Estimating anatomical trajectories with Bayesian mixed-effects modeling.

We introduce a mass-univariate framework for the analysis of whole-brain structural trajectories using longitudinal Voxel-Based Morphometry data and Bayesian inference. Our approach to developmental and aging longitudinal studies characterizes heterogeneous structural growth/decline between and within groups. In particular, we propose a probabilistic generative model that parameterizes individual and ensemble average changes in brain structure using linear mixed-effects models of age and subject-specific covariates. Model inversion uses Expectation Maximization (EM), while voxelwise (empirical) priors on the size of individual differences are estimated from the data. Bayesian inference on individual and group trajectories is realized using Posterior Probability Maps (PPM). In addition to parameter inference, the framework affords comparisons of models with varying combinations of model order for fixed and random effects using model evidence. We validate the model in simulations and real MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. We further demonstrate how subject specific characteristics contribute to individual differences in longitudinal volume changes in healthy subjects, Mild Cognitive Impairment (MCI), and Alzheimer's Disease (AD).

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects.

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18-94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease.

Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation.

BACKGROUND: The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. METHOD: The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.

In Vivo Detection of Changes Related to Cortical Columnar Organization and Neuroinflammation Across the AD Continuum.

BACKGROUND: Alzheimer's disease (AD) neuropathology reveals progressive microstructural alterations of cortical architecture. Recent studies reported intriguing biphasic trajectories of cortical structural changes in the early stages of Alzheimer's disease (AD), comprising decreased mean diffusivity (MD) and increased cortical thickness in cognitively normal amyloid-positive individuals, ahead of increases and decreases, respectively, in subsequent disease stages. OBJECTIVE: To better understand the cytoarchitectural correlates of these observations, we assessed novel cortical diffusion tensor imaging (DTI) metrics that are correlated with disruption of cortical minicolumns and protein deposition. DESIGN: Cross-sectional and longitudinal analysis of whole brain and temporal lobe cortical diffusivity measures. Investigation of associations between baseline cortical diffusivity values and 24-month longitudinal structural-MRI changes. Investigations of the relationships between cortical diffusivity measures and biomarkers of neuroinflammation. SETTING: Alzheimer's Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: Twenty-four amyloid-negative controls (CN-), 28 amyloid-positive controls (CN+), 46 amyloid-positive subjects with mild cognitive impairment (MCI+) and 22 amyloid-positive subjects with AD were included. MEASUREMENTS: 3DT1 and DTI scans at baseline and approximately 24-month follow-up were used to calculate cortical MD and three novel cortical diffusivity measures: the angle between the radial minicolumnar axis and the principal diffusion direction (AngleR); the diffusion components perpendicular to the minicolumns (PerpPD+), and the principal diffusion component parallel with the minicolumns (ParlPD). Cortical macrostructural measurements (cortical volume fraction and cortical thickness), were used to test the hypothesis that baseline cortical diffusivity values can predict change in structural MRI outcomes over approximately 24 months. CSF soluble TREM2 and progranulin (PGRN) concentrations were used to investigate associations with microglial activity and potentially other aspects of neuroinflammation. RESULTS: Cortical diffusivity metrics revealed a dependence on disease stage, with AngleR and PerpPD+ displaying biphasic relationships and ParlPD a monotonic relationship with clinical severity. The novel metrics were able to differentiate between Amyloid+ and Amyloid- controls (AngleR) and to differentiate among disease stages along the AD continuum (PerpPD+). Linear regression revealed significant associations between baseline cortical diffusivity values and subsequent 24-month longitudinal structural-MRI changes. AngleR values were significantly associated with CSF sTREM2 and PGRN concentrations. CONCLUSIONS: Cortical diffusivity parameters reflecting minicolumnar organization and neuroinflammation may provide a sensitive and biologically interpretable measurement of cortex quality and microstructure across the AD continuum.

Endoscope decontamination incidents in England 2003-2004.

An Endoscope Task Force was established following the report of an endoscope decontamination failure in May 2004. The Task Force reviewed endoscope decontamination incidents in England from 2003 to 2004 and made recommendations to prevent further recurrences. Twenty-one incidents were reported from 19 National Health Service (NHS) Trusts, 18 of which matched the Task Force definition of an incident. Eight incidents involved failures to decontaminate auxiliary endoscope channels, seven incidents highlighted problems with automated endoscope reprocessors, and the remaining three involved disinfection practices not recommended by the British Society of Gastroenterology Guidelines. Following an assessment of the risk of transmission from blood-borne viruses, the Task Force recommended that look-back exercises were not indicated. The nature of the incidents suggested that there were problems associated with defining roles and responsibilities for endoscope decontamination, staff training and incompatibility between endoscopes and reprocessors. The Medicines and Healthcare Products Regulatory Agency subsequently issued recommendations to all NHS Trusts carrying out endoscopies.

