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Synaptic loss is an early feature of neurodegenerative disease models, and is severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synaptic density in vivo. This study used [Eleven participants with clinically probable bvFTD and 25 age- and sex-matched healthy controls were included. Participants underwent dynamic [Patients with bvFTD showed severe synaptic loss compared to controls. [In accordance with preclinical models, and human postmortem evidence, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to severity. [

BackgroundIn 2019, a migrant camp on the Greek island of Samos designed for 650 people was home to over 5500. Migration rates from conflict zones remain high. We aimed to quantitatively describe demographics, living conditions and health needs in the reception centre community of Samos, Greece.MethodsA questionnaire was designed with reference to international humanitarian standards for reception centre following a consultative process with representatives of the asylum-seeker population. Domains assessed included demographics; living conditions; safety/vulnerability; and health. The questionnaire was piloted and then following feedback from participants, conducted in June 2019 on a sample of 500 asylum seekers attending Non-Governmental Organisation (NGO) centres supporting the Samos reception centre. Results500 participants: 60.6% male, 35.0% female and 4.4% did not report gender. 79.4% lived in tents. Respondents were predominantly from Afghanistan and the Democratic Republic of Congo (DRC). Respondents reported a total of 570 children in their care. 20.6% of women were pregnant. 35.4% had experienced physical violence; 7.8% reported Sexual/ Gender-based violence (SGBV). 83% reported psychological distress, 71% skin disease, 66% diarrhoea and vomiting and 64% respiratory disease. Accommodation, sanitation, and nutrition fell below internationally recognised standards, and poor access to water was significantly associated (p < 0.001) with respiratory disease, diarrhoea and vomiting, skin disease and psychological distress. ConclusionLiving conditions in the over-burdened Samos camp fall far below accepted basic humanitarian standards and are associated with overall poor health status in the camp population. Further research is imperative to analyse and monitor the diverse, varying needs of asylum-seekers in the Greek island hotspots and inform policies to improve conditions.

The hippocampus is one of the first regions to demonstrate atrophy during the prodromal stage of Alzheimer's disease. Volumetric analysis of its individual subfields could provide biomarkers with higher sensitivity than whole hippocampal volume during an earlier disease stage. We quantified the hippocampal subfields volume in a large cohort comprising healthy participants (aged 40-59) with dementia family history (FH) and controls (without FH), examined at 2 time points across 2 years. Subfield volumes were quantified using both a T1-weighted and a high-resolution T2 hippocampal magnetic resonance imaging acquisition with Freesurfer. The participants were stratified based on dementia FH, APOE genotype, and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score. Whole hippocampal volume did not differ between the groups. The volume of the molecular layer was lower in participants with an APOE ε4 genotype, but there were no differences between subjects with and without dementia FH or with an increasing CAIDE score. The molecular layer may be the first hippocampal region to demonstrate volumetric alterations in subjects at risk of dementia.

Aims To explore the integration and delivery of oncology led referrals to palliative care (PC) by examining physician attitudes and referral practices. Methods An online survey was circulated to oncologists and PC physicians in Ireland. Results The study (N = 100) comprised sixty-nine oncologists (69%) and thirty-one PC physicians (31%). Ninety-two(92%) believe patients with advanced cancer should receive concurrent treatment, however only 53% of oncologists(N = 37) routinely refer. Regarding end-of-life (EOL) care: 81% of oncologists (N = 55) are directly involved in its administration, despite 84% (N = 53) agreeing patients benefit when PC specialists coordinate EOL care. Conclusion The gulf between positive attitudes and limited implementation suggests the need for interdisciplinary changes to facilitate integration of PC in clinical practice in Ireland.

BACKGROUND: Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. OBJECTIVE: To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. METHODS: Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. RESULTS: For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. CONCLUSIONS: Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans.

