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The potential of antiferroelectrics to exhibit a negative capacitance regime has been largely overlooked as all the attention focused on their polar counterparts, ferroelectrics. We use nonequilibrium first-principles-based molecular dynamics to probe a negative capacitance regime in prototypical antiferroelectric PbZrO 3. Simulations predict that this antiferroelectric can exhibit a negative capacitance/susceptibility regime in response of polarization to an internal electric field, which is a superposition of applied and residual depolarizing fields. Consequently, the regime emerges when the polarization surface charge in the polar phase of antiferroelectric is not fully screened, as is often the case in thin films and nanostructures. The negative capacitance regime occurs below the Curie temperature and disappears in the paraelectric phase. We find that the time the material spends in the negative capacitance regime is proportional to the time needed to complete antipolar–polar (or its reverse) transition and shortens as the frequency of the applied field increases. Moreover, a negative susceptibility value exhibits strong dependence on the quality of surface charge screening with the largest in magnitude values occurring in the vicinity of the transition into a negative capacitance regime. [ABSTRACT FROM AUTHOR]

We present radial velocity measurements of the very bright (V ∼ 5.7) nearby F star, DMPP-4 (HD 184960). The anomalously low Ca ii H&K emission suggests mass-loss from planets orbiting a low activity host star. Periodic radial velocity variability with ∼10 m s−1 amplitude is found to persist over a >4 yr time-scale. Although the non-simultaneous photometric variability in four TESS sectors supports the view of an inactive star, we identify periodic photometric signals and also find spectroscopic evidence for stellar activity. We used a posterior sampling algorithm that includes the number of Keplerian signals, N p, as a free parameter to test and compare (1) purely Keplerian models (2) a Keplerian model with linear activity correlation and (3) Keplerian models with Gaussian processes. A preferred model, with one Keplerian and quasi-periodic Gaussian process indicates a planet with a period of |$P_\textrm {b} = 3.4982^{+0.0015}_{-0.0027}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.8}_{-1.9}$| M⊕. Without further high-time resolution observations over a longer time-scale, we cannot definitively rule out the purely Keplerian model with two candidates planets with |$P_\textrm {b} = 2.4570^{+0.0026}_{-0.0462}$| d, minimum mass |$m_\textrm {b}\, \textrm {sin}\, i = 8.0^{+1.1}_{-1.5}$| M⊕ and |$P_\textrm {c} = 5.4196^{+0.6766}_{-0.0030}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.4}_{-1.6}$| M⊕. The candidate planets lie in the region below the lower-envelope of the Neptune Desert. Continued mass-loss may originate from the highly irradiated planets or from an as yet undetected body in the system. [ABSTRACT FROM AUTHOR]

