APOE epsilon 4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease

INTRODUCTION: Pathogenesis of Alzheimer's disease (AD) in apolipoprotein E ε4 (APOE ε4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function. METHODS: We compared levels of CSF neurogranin (Ng) between APOE ε4 carriers and noncarriers in 399 subjects with normal cognition, mild cognitive impairment (MCI), and AD. We examined associations between Ng levels and age, education, gender, CSF-Aβ42, and tau protein. RESULTS: Neurogranin levels were significantly higher in APOE ε4 carriers compared to APOE ε4 noncarriers with MCI. Levels of Ng between the APOE ε4 carriers and APOE ε4 noncarriers with AD did not differ. Ng levels were correlated with MMSE and levels of tau and Aβ42. DISCUSSION: Significantly higher CSF Ng levels in APOE ε4 carriers with MCI may reflect synaptic injury underlying early cognitive impairment. Neurogranin may be an early biomarker of AD and important for disease diagnosis and timing of intervention in APOE ε4 carriers

Market distortions and corporate governance

This paper studies corporate governance when a firm faces imperfect competition. We derive firms' decisions from utility maximization by individuals. This reduces the usual monopoly distortion. We find that corporate governance can effect the equilibrium in the product (or input) markets. This enables us to endogenize the objective function of the firm. If the firm cannot commit not to change its constitution, we find a Coaselike result where all market power is lost in the limit. We present a more abstract model of governance in the presence of market distortions and discuss its implications for the governance of universities

Aerial dissemination of Clostridium difficile spores

Background: Clostridium difficile-associated diarrhoea (CDAD) is a frequently occurring healthcare-associated infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. Environmental contamination is known to play an important contributory role in the spread of CDAD and it is suspected that contamination might be occurring as a result of aerial dissemination of C. difficile spores. However previous studies have failed to isolate C. difficile from air in hospitals. In an attempt to clarify this issue we undertook a short controlled pilot study in an elderly care ward with the aim of culturing C. difficile from the air. Methods: In a survey undertaken during February (two days) 2006 and March (two days) 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study) during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control). Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates. Results: On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air). One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007. Conclusion: This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C. difficile, a finding which may help to explain why CDAD is so persistent within hospitals and difficult to eradicate. Although preliminary, the findings reinforce concerns that current C. difficile control measures may be inadequate and suggest that improved ward ventilation may help to reduce the spread of CDAD in healthcare facilities

Illusory perceptions of space and time preserve cross-saccadic perceptual continuity

When voluntary saccadic eye movements are made to a silently ticking clock, observers sometimes think that the second hand takes longer than normal to move to its next position. For a short period, the clock appears to have stopped (chronostasis). Here we show that the illusion occurs because the brain extends the percept of the saccadic target backwards in time to just before the onset of the saccade. This occurs every time we move the eyes but it is only perceived when an external time reference alerts us to the phenomenon. The illusion does not seem to depend on the shift of spatial attention that accompanies the saccade. However, if the target is moved unpredictably during the saccade, breaking perception of the target's spatial continuity, then the illusion disappears. We suggest that temporal extension of the target's percept is one of the mechanisms that 'fill in' the perceptual 'gap' during saccadic suppression. The effect is critically linked to perceptual mechanisms that identify a target's spatial stability

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

Modification of hyperacute canine renal homograft and pig-to-dog heterograft rejection by the intra-arterial infusion of citrate

Hyperacute rejection was studied in seven presensitized canine recipients of renal homografts and in 22 canine recipients of pig kidneys. Under both experimental circumstances, untreated animals rejected the grafts within a few minutes. With the intra-arterial infusion of sodium citrate, hyperacute heterograft rejection was forestalled for the duration of therapy, and with homografts the benefit outlasted treatment by many hours. The protection of heterografts was not due solely to anticoagulation by the citrate, since heparin in large doses did not accomplish the same thing. A contributory factor may have been complement inhibition since removal of complement by the grafts was greatly reduced in the citrate-treated animals. © 1971

A Guide for applying a revised version of the PARIHS framework for implementation

<p>Abstract</p> <p>Background</p> <p>Based on a critical synthesis of literature on use of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, revisions and a companion <it>Guide </it>were developed by a group of researchers independent of the original PARIHS team. The purpose of the <it>Guide </it>is to enhance and optimize efforts of researchers using PARIHS in implementation trials and evaluations.</p> <p>Methods</p> <p>Authors used a planned, structured process to organize and synthesize critiques, discussions, and potential recommendations for refinements of the PARIHS framework arising from a systematic review. Using a templated form, each author independently recorded key components for each reviewed paper; that is, study definitions, perceived strengths/limitations of PARIHS, other observations regarding key issues and recommendations regarding needed refinements. After reaching consensus on these key components, the authors summarized the information and developed the <it>Guide</it>.</p> <p>Results</p> <p>A number of revisions, perceived as consistent with the PARIHS framework's general nature and intent, are proposed. The related <it>Guide </it>is composed of a set of reference tools, provided in Additional files. Its core content is built upon the basic elements of PARIHS and current implementation science.</p> <p>Conclusions</p> <p>We invite researchers using PARIHS for targeted evidence-based practice (EBP) implementations with a strong task-orientation to use this <it>Guide </it>as a companion and to apply the revised framework prospectively and comprehensively. Researchers also are encouraged to evaluate its use relative to perceived strengths and issues. Such evaluations and critical reflections regarding PARIHS and our <it>Guide </it>could thereby promote the framework's continued evolution.</p

The treatment of segmental tibial fractures: does patient preference differ from surgeon choice?

INTRODUCTION: Segmental tibial fractures are complex injuries with a prolonged recovery time. Current definitive treatment options include intramedullary fixation or a circular external fixator. However, there is uncertainty as to which surgical option is preferable and there are no sufficiently rigorous multi-centre trials that have answered this question. The objective of this study was to determine whether patient and surgeon opinion was permissive for a randomised controlled trial (RCT) comparing intramedullary nailing to the application of a circular external fixator. MATERIALS AND METHODS: A convenience questionnaire survey of attending surgeons was conducted during the United Kingdom's Orthopaedic Trauma Society annual meeting 2017 to determine the treatment modalities used for a segmental tibial fracture (n=63). Patient opinion was obtained from clinical patients who had been treated for a segmental tibial fracture as part of a patient and public involvement focus group with questions covering the domains of surgical preference, treatment expectations, outcome, the consent process and follow-up regime (n=5). RESULTS: Based on the surgeon survey, 39% routinely use circular frame fixation following segmental tibial fracture compared to 61% who use nail fixation. Nail fixation was reported as the treatment of choice for a closed injury in a healthy patient in 81% of surgeons, and by 86% for a patient with a closed fracture who was obese. Twenty-one percent reported that they would use a nail for an open segmental tibia fracture in diabetics who smoked, whilst 57% would opt for a nail for a closed injury with compartment syndrome, and only 27% would use a nail for an open segmental injury in a young fit sports person. The patient and public preference exercise identified that sleep, early functional outcomes and psychosocial measures of outcomes are important. CONCLUSION: We concluded that a RCT comparing definitive fixation with an intramedullary nail and a circular external fixator is justified as there remains uncertainty on the optimal surgical management for segmental tibial fractures. Furthermore, psychosocial factors and early post-operative outcomes should be reported as core outcome measures as part of such a trial