bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhegmatogenous Retinal Detachment and Solar Radiation in Northwestern Spain
Authors: Sevillano Torrado Carlos , Viso Eloy , Moreira Santiago , Blanco María José , Gude Francisco
Published: October 2019

Objective: The aim of this study was to investigate the association between rhegmatogenous retinal detachment (RRD) and solar radiation in northwestern Spain. Methods: All RRD cases in Pontevedra from 2008 and 2014 were retrospectively analyzed. Climatological data from 4 weather stations in the area were collected. The association between RRD incidence and solar radiation was investigated. Results: A total of 256 RRD cases were identified. There was a seasonal variation in the incidence of RRD with a maximum number of incident cases observed in June and July and a minimum number of cases observed in January and December. An association was found between RRD incidence and solar radiation both monthly (p = 0.004) and bimonthly (p = 0.057). The right eye was more frequently affected than the left eye (p = 0.035). RD cases other than rhegmatogenous showed neither seasonality nor association with radiation. Conclusions: Solar radiation may play a role in RRD genesis in our area. Laterality could be related to the amount of radiation reaching each eye.
ПЕРСПЕКТИВНІСТЬ ЗАСОСУВАННЯ ГУСТОГО ЕКСТРАКТУ З ШПИНАТУ ГОРОДНЬОГО ЛИСТЯ ЯК МЕМБРАНОПРОТЕКТОРНОГО ЗАСОБУ ЗА УМОВ ТОКСИЧНОГО ГЕПАТИТУ
Authors: Nykyforuk A. Y. , Fira L. S. , Lykhatskyі P. G.
Published: October 2019

Мета роботи. Дослідити мембранопротекторні властивості густого екстракту зі шпинату городнього листя за умов токсичного ураження печінки тетрахлорметаном.

Матеріали й методи. Експерименти проведені на білих щурах-самцях, яким моделювали токсичний гепатит шляхом ураження печінки тетрахлорметаном. Токсикант вводили в дозі 1,0 мл/кг маси тіла тварин. Густий екстракт зі шпинату використовували у дозі 150 мг/кг маси тіла, препарат порівняння силімарин у дозі  100 мг/кг маси тіла.  Евтаназію щурів проводили під тіопенталовим наркозом на 4-ту, 7-у та 10-у добу експерименту з дотриманням усіх правил Конвенції із захисту хребетних тварин. Активність мембранодеструктивних процесів оцінювали за аланін- та аспрататамінотрансферазною, гама-глутамілтранспептидазною активністю та еритроцитарним індексом інтоксикації. Для статистичної обробки даних використовували параметричні (за Стьюдентом) та непараметричні (Вілкоксоном) методи дослідження.

Результати й обговорення. Встановлено, що ураження щурів тетрахлорметаном призводить до вірогідного підвищення у сироватці крові активності амінотрансфераз та гамаглутамілтранспептидази у всі терміни дослідження (4,7 та 10 доби  від початку експерименту). У печінці щурів спостерігалось прогресуюче зниження активності ензимів, що є наслідком порушення проникності плазматичних мембран гепатоцитів. У крові щурів, уражених тетрахлорметаном, відмічено підвищення відсотку проникнення еритроцитарних мембран. Використаний густий екстракт зі шпинату городнього листя проявив ефективний вплив на досліджувані показники і за ефективністю незначно поступався препарату силімарину. 

Висновки. Ураження печінки щурів тетрахлорметаном призводить до порушення проникності плазматичних мембран гепатоцитів та еритроцитів, максимальні зміни яких відмічено у кінці дослідження. Співставлення ефективності застосування силімарину та екстракту зі шпинату городнього листя підтверджує мембранопротекторні властивості даного засобу, що робить перспективним подальші дослідження його фармакологічної активності.
ЗАМІЩЕНІ 3-R-7,8-ДИГІДРО-2Н-ПІРОЛО[1,2-а][1,2,4]ТРИАЗИНО[2,3-с]ХІНАЗОЛІН-5а(6Н)-АЛКІЛКАРБОНОВІ КИСЛОТИ – ПЕРСПЕКТИВНИЙ КЛАС МАЛОТОКСИЧНИХ ПРОТИЗАПАЛЬНИХ АГЕНТІВ
Authors: Stavytskyi V. V. , Voskoboinik O.Yu. , Nosulenko I.S. , Klimova O.O. , Brazhko O. A. , Kovalenko S. I.
Published: October 2019

Мета роботи. Дослідження протизапальної активності та гострої токсичності оригінальних 3-R-7,8-дигідро-2Н-піроло[1,2-а][1,2,4]триазино[2,3-с]хіназолін-5а(6Н)-алкілкарбонових кислот.