Introduction: Zuranolone (ZRN) is a positive allosteric modulator of both synaptic and extrasynaptic gamma-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the US and under investigation for adults with major depressive disorder (MDD). The randomised, double-blind, placebo-controlled, Phase 3 CORAL Study assessed the efficacy and safety of ZRN 50 mg vs placebo, each co-initiated with an open-label standard-of-care antidepressant (ADT). Patients who completed CORAL could roll over into open-label SHORELINE, which assessed the safety and tolerability of ZRN 50 mg and need for repeat treatment courses in adults with MDD. Objectives: To assess the safety and tolerability (primary endpoint) and need for repeat ZRN 50 mg treatment courses (secondary endpoint) in adults with MDD who previously enrolled in CORAL. Methods: CORAL enrolled adults (18–64 years) with MDD and 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥24. After completing the 6-week CORAL Study, patients who enrolled in SHORELINE could enter a 46-week observation period to assess the safety and need for 14-day repeat ZRN treatment course(s), with a total of ≤4 repeat treatment courses permitted. Patients were screened every 2 weeks with the 9-item Patient Health Questionnaire, and scores ≥10 prompted a HAMD-17 assessment within 1 week. Patients with HAMD-17 total score ≥20 were eligible for repeat ZRN course(s) ≥8 weeks after completing the prior ZRN treatment course. Results: Among the 190 patients from CORAL who rolled over into SHORELINE and received ≥1 ZRN treatment course in either study, 133 (70.0%) had received ZRN+ADT and 57 (30.0%) received placebo+ADT in CORAL. Overall, 118 rollover patients received ≥1 open-label ZRN treatment course in SHORELINE. For patients who received ≥1 ZRN treatment course in either study, 76.8% received 1 (54.2%; 103/190) or 2 (22.6%; 43/190) total ZRN treatment courses across both studies in up to 1 year in study. The most common (>5%) treatment-emergent adverse events (TEAEs) during treatment and 14 days following the last ZRN dose were somnolence (16.1% of patients), dizziness (8.5%), headache (8.5%), fatigue (7.6%), sedation (5.9%), and nausea (5.1%); study-period TEAEs (73.7%; 87/118) for the majority of patients were mild/moderate (69.5%; 82/118) in severity and occurred primarily during the treatment period (58.5%; 69/118). No signals for increased suicidal ideation/behaviour were observed. Conclusions: Safety and tolerability among rollover patients were consistent with previous studies; most of the TEAEs reported by adults with MDD who received ZRN were mild/moderate in severity. Most patients who rolled over from CORAL to SHORELINE received ≤2 total treatment courses in up to 1 year in study. Disclosure of Interest: G. Mattingly Grant / Research support from: Akili, Alkermes, Allergan (now AbbVie), Axsome, Boehringer, Janssen, Lundbeck, Medgenics, NLS-1 Pharma AG, Otsuka, Reckitt Benckiser, Roche, Sage, Sunovion, Supernus, Takeda, and Teva, Consultant of: Akili, Alkermes, Allergan (now AbbVie), Axsome, Ironshore, Intra-Cellular Therapies, Janssen, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Rhodes, Sage, Sunovion, Takeda, and Teva, Speakers bureau of: Alkermes, Allergan (now AbbVie), Ironshore, Janssen, Lundbeck, Otsuka, Sunovion, and Takeda, S. Mathew Grant / Research support from: Biohaven Pharmaceuticals, Boehringer-Ingelheim, Janssen, Merck, Sage Therapeutics, Inc., and VistaGen Therapeutics, Consultant of: Allergan (now AbbVie), Alkermes, Almatica Pharma, Axsome Therapeutics, BioXcel Therapeutics, Boehringer-Ingelheim, Clexio Biosciences, COMPASS Pathways, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Inc., Seelos Therapeutics, Signant Health, and Sunovion, S. Parikh Grant / Research support from: Aifred, Assurex, Janssen, Mensante, Sage Therapeutics, Inc., and Takeda, S. Aaronson Grant / Research support from: COMPASS Pathways and Neuronetics; has served as a consultant to Genomind, Inc., Janssen, LivaNova PLC, Neuronetics; and Sage Therapeutics, Inc., Speakers bureau of: Janssen and Sunovion Pharmaceuticals, Inc., B. Baune Speakers bureau of: Angelini, AstraZeneca, Biogen, Bristol Myers Squibb, Janssen, LivaNova, Lundbeck, Novartis, Otsuka, Pfizer, Servier, Sumitomo Pharma, Wyeth, and Boehringer-Ingelheim, A. Czysz Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., I. Nandy Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., V. Ona Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., C. Brown Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., S. Kyaga Employee of: Biogen Inc., F. Forrestal Employee of: Biogen Inc., S. Levin Employee of: Biogen Inc., J. Doherty Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., G. Mattingly: None Declared [ABSTRACT FROM AUTHOR]

Alluvial sand and gravel (ASG) aquifers are highly heterogeneous and exhibit strong, spatially variable anisotropy, often interspersed by buried paleo‐channels of increased hydraulic conductivity. Groundwater flow and solute transport is often characterized by preferential flow caused by anisotropic properties in ASG aquifers. Connected ASG subsurface structures such as buried paleo‐channels, however, are difficult to reproduce with commonly used techniques, and anisotropy is rarely considered in applied groundwater models. To ease the notoriously difficult problem of how to consider anisotropy, we propose a novel modeling framework based on calibration of an integrated surface‐subsurface hydrological model via spatially varying, preferred anisotropy pilot point inversion. The inversion leverages hydraulic and tracer‐based observations representing multiple spatial and temporal scales. We demonstrate the applicability of the framework on a real‐world ASG site used for drinking water production, and we quantify the information content of observations to identify connected paleo‐channels and provide guidance for optimal field‐data acquisition. Plain Language Summary: Mountainous river corridors are used worldwide for drinking water production, as they represent a relatively safe and sustainable source of drinking water. The valley‐fill of mountainous river corridors is a result of millennia of fluvio‐glacial erosion and deposition via braided river systems and consists primarily of poorly sorted sand and gravel. Groundwater flow and solute transport through such alluvial sand and gravel (ASG) aquifers is characterized by preferential flow paths caused by formerly active, now buried meanders (i.e., paleo‐channels). The identification of paleo‐channels in ASG aquifers is crucial for safe drinking water production, but they are notoriously difficult to identify with the commonly used techniques. We propose a new modeling framework based on the calibration of an integrated surface‐subsurface hydrological model via spatially varying, preferred anisotropy pilot point inversion using both hydraulic and tracer observations. The new modeling framework is more efficient than other approaches to model flow through complex ASG aquifers and doesn't require precise prior knowledge of the location of paleo‐channels. The applicability and robustness of the framework is demonstrated on an ASG drinking water wellfield located in the Swiss Alps. Key Points: Novel framework for identifying and quantifying groundwater flow through buried paleo‐channelsHeterogeneous hydraulic conductivity fields were identified based on spatially varying, preferred anisotropy‐constrained inversionThe fraction of infiltrating stream water in the aquifer and stream‐aquifer exchange fluxes best inform the paleo‐channel [ABSTRACT FROM AUTHOR]

