of victims with respect to their distance from others along the street network. The results are visualised in a map form using a GIS platform. Results Data on mortality rates and space-time distribution of the victims were collected from various sources and were successfully merged and digitised, thus allowing the production of new map outputs and new interpretation of the 1854 cholera outbreak in London, covering more cases than Snow’s original report and also adding new insights into their space-time distribution. They confirmed that areas in the immediate vicinity of the Broad Street pump indeed suffered from excessively high mortality rates, which has been suspected for the past 160 years but remained unconfirmed. No distinctive pattern was found in the space-time distribution of victims’ locations. Conclusions The high mortality rates identified around the Broad Street pump are consistent with Snow’s theory about cholera being transmitted through contaminated water. The absence of a clear space-time pattern also indicates the water-bourne, rather than the then popular belief of air bourne, nature of cholera. The GIS data constructed in this study has an academic value and would cater for further research on Snow’s map