Матеріали і методи. Дослідження протизапальної активності проводили на моделі карагенінового набряку лапки білих щурів-самців лінії «Вістар» масою 140 – 220 г. Досліджувані речовини вводили перорально у вигляді водної суспензії, стабілізованої Твіном 80, за допомогою атравматичного зонда в дозі 25 мг/кг, натрію диклофенак – 10 мг/кг. Показники гострої токсичності досліджуваних сполук було спрогнозовано in silico (програмні пакети GUSAR і TEST) та встановлено in vivo на білих безпородних мишах обох статей масою 16 – 24 г. Синтезовані сполуки вводили одноразово внутрішньоочеревинно у вигляді тонкої суспензії у фізіологічному розчині, стабілізованої Твіном 80. Середньолетальні дози (ЛД50) визначали за методом В. Прозоровського. Статистичну обробку даних проводили за загальноприйнятими підходами за допомогою статистичного пакета програм «STATISTICA® for Windows 6.0» (StatSoft Inc, № АХХR712D833214FAN5).

Результати й обговорення. Вивчення протизапальної дії похідних піроло[1,2-a][1,2,4]триазино[2,3-c]хіназоліну показало, що досліджувані сполуки є високоактивними протизапальними агентами, які за рівнем дії конкурують або перевищують препарат порівняння «Натрію диклофенак». Найбільш активною виявилась 3-(3-метил-2,8-діоксо-7,8-дигідро-2H-піроло[1,2-a][1,2,4]триазино[2,3-c]хіназолін-5a(6H)-іл)пропанова кислота (5), яка за рівнем дії перевищує препарат порівняння більше ніж на 20 %. Результати вивчення гострої токсичності похідних піроло[1,2-a][1,2,4]триазино[2,3-c]хіназолінів, проведені методами in silico та in vivo, корелюють поміж собою. Внутрішньоочеревинне введення досліджуваних сполук білим безпородним мишам у дозах від 500 до 1500 мг/кг дозволило віднести їх до IV та V класу токсичності (малотоксичні та практично нетоксичні сполуки, згідно із класифікацією токсичності при парентеральних способах введення).

Висновки. Досліджено протизапальну активність та гостру токсичність серед оригінальних піроло[1,2-а][1,2,4]триазино[2,3-с]хіназолінів і встановлено, що більшість досліджуваних сполук проявляють виражену протизапальну дію при внутрішньошлунковому введенні та належать до практично нетоксичних або малотоксичних сполук (IV-V клас). Обговорено взаємозв’язок «хімічна будова – протизапальна активність» і показано, що введення залишку пропанової кислоти в положення 5а зазначеної системи є виправданим у плані пошуку сполук з антиексудативною дією, а зазначені структури є перспективною групою для проведення подальшого спрямованого синтезу і фармакологічних досліджень із метою створення на їх основі нових нестероїдних протизапальних засобів.
Revisited phylogeny of Bethylinae (Hymenoptera, Bethylidae) solves basal polytomy
Authors: Ramos Magno S. , Azevedo Celso O.
Published: October 2019

Bethylinae are a morphologically well-defined subfamily of Bethylidae, with remarkable characters, such as strongly convex clypeal carina and bifid and angled tarsal claws. However, there is no consensus about the phylogenetic relationships among the genera within the family, regarding mainly Eupsenella and Lytopsenella. To resolve this problem, a phylogeny of the Bethylinae is inferred based on parsimony analyses separately of 43 and 44 morphological characters for males and females, respectively. We performed combined analyses of both sexes with 49 morphological characters, including genitalia. We present a phylogenetic analysis, including a total 118 species of Bethylinae. Male and female characters were included in these analyses. We discuss wing morphology and deformability of forewings for the first time. In summary, the basal polytomy was solved for the first time. Seven of the eight genera were recovered as monophyletic groups. The unique exception is Goniozus, which was retrieved as paraphyletic in all topologies.
Pantagruelismus und Hexenangst
Authors: Bulang Tobias
Published: October 2019

The Alsacian author Johann Fischart translated Rabelais’ Gargantua as well as Bodin’s Démonomanie des sorciers. This study aims to clarify the connection between these most opposite texts. How does Rabelaisian laughter in German context connect to early modern witch-hunt ideology? Starting point of this investigation are Fischart’s puns and their lexical, phraseological, intertextual and interdiscoursive dimensions.
Citizenship or Inheritance? The Phratry in Classical Athens
Authors: Joyce Christopher
Published: October 2019

This article challenges the modern orthodoxy which states that phratry membership was a necessary precondition of Athenian citizenship in the fifth and fourth centuries BC and argues that the purpose of the phratry was to establish not claims to citizenship, even though membership in a phratry was proof of citizenship, but inheritance entitlements. It questions the widespread assumption that citizens needed to be born of unions legally cemented by engyê. In turn, it challenges a recent attempt to argue that legitimacy of birth and legitimacy in community were one and the same. Finally, in examines passages of orators which show that the concern of the phratry was to establish not the right to participate in Athenian polity, which was the business of the deme to determine, but the right to inherit property, and in the light of those conclusions argues that while membership in the phratry proved citizenship, it was not essential or necessary for each and every citizen of Athens to be a member of a phratry, the chief purpose of which was to establish inheritance claims.
From Illiberal to Incorrigible: A New Strategy for Humanitarian Enforcement Action in Syria
Authors: Roele Isobel
Published: October 2019

