Ancient DNA, lipid biomarkers and palaeoecological evidence reveals construction and life on early medieval lake settlements.

Direct evidence of ancient human occupation is typically established through archaeological excavation. Excavations are costly and destructive, and practically impossible in some lake and wetland environments. We present here an alternative approach, providing direct evidence from lake sediments using DNA metabarcoding, steroid lipid biomarkers (bile acids) and from traditional environmental analyses. Applied to an early Medieval Celtic settlement in Ireland (a crannog) this approach provides a site chronology and direct evidence of human occupation, crops, animal farming and on-site slaughtering. This is the first independently-dated, continuous molecular archive of human activity from an archeological site, demonstrating a link between animal husbandry, food resources, island use. These sites are under threat but are impossible to preserve in-situ so this approach can be used, with or without excavation, to produce a robust and full site chronology and provide direct evidence of occupation, the use of plants and animals, and activities such as butchery.

Mapping the birch and grass pollen seasons in the UK using satellite sensor time-series.

Grass and birch pollen are two major causes of seasonal allergic rhinitis (hay fever) in the UK and parts of Europe affecting around 15-20% of the population. Current prediction of these allergens in the UK is based on (i) measurements of pollen concentrations at a limited number of monitoring stations across the country and (ii) general information about the phenological status of the vegetation. Thus, the current prediction methodology provides information at a coarse spatial resolution only. Most station-based approaches take into account only local observations of flowering, while only a small number of approaches take into account remote observations of land surface phenology. The systematic gathering of detailed information about vegetation status nationwide would therefore be of great potential utility. In particular, there exists an opportunity to use remote sensing to estimate phenological variables that are related to the flowering phenophase and, thus, pollen release. In turn, these estimates can be used to predict pollen release at a fine spatial resolution. In this study, time-series of MERIS Terrestrial Chlorophyll Index (MTCI) data were used to predict two key phenological variables: the start of season and peak of season. A technique was then developed to estimate the flowering phenophase of birch and grass from the MTCI time-series. For birch, the timing of flowering was defined as the time after the start of the growing season when the MTCI value reached 25% of the maximum. Similarly, for grass this was defined as the time when the MTCI value reached 75% of the maximum. The predicted pollen release dates were validated with data from nine pollen monitoring stations in the UK. For both birch and grass, we obtained large positive correlations between the MTCI-derived start of pollen season and the start of the pollen season defined using station data, with a slightly larger correlation observed for birch than for grass. The technique was applied to produce detailed maps for the flowering of birch and grass across the UK for each of the years from 2003 to 2010. The results demonstrate that the remote sensing-based maps of onset flowering of birch and grass for the UK together with the pollen forecast from the Meteorology Office and National Pollen and Aerobiology Research Unit (NPARU) can potentially provide more accurate information to pollen allergy sufferers in the UK.

Factors impacting on patient perception of procedural success and satisfaction following treatment for varicose veins.

BACKGROUND: Patient-reported outcome measures (PROMs) have been collected from patients undergoing varicose vein treatments in the National Health Service since 2009. The aim of this retrospective cohort study was to examine PROMs for varicose vein interventions, characterizing factors that might predict patient-reported perception of procedural success and satisfaction. METHODS: Centrally compiled PROMs data for varicose vein procedures carried out from 2009 to 2011 were obtained from the Hospital Episode Statistics data warehouse for England. As data were not distributed normally, non-parametric statistical tests were employed. RESULTS: Data for 35 039 patient episodes (62·8 per cent women) were available for analysis. Some 23·4 per cent of patients reported a degree of anxiety or depression before treatment; a formal diagnosis of depression was present in 7·8 per cent. Quality of life, measured by generic EQ-5D-3L™ index and the Aberdeen Varicose Vein Questionnaire (AVVQ) improved after intervention by 11·7 per cent (0·77 to 0·86) and 40·1 per cent (18·95 to 11·36) respectively. No significant improvement was found in EQ-5D™ visual analogue scale scores. There was a significant improvement in self-perceived anxiety or depression after the intervention (P < 0·001, McNemar-Bowker test). Both preoperative and postoperative depression or anxiety had a statistically significant relationship with self-reported success and satisfaction (both P < 0·001, χ(2) test). CONCLUSION: This analysis of PROMs is evidence that treatment of varicose veins improves quality of life, and anxiety or depression. Preoperative and postoperative anxiety or depression scores impact on patient-perceived success and satisfaction rates.