Could epithelial ovarian cancer be associated with chlamydial infection?

PURPOSE OF INVESTIGATION: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancy in the UK. The pathogenesis of this disease is poorly understood. Our hypothesis was that chlamydial infection might play a role in the pathogenesis of EOC. METHODS: 122 serum samples of patients undergoing surgery for benign or malignant gynaecological conditions were analysed. There was a total of 41 patients with EOC (33.6%), 27 with benign cystadenomas (22.1%) and 54 with normal ovaries (44.3%). RESULTS: There was a higher incidence of IgA seropositivity and lower incidence of IgG seropositivity in the EOC group compared with the other groups; however, this was not statistically significant. There was no statistical difference in the serum IgM antibodies to chlamydia in the three different groups. CONCLUSION: Although chronic infection and persistent inflammation may contribute to the pathogenesis of EOC, and chlamydia is a common genital tract pathogen, our study did not find an association between chlamydia and EOC.

Reducing hospital-acquired infection by design: the new University College London Hospital.

The planning and building of new University College London Hospital has provided a challenge to the Infection Control Team to ensure all areas are easy to clean, air flows are correct and appropriate and that there is every opportunity for handwashing. The seven year process illustrates the paper by Stockley et al. ['Stockley JM, Constantine CE, Orr KE, The Association of Medical Microbiologists' New Hospital Developments Project Group. Building new hospitals: a UK infection control perspective.

Gastrointestinal endoscopy decontamination failure and the risk of transmission of blood-borne viruses: a review.

The risk of blood-borne virus transmission with an inadequately decontaminated endoscope during gastrointestinal endoscopy remains unclear, although it is likely to be low. A systematic review of the literature was undertaken to determine previous episodes of blood-borne virus transmission in these circumstances. In total, 31 articles were included in this review. No articles relating to possible transmission of human immunodeficiency virus were identified. The articles included were generally case series or case reports and were written prior to the comprehensive endoscope decontamination guidelines in use today. The results suggest that hepatitis B and hepatitis C transmission are low during endoscopy with an inadequately decontaminated endoscope.

Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises.

The epidemics of severe acute respiratory syndrome (SARS) in 2003 highlighted both short- and long-range transmission routes, i.e. between infected patients and healthcare workers, and between distant locations. With other infections such as tuberculosis, measles and chickenpox, the concept of aerosol transmission is so well accepted that isolation of such patients is the norm. With current concerns about a possible approaching influenza pandemic, the control of transmission via infectious air has become more important. Therefore, the aim of this review is to describe the factors involved in: (1) the generation of an infectious aerosol, (2) the transmission of infectious droplets or droplet nuclei from this aerosol, and (3) the potential for inhalation of such droplets or droplet nuclei by a susceptible host. On this basis, recommendations are made to improve the control of aerosol-transmitted infections in hospitals as well as in the design and construction of future isolation facilities.

Rectal gonorrhoea in men -- is microscopy still a useful tool?

Rectal gonorrhoea (GC) in men may cause anal discharge or proctitis, but these symptoms have been shown to correlate poorly with rectal infection. Culture of Neisseria gonorrhoeae from an exposed site offers a readily available, sensitive and cheap diagnostic test, and is currently the gold standard for diagnosis; however, these results can take a few days and therefore do not offer an instant diagnosis. Gram staining of rectal smears for N. gonorrhoeae has a low sensitivity but a high specificity when performed by experienced personnel. We audited whether rectal microscopy increased the number of patients diagnosed and treated for rectal GC at initial presentation at one inner London genitourinary clinic over a 12-month period. One hundred and thirty-six episodes of rectal GC were identified in 132 men. In all, 134/136 had rectal microscopy of whom, 47/134 (35%) were smear-positive for GC. Of the 136 cases, 90 received antibiotics for GC at their first presentation. Twenty-four of 90 (27%) would not have been treated until culture results were available, if rectal microscopy had not been performed. These results suggest that rectal microscopy remains an important tool and increases the proportion of men treated for GC at their first attendance.

Decontamination of breast pump milk collection kits and related items at home and in hospital: guidance from a Joint Working Group of the Healthcare Infection Society & Infection Prevention Society.

INTRODUCTION: A variety of methods are in use for decontaminating breast pump milk collection kits and related items associated with infant feeding. This paper aims to provide best practice guidance for decontamination of this equipment at home and in hospital. It has been compiled by a joint Working Group of the Healthcare Infection Society and the Infection Prevention Society. METHODS: The guidance has been informed by a search of the literature in Medline, the British Nursing Index, the Cumulative Index to Nursing & Allied Health Literature, Midwifery & Infant Care and the results of two surveys of UK neonatal units in 2002/3 and 2006, and of members of the Infection Prevention Society in 2014. Since limited good quality evidence was available from these sources much of the guidance represents good practice based on the consensus view of the Working Group. KEY RECOMMENDATIONS: Breast pump milk collection kits should not be reused by different mothers unless they have been sterilized in a Sterile Services Department between these different users.When used by the same mother, a detergent wash followed by thorough rinsing and drying after each use gives acceptable decontamination for most circumstances, as long as it is performed correctly.Additional decontamination precautions to washing, rinsing and drying may be used if indicated by local risk assessments and on advice from the departmental clinicians and Infection Prevention and Control Teams. The microbiological quality of the rinse water is an important consideration, particularly for infants on neonatal units.If bottle brushes or breast/nipple shields are used, they should be for use by one mother only. Decontamination should be by the processes used for breast pump milk collection kits.Dummies (soothers, pacifiers or comforters) needed for non-nutritive sucking by infants on neonatal units, should be for single infant use. Manufacturers should provide these dummies ready-to-use and individually packaged. They must be discarded at least every 24 hours or immediately if soiled with anything other than the baby's saliva. No attempt should be made to decontaminate the dummies, either before or during use. CONCLUSION: This guidance provides practical recommendations to support the safe decontamination of breast pump milk collection kits for healthcare professionals to use and communicate to other groups such as parents and carers.

Decontamination of breast pump milk collection kits and related items at home and in hospital: guidance from a Joint Working Group of the Healthcare Infection Society and Infection Prevention Society.

INTRODUCTION: A variety of methods are in use for decontaminating breast pump milk collection kits and related items associated with infant feeding. This paper aims to provide best practice guidance for decontamination of this equipment at home and in hospital. It has been compiled by a Joint Working Group of the Healthcare Infection Society and the Infection Prevention Society. METHODS: The guidance has been informed by a search of the literature in Medline, the British Nursing Index, the Cumulative Index to Nursing and Allied Health Literature, Midwifery and Infant Care, and the results of two surveys of UK neonatal units in 2002/3 and 2006, and of members of the Infection Prevention Society in 2014. Since limited good quality evidence was available from these sources, much of the guidance represents good practice based on the consensus view of the Working Group. CONCLUSION: This guidance provides practical recommendations to support the safe decontamination of breast pump milk collection kits for healthcare professionals to use and communicate to other groups such as parents and carers.

Quinolones in sexually transmitted diseases. Global experience.

The role of quinolones in sexually transmitted diseases is still being defined. In vitro and in vivo efficacy of established agents against gonorrhoea after a single oral dose is well established, although problems with emerging resistance have been identified. However, among these agents only ofloxacin is reliably active against Chlamydia trachomatis infection, and only as a course of treatment. Preliminary trials with sparfloxacin are encouraging. Other new agents show potentially useful in vitro activity, but clinical studies are awaited. To date, clinical activity of quinolones in bacterial vaginosis has been disappointing. The efficacy of newer agents with anaerobic activity will be of interest. Chancroid can be cured with ciprofloxacin or ofloxacin; resistance has been reported, but is not yet clinically significant. Ofloxacin appears to be effective therapy for pelvic inflammatory disease, without the need for additional anaerobe cover. The possibility of improved clinical efficacy justifies further in vitro and in vivo studies.

Quinolones in sexually transmitted diseases: state of the art.

Progress in the development of fluoroquinolones for the treatment of sexually transmitted diseases has been slow. New compounds have appeared with good in vitro activity against the gonococcus, Chlamydia trachomatis and the genital mycoplasmas. However, there have been increasing reports of clinically relevant resistance by the gonococcus, and chlamydial and mycoplasmal resistance in vitro has been described. Formally reported treatment studies have not been forthcoming, despite an emerging role for the newer fluoroquinolones in the ambulatory treatment of pelvic inflammatory disease.

Quinolones in sexually transmitted diseases.

The role of quinolones in the treatment of sexually transmitted diseases is assessed. Little is known of their activity against Treponema pallidum. These compounds are all highly active against Neisseria gonorrhoeae, and have produced good in vivo results with a single dose. Only the more recent compounds show useful antichlamydial activity in vitro. Clinical trials with ofloxacin demonstrate the efficacy of a single daily dose for 7 days for chlamydial genital infection in men and women. Results for treatment of bacterial vaginosis have so far been disappointing. Ciprofloxacin and fleroxacin are effective for chancroid. The potential for treating pelvic inflammatory disease with new quinolones is discussed.

Concurrent gonococcal and chlamydial infection: how best to treat.

Clinicians treating concurrent gonococcal and chlamydial infections have a variety of drugs to choose from. Neisseria gonorrhoeae is adept at developing resistance and the choice of antibiotic must be dictated to some extent by the patterns of resistance in the locality of the clinician. In contrast, resistance of Chlamydia trachomatis to some classes of drugs has been shown in vitro but does not appear to be clinically important at present. The success of treatment depends on patient compliance with the drug administration schedule. With these organisms, which can be carried asymptomatically, many patients are unlikely to comply with courses of antibiotics. Although single-dose therapy with azithromycin is available and established for chlamydial genital infection, it is more expensive and difficult to justify in a cash limited Healthcare system, and its efficacy for treating concurrent gonococcal infection requires further study. In patients where compliance is likely to be of concern, its use may be justified. Another major deterrent for completing antibiotic courses is the adverse effect profile. Most of the available drugs cause only minor adverse effects, in particular gastrointestinal. Ofloxacin has a better profile than doxycycline but is considerably more expensive. Newer fluoroquinolones, found to be effective in vitro, are being assessed in clinical studies. However, more evidence is required before recommending these over the tried and tested therapies.

Use of the ultracentrifuge vertical rotor in the detection of rubella-specific IgM on a sucrose density gradient.

A comparison was made of the performance of swing-out and vertical ultracentrifuge rotors in the detection of rubella-specific IgM on a sucrose density gradient. Tests were performed on 30 sera, of which 11 were found to contain rubella-specific IgM by both methods. The centrifugation time for the swing-out rotor was 16 hours at 35,000 rpm. This was reduced to 2 hours using the vertical rotor at 50,000 rpm. Routine use of the vertical rotor would allow a reduction in the time taken to perform the test, increase the number of sera tested each time, and reduce wear on the ultracentrifuge.

Interrelationship of Chlamydia trachomatis and other pathogens in the female genital tract.

The isolation of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Candida albicans in the female genital tract was studied in 1323 patients attending a venereal disease clinic. Disruption of the cell monolayers use for the isolation of C. trachomatis was significantly associated with the presence of T. vaginalis; this effect was markedly reduced by the addition of vancomycin to gentamicin and amphotericin B in the transport and growth media. The only significant positive association was the more frequent isolation of C. trachomatis in the presence of N. gonorrhoeae. There was a negative association between N. gonorrhoeae and C. albicans and between T. vaginalis and C. albicans, the fungus being isolated significantly less frequently when these microorganisms were present.

The Vitek analyser for routine bacterial identification and susceptibility testing: protocols, problems, and pitfalls.

Automated and semiautomated technology in microbiology has seen great advances in recent years. The choice of automated equipment for the identification and susceptibility testing of bacteria in a routine diagnostic laboratory depends on speed, accuracy, ease of use, and cost factors. The Vitek analyser (bioMerieux, UK) was installed in a busy diagnostic teaching hospital laboratory in London. This report describes one year's experience. Changes to work practice as a result of incorporating the equipment into the laboratory, and the advantages and disadvantages of automation in key areas are described in detail, together with possible solutions to problems. The Vitek analyser was found to be valuable for the speed and accuracy with which results were available for the common bacterial pathogens. Results of susceptibility testing were standardised according to NCCLS guidelines and used breakpoint MICs to ascertain susceptibility and resistance; they were an improvement on disc testing. This equipment is not a reference facility for difficult to identify organisms and many manual techniques, including some disc susceptibility testing, will have to be retained by the laboratory.