The Syrian civil war has caused heartbreaking human suffering. Proponents of decisive action to end this suffering have tended to frame their case in terms of liberal values such as democracy, human rights and the rule of law. In framing the humanitarian issue in this way, advocates of UN Security Council involvement have emphasized the illiberality of the ‘Assad regime’ in order to promote the acceptability of coercive enforcement action under Chapter VII of the UN Charter. I argue that this rationale is counterproductive as it guarantees that the Russian Federation will veto any proposal for Chapter VII measures. Russia favours an inclusive Syrian-led political solution to the Syrian civil war and fears that any invocation of Chapter VII will provide Western powers with carte blanche for regime change, effectively repeating – in Russia’s eyes – NATO’s action in Libya in 2011. This article offers an alternative way of framing arguments for humanitarian enforcement action that is intended to side-step Russia’s objections. This strategic re-framing replaces the logic of illiberality with the logic of incorrigibility. This strategy takes its inspiration from Michel Foucault’s work on disciplinary power, making an admittedly unorthodox use of Foucauldian analytics to do so. The incorrigibility strategy seeks to bypass Russian fears about regime change by adopting a threshold for Chapter VII action based on a measured phenomenon – the repeated failure by the parties to correct their behaviour in line with UNSC prescriptions. Apart from providing a threshold for enforcement action, the logic of incorrigibility also shapes the eventual Chapter VII measures taken because it focuses on correcting the parties’ behaviour and because it yields highly specified and relatively controllable mandates for coercive action which limit states’ interpretation of what is required of them to carry out the UNSC’s decisions.
Liberalism in International Trade, Illiberalism in Domestic Economic Governance and Human Rights Protection in the Context of the WTO
Authors: Mulyun Vladislav
Published: October 2019

This analysis focuses on one aspect of liberalism – the fundamental human right to fair trial – and discovers the possibility for private actors to protect domestically their (human) rights violated by infringements of WTO commitments.

In the course of the discussion of relations between the issues of human rights protection and WTO States obligations several dimensions can be revealed.
A Glass Half Empty? Execution of Judgments of the European Court of Human Rights in Central and Eastern Europe
Authors: Černič Jernej Letnar
Published: October 2019

This article critically examines weak execution of judgements of the European Court of Human Rights from the perspective of on-going innate struggle between ideas of liberalism and illiberalism in transitional societies of Central and Eastern European countries. This article thereafter identifies and analyses the reasons for poor execution of judgements in most Central and Eastern European states from the perspective of (il)liberalism, trying to draw out lessons concerning the understanding of current failures of those states to comply with the European Convention for the Protection of Human Rights and Fundamental Freedoms. Equipped with this knowledge, this article goes on to argue that some common reasons for non-execution of judgement can be identified across Central and Eastern European states. It argues that those reasons can be inter alia located in legal formalisms, authoritarian judicial cultures and lack of self-criticisms of judicial structures. To this end, this article suggests how Central and Eastern European states could overcome the hurdles posed by remains of socialist legal culture in a manner that will live up to their obligations concerning execution of judgements of the European Court of Human Rights.
Frequency-Domain Analysis of the Energy Budget in an Idealized Coupled Ocean–Atmosphere Model
Authors: Martin Paige E. , Arbic Brian K. , McC. Hogg Andrew , Kiss Andrew E. , Munroe James R. , Blundell Jeffrey R.
Published: October 2019

Climate variability is investigated by identifying the energy sources and sinks in an idealized, coupled, ocean–atmosphere model, tuned to mimic the North Atlantic region. The spectral energy budget is calculated in the frequency domain to determine the processes that either deposit energy into or extract energy from each fluid, over time scales from one day up to 100 years. Nonlinear advection of kinetic energy is found to be the dominant source of low-frequency variability in both the ocean and the atmosphere, albeit in differing layers in each fluid. To understand the spatial patterns of the spectral energy budget, spatial maps of certain terms in the spectral energy budget are plotted, averaged over various frequency bands. These maps reveal three dynamically distinct regions: along the western boundary, the western boundary current separation, and the remainder of the domain. The western boundary current separation is found to be a preferred region to energize oceanic variability across a broad range of time scales (from monthly to decadal), while the western boundary itself acts as the dominant sink of energy in the domain at time scales longer than 50 days. This study paves the way for future work, using the same spectral methods, to address the question of forced versus intrinsic variability in a coupled climate system.
Variational Retrieval of Rain Microphysics and Related Parameters from Polarimetric Radar Data with a Parameterized Operator
Authors: Mahale Vivek N. , Zhang Guifu , Xue Ming , Gao Jidong , Reeves Heather D.
Published: October 2019

A variational retrieval of rain microphysics from polarimetric radar data (PRD) has been developed through the use of S-band parameterized polarimetric observation operators. Polarimetric observations allow for the optimal retrieval of cloud and precipitation microphysics for weather quantification and data assimilation for convective-scale numerical weather prediction (NWP) by linking PRD to physical parameters. Rain polarimetric observation operators for reflectivity ZH, differential reflectivity ZDR, and specific differential phase KDP were derived for S-band PRD using T-matrix scattering amplitudes. These observation operators link the PRD to the physical parameters of water content W and mass-/volume-weighted diameter Dm for rain, which can be used to calculate other microphysical information. The S-band observation operators were tested using a 1D variational retrieval that uses the (nonlinear) Gauss–Newton method to iteratively minimize the cost function to find an optimal estimate of Dm and W separately for each azimuth of radar data, which can be applied to a plan position indicator (PPI) radar scan (i.e., a single elevation). Experiments on two-dimensional video disdrometer (2DVD) data demonstrated the advantages of including ΦDP observations and using the nonlinear solution rather than the (linear) optimal interpolation (OI) solution. PRD collected by the Norman, Oklahoma (KOUN) WSR-88D on 15 June 2011 were used to successfully test the retrieval method on radar data. The successful variational retrieval from the 2DVD and the radar data demonstrate the utility of the proposed method.
Drylines in Argentina: Synoptic Climatology and Processes Leading to Their Genesis
Authors: Bechis Hernán , Salio Paola , Ruiz Juan José
Published: October 2019

Drylines have been identified as relevant synoptic-scale phenomena that frequently occur in several regions around the world. Despite previous works and the experience of local forecasters that recognizes the occurrence of drylines in Argentina and suggests its possible association with convection initiation, knowledge about the mechanisms leading to the genesis of these features is poor. This paper presents the first synoptic climatology of these drylines as well as a first approach to the understanding of the processes leading to their formation. The climatology is based on an automated algorithm for dryline identification applied to reanalysis data. We found that drylines are more frequent between the northern Patagonia plateau and the central Argentinean plains. A composite analysis is performed to analyze the processes leading to the formation of synoptic-scale drylines within this region. It was found that these drylines form in the confluence between a warm and moist air mass driven by a northwesterly flow and drier air flowing east over the northern Patagonia plateau. The dry air originates on top of the Pacific maritime boundary layer and experiences lee subsidence after crossing the Andes range creating an area of dry and warm air that is advected to the east by the westerly synoptic-scale flow, and transported downward during the day due to strong boundary layer turbulence. At the same time, surface heating over the plateau leads to substantial warming of the originally colder dry air behind the dryline, thus reversing the horizontal temperature gradient across the dryline.
Formation of Wind Gusts in an Extratropical Cyclone in Light of Doppler Lidar Observations and Large-Eddy Simulations
Authors: Pantillon Florian , Adler Bianca , Corsmeier Ulrich , Knippertz Peter , Wieser Andreas , Hansen Akio
Published: October 2019

Damaging gusts in windstorms are represented by crude subgrid-scale parameterizations in today’s weather and climate models. This limitation motivated the Wind and Storms Experiment (WASTEX) in winter 2016–17 in the Upper Rhine Valley over southwestern Germany. Gusts recorded at an instrumented tower during the passage of extratropical cyclone “Thomas” on 23 February 2017 are investigated based on measurements of radial wind with ≈70-m along-beam spacing from a fast-scanning Doppler lidar and realistic large-eddy simulations with grid spacings down to 78 m using the Icosahedral Nonhydrostatic model. Four wind peaks occur due to the storm onset, the cold front, a precipitation line, and isolated showers. The first peak is related to a sudden drop in dewpoint and results from the downward mixing of a low-level jet and a dry layer within the warm sector characterized by extremely high temperatures for the season. While operational convection-permitting forecasts poorly predict the storm onset overall, a successful ensemble member highlights the role of upstream orography. Lidar observations reveal the presence of long-lasting wind structures that result from a combination of convection- and shear-driven instability. Large-eddy simulations contain structures elongated in the wind direction that are qualitatively similar but too coarse compared to the observed ones. Their size is found to exceed the effective model resolution by one order of magnitude due to their elongation. These results emphasize the need for subkilometer-scale measuring and modeling systems to improve the representation of gusts in windstorms.
Efficacy and safety of biologic agents and tofacitinib in moderate‐to‐severe ulcerative colitis: A systematic overview of meta‐analyses
Authors: Pantavou Katerina , Yiallourou Anneza I , Piovani Daniele , Evripidou Despo , Danese Silvio , Peyrin-Biroulet Laurent , Bonovas Stefanos , Nikolopoulos Georgios K
Published: October 2019

Background

Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib.

Objectives

We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate‐to‐severe UC.

Methods

PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta‐analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events.

Results

The overview involved 31 meta‐analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab.

Conclusions

Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision‐making.
Systematic review and meta-analysis of tick-borne disease risk factors in residential yards, neighborhoods, and beyond
Authors: Fischhoff Ilya R. , Bowden Sarah E. , Keesing Felicia , Ostfeld Richard S.
Published: October 2019

Background

Exposure to blacklegged ticks Ixodes scapularis that transmit pathogens is thought to occur peri-domestically. However, the locations where people most frequently encounter infected ticks are not well characterized, leading to mixed messages from public health officials about where risk is highest.

Methods

We conducted a systematic review and meta-analysis on spatial risk factors for tick-borne disease and tick bites in eastern North America. We examined three scales: the residential yard, the neighborhood surrounding (but not including) the yard, and outside the neighborhood. Nineteen eligible studies represented 2741 cases of tick-borne illness and 1447 tick bites. Using random effects models, we derived pooled odds ratio (OR) estimates.

Results

The meta-analysis revealed significant disease risk factors at the scale of the yard (OR 2.60 95% CI 1.96 – 3.46), the neighborhood (OR 4.08 95% CI 2.49 – 6.68), and outside the neighborhood (OR 2.03 95% CI 1.59 – 2.59). Although significant risk exists at each scale, neighborhood scale risk factors best explained disease exposure. Analysis of variance revealed risk at the neighborhood scale was 57% greater than risk at the yard scale and 101% greater than risk outside the neighborhood.

Conclusions

This analysis emphasizes the importance of understanding and reducing tick-borne disease risk at the neighborhood scale. Risk-reducing interventions applied at each scale could be effective, but interventions applied at the neighborhood scale are most likely to protect human health.

Trial registration

The study was registered with PROSPERO: CRD42017079169.
Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with ‘refractoriness to treatment’: a cohort study
Authors:   on behalf of the TeMpOH-1 study group, Henriquez Dacia D. C. A. , Gillissen Ada , Smith Sharissa M. , Cramer Roos A. , van den Akker Thomas , Zwart Joost J. , van Roosmalen Jos J. M. , Bloemenkamp Kitty W. M. , van der Bom Johanna G.
Published: October 2019

Background

The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions.

Methods

In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission.

Results

One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment.

Conclusion

The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.
Assessing public awareness of clubfoot and knowledge about the importance of early childhood treatment: a cross-sectional survey
Authors: Alsiddiky Abdulmonem , Alrwibaah Salman , Alqahtani Abdulrahman , Alnujidi Abdulmalek , Alhomaidhi Abdullah , Almasoud Abdulla , Alatassi Raheef
Published: October 2019

Background

Clubfoot is a treatable abnormality that can be managed with early intervention. However, there is a lack of public knowledge regarding clubfoot, which can delay treatment. This study aimed to assess the public awareness of clubfoot and knowledge regarding the importance of treatment in early childhood.

Methods

This cross-sectional survey spanned 6 months, from June through November 2018, and involved persons living in Saudi Arabia. To collect data on public awareness of clubfoot risk factors, treatment, and prognosis, a questionnaire was developed by orthopedic experts and disseminated online. The target population included people of both genders and all age groups from the general population, regardless of their knowledge of someone with clubfoot.

Results

By the end of the study period, 746 participants completed the online survey. In total, 520 of the respondents (69.7%) had never heard about clubfoot syndrome. Among the participants, 5.4% had a child with clubfoot syndrome and 4.6% were aware of clubfoot because they had an affected child. The top resource accessed by respondents for obtaining knowledge about clubfoot was social media channels (38.4%), followed by obtaining knowledge from relatives and friends (19.9%). The most reported perceived cause of clubfoot was hereditary and genetic disorders (58.4%), followed by neurological disorders (39.9%).

Conclusions

Results show that there is low public knowledge of clubfoot which may be attributed to a lack of awareness campaigns. We recommend increasing awareness regarding clubfoot through social media platforms and public campaigns in key locations, such as malls, as this may encourage people to seek early treatment. This is important because early management of clubfoot is less invasive and with regular follow-up, leads to better patient outcomes.
Correction to: The 2018 UK NHS Digital annual report on the Improving Access to Psychological Therapies programme: a brief commentary
Authors: Moller Naomi Petra , Ryan Gemma , Rollings Jasmine , Barkham Michael
Published: October 2019

Following publication of the original article [1], we have been notified that one of the authors’ names is spelled incorrectly. In this Correction the incorrect and correct author name are shown.
How clinical teaching teams deal with educational change: ‘we just do it’
Authors: Bank L. , Jippes M. , van Rossum T. R. , den Rooyen C. , Scherpbier A. J. J. A. , Scheele F.
Published: October 2019

Background

In postgraduate medical education, program directors are in the lead of educational change within clinical teaching teams. As change is part of a social process, it is important to not only focus on the program director but take their other team members into account. The purpose of this study is to provide an in-depth insight into how clinical teaching teams manage and organize curriculum change processes, and implement curriculum change in daily practice.

Methods

An explorative qualitative semi-structured interview study was conducted between October 2016 and March 2017. A total of six clinical teaching teams (n = 6) participated in this study, i.e. one program director, one clinical staff member, and one trainee from each clinical teaching team (n = 18). Data were analysed and structured by means of thematic analysis.

Results

The analysis yielded to five factors that positively impact change: shared commitment, reinvention, ownership, supportive structure and open culture. Factors that negatively impact change were: resistance, behaviour change, balance between different tasks, lack of involvement, lack of consensus, and unsafe culture and hierarchy. Overall, no clear change strategy could be recognized.

Conclusions

Insight was gathered in factors facilitating and hindering the implementation of change. It seems particularly important for clinical teaching teams to be able to create a sense of ownership among all team members by making a proposed change valuable for their local context as well as to be capable of working together as a team. Cultural factors seem to be particularly relevant in a team’s ability to accomplish this.
Forming and implementing community advisory boards in low- and middle-income countries: a scoping review
Authors: Zhao Yang , Fitzpatrick Thomas , Wan Bin , Day Suzanne , Mathews Allison , Tucker Joseph D.
Published: October 2019

Background

Community advisory boards (CABs) have expanded beyond high-income countries (HICs) and play an increasing role in low- and middle-income country (LMIC) research. Much research has examined CABs in HICs, but less is known about CABs in LMICs. The purposes of this scoping review are to examine the creation and implementation of CABs in LMICs, including identifying frequently reported challenges, and to discuss implications for research ethics.

Methods

We searched five databases (PubMed, Embase, Global Health, Scopus, and Google Scholar) for publications describing or evaluating CABs in LMICs. Two researchers independently reviewed articles for inclusion. Data related to the following aspects of CABs were extracted from included publications: time, country, financial support, research focus, responsibilities, and challenges. Thematic analyses were used to summarize textual data describing challenges.

Results

Our search yielded 2005 citations, 83 of which were deemed eligible for inclusion. Most studies (65) were published between 2010 and 2017. Upper-middle-income countries were more likely to have studies describing CABs, with South Africa (17), China (8), and Thailand (7) having the greatest numbers. The United States National Institutes of Health was the main source of financial support for CABs. Many CABs (53/88, 60%) focused on HIV research. Thirty-four studies reported how CABs influenced the informed consent process for clinical trials or other aspects of research ethics. CAB responsibilities were related to clinical trials, including reviewing study protocols, educating local communities about research activities, and promoting the ethical conduct of research. Challenges faced by CABs included the following: incomplete ethical regulations and guidance; limited knowledge of science among members of communities and CABs; unstable and unbalanced power relationships between researchers and local communities; poor CAB management, including lack of formal participation structures and absence of CAB leadership; competing demands for time that limited participation in CAB activities; and language barriers between research staff and community members. Several challenges reflected shortcomings within the research team.

Conclusions

Our findings examine the formation and implementation of CABs in LMICs and identify several ethical challenges. These findings suggest the need for further ethics training among CAB members and researchers in LMICs.
Multimorbidity and healthcare resource utilization in Switzerland: a multicentre cohort study
Authors: Aubert Carole E. , Fankhauser Niklaus , Marques-Vidal Pedro , Stirnemann Jérôme , Aujesky Drahomir , Limacher Andreas , Donzé Jacques
Published: October 2019

Background

Multimorbidity is associated with higher healthcare resource utilization, but we lack data on the association of specific combinations of comorbidities with healthcare resource utilization. We aimed to identify the combinations of comorbidities associated with high healthcare resource utilization among multimorbid medical inpatients.

Methods

We performed a multicentre retrospective cohort study including 33,871 multimorbid (≥2 chronic diseases) medical inpatients discharged from three Swiss hospitals in 2010–2011. Healthcare resource utilization was measured as 30-day potentially avoidable readmission (PAR), prolonged length of stay (LOS) and difference in median LOS. We identified the combinations of chronic comorbidities associated with the highest healthcare resource utilization and quantified this association using regression techniques.

Results

Three-fourths of the combinations with the strongest association with PAR included chronic kidney disease. Acute and unspecified renal failure combined with solid malignancy was most strongly associated with PAR (OR 2.64, 95%CI 1.79;3.90). Miscellaneous mental health disorders combined with mood disorders was the most strongly associated with LOS (difference in median LOS: 17 days) and prolonged LOS (OR 10.77, 95%CI 8.38;13.84). The number of chronic diseases was strongly associated with prolonged LOS (OR 9.07, 95%CI 8.04;10.24 for ≥10 chronic diseases), and to a lesser extent with PAR (OR 2.16, 95%CI 1.75;2.65 for ≥10 chronic diseases).

Conclusions

Multimorbidity appears to have a higher impact on LOS than on PAR. Combinations of comorbidities most strongly associated with healthcare utilization included kidney disorders for PAR, and mental health disorders for LOS.
Tumour heterogeneity revealed by unsupervised decomposition of dynamic contrast-enhanced magnetic resonance imaging is associated with underlying gene expression patterns and poor survival in breast cancer patients
Authors: Fan Ming , Xia Pingping , Liu Bin , Zhang Lin , Wang Yue , Gao Xin , Li Lihua
Published: October 2019

Background

Heterogeneity is a common finding within tumours. We evaluated the imaging features of tumours based on the decomposition of tumoural dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data to identify their prognostic value for breast cancer survival and to explore their biological importance.

Methods

Imaging features (n = 14), such as texture, histogram distribution and morphological features, were extracted to determine their associations with recurrence-free survival (RFS) in patients in the training cohort (n = 61) from The Cancer Imaging Archive (TCIA). The prognostic value of the features was evaluated in an independent dataset of 173 patients (i.e. the reproducibility cohort) from the TCIA I-SPY 1 TRIAL dataset. Radiogenomic analysis was performed in an additional cohort, the radiogenomic cohort (n = 87), using DCE-MRI from TCGA-BRCA and corresponding gene expression data from The Cancer Genome Atlas (TCGA). The MRI tumour area was decomposed by convex analysis of mixtures (CAM), resulting in 3 components that represent plasma input, fast-flow kinetics and slow-flow kinetics. The prognostic MRI features were associated with the gene expression module in which the pathway was analysed. Furthermore, a multigene signature for each prognostic imaging feature was built, and the prognostic value for RFS and overall survival (OS) was confirmed in an additional cohort from TCGA.

Results

Three image features (i.e. the maximum probability from the precontrast MR series, the median value from the second postcontrast series and the overall tumour volume) were independently correlated with RFS (p values of 0.0018, 0.0036 and 0.0032, respectively). The maximum probability feature from the fast-flow kinetics subregion was also significantly associated with RFS and OS in the reproducibility cohort. Additionally, this feature had a high correlation with the gene expression module (r = 0.59), and the pathway analysis showed that Ras signalling, a breast cancer-related pathway, was significantly enriched (corrected p value = 0.0044). Gene signatures (n = 43) associated with the maximum probability feature were assessed for associations with RFS (p = 0.035) and OS (p = 0.027) in an independent dataset containing 1010 gene expression samples. Among the 43 gene signatures, Ras signalling was also significantly enriched.

Conclusions

Dynamic pattern deconvolution revealed that tumour heterogeneity was associated with poor survival and cancer-related pathways in breast cancer.
Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest
Authors: Rueda Ferran , Cediel Germán , García-García Cosme , Aranyó Júlia , González-Lopera Marta , Aranda Nevado M. Cruz , Serra Gregori Judith , Oliveras Teresa , Labata Carlos , Ferrer Marc , El Ouaddi Nabil , Bayés-Genís Antoni
Published: October 2019

Background

Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA).

Methods

Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed.

Results

Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3–5). Patients with CPC 3–5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1–20.4] ng/mL) compared to those with CPC 1–2 (7.6 [IQR, 4.1–13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01–1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61–40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84–34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32–10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48–1.44), which allowed reclassification of 37.1% of patients.

Conclusions

After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.
On an extension of Hadamard fractional derivative
Authors: Samraiz Muhammad , Set Erhan , Hasnain Muhammad , Rahman Gauhar
Published: October 2019

In this paper, we introduce a new approach to the fractional derivation which generalizes the classical Hadamard fractional derivative. We prove some properties of this new approach and also establish some results by addressing some standard functions.
A new application of Schrödinger-type identity to singular boundary value problem for the Schrödinger equation
Authors: Meng Bo
Published: October 2019

In this paper, we present a modified Schrödinger-type identity related to the Schrödinger-type boundary value problem with mixed boundary conditions and spatial heterogeneities. This identity can be regarded as an $L^{1}$

L
1

-version of Fisher–Riesz’s theorem and has a broad range of applications. Using it and fixed point theory in $L^{1}$

L
1

-metric spaces, we prove that there exists a unique solution for the singular boundary value problem with mixed boundary conditions and spatial heterogeneities. We finally provide two examples, which show the effectiveness of the Schrödinger-type identity method.
Risk factors for Blastocystis infection in HIV/AIDS patients with highly active antiretroviral therapy in Southwest China
Authors: Zhang Shun-Xian , Kang Fen-Yan , Chen Jia-Xu , Tian Li-Guang , Geng Lan-Lan
Published: October 2019

Background

Blastocystis is a widespread zoonotic protozoan of mammalian species, especially in HIV/AIDS individuals. The aim of this study was to analyze the prevalence and risk factors related with Blastocystis infection among HIV/AIDS patients in Southwest China.

Methods

The cross-sectional study was performed in 311 HIV/AIDS cases in Tengchong City, Yunnan Province from July 2016 to March 2017. For each subject, stool specimen was collected to detect the Blastocystis, and the blood sample was used to detect HIV virus load and CD4+ T cell count, in addition, structured questionnaire was used to collect the basic information and risk factors.

Findings

The result showed that the detection rate of Blastocystis was 3.86% (95% CI: 2.22–6.62) among HIV/AIDS patients. Both raising animal (OR = 12.93, 95% CI: 1.54–108.36) and drinking un-boiled water (OR = 8.17, 95% CI: 1.76–37.90) were risk factors for Blastocystis infection in HIV/AIDS individuals. In addition, the interaction of CD4+ T cell count and HIV virus load was also contribution to Blastocystis infection (P = 0.007).

Conclusions

A high prevalence of Blastocystis infection was found in HIV/AIDS patients in Tengchong. Poor hygienic habits, the interaction of HIV virus load and CD4+ T cell count were identified as main risk factors for infection. These results will help us to develop efficient control strategies to intervene with and prevent the occurrence of Blastocystis among HIV-infected individuals.
Chitosan enhances rosmarinic acid production in shoot cultures of Melissa officinalis L. through the induction of methyl jasmonate
Authors: Fooladi vanda Ghazaleh , Shabani Leila , Razavizadeh Roya
Published: October 2019

Background

Chitosan is a polycationic polysaccharide derived from chitin that has been recognized as an effective elicitor in the production of secondary metabolites of many medicinal plants. In this study, the effect of abiotic elicitor (chitosan) at various concentrations on rosmarinic acid (RA) and total phenolic accumulation in shoot cultures of lemon balm was investigated.

Results

Treatment of shoots by chitosan led to a noticeable induction of phenylalanine ammonia-lyase (PAL), catalase (CAT), guaiacol peroxidase (GPX) and lipoxygenase (LOX) activities. Besides, the expression ofPAL1,TATandRASgenes and accumulation of RA and phenolic compound increased in chitosan-treated lemon balm shoots. Chitosan treatment also increased H2O2accumulation and the expression ofRBOH, an essential gene implicated in ROS production. Also, the up-regulation of theOPRgene by exogenous chitosan was associated with the induction of endogenous JA determined by GC-MASS.

Conclusion

The present study showed that the induced production of rosmarinic acid by chitosan involves the trigger of defense-related enzymes, up-regulated expression ofTATandRASgenes, and stimulation of JA biosynthesis.
Surgical outcomes in adults with purpura fulminans: a systematic review and patient-level meta-synthesis
Authors: Klifto Kevin M. , Gurno Caresse F. , Grzelak Michael J. , Seal Stella M. , Asif Mohammed , Hultman C. Scott , Caffrey Julie A.
Published: October 2019

Background

Cutaneous manifestations of purpura fulminans (PF) present many challenges for clinicians and surgeons. In a state of septic shock complicated by limb ischemia, surgical interventions are necessary to control the pathological cascade and improve patient outcomes. The objective of this article was to report etiologies and surgical outcomes associated with cutaneous manifestations in adults.

Methods

This systematic review and meta-analysis compared 190 adult patients with etiologies, signs and symptoms, and surgical outcomes associated with cutaneous manifestations of PF. The PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were systematically and independently searched. Patient and clinical characteristics, surgical interventions, outcomes, and complications were recorded.

Results

Seventy-nine studies were eligible for the systematic review, and 77 were eligible for meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and Cochrane guidelines. A total of 71/190 (38%) cases reported surgical debridement. Fasciotomies were reported in 12/190 (6%) cases and 20 procedures. Amputations were reported in 154/190 (81%) cases. Reconstruction was reported in 45 cases. Skin grafts were applied in 31 cases. Flaps were used for reconstruction in 28 cases. Median (IQR) surgical procedures per patient were 4 (4, 5) procedures. Infectious organisms causing PF were 32% Neisseria meningitidis (n = 55) and 32% Streptococcus pneumonia (n = 55). Coagulase-negative Staphylococcus (95% confidence interval (CI)(8.2–177.9), p = 0.032), Haemophilus influenza (95%CI (7.2–133), p = 0.029), Streptococcus pneumonia (95% CI (13.3–75.9), p = 0.006), and West Nile Virus (95%CI (8.2–177.9), p = 0.032) were associated with significantly more extensive amputations compared to other organisms.

Conclusion

This systematic review and patient-level meta-analysis found the most common presentation of PF was septic shock from an infectious organism. Neisseria meningitidis and Streptococcus pneumonia were equally the most common organisms associated with PF. The majority of cases were not treated in a burn center. The most common surgeries were amputations, with below-the-knee-amputations being the most common procedure. Skin grafting was the most commonly performed reconstructive procedure. The most common complications were secondary infections. Organisms with significantly more extensive amputations were coagulase-negative Staphylococcus, Haemophilus influenza, Streptococcus pneumonia, and West Nile Virus. Interpretation of findings should be cautioned due to limited sample data.