bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoelliptic Diffusions: Filtering and Inference from Complete and Partial Observations
Authors: Ditlevsen Susanne , Samson Adeline 
Published: December 2018

SummaryThe statistical problem of parameter estimation in partially observed hypoelliptic diffusion processes is naturally occurring in many applications. However, because of the noise structure, where the noise components of the different co-ordinates of the multi-dimensional process operate on different timescales, standard inference tools are ill conditioned. We propose to use a higher order scheme to approximate the likelihood, such that the different timescales are appropriately accounted for. We show consistency and asymptotic normality with non-typical convergence rates. When only partial observations are available, we embed the approximation in a filtering algorithm for the unobserved co-ordinates and use this as a building block in a stochastic approximation expectation–maximization algorithm. We illustrate on simulated data from three models: the harmonic oscillator, the FitzHugh–Nagumo model used to model membrane potential evolution in neuroscience and the synaptic inhibition and excitation model used for determination of neuronal synaptic input.
Towards improved control of inflammatory bowel disease
Authors: Eberhardson Michael , Hedin Charlotte R. H. , Carlson Marie , Tarnawski Laura , Levine Yaakov A. , Olofsson Peder S. 
Published: December 2018

AbstractInflammatory bowel disease (IBD) is characterized by activation of both the innate and adaptive immune system in genetically susceptible individuals, resulting in chronic intestinal inflammation. The triggers that initiate and perpetuate this continuous inflammation are the subject of much speculation and research, although the central role of the intestinal microbiota is recognized, and is even a target for treatment in some circumstances. The mainstay of modern IBD treatment is suppression of the immune response towards as yet unspecified antigens, and conventional therapy includes corticosteroids, 5‐aminosalicylic acid (5‐ASA), thiopurines and methotrexate. Reducing activity of specific mediators has proven efficacious, including adhesion molecules, such as the gut‐homing integrin α4β7 expressed on the surface of circulating immune cells, and cytokines, such as tumour necrosis factor α (TNF‐α). This has been achieved using biologic agents including monoclonal antibodies. Recent discoveries in immunology and neuroscience have revealed that signals in the peripheral nervous system regulate inflammation, including levels of TNF‐α. The understanding of the mechanisms of the neuro‐immune communication involved in inflammation control in the gut is evolving, but is as yet incomplete. Clinical studies using implanted vagus nerve stimulators for treatment of IBD show encouraging results. Accordingly, the neural reflex control of inflammation is emerging as a potential therapeutic target in treatment of IBD. Here, we review current therapeutic options and neural reflex control of gut immunity in the context of intestinal inflammation.
Patterns in autobiographical reminiscing among early adults: Implications for forgiveness and self‐compassion
Authors: Booker Jordan A. 
Published: December 2018

AbstractThe ways early adults recount autobiographical experiences are associated with adjustment. Most prior research on autobiographical reminiscing has taken a variable‐oriented approach to examine relations of reminiscing variables with outcomes. The present study takes a person‐oriented approach to (a) identify systematic within‐individual patterns of reminiscing across multiple autobiographical memories; and (b) examine whether these patterns of reminiscing are uniquely related to self‐compassion and forgiveness. Participants were early adults (18 to 24 years) from undergraduate (n = 221) and community (n = 145) contexts. Participants self‐reported forgiveness and self‐compassion and described three autobiographical memories about past challenges: (a) a time they hurt someone else; (b) a time they were hurt by someone; and (c) a time they experienced a personal setback. Each memory was rated for positive self‐meaning (personal growth) and distancing of the current self from the past event (subjective distancing). Cluster analyses showed three subgroup patterns for personal growth and five subgroup patterns for subjective distancing. Participants displaying a pattern of higher personal growth across memories reported the highest forgiveness. Findings point to meaningful heterogeneity in autobiographical reminiscing and support the utility of a person‐oriented approach in providing a holistic view of early adults’ approaches for recollecting lived experiences.
Monitoring the microbial contamination of donor cornea during all preservation phases: A prospective study in the Eye Bank of Rome
Authors: Vignola Rossella , Giurgola Laura , Colabelli Gisoldi Rossella Anna Maria , Gaudio Mariarosa , D’Amato Tóthová Jana , Pocobelli Augusto 
Published: December 2018