This paper presents the results from a prediction event, organized by the University of Western Australia (UWA) and the National Geotechnical Centrifuge Facility (NGCF), and performed as part of the International Symposium on Frontiers in Offshore Geotechnics to assess uncertainty in predicting the monotonic and cyclic lateral response of conductors. Geotechnical professionals from around the world were invited to predict the response of a model conductor (a flexible pile) subjected to a series of loading sequences in a centrifuge. A normally consolidated fine-grained soil was used in the tests, which was characterized by soil elements and in-flight T-bar penetrometer testing. While some participants provided accurate predictions, the mean response was an overestimate of the monotonic and cyclic load at the pile head, which was significant for large and very small displacements. An analysis of the submissions is presented to quantify the variability of the predictions received, assess the consequences of each design, and relay the uncertainty associated with engineering judgment in design. [ABSTRACT FROM AUTHOR]

Aotearoa's (New Zealand's) biological heritage is in decline due to threats such as climate change and habitat destruction. Aotearoa's biological heritage and the wider environment are critical to the Māori world view and culture and Māori have long advocated for greater engagement in efforts to reverse this decline. One negative outcome of localised declines in biological heritage is a concomitant loss of local Māori language (dialectical) terms. Compounding this is the growing use of standardised Māori terms that can displace local dialectical terms. This also runs the risk of losing the associated mātauranga (knowledge) that is inherent in the meaning of these local terms for their unique flora and fauna. Retaining this biocultural knowledge is considered important and could play a role in conservation efforts. This collaborative research addressed the concerns articulated by a Māori biological heritage expert about the loss of their own unique local Māori terms for flora and fauna. The research explored ways to retain and empower local indigenous biocultural terms via the creation of a static visual educational resource for Tūhoe–Tuawhenua youth displaying the forest vegetation of their rohe (area that defines a tribe's traditional mandate or authority). The plants in the final resource are identified by their local Māori term and their corresponding scientific name. Depicting ecological accuracy in the artwork was a specific requirement of the kaumātua and created some unique outcomes in how the artwork formed. The approaches employed in this research and an analysis of the results and wider implementation are discussed. The loss of Māori dialects has allowed the loss of mātauranga, leading to the loss of dialectal terms for local flora and fauna. This collaborative research addressed the concerns articulated by a Māori biocultural heritage expert about the loss of their own unique local Māori terms for flora and fauna. [ABSTRACT FROM AUTHOR]

With a growing interest in the use of virtual reality (VR) for dissemination of cultural heritage sites, the question of how to leverage existing documentation as content for virtual experiences becomes a potentially valuable opportunity. Notably, as sites are increasingly documented with building information modelling (BIM) for the purposes of conservation, there is potential to give these models a second life as content for public education and promotion. However, although software exist for viewing BIM in VR headsets, they are inadequate for complex models typical of heritage buildings, and lack functionality for integrating custom didactic content and storytelling. To make BIM performative in VR and allow for custom content, a workflow was developed to translate BIM into game engine scenes — which optimizes geometry following performance guidelines of VR while maintaining the high visual fidelity of the BIM. As a case study, six heritage spaces of the Centre Block of the Canadian Parliament which had been previously documented and modelled by CIMS were prepared for Unity3D, enabling their later use in a storytelling experience. [ABSTRACT FROM AUTHOR]

The article offers information on the activity of running. In trying to answer the question why men run, a physiologist might contend that men run because they have running bodies, hearts, muscles, and bones. Man is primarily a land animal. For certain periods, he depended on himself wherever and whenever he wanted to go. Running is the prime activity in the Olympic Games. It attracts world-wide attention. Finland has produced more Olympic champions in running than any other country. Gunder Haegg of Sweden took the sport of running because of the influence of his father and friends.

For this set of tests, the strain rate of the T-bar and centrifuge tests (calculated as the displacement normalized by the T-bar/pile diameter and divided by the time) were broadly comparable, as can be observed from Fig. Undrained shear strength against strain rate of simple shear, T-bar, and centrifuge tests. As noted in the original paper, the T-bar undrained shear strength gradient yielded a very similar value as the strength gradient calculated from the simple shear tests at a slow rate, despite the T-bars being performed at (considerably) higher strain rate than the slow simple shear tests. [Extracted from the article]

The balsam twig aphid Mindarus abietinus Koch (Hemiptera: Aphididae), the spruce spider mite Oligonychus ununguis (Jacobi) (Acari: Tetranychidae), and the pine needle scale Chionaspis pinifoliae (Fitch) (Hemiptera: Diaspididae) are three important pests for the Christmas tree industry of Québec, Canada. Temperature-dependent development rates for postdiapause overwintering eggs of these species have never been studied for populations of southern Québec, where the vast majority of Christmas trees are grown. The accumulation of physiological time in growing degree days (GDD) is a standard tool to predict egg eclosion dates for pests, when first generation immatures are most vulnerable to insecticidal control. Development rates for postdiapause eggs were tested at four or five constant temperatures in the 11–23°C range under controlled conditions, based on time before hatching for eggs collected in a balsam fir plantation in late winter. The standard linear model and three published nonlinear models were fitted to the data and compared for their ability to estimate key biological temperature parameters and to predict development rates of postdiapause eggs. Validation of model predictions of egg eclosion time on balsam fir in the field was reasonably accurate using the classical linear model where field-accumulated GDD were calculated with a particular interpretation of the average method based on daily maximum and minimum temperatures. The linear model could predict mean egg eclosion within around 5 d of eclosion dates observed in the field. Le puceron des pousses du sapin Mindarus abietinus Koch (Hemiptera : Aphididae), le tétranyque de l'épinette Oligonychus ununguis (Jacobi) (Acari : Tetranychidae) et la cochenille des aiguilles du pin Chionaspis pinifoliae (Fitch) (Hemiptera : Diaspididae) sont d'importants ravageurs des arbres de Noël au Québec. Le développement des œufs hivernants postdiapausants, en fonction de la température, n'a jamais été étudié pour les populations du sud du Québec, où cette culture est concentrée. L'accumulation du temps physiologique en degrés-jours de croissance (DJ) est un outil essentiel pour prédire la date d'éclosion des œufs de ravageurs, alors que les immatures de première génération sont vulnérables aux traitements insecticides. Le taux de développement des œufs hivernants a été mesuré en conditions contrôlées pour quatre ou cinq températures constantes dans la gamme 11–23°C, calculé selon le temps de développement jusqu'à l'éclosion d'œufs collectés sur le sapin baumier. Le modèle linéaire standard et trois modèles non linéaires publiés ont été évalués pour leur capacité à prédire les paramètres biologiques de réponse à la température et le taux de développement. La prédiction de l'éclosion des œufs sur le terrain a été validée avec le calcul du temps physiologique accumulé en DJ avec une interprétation particulière de la méthode des moyennes basée sur les températures quotidiennes maximales et minimales, en association avec le modèle linéaire. Cela a permis de prédire l'éclosion printanière sur le terrain à environ cinq jours près. [ABSTRACT FROM AUTHOR]

SUMMARY Objective Retrospective audit of IVIG Request Forms in four Ontario tertiary care centres: to determine the case mix of new IVIG requests, to authenticate information provided, and to determine documentation of clinical efficacy. Aims To understand contributors to increases in IVIG utilisation and to determine whether IVIG is being used and monitored appropriately. Introduction Intravenous immunoglobulin ( IVIG) use in Canada is high compared with other developed countries. We performed a retrospective audit of new IVIG Request Forms across four tertiary care centres in Ontario, one with an active surveillance programme, to determine the case mix, authenticate information provided and assess documentation of efficacy. Methods Consecutive adult patients with a first-time IVIG request in 2014 were included. The ordering physician specialty, form completeness, documentation of diagnostic criteria for the medical condition and indication for IVIG use and documentation of efficacy were assessed by form and chart review. Results Of 178 patients, the most common indications for IVIG were immune thrombocytopenia (24.2%) and secondary immune deficiency (20.2%). The most frequent prescribers were haematologists (37.6%) and neurologists (10.7%). Other conditions not listed on the form represented 24.2% of cases, with most not indicated in current guidelines. A total of 32.6% of cases overall lacked verification of diagnostic criteria and 51.7% lacked verification for IVIG utilisation criteria, with the number of cases meeting criteria based on documentation being higher at the active surveillance site ( P = 0.005). A total of 19.1% of cases had a discrepancy between the indication written on the form and the documented clinical diagnosis. A total of 18.7% of clinic notes following IVIG had no mention of efficacy. Conclusion Our audit demonstrates a lack of compliance with IVIG Request Form requirements, a lack of documentation of diagnostic criteria and efficacy, and suggests inappropriate use of IVIG. Current implementation of the form may not be sufficient as a strategy for improving appropriate IVIG use. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. Aim: To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. Design: Prospective observational study. Methods: 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. Results: Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P=0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. Conclusion: A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment. [ABSTRACT FROM AUTHOR]

A constant-volume direct simple shear apparatus was used to investigate the effects of confining stress, initial static shear stress and void ratio on the liquefaction resistance of fine-grained tailings. The cyclic resistance ratio (also expressed as the overburden stress correction factor) was found to decrease with increasing confining stresses in the range 100-400 kPa and to gradually increase from 400 kPa onwards, when samples were tested at the same initial void ratio. The presence of an initial static shear stress decreased the liquefaction resistance. A key outcome of the work was to reveal the critical importance of density on liquefaction susceptibility of compressible tailings. Thus, a combined correction factor to account for overburden stress and density on cyclic resistance was proposed. [ABSTRACT FROM AUTHOR]

Studies of drug–cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2–8 μM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied – mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents. [ABSTRACT FROM AUTHOR]

Background:Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer.Methods:We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype.Results:Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m−2) and endometrioid subtypes (pHR: 1.08 per 5 kg m−2), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m−2) subtype, but only the association with high-grade serous cancers was significant.Conclusions:Higher BMI is associated with adverse survival among the majority of women with ovarian cancer. [ABSTRACT FROM AUTHOR]

This paper presents the results from a series of centrifuge tests and three-dimensional finite-element (FE) analyses, which examined the benefits of combining a footing with a monopile as a solution for foundations that are subjected to large moment loading, such as those used for towers and wind turbines. The experiments were carried out in silica sand and involved monotonic application of lateral loads at an equivalent prototype height of 26 m above the foundations. Tests were conducted on piled footings, monopiles, and unpiled footings. These experimental results together with the findings from the FE analyses show that the footing interacts positively with the piled foundation and that both the rotational stiffness and capacity of the combined piled footing system are greater than the sum of the individual contributions. Increased capacity arises as the footing causes a significant reduction in moment loading on the pile (hence facilitating the application of larger loads), primarily owing to an increased footing effective area arising from the tension capacity of the pile. [ABSTRACT FROM AUTHOR]

Introduction: Poor adherence reduces the potential benefits of osteoporosis therapy, lowering gains in bone mineral density resulting in increased risk of fractures. Aim: To compare prescribing and adherence patterns of anti-osteoporotic medications in patients admitted to an urban teaching hospital in Ireland with a fragility type fracture to patients admitted to a rural hospital in the North Western region. Methodology: We identified all patients >55 years admitted to Sligo General Hospital between 2005 and 2008 with a fragility fracture ( N = 744) using the hospital in-patient enquiry system (HIPE). The medical card number of those patients eligible for the primary care reimbursement services scheme (PCRS) facilitated the linkage of the HSE-PCRS scheme database to the HIPE database which enabled a study to identify persistence rates of patients prescribed osteoporosis therapy after discharge. The results were compared to the findings of a similar study carried out in St. James's Hospital, Dublin. Results: The 12 months post-fracture prescribing increased from 11.0 % (95 % CI 9.6, 12.4) in 2005 to 47 % (95 % CI 43.6, 50.3) in 2008 in the urban setting and from 25 % (95 % CI 21.5, 28.9) to 39 % (95 % CI 34.5, 42.7) in the rural setting. Adherence levels to osteoporosis medications at 12 months post-initiation of therapy was <50 % in both study groups. Patients on less frequent dosing regimes were better adherers. Conclusion: The proportion of patients being discharged on anti-osteoporosis medications post-fragility fracture increased between 2005 and 2008 in both patient groups. Sub-optimal adherence levels to osteoporosis medications continue to be a major concern. [ABSTRACT FROM AUTHOR]

After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1MKK4dJNKdAP-1 signaling cascade appears to be activation of draper expression after axon injury. [ABSTRACT FROM AUTHOR]

ABSTRACT A passive seismic experiment was conducted in April/May 2010 in the Albertine Graben region in Uganda to record low-frequency seismic signals and explore the possibility of their exploitation in this area as a direct hydrocarbon indicator (DHI). Recordings were made at locations directly overlying both hydrocarbon and water-bearing strata within the sedimentary basin as well as reference sites external to the basin, directly on the basement. Contrary to findings published in some literature to date, we found that spatial variations in the analysed wavefield parameters correlate with the underlying geology rather than the presence or absence of hydrocarbons. Inversion of the surface-wave (fundamental mode) dispersion curve as well as the observed horizontal-to-vertical spectral ratio of both surface and body waves provide evidence that the observed spectral variations can be explained solely by a simple layered/gradient velocity model, without the presence of any kind of anomaly that could be attributed exclusively to a hydrocarbon reservoir. Consequently, it is recommended that knowledge of the geological and velocity structure is sought when analysing passive low-frequency seismic data sets. This is a fundamental prerequisite in order to guard against misinterpretation of the spatial variation of seismic derived attributes as DHIs. [ABSTRACT FROM AUTHOR]

The article discusses the depiction of the mythological narrative of the Judgment of Paris in Roman wall paintings. The author notes that a recurring feature of these Roman compositions is the depiction of a water channel that physically separates the figure of Paris from the goddesses. It is argued that these water features can be understood as miniature representations of the Hellespont, the body of water that separates Europe from Asia. This motif, according to the author, may refer to the fact that the judgment of Paris indirectly led to the Trojan War, an event that set in motion the permanent state of conflict between East and West.

The data set used for calibration of regional numerical models which simulate groundwater flow and vadose zone processes is often dominated by head observations. It is to be expected therefore, that parameters describing vadose zone processes are poorly constrained. A number of studies on small spatial scales explored how additional data types used in calibration constrain vadose zone parameters or reduce predictive uncertainty. However, available studies focused on subsets of observation types and did not jointly account for different measurement accuracies or different hydrologie conditions. In this study, parameter identifiability and predictive uncertainty are quantified in simulation of a 1-D vadose zone soil system driven by infiltration, evaporation and transpiration. The worth of different types of observation data (employed individually, in combination, and with different measurement accuracies) is evaluated by using a linear methodology and a nonlinear Pareto-based methodology under different hydrological conditions. Our main conclusions are (1) Linear analysis provides valuable information on comparative parameter and predictive uncertainty reduction accrued through acquisition of different data types. Its use can be supplemented by nonlinear methods. (2) Measurements of water table elevation can support future water table predictions, even if such measurements inform the individual parameters of vadose zone models to only a small degree. (3) The benefits of including ET and soil moisture observations in the calibration data set are heavily dependent on depth to groundwater. (4) Measurements of groundwater levels, measurements of vadose ET or soil moisture poorly constrain regional groundwater system forcing functions. [ABSTRACT FROM AUTHOR]

An improved flow rating equation for full-barrel flows through a gated culvert was developed by calibrating a flow model to measured flow data with the Pareto-based approach to inverse parameter estimation. The computed Pareto front was used to identify the appropriate minimum values of both a measurement objective function that depicted differences between measured and computed flows and a Tikhonov regularization objective function that reflected deviations from preferred parameter values. Agreement between measured and computed values was generally good. Additionally, Pareto-based techniques were used to estimate the 95% confidence intervals of several predicted flow rates associated with a set of measured flows that were not included in the calibration dataset. Overall, this study revealed that Pareto-based parameter estimation techniques are useful for obtaining the best flow rating equation that can be achieved given the available flow data along with the engineer’s knowledge of the flow parameters for the gated culvert. [ABSTRACT FROM AUTHOR]

Purpose: Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail. Methods: Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results: Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987). Conclusions: Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype. [ABSTRACT FROM AUTHOR]

In recent years there has been a growth in the number of independent health policy analysis institutes in low- and middle-income countries which has occurred in response to the limitation of government analytical capacity and pressures associated with democratization. This study aimed to: (i) investigate the contribution made by health policy analysis institutes in low- and middle-income countries to health policy agenda setting, formulation, implementation and monitoring and evaluation; and (ii) assess which factors, including organizational form and structure, support the role of health policy analysis institutes in low- and middle-income countries in terms of positively contributing to health policy. Six case studies of health policy analysis institutes in Bangladesh, Ghana, India, South Africa, Uganda and Vietnam were conducted including two NGOs, two university and two government-owned policy analysis institutes. Case studies drew on document review, analysis of financial information, semi-structured interviews with staff and other stakeholders, and iterative feedback of draft findings. Some of the institutes had made major contributions to policy development in their respective countries. All of the institutes were actively engaged in providing policy advice and most undertook policy-relevant research. Relatively few were engaged in conducting policy dialogues, or systematic reviews, or commissioning research. Much of the work undertaken by institutes was driven by requests from government or donors, and the primary outputs for most institutes were research reports, frequently combined with verbal briefings. Several factors were critical in supporting effective policy engagement. These included a supportive policy environment, some degree of independence in governance and financing, and strong links to policy makers that facilitate trust and influence. While the formal relationship of the institute to government was not found to be critical, units within government faced considerable difficulties. [ABSTRACT FROM AUTHOR]

Background Young drug misusers and the homeless both have a greater risk of death than their peers. This study sought to estimate the additional impact of homelessness on the risk of death for young drugs misusers. Methods From all admissions to NHS hospitals in Scotland between 1986 and 2001, those that were: drug misuse related, for people born between 1970 and 1986 and aged over 15 years (n=13 303), were selected. All subsequent admissions and registrations of death were linked to this dataset. Each admission was coded as homeless if the health board of residence was coded as 'no fixed abode'. 5-year survival after an admission was modelled using (1) life table and (2) proportional hazard models and then (3) differences in causes of deaths were explored. Results Immediately after a drugs-related hospital admission there was no difference in survival between the homeless and those with a 'fixed address'. However, over a 3-year period the risk for those who were homeless was 3.5 times greater (CI 95% 1.2 to 12.8). This elevated risk seemed to be particularly focused on the second year after an admission. The causes of death were similar for the two groups. Conclusion Although a homeless hospital admission is associated with a greater risk of death for young drug users, it is also a point in time when a young person is in contact with public services. An attempt to link their discharge with housing services would seem a potentially productive policy. [ABSTRACT FROM AUTHOR]

The authors propose an algorithm based on the knowledge of training sequences to obtain an asymptotically unbiased estimator of non-linear multiple-input multiple-output (MIMO) channels, which involves the radio frequency front-end non-linearity and linear frequency selective MIMO channels. Although the impact of non-linearity in the transmitter side has been widely studied, most work on the channel estimation assumes linear channel models and ignores the non-linear effects. In this study, we develop a non-linear channel estimator that can simultaneously estimate the linear MIMO channel model and non-linearity of the transmitter is developed. With these two sets of parameters, the non-linear channel model can be fully described. This channel estimation algorithm is implemented over an empirical MIMO channel model using an orthogonal frequency division multiplexing system. [ABSTRACT FROM AUTHOR]

Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC. [ABSTRACT FROM AUTHOR]

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. [ABSTRACT FROM AUTHOR]