Background: Cerebrospinal fluid (CSF) measures of tau and amyloid proteins have now been largely accepted to be a diagnostic tool to aid the clinical diagnosis of Alzheimer's disease (AD), but CSF is not routinely obtained in most clinical settings. There is a need, therefore, to uncover additional readily accessible peripheral biomarkers that will enable comprehensive detection of AD-specific proteins in blood and blood derivates. Objectives: Blood platelets contain proteins found in neuronal cell lines, including tau protein. Since tau protein is a characteristic of AD-neuropathology, platelet tau protein may be closely related to the central nervous process occurring in neurodegeneration. Method: Platelets from 25 AD and 26 control subjects were analysed for the microtubule-binding and C-terminal region, as well as two tau phosphorylation sites (Ser202/Thr205 and Thr181). Results: Tau protein measures did not discriminate between AD and control individuals. However, subjects with MMSE 24-27 had elevated C-terminal end tau protein (p=0.049) compared to those with MMSE >27, whereas older AD subjects (>80 years) showed higher t-tau protein in comparison to younger AD ( Conclusions: These initial findings not only confirm that platelet tau protein can be measured, but also indicate that platelet tau measures merit further study as they may be useful in indicating early stages of cognitive impairment. Further studies on larger number of participants are needed to confirm our findings.

While gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, the vast majority of MBHs are considered dormant. Occasionally, a star passing too near a MBH is torn apart by gravitational forces, leading to a bright panchromatic tidal disruption flare (TDF). While the high-energy transient Swift J164449.3+573451 ("Sw 1644+57") initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that the observations (Levan et al. 2011) suggest a sudden accretion event onto a central MBH of mass ~10^6-10^7 solar masses. We find evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 with a smaller-scale blazar. The phenomenologically novel Sw 1644+57 thus connects the study of TDFs and active galaxies, opening a new vista on disk-jet interactions in BHs and magnetic field generation and transport in accretion systems., Submitted, 32 pages including supplemental online material

SummaryTwo young dogs examined for hindlimb lameness were found to have healed femoral fractures, 2-4 cm of femoral shortening, and 1 cm of compensatory ipsilateral tibial overgrowth. Neither dog had had surgery or internal fixation. Although tibial overgrowth partially corrected for limb shortening, both dogs had chronic intermittent lameness due to malformation of the femoral condyles and secondary stifle osteoarthritis.Compensatory tibial overgrowth was found in two young dogs with femoral fractures which had healed without any surgical reduction or internal fixation. Tibial overgrowth of approximately 1 cm in each case partially compensated for 2-4 cm of femoral shortening.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.

We have compared two methods of reducing hypotension during spinal anaesthesia in elderly patients, 6% hetastarch and crystalloid or methoxamine 10 mg i.m., in terms of haemodynamic stability and requirements for additional vasopressors. Sixty-two patients (aged 60-97 yr) undergoing surgical fixation of fractured neck of femur were allocated randomly to receive 6% hetastarch (Hespan) 500 ml followed by Hartmann's solution 500 ml (group HS, n = 32) or a bolus injection of methoxamine 10 mg i.m. (group MX, n = 30), 10 min before induction of spinal anaesthesia with 0.5% hyperbaric bupivacaine 2.25-3.0 ml. Arterial pressure was measured non-invasively by an oscillotonometer at 2-min intervals from 0 to 40 min and at 5-min intervals thereafter. Methoxamine 2 mg i.v. was given if systolic arterial pressure (SAP) decreased to < 100 mm Hg. Hypotension was defined as a 25% decrease from baseline SAP or mean arterial pressure (MAP). Patient data, sensory level and blood loss were similar in the two groups. SAP and MAP increased initially from baseline until induction of spinal anaesthesia and then decreased for 30 min in both groups, but remained higher in group MX (P < 0.05). Heart rate (HR) decreased from baseline in group MX (P < 0.05) and was less than in group HS at all times from 2 to 60 min (P < 0.01). The incidence of SAP hypotension (47% vs 75%; P = 0.03, odds ratio (OR) = 3.43) and MAP hypotension (47% vs 67%; P = 0.09, OR = 2.51) was less in group MX than in group HS. Requirements for rescue methoxamine i.v. (27% vs 53%, P = 0.04, OR = 3.11) was less in group MX than in group HS but the dose of rescue methoxamine given (mean 6.3 (95% confidence intervals 3.0-9.6) vs 8.9 (5.6-12.2) mg) and time to onset of hypotension (20.7 (14.5-26.7) vs 17.3 (11.4-23.1) min) were similar in groups MX and HS, respectively. We conclude that methoxamine 10 mg i.m., given 10 min before induction of spinal anaesthesia in normovolaemic elderly patients, reduced subsequent SAP and MAP hypotension, HR and requirements for rescue vasopressor therapy compared with a combination of 6% hetastarch 500 ml and crystalloid 500 ml. The previously reported benefit of such volume administration may not extend to the elderly.