Safety of carotid intervention following thrombolysis in acute ischaemic stroke.

OBJECTIVES: Thrombolysis is effective in improving clinical outcome in the treatment of acute ischaemic stroke. However, thrombolysis results in low recanalisation rates, particularly in the event of carotid occlusion. Carotid intervention is indicated in stroke resulting from significant carotid atherosclerosis, but intervention soon after thrombolysis may be associated with increased risks. This study aims to assess the safety of carotid intervention post-thrombolysis for acute ischaemic stroke. DESIGN: Systematic review. MATERIALS AND METHODS: MEDLINE and EMBASE were searched on 29 May 2014. Inclusion criteria were (i) intra-arterial or intravenous thrombolysis for acute ischaemic stroke; (ii) carotid intervention within 14 days of thrombolysis; and (iii) derivable primary outcome. The primary outcome was 30-day stroke or death. A meta-analysis of incidence was completed for the 30-day stroke or death rates using Freeman-Tukey arcsine transformations and assuming random effects. Point estimates with confidence intervals (CIs) were generated and heterogeneity was assessed. The strength of recommendations and quality of underlying evidence were assessed using the American College of Chest Physicians (ACCP) grading system. RESULTS: Nine included publications recorded 114 carotid endarterectomy (CEA) and four angioplasty interventions. The point estimate of 30-day stroke or death for CEA was 4.93% (95% CI 1.83-9.44), representing four of 114. The strength of recommendation and quality of underlying evidence for CEA as per the ACCP grading system was determined as 1C. There were no cases of stroke or death in patients undergoing angioplasty post-thrombolysis (0/4). CONCLUSIONS: Early CEA post-thrombolysis appears safe, with stroke or death rates similar to that of the operation without thrombolysis. However, the wide CI obtained highlights the uncertainty of this result. Further, we emphasise that this recommendation is supported by low-quality evidence. Additional data are required to confirm the safety of surgery and early endovascular therapy post-thrombolysis.

Exploring the spatio-temporal relationship between two key aeroallergens and meteorological variables in the United Kingdom.

Constructing accurate predictive models for grass and birch pollen in the air, the two most important aeroallergens, for areas with variable climate conditions such as the United Kingdom, require better understanding of the relationships between pollen count in the air and meteorological variables. Variations in daily birch and grass pollen counts and their relationship with daily meteorological variables were investigated for nine pollen monitoring sites for the period 2000-2010 in the United Kingdom. An active pollen count sampling method was employed at each of the monitoring stations to sample pollen from the atmosphere. The mechanism of this method is based on the volumetric spore traps of Hirst design (Hirst in Ann Appl Biol 39(2):257-265, 1952). The pollen season (start date, finish date) for grass and birch were determined using a first derivative method. Meteorological variables such as daily rainfall; maximum, minimum and average temperatures; cumulative sum of Sunshine duration; wind speed; and relative humidity were related to the grass and birch pollen counts for the pre-peak, post peak and the entire pollen season. The meteorological variables were correlated with the pollen count data for the following temporal supports: same-day, 1-day prior, 1-day mean prior, 3-day mean prior, 7-day mean prior. The direction of influence (positive/negative) of meteorological variables on pollen count varied for birch and grass, and also varied when the pollen season was treated as a whole season, or was segmented into the pre-peak and post-peak seasons. Maximum temperature, sunshine duration and rainfall were the most important variables influencing the count of grass pollen in the atmosphere. Both maximum temperature (pre-peak) and sunshine produced a strong positive correlation, and rain produced a strong negative correlation with grass pollen count in the air. Similarly, average temperature, wind speed and rainfall were the most important variables influencing the count of birch pollen in the air. Both wind speed and rain produced a negative correlation with birch pollen count in the air and average temperature produced a positive correlation.

Pollen season and climate: is the timing of birch pollen release in the UK approaching its limit?

In light of heightened interest in the response of pollen phenology to temperature, we investigated recent changes to the onset of Betula (birch) pollen seasons in central and southern England, including a test of predicted advancement of the Betula pollen season for London. We calculated onset of birch pollen seasons using daily airborne pollen data obtained at London, Plymouth and Worcester, determined trends in the start of the pollen season and compared timing of the birch pollen season with observed temperature patterns for the period 1995-2010. We found no overall change in the onset of birch pollen in the study period although there was evidence that the response to temperature was nonlinear and that a lower asymptotic start of the pollen season may exist. The start of the birch pollen season was strongly correlated with March mean temperature. These results reinforce previous findings showing that the timing of the birch pollen season in the UK is particularly sensitive to spring temperatures. The climate relationship shown here persists over both longer decadal-scale trends and shorter, seasonal trends as well as during periods of 'sign-switching' when cooler spring temperatures result in later start dates. These attributes, combined with the wide geographical coverage of airborne pollen monitoring sites, some with records extending back several decades, provide a powerful tool for the detection of climate change impacts, although local site factors and the requirement for winter chilling may be confounding factors.

fMRI and MEG analysis of visceral pain in healthy volunteers.

BACKGROUND: Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis. METHODS: Liminal and painful rectal barostat balloon inflation thresholds were assessed in 14 female healthy volunteers. Subliminal, liminal and painful 40s periods of distension were applied in a pseudo-randomized paradigm during fMRI and MEG neuroimaging. Functional MRI data analysis was performed comparing standard box-car models of the full 40s of stimulus (Block) with models of the inflation (Ramp-On) and deflation (Ramp-Off) of the barostat. Similar models were used in MEG analysis of oscillatory activity. KEY RESULTS: Modeling the data using a standard Block analysis failed to detect areas of interest found to be active using Ramp-On and Ramp-Off models. Ramp-On generated activity in anterior insula and cingulate regions and other pain-matrix associated areas. Ramp-Off demonstrated activity of a network of posterior insula, SII and posterior cingulate. Active areas were consistent with those identified from MEG data. CONCLUSIONS & INFERENCES: In studies of visceral pain, fMRI model design strongly influences the detected activity and must be accounted for to effectively explore the fMRI data in healthy subjects and within patient groups. In particular a strong cortical response is detected to inflation and deflation of the barostat, rather than to its absolute volume.

Developing guidelines for venous thromboembolism for The National Institute for Clinical Excellence: involvement of the orthopaedic surgical panel.

Following the publication in 2007 of the guidelines from the National Institute for Health and Clinical Excellence (NICE) for prophylaxis against venous thromboembolism (VTE) for patients undergoing surgery, concerns were raised by British orthopaedic surgeons as to the appropriateness of the recommendations for their clinical practice. In order to address these concerns NICE and the British Orthopaedic Association agreed to engage a representative panel of orthopaedic surgeons in the process of developing expanded VTE guidelines applicable to all patients admitted to hospital. The functions of this panel were to review the evidence and to consider the applicability and implications in orthopaedic practice in order to advise the main Guideline Development Group in framing recommendations. The panel considered both direct and indirect evidence of the safety and efficacy, the cost-effectiveness of prophylaxis and its implication in clinical practice for orthopaedic patients. We describe the process of selection of the orthopaedic panel, the evidence considered and the contribution of the panel to the latest guidelines from NICE on the prophylaxis against VTE, published in January 2010.

Neuroimaging of individuals with Down's syndrome at-risk for dementia: evidence for possible compensatory events.

BACKGROUND: We report functional and structural brain indicators that may precede the onset of dementia in individuals with Down's syndrome (DS). METHODS: Middle-aged adults with DS (n=19), a group known to be at high risk for dementia, were studied with (1) positron emission tomography (PET) to determine cerebral glucose metabolic rate (GMR), (2) structural magnetic resonance imaging (MRI) to determine gray matter volume (GM), and (3) ratings of potential dementia indicators based on a structured interview of caregiver observations designed to evaluate individuals with low intelligence. RESULTS: Although none of the participants showed clinical signs of dementia, ratings of dementia indicators were correlated to both functional and structural imaging. The strongest correlations (p<.05, corrected for multiple comparisons) included the combination of higher GMR and decreased GM volume in parts of the temporal cortex, including the parahippocampus/hippocampus, in the thalamus, caudate, and frontal lobe (BA 47). INTERPRETATION: The combination of increased GMR overlapping with less gray matter in these areas may be consistent with a compensatory brain response to an early stage of the disease process.

Safe magnetic resonance scanning of patients with metallic middle ear implants.

OBJECTIVE: To determine the MR scanning risk to patients with otologic implants. DESIGN: We used a repeated-measures study with an additional control measure to assess two aspects of risk; (i) movement of the device in the magnetic field, and (ii) absorption of energy leading to local heating. We used an ex vivo test method that met with international standards. We measured the effects in a Philips Intera Achieva 3 Tesla (T) MR scanner using a Sense Head 8 channel RF coil. SETTING: University-based magnetic resonance research facility. MAIN OUTCOME MEASURES: Heating or displacement of the stapedectomy pistons. RESULTS: No evidence of displacement or heating was found. CONCLUSION: Complying with the ex vivo standard testing protocols, the Schuknecht and McGee wire pistons (device product numbers 140106 and 140108, respectively) were found to be safe in a 3 T MR scanner. These conclusions can be extrapolated to the in vivo case.

The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people.

Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic resonance imaging was used to measure BOLD responses to a cognitive task in 16 healthy young subjects. The data presented show an increase in the BOLD signal intensity in response to a cognitive task following ingestion of flavanol-rich cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of altered neuronal activity, or a change in vascular responsiveness, or both--the net effect then being dependent on which of the two effects is dominant. No significant effects were evident in behavioral reaction times, switch cost, and heart rate after consumption of this moderate dose of cocoa flavanols. A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health.

Effect of pregnancy on effectiveness of laparoscopic Nissen fundoplication.

BACKGROUND: Symptoms of gastroesophageal reflux disease (GERD) are experienced by up to 85% of pregnant women. Some young women on maintenance proton pump inhibitor (PPI) treatment are choosing surgery to stop their medical treatment and avoid severe symptoms during pregnancy. There are no reports describing the effect of pregnancy on the long-term efficacy of laparoscopic Nissen fundoplication. The aim of this study was to evaluate the effect of pregnancy on the efficacy of laparoscopic Nissen fundoplication. METHODS: This study surveyed 146 women of childbearing age with proven GERD who had undergone laparoscopic Nissen fundoplication from 1992 through 2002. The patients who became pregnant (group 1) were compared with those who did not (group 2). RESULTS: The study focused on 25 patients who became pregnant after surgery. Of these patients, 40% (n = 10) had chosen surgery as a way to discontinue PPI treatment before pregnancy. The mean time from laparoscopic Nissen fundoplication to pregnancy was 25.9 +/- 4.6 months. A total of 19 patients (76%) had no reflux symptoms, whereas 5 (20%) required antacids during pregnancy. One patient (4%) experienced an acute intrathoracic stomach migration during her pregnancy and required emergency open surgery, which resulted in the loss of her fetus. After pregnancy, six patients (24%) had recurrence of GERD symptoms, and three (12%) required a redo fundoplication. The higher rate of GERD recurrence (24% vs 16.7%) and redo surgery (12% vs 4%) in group 1 did not reach statistical significance, but showed a definite trend. CONCLUSION: For most patients, laparoscopic Nissen fundoplication is effective in controlling GERD symptoms during and after pregnancy.

Identification and characterisation of constitutional chromosome abnormalities using arrays of bacterial artificial chromosomes.

Constitutional chromosome deletions and duplications frequently predispose to the development of a wide variety of cancers. We have developed a microarray of 6000 bacterial artificial chromosomes for array-based comparative genomic hybridisation, which provides an average resolution of 750 kb across the human genome. Using these arrays, subtle gains and losses of chromosome regions can be detected in constitutional cells, following a single overnight hybridisation. In this report, we demonstrate the efficiency of this procedure in identifying constitutional deletions and duplications associated with predisposition to retinoblastoma, Wilms tumour and Beckwith-Wiedemann syndrome.

Natural therapies for ocular disorders, part two: cataracts and glaucoma.

Pathophysiological mechanisms of cataract formation include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Nutrients to increase glutathione levels and activity include lipoic acid, vitamins E and C, and selenium. Cataract patients also tend to be deficient in vitamin A and the carotenes, lutein and zeaxanthin. The B vitamin riboflavin appears to play an essential role as a precursor to flavin adenine dinucleotide (FAD), a co-factor for glutathione reductase activity. Other nutrients and botanicals, which may benefit cataract patients or help prevent cataracts, include pantethine, folic acid, melatonin, and bilberry. Diabetic cataracts are caused by an elevation of polyols within the lens of the eye catalyzed by the enzyme aldose reductase. Flavonoids, particularly quercetin and its derivatives, are potent inhibitors of aldose reductase. Glaucoma is characterized by increased intraocular pressure (IOP) in some but not all cases. Some patients with glaucoma have normal IOP but poor circulation, resulting in damage to the optic nerve. Faulty glycosaminoglycan (GAG) synthesis or breakdown in the trabecular meshwork associated with aqueous outflow has also been implicated. Similar to patients with cataracts, those with glaucoma typically have compromised antioxidant defense systems as well. Nutrients that can impact GAGs such as vitamin C and glucosamine sulfate may hold promise for glaucoma treatment. Vitamin C in high doses has been found to lower IOP via its osmotic effect. Other nutrients holding some potential benefit for glaucoma include lipoic acid, vitamin B12, magnesium, and melatonin. Botanicals may offer some therapeutic potential. Ginkgo biloba increases circulation to the optic nerve; forskolin (an extract from Coleus forskohlii) has been used successfully as a topical agent to lower IOP; and intramuscular injections of Salvia miltiorrhiza have shown benefit in improving visual acuity and peripheral vision in people with glaucoma.

The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis.

Gelsolin is an actin-binding/severing protein expressed in intracellular and secreted forms. It is a major regulator of the form and function of the actin cytoskeleton in most all cells. Here we demonstrate that female mice with a targeted deletion of the gelsolin gene (Gsn-/-) have defects in mammary gland morphogenesis. Two distinct defects were identified in the gelsolin-null mammary gland. First, the mammary anlage from Gsn-/- mice failed to elongate at the onset of puberty and remained rudimentary until approximately 9 weeks of age, early block (Gsn-/-(EB)). Second, after the mammary epithelium had filled the mammary fat pad, a complete lack of terminal branching, or late block, was observed (Gsn-/-(LB)). The Gsn-/-(EB) was seen in 70% of Gsn-/- mice and appeared to be dependent on a modifier gene(s) in addition to the loss of gelsolin. Gsn-/-(LB) was observed in all Gsn-/- mice. Terminal end buds (TEBs) were not evident in the mammary anlage from Gsn-/-(EB) mice until approximately 9 weeks of age. Cellular proliferation in the terminal ductal regions of Gsn-/-(EB) females was detected by bromodeoxyuridine incorporation, but was less than that found in the TEBs of age-matched controls. In mice deficient for gelsolin, mammary gland architecture was unaltered at the histological level. Lobuloalveolar development was delayed in response to pregnancy in mammary glands of Gsn-/- mice but was otherwise normal. Lactation and involution in the gelsolin-null animals were similar to those of wild-type mice. Transplantation of epithelium devoid of gelsolin into a wild-type (GsnWT) mammary fat pad resulted in proper arborization of the ductal tree. Transplantation of GsnWT epithelium into the Gsn-/- fat pad recapitulated the lack of terminal branching seen in Gsn-/- females. These results indicate that gelsolin is required in the mammary stroma for proper ductal morphogenesis. Our results provide the first evidence of an actin regulatory protein affecting mammary ductal growth through stromal-epithelial communication.