Background: Disease-specific biomarkers should reflect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. Several synaptic proteins have been described in cerebrospinal fluid (CSF) of patients with dementia. In Lewy body disease α-synuclein is incorporated within Lewy bodies and α-, β- and γ-synucleins in dystrophic neuritis. These pathological changes are expected to be seen in CSF. Methods: A total of 25 CSF post-mortem samples (8 control and 17 subjects with dementia) were used to quantify α- and γ-synucleins and IgG. Results: We describe for the first time the presence of γ-synuclein in CSF. There is an elevation of both α- and γ-synucleins in CSF from elderly individuals with Alzheimer’s disease, Lewy body disease (LBD) and vascular dementia (CVD), compared to normal controls. γ-Synuclein showed a greater elevation in LBD, IgG in CVD. The elevation of α- and γ-synucleins was seen from Braak stage III onwards and remained stable until Braak stage VI. These results were not influenced by age at death or post-mortem delay. Conclusions: The reported increases in α- and γ-synucleins and IgG in the ventricular CSF of individuals with dementia are novel findings. They now need to be explored further using a greater number of cases in each subgroup, using lumbar CSF samples to determine their applicability and relevance to a clinical diagnostic setting. It needs to be established whether using these markers may help to discriminate LBD from other types of neurodegenerative and vascular dementias. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: There is poor access to neurology services for patients in the community.Aim: To describe the training of GPs with special interest (GPwSI) in headache and the setting up of a GPwSI clinic in general practice, and report on a comparison with the existing neurology service in terms of case severity, patient satisfaction, and cost.Design Of Study: New service provision and evaluation by a questionnaire survey.Setting: General practice and hospital neurology service in inner-city London.Method: The intervention involved training GPs as GPwSIs and setting up a GP headache service. A questionnaire survey was conducted, measuring headache impact, satisfaction, and cost estimates.Results: Headache impact was not significantly different between the two groups of patients, referred to hospital and to a GPwSI. Patients were significantly more satisfied with the GPwSI service, particularly that the service was effective in helping to relieve their symptoms (89% versus 76%; adjusted odds ratio=7.7; 95% confidence interval=2.7 to 22.4). The cost per first appointment was estimated to be pound sterling 136, with pound sterling 68 for subsequent contacts. These are lower than costs for neurologist contacts.Conclusion: GPwSI services can satisfy the needs of patients with similar headache impact at costs that are lower than those for secondary care services. [ABSTRACT FROM AUTHOR]

Background: Pharmacoepidemiology is a discipline that applies epidemiological methodologies to the study of drug use, especially the safety of drug use in a large group of people. But this methodology has not been widely utilized to assess drug safety in pediatrics for children aged between 0 and 18 years.Objectives: (1) To describe current gaps in evaluating pediatric drug safety; (2) to use published examples demonstrating the value of pharmacoepidemiology in detecting and quantifying adverse drug events in pediatrics; (3) to review pharmacoepidemiological study designs, their strengths and limitations, and examples of their applications in the field of drug safety evaluation; and (4) to provide recommendations about selecting an appropriate study design and minimizing a major methodological limitation.Overview: Only about 20% of approved drugs are licensed for pediatric use, and many prescription drugs are used as 'off label' or 'unlicensed' pediatric treatments. Among this small percentage of licensed pediatric drugs, pre-marketing trials may not adequately address all drug-related safety issues in pediatrics. Consequently, an important gap exists in pediatric drug safety evaluation. Pharmacoepidemiology offers a number of advantages in detecting and quantifying adverse drug events in pediatrics. Each pharmacoepidemiological study design has its own strengths and limitations in the evaluation of drug safety. An appropriate study design depends on the underlying research question being addressed. Confounding by indication, the most serious and challenge form of confounding in pharmacoepidemiological designs, could lead to misleading claims about the relationship between drug use and the development of potential adverse drug events, and should be adequately controlled.Conclusions: Pharmacoepidemiology is a powerful methodology that offers many advantages to assess pediatric drug safety such as large sample size, long period of follow-up, and good generalizibility. But this methodology should be applied judiciously to maximize its potential. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of a circular footing of finite but nonzero stiffness embedded in an isotropic nonhomogeneous elastic half-space. The problem is solved by coupling the scaled boundary finite-element method with axisymmetric shell finite elements. The coupling of the two methods is validated by comparing computed solutions with analytical solutions for a flexible footing subjected to a uniformly distributed vertical load embedded in an elastic full-space. Based on the finding that the bending stiffness of the footing dictates the response for vertical and moment load cases, whereas the normal stiffness of the footing dominates the horizontal response, a convenient method for estimating dimensionless elastic stiffness coefficients is presented graphically. New results are presented for homogeneous and Gibson soil profiles and Poisson’s ratios of 0.2 and 0.499, to represent both sand and clay. An example demonstrating a practical application of these results is also provided. [ABSTRACT FROM AUTHOR]

Solutions are presented for stiffness coefficients to represent the elastic behavior of a caisson foundation embedded in soil. The solutions use a novel numerical technique, the scaled boundary finite element method, combined with shell elements to represent the foundation itself. The stiffness coefficients take into account the possibility of nonhomogeneity in the soil (stiffness varying with depth), the geometry of the foundation, and the contribution to the stiffness of the skirt of the caisson foundation. Tabulated values allow a simple curve fit to the stiffness values to be employed for particular cases. The accuracy of the method is tested against previous solutions for particular cases. Example calculations are given to illustrate the method. [ABSTRACT FROM AUTHOR]

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Provides information on a study that determined the prevalence of asthma and work related respiratory symptoms among medical radiation technologists compared with physiotherapists and to identify work related factors in the darkroom environment that are associated with these outcomes. Methodology of the study; Results and discussion on the study; Conclusions.