Abstract #1052 Introduction Mesenchymal Stem Cells (MSCs) are a subset of pluripotent non-haematopoeitic stem cells within the bone marrow stroma. Chemokines secreted by MSCs have been shown to influence the morphology and proliferative activity of cells within their vicinity. Dynamic reciprocal interactions occurring between circulating breast cancer cells and MSCs within the bone marrow microenvironment may facilitate further metastatic propagation and dissemination. Monocyte Chemotactic Protein-1 (MCP-1/CCL2) and Stromal Cell Derived factor 1-α (SDF-1a/CXCL12) are inflammatory chemokines with tumorigenic potential that may facilitate the cultivation of a pre-metastatic niche. Both of these chemokines have been associated with promoting and directing metastatic spread in breast cancer patients, and are know to be secreted by MSCs. The aim of this study was to elucidate the impact MSCs have on breast cancer cells and to potentially identify factors mediating these effects. Methods MSCs were isolated from bone marrow aspirates of healthy volunteers, and their pluripotency confirmed prior to use. Breast Cancer Cell lines (MDA-MB-231 & T47D) were cultured individually and on a monolayer of MSCs for a period of 72hrs. Conditioned medium was harvested from cells cultured individually and co-culture populations. The concentrations of CCL2, CXCL12 and VEGF were quantified using ELISA. Breast cancer cells were retrieved following co-culture using epithelial specific magnetic beads. RNA was extracted and changes in expression of target genes following co-culture with MSCs was investigated using RQ-PCR. Targets included CCL2, CXCL12, their cognate receptors CCR2 and CXCR4, as well as Her2, Ki-67, MMP11 - genes previously related to breast cancer tumorigenicity. Results While there was no significant change in secretion of SDF-1α or VEGF upon direct co-culture of breast cancer cells with MSCs, there was a significant increase in MCP-1 secreted by the mixed cell populations compared to those cultured alone (P Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1052.

An analysis of the serial radiographs of sixty-eight patients who were treated for congenital dislocation of the hip revealed that a growth disturbance of the proximal end of the femur that was caused by partial or complete physeal closure developed in thirty-three of these patients. The disturbances were related to the character of the metaphyseal growth-disturbance lines and were subsequently classified according to the site and extent of physeal closure. In order to study this problem, we divided the physis of the proximal end of the femur into two contiguous sections: a medial and a lateral portion. Two typical patterns of premature closure were identified: one located at the junction of the medial and lateral portions of the physis and the other located in the area of the medial portion of the physis alone. The pattern of physeal closure, together with the age of the patient at the time of closure, determines the subsequent growth of the proximal end of the femur. The final outcome of growth of the proximal end of the femur can be predicted within six months after the initial treatment. Epiphyseal changes were found to be of no prognostic significance in the absence of physeal closure.

In congenital dislocation of the hip, growth-disturbance lines as shown radiographically regularly occur in the proximal end of the femur after operative procedures are performed under general anesthesia. They can be seen in children who are between the ages of six months and four years and tend to disappear over several years. I think that the final shape of the femoral neck can be predicted by closely observing the development and displacement of the growth-disturbance lines that are induced at the time of surgical treatment.

Objective: This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo. Methods: One hundred and twelve older (≥60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up. Results: At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (±SD) averaged 176±12/86±7 mmHg and 24-h SBP/DBP 151±15/81±10 mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo