Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS. Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology, immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and microglial/macrophage activation. Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range 60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like structures. White matter lesion area was unchanged when compared with the progressive MS cases with little subpial cortical demyelination. Conclusion: Analysis of whole coronal macrosections reveals cortical demyelination is more extensive than reported by conventional histological methods. Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms. Biomarkers and/or imaging correlates of this subpial pathology are required if we are to fully comprehend the clinical disease process

Memory properties and charge effect study in Si nanocrystals by scanning capacitance microscopy and spectroscopy

In this letter, isolated Si nanocrystal has been formed by dewetting process with a thin silicon dioxide layer on top. Scanning capacitance microscopy and spectroscopy were used to study the memory properties and charge effect in the Si nanocrystal in ambient temperature. The retention time of trapped charges injected by different direct current (DC) bias were evaluated and compared. By ramp process, strong hysteresis window was observed. The DC spectra curve shift direction and distance was observed differently for quantitative measurements. Holes or electrons can be separately injected into these Si-ncs and the capacitance changes caused by these trapped charges can be easily detected by scanning capacitance microscopy/spectroscopy at the nanometer scale. This study is very useful for nanocrystal charge trap memory application

The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

<b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

Pharmacokinetics and tissue distribution of PGG–paclitaxel, a novel macromolecular formulation of paclitaxel, in nu/nu mice bearing NCI-460 lung cancer xenografts

PGG–PTX is a water-soluble formulation of paclitaxel (PTX), made by conjugating PTX to poly(l-γ-glutamylglutamine) acid (PGG) via ester bonds, that spontaneously forms a nanoparticle in aqueous environments. The purpose of this study was to compare the pharmacokinetics and tissue distribution of PTX following injection of either free PTX or PGG–PTX in mice. Both [3H]PTX and PGG–[3H]PTX were administered as an IV bolus injection to mice bearing SC NCI-H460 lung cancer xenografts at a dose of 40-mg PTX equivalents/kg. Plasma, tumor, major organs, urine, and feces were collected at intervals out to 340 h. Total taxanes, taxane extractable into ethyl acetate, and native PTX were quantified by liquid scintillation counting and HPLC. Conjugation of PTX to the PGG polymer increased plasma and tumor C max, prolonged plasma half-life and the period of accumulation in tumor, and reduced washout from tumor. In plasma injection of PGG–PTX increased total taxane AUC0–340 by 23-fold above that attained with PTX. In tumors, it increased the total taxane by a factor of 7.7, extractable taxane by 5.7, and native PTX by a factor of 3.5-fold. Conjugation delayed and reduced total urinary and fecal excretion of total taxanes. Incorporation of PTX into the PGG–PTX polymer significantly prolonged the half-life of total taxanes, extractable taxane, and native PTX in both the plasma and tumor compartments. This resulted in a large increase in the amount of active PTX delivered to the tumor. PGG–PTX is an attractive candidate for further development

Predicting Visibility of Aircraft

Visual detection of aircraft by human observers is an important element of aviation safety. To assess and ensure safety, it would be useful to be able to be able to predict the visibility, to a human observer, of an aircraft of specified size, shape, distance, and coloration. Examples include assuring safe separation among aircraft and between aircraft and unmanned vehicles, design of airport control towers, and efforts to enhance or suppress the visibility of military and rescue vehicles. We have recently developed a simple metric of pattern visibility, the Spatial Standard Observer (SSO). In this report we examine whether the SSO can predict visibility of simulated aircraft images. We constructed a set of aircraft images from three-dimensional computer graphic models, and measured the luminance contrast threshold for each image from three human observers. The data were well predicted by the SSO. Finally, we show how to use the SSO to predict visibility range for aircraft of arbitrary size, shape, distance, and coloration

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes

Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy

Gonadal function was assessed in male lymphoma survivors based on serum hormone levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and observation time. Male patients ⩽50 years at diagnosis treated for Hodgkin's (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1 January 1980 to 31 December 2002 were included. Five treatment groups were defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and NHL)(‘No/low'), 2: medium gonadotoxicity chemotherapy for NHL (‘med-NHL'), 3: medium gonadotoxicity chemotherapy for HL (‘med-HL'), 4: highly gonadotoxic chemotherapy for NHL (‘high-NHL'), 5: highly gonadotoxic chemotherapy for HL (‘high-HL'). Gonadal hormone levels were categorised into three groups: 1: All gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH, SHBG and testosterone within normal range (exocrine hypogonadism), 3: Testosterone below and/or LH above normal range (endocrine hypogonadism). One hundred and forty-four (49%) of the patients had normal gonadal hormones, 60 (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had endocrine hypogonadism. Compared to those treated with no/low gonadotoxic chemotherapy patients from all other treatment groups had significantly elevated risk for exocrine hypogonadism. Patients from the other treatment groups, except those in the med-NHL group, also had significantly elevated risk for endocrine hypogonadism compared with the group treated with no/low gonadotoxic chemotherapy. Men aged above 50 years at survey were about five times more likely to have endocrine hypogonadism compared with those less than 40 years. Because of the adverse health effects following long-lasting endocrine hypogonadism, gonadal hormones should be assessed regularly in male lymphoma survivors, especially after treatment with alkylating agents and high-dose chemotherapy with autologous stem cell support and in male patients who are 50 years and older

Larval rearing without aeration: a case study of the seven-band grouper Epinephelus septemfasciatus using a wave maker

マハタ種苗生産の初期減耗を軽減する飼育技法開発の基礎知見を得るために，通気による従来の飼育方法（容量1 kL，φ130 ㎝，水深70 ㎝：通気量200 mL/分）と，直径5 ㎝の球を水面で上下させて（1 Hz）水面に波を発生させる造波装置を用いた飼育方法で仔魚の生残を比較した。21 日間の飼育実験での造波装置の生残率は55.5％（n=1）で，対照区のそれ（11.6±14.3％, n=3）よりも顕著に高い値を示した。造波装置による水槽垂直断面の流れを計測したところ，波が水深とともに減衰していくのが確かめられた

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care