AbstractBackgroundIn most European eye banks, human donor corneas are microbiologically tested after storage in organ culture conditions, and the tissues that are free of contamination are distributed for transplantation. In this prospective study, 100 donor corneas were tested for microbial contamination after cold storage, corneal culture and corneal deswelling at the Eye Bank of Rome.MethodsSamples of cold storage medium (EUSOL‐C), corneal culture medium (TISSUE‐C) and deswelling medium (CARRY‐C) were tested after three, seven and one days of corneal storage, respectively. The CARRY‐C medium, used to transport the cornea to the operation theatre, was retested 1 day after transplantation. The TISSUE‐C and CARRY‐C media were also tested after removing antimicrobial and antifungal agents using a dedicated device.ResultsWe found 67% of the EUSOL‐C samples were contaminated mainly by Staphylococcus spp, 14% of TISSUE‐C media were contaminated by bacteria and fungi and 3% of CARRY‐C media by Staphylococcus spp The analysis performed after removing the antimicrobial and antifungal agents showed growth in three additional TISSUE‐C samples (S viridans, S haemolyticus and E faecalis) and one CARRY‐C (S cerevisiae and P acnes).ConclusionTissue contamination was unexpectedly high on arrival to the eye bank, indicating the need to review and update decontamination procedures during tissue recovery, and renew training for the recovery teams. Storing donor corneas in organ culture conditions significantly reduced the microorganism burden. Using devices to remove antimicrobial and antifungal agents from samples before testing can increase the sensitivity of the standard microbiological method, and thus help further reduce the risk of microbial transmission.
The role of deforestation on American cutaneous leishmaniasis incidence: spatial‐temporal distribution, environmental and socioeconomic factors associated in the Brazilian Amazon
Authors: Rodrigues Maria Gabriela de Almeida , Sousa José Diego de Brito , Dias Ádila Liliane Barros , Monteiro Wuelton Marcelo , Sampaio Vanderson de Souza 
Published: December 2018

AbstractObjectiveTo analyse the temporal and spatial distribution as well as the environmental and socioeconomic factors associated with cutaneous leishmaniasis incidence in the state of Amazonas, Brazil from 2007 to 2015.MethodsSpatial and temporal distribution was evaluated from sequential thematic maps of the mean incidence rates of the disease. A negative binomial regression analysis was performed to evaluate the association of the factors studied with the mean incidence rate of ACL.ResultsThe average proportion of deforestation was negatively associated with the average incidence rate of cutaneous leishmaniasis in municipalities (β = −2.178; P = 0.019; 95%CI −3.996, −0.361), and the health system performance index (effectiveness) (β = −0.852; P = 0.008; 95%CI −1.481, −0.225). Conversely, the municipal human development index (MHDI) was a factor positively related to the average incidence among the municipalities (β = 7.728; P = 0.003; 95%CI 2.716, 12.738).ConclusionOur study shows the important impact of socioeconomic and environmental factors on ACL incidence in the Amazonas State.
Gender exploitative and gender transformative aspects of employing Health Extension Workers under Ethiopia's Health Extension Program
Authors: Jackson Ruth , Kilsby Di , Hailemariam Assefa 
Published: December 2018

AbstractObjectivesTo apply a gender lens to Ethiopia's Health Extension Program and the role of Health Extension Workers (HEWs).MethodsInterviews with 45 HEWs and four focus group discussions with 14 of the same HEWS from three regions in rural Ethiopia: Afar Region; Tigray Region (Adwa Woreda); and two locations in Southern Nations, Nationalities and People's Region (Aleta Wondo Woreda and Kafa Zone). Two focus group discussions were conducted in Afar Region with 17 Women Extension Workers employed by Afar Pastoralist Development Association.ResultsUsing the Gender Equality Continuum as a gender analysis tool, we found that Ethiopia's Health Extension Program is gender aware by directly linking improved health outcomes for women and their empowerment. However, for HEWs who inhabit a gendered space and place from home to district health centres, there can be unexpected consequences that accommodate existing gender inequalities, are blind to them and perhaps even generate new forms of exploitation.ConclusionsThe Health Extension Program could have more transformative outcomes for HEWs and also for communities if changing gender norms was given more attention and constraints to gender equality were reduced. Community Health Worker (CHW) programs should focus on better understanding on the role of gender for CHWs across health systems.
μ‐Opioid receptors in primary sensory neurons are essential for opioid analgesic effect on acute and inflammatory pain and opioid‐induced hyperalgesia
Authors: Sun Jie , Chen Shao‐Rui , Chen Hong , Pan Hui‐Lin 
Published: December 2018

Key points
μ‐Opioid receptors (MORs) are expressed peripherally and centrally, but the loci of MORs responsible for clinically relevant opioid analgesia are uncertain.
Crossing Oprm1flox/flox and AdvillinCre/+ mice completely ablates MORs in dorsal root ganglion neurons and reduces the MOR expression level in the spinal cord.
Presynaptic MORs expressed at primary afferent central terminals are essential for synaptic inhibition and potentiation of sensory input by opioids.
MOR ablation in primary sensory neurons diminishes analgesic effects produced by systemic and intrathecal opioid agonists and abolishes chronic opioid treatment‐induced hyperalgesia.
These findings demonstrate a critical role of MORs expressed in primary sensory neurons in opioid analgesia and suggest new strategies to increase the efficacy and reduce adverse effects of opioids.
AbstractThe pain and analgesic systems are complex, and the actions of systemically administered opioids may be mediated by simultaneous activation of μ‐opioid receptors (MORs, encoded by the Oprm1 gene) at multiple, interacting sites. The loci of MORs and circuits responsible for systemic opioid‐induced analgesia and hyperalgesia remain unclear. Previous studies using mice in which MORs are removed from Nav1.8‐ or TRPV1‐expressing neurons provided only an incomplete and erroneous view about the role of peripheral MORs in opioid actions in vivo. In the present study, we determined the specific role of MORs expressed in primary sensory neurons in the analgesic and hyperalgesic effects produced by systemic opioid administration. We generated Oprm1 conditional knockout (Oprm1‐cKO) mice in which MOR expression is completely deleted from dorsal root ganglion neurons and substantially reduced in the spinal cord, which was confirmed by immunoblotting and immunocytochemical labelling. Both opioid‐induced inhibition and potentiation of primary sensory input were abrogated in Oprm1‐cKO mice. Remarkably, systemically administered morphine potently inhibited acute thermal and mechanical nociception and persistent inflammatory pain in control mice but had little effect in Oprm1‐cKO mice. The analgesic effect of intrathecally administered morphine was also profoundly reduced in Oprm1‐cKO mice. Additionally, chronic morphine treatment‐induced hyperalgesia was absent in Oprm1‐cKO mice. Our findings directly challenge the notion that clinically relevant opioid analgesia is mediated mostly by centrally expressed MORs. MORs in primary sensory neurons, particularly those expressed presynaptically at the first sensory synapse in the spinal cord, are crucial for both opioid analgesia and opioid‐induced hyperalgesia.
Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women
Authors: Molgat‐Seon Yannick , Ramsook Andrew H. , Peters Carli M. , Schaeffer Michele R. , Dominelli Paolo B. , Romer Lee M. , Road Jeremy D. , Guenette Jordan A. , Sheel A. William 
Published: December 2018

Key points
The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex‐differences in respiratory system morphology.
During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea.
Using a single‐blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate‐intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults.
When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.
AbstractWe aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60–80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6‐min bouts of cycling at ventilatory threshold, in a single‐blind randomized manner, while breathing: (i) normoxic helium‐oxygen (HEL) to reduce the work of breathing (Wb) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2O L−1 s−1 to increase Wb; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category‐ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: –21 ± 6%, women: –17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.
Impact of a structured patient support program on adherence and persistence in basal insulin therapy for type 2 diabetes
Authors: Zhou Fang Liz , Yeaw Jason , Karkare Swapna U , DeKoven Mitch , Berhanu Paulos , Reid Timothy 
Published: December 2018

ObjectiveTreatment adherence and persistence are essential to achieving therapeutic goals in diabetes and may be improved by patient support programs (PSPs). The COACH Program was launched in 2015 with the goal of supporting patients with diabetes who are prescribed insulin glargine 300 U/mL (Gla-300). The study objective was to assess the program’s impact on persistence and adherence with therapy among patients with type 2 diabetes.Research design and methodsA retrospective 12-month analysis was conducted to compare treatment adherence and persistence in patients treated with Gla-300 who actively participated in the COACH PSP versus those who did not enroll using COACH engagement and claims data for the identification period from February 1, 2016 to July 31, 2016. COACH (n=544) and non-COACH (n=544) participants were matched on selected baseline characteristics.ResultsCOACH participants were more likely to be adherent to (68.0% vs 61.4%, p= 0.0201; OR: 1.81, p=0.0002) and persistent (48.5% vs 42.1%, p= 0.0309; discontinuation HR: 0.60, p<0.0001) with Gla-300 than non-COACH patients during the 12-month follow-up after controlling for clinical confounders. Additionally, both insulin-naive and basal insulin switcher COACH participants, respectively, were more likely to be adherent (OR: 2.25, p=0.0082 and OR: 1.662, p=0.0364) and persistent (discontinuation HR: 0.53, p=0.0054 and HR: 0.67, p=0.0492) than non-COACH patients. Finally, COACH participants with greater level of engagement showed better persistence.ConclusionThese data demonstrate that participation and engagement with COACH PSPs are associated with improved persistence and adherence to Gla-300 among patients with type 2 diabetes.
Observational study of clinical characteristics of dome-shaped macula in Chinese Han with high myopia at Zhongshan Ophthalmic Centre
Authors: Zhao Xiujuan , Ding Xiaoyan , Lyu Cancan , Li Shiyi , Lian Yu , Chen Xiaohong , Tanumiharjo Silvia , Zhang Aiyuan , Lu Jinge , Liang Xiaoling , Jin Chenjin , Lu Lin 
Published: December 2018

PurposeTo evaluate the prevalence of dome-shaped macula (DSM) in highly myopic eyes among Chinese Han and to detect the correlation with myopic maculopathy and macular complications.MethodsA total of 736 Chinese Han patients (1384 eyes) with high myopia (refractive error≤6.0 diopters or axial length ≥26.5 mm) are reviewed based on information entered into a high-myopia database at Zhongshan Ophthalmic Centre. Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) are measured. The prevalence of DSM in patients with myopic maculopathy is categorised from C0 to C4. Clinical features, including macular complications, SFCT and PFCT, are compared between myopic eyes with and without DSM.ResultsAmong the 1384 eyes, 149 (10.77%) show DSM. In highly myopic eyes without macular complications, the best corrected visual acuity is significantly worse in patients with DSM (p=0.002), and the ratio between subfoveal and parafoveal choroidal thickness (S/PCT) is significantly elevated in patients with DSM (p=0.021). The proportion of foveal schisis (17.24% vs 62.86%) is much lower in eyes with DSM compared with those without DSM. However, the proportions of extrafoveal schisis (39.66% vs 5.37%), foveal serous retinal detachment (SRD) (5.17% vs 0) and epiretinal membrane (ERM) (24.14% vs 10.74%) are much higher in eyes with DSM. The proportion of DSM was lower in C0 and C1, but higher proportion of DSM was found in C3 and C4.ConclusionsDSM is found in 10.77% of highly myopic eyes among Chinese Han. DSM might be a protective mechanism for foveal schisis and a risk factor for extrafoveal schisis, SRD and ERM.
Use of C-reactive protein to tailor antibiotic use: a systematic review and meta-analysis
Authors: Petel Dara , Winters Nicholas , Gore Genevieve C , Papenburg Jesse , Beltempo Marc , Lacroix Jacques , Fontela Patricia S 
Published: December 2018

Background and objectivesC-reactive protein (CRP) has been proposed to guide the use of antibiotics. However, study results are controversial regarding the benefits of such a strategy. We synthesised the evidence of CRP-based algorithms on antibiotic treatment initiation and on antibiotic treatment duration in adults, children and neonates, as well as their safety profile.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE, CENTRAL and CINAHL from inception to 20 July 2017.Eligibility criteria for selecting studiesWe included randomised controlled trials (RCTs), non-RCTs and cohort studies (prospective or retrospective) investigating CRP-guided antibiotic use in adults, children and neonates with bacterial infection.Data extraction and synthesisTwo researchers independently screened all identified studies and retrieved the data. Outcomes were duration of antibiotic use, antibiotic initiation, mortality, infection relapse and hospitalisation. We assessed the quality of the included studies using the Cochrane Collaboration’s tool (RCTs), and A Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions and the Newcastle-Ottawa scale (non-RCTs). We analysed our results using descriptive statistics and random effects models.ResultsOf 11 165 studies screened, 15 were included. In five RCTs in adult outpatients, the risk difference for antibiotic treatment initiation in the CRP group was −7% (95% CI: −10% to –4%), with no difference in hospitalisation rate. In neonates, CRP-based algorithms shortened antibiotic treatment duration by −1.45 days (95% CI −2.61 to –0.28) in two RCTs, and by −1.15 days (95% CI −2.06 to –0.24) in two cohort studies, with no differences in mortality or infection relapse.ConclusionThe use of CRP-based algorithms seems to reduce antibiotic treatment duration in neonates, as well as to decrease antibiotic treatment initiation in adult outpatients. However, further high-quality studies are still needed to assess safety, particularly in children outside the neonatal period.PROSPERO registration numberCRD42016038622