Radiographers or medical radiation technologists (MRTs) may develop occupational asthma, respiratory symptoms and 'darkroom disease'. However, the prevalence of asthma and the relative roles of sensitization versus irritation and inhalation accidents are unclear. These workers have exposure to chemicals, including glutaraldehyde, formaldehyde, SO2 and acetic acid, which can be sensitizers and irritants. We undertook a questionnaire survey to ascertain, among MRTs as compared with a control group of physiotherapists, the prevalence of physician-diagnosed asthma, the prevalence in the past 12 months of three or more of the nine respiratory symptoms previously validated to be sensitive and specific for the presence of selfreported asthma and the relation among MRTs of these symptoms to work exposures. The response rate was 63% in each group. Responses were analyzed among 1110 MRTs and 1523 physiotherapists who never smoked. The prevalence of asthma since starting in the profession was greater among MRTs (6.44 versus 3.95%) and this differed across gender, being 30% greater among females but 5-fold greater among males. The prevalence of reporting three or more respiratory symptoms and two or more work-related symptoms in the past 12 months were 1.9- and 3.8-fold greater among MRTs, respectively. Among MRTs, respiratory symptoms were associated with a number of workplace and exposure factors likely to generate aerosol or chemical exposures, including processors not having local ventilation, a leaking processor in which clean up was delayed, clean up of a chemical processor spill, mixing fixer and developer chemicals and freeing a film jam. However, these outcomes were not associated with routine tasks unlikely to generate exposures. Males reported that they carried out tasks with expected exposure to chemicals more frequently than females. These findings suggest excess asthma and respiratory symptoms with a work-related etiology among MRTs. [ABSTRACT FROM AUTHOR]

Presents a study conducted to quantify the degree of weight loss and malnutrition present in patients with chronic graft-versus-host disease. Background on the disease; Methodology; Results.

Radiographers or medical radiation technologists (MRTs) may develop occupational asthma, respiratory symptoms and ‘darkroom disease’. However, the prevalence of asthma and the relative roles of sensitization versus irritation and inhalation accidents are unclear. These workers have exposure to chemicals, including glutaraldehyde, formaldehyde, SO2 and acetic acid, which can be sensitizers and irritants. We undertook a questionnaire survey to ascertain, among MRTs as compared with a control group of physiotherapists, the prevalence of physician-diagnosed asthma, the prevalence in the past 12 months of three or more of the nine respiratory symptoms previously validated to be sensitive and specific for the presence of selfreported asthma and the relation among MRTs of these symptoms to work exposures. The response rate was 63% in each group. Responses were analyzed among 1110 MRTs and 1523 physiotherapists who never smoked. The prevalence of asthma since starting in the profession was greater among MRTs (6.44 versus 3.95%) and this differed across gender, being 30% greater among females but 5-fold greater among males. The prevalence of reporting three or more respiratory symptoms and two or more work-related symptoms in the past 12 months were 1.9- and 3.8-fold greater among MRTs, respectively. Among MRTs, respiratory symptoms were associated with a number of workplace and exposure factors likely to generate aerosol or chemical exposures, including processors not having local ventilation, a leaking processor in which clean up was delayed, clean up of a chemical processor spill, mixing fixer and developer chemicals and freeing a film jam. However, these outcomes were not associated with routine tasks unlikely to generate exposures. Males reported that they carried out tasks with expected exposure to chemicals more frequently than females. These findings suggest excess asthma and respiratory symptoms with a work-related etiology among MRTs. [ABSTRACT FROM AUTHOR]

Focuses on the achievement of a first draft of the complete human genome sequence and its expected influence on epilepsy research in the future. Identification of anticonvulsant drug targets ; Genetic stratification of patients to improve therapy; Experiments with DNA microarrays.

Summary Thep16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in thep16 gene in DNA from a series of human breast cancer specimens and normal human breast tissue (from reductive mammaplasty). Thep16 region examined was unmethylated in the four normal human breast specimens and in four out of nine breast tumours. In the other five independent breast tumour specimens, a uniform pattern of DNA methylation was observed. Of the nine major sites of DNA methylation in the amplified region from these tumour DNAs, four were in non-CG sequences. This unusual concentration of non-CG methylation sites was not a general phenomenon present throughout the genome of these tumour cells because the methylated CpG island regions of interspersed L1 repeats had a pattern of (almost exclusively) CG methylation similar to that found in normal breast tissue DNA and in DNA from tumours with unmethylatedp16 genes. These data suggest that DNA methylation of thep16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to theraputic manipulation. [ABSTRACT FROM AUTHOR]