bluuebunny/crossref_metadata_2025 huggingface dataset:
BLAME AND WRONGDOING
Authors: Brown Jessica
Published: September 2017

The idea that one can blamelessly violate a norm is central to ethics and epistemology. The paper examines the prospects for an account of blameless norm violation applicable both to norms governing action and norms governing belief. In doing so, I remain neutral on just what are the norms governing action and belief. I examine three leading suggestions for understanding blameless violation of a norm which is not overridden by another norm: (1) doxastic accounts; (2) epistemic accounts; and (3) appeal to expected value. We see that all of these accounts face problems when understood as accounts of blameless norm violation applicable to both belief and action. This leaves a variety of options including (1) seeking an alternative account of blameless norm violation common to belief and action; (2) concluding that we cannot determine the correct account of blameless norm violation independently of what are the norms of belief; and (3) abandoning the project of finding a common account of blameless norm violation common to ethics and epistemology.
A spectral refinement of the Bergelson–Host–Kra decomposition and new multiple ergodic theorems
Authors: MOREIRA JOEL , RICHTER FLORIAN KARL
Published: September 2017

We investigate how spectral properties of a measure-preserving system$(X,{\mathcal{B}},\unicode[STIX]{x1D707},T)$are reflected in the multiple ergodic averages arising from that system. For certain sequences$a:\mathbb{N}\rightarrow \mathbb{N}$, we provide natural conditions on the spectrum$\unicode[STIX]{x1D70E}(T)$such that, for all$f_{1},\ldots ,f_{k}\in L^{\infty }$,$$\begin{eqnarray}\lim _{N\rightarrow \infty }\frac{1}{N}\mathop{\sum }_{n=1}^{N}\mathop{\prod }_{j=1}^{k}T^{ja(n)}f_{j}=\lim _{N\rightarrow \infty }\frac{1}{N}\mathop{\sum }_{n=1}^{N}\mathop{\prod }_{j=1}^{k}T^{jn}f_{j}\end{eqnarray}$$in$L^{2}$-norm. In particular, our results apply to infinite arithmetic progressions,$a(n)=qn+r$, Beatty sequences,$a(n)=\lfloor \unicode[STIX]{x1D703}n+\unicode[STIX]{x1D6FE}\rfloor$, the sequence of squarefree numbers,$a(n)=q_{n}$, and the sequence of prime numbers,$a(n)=p_{n}$. We also obtain a new refinement of Szemerédi’s theorem via Furstenberg’s correspondence principle.
Under-reporting giardiasis: time to consider the public health implications
Authors: CURRIE S. L. , STEPHENSON N. , PALMER A. S. , JONES B. L. , ALEXANDER C. L.
Published: September 2017

Giardiasis is a treatable disease, caused by the flagellated protozoan parasite, Giardia duodenalis (G. duodenalis). It is one of the most common enteric parasites found globally to cause gastrointestinal disturbances, and infections may result in long-term irritable bowel syndrome-like symptoms. It is a common misconception that giardiasis is associated with foreign travel, which results in locally acquired cases in the UK being underdiagnosed. This report highlights the findings from one large Scottish Health Board, arising from a change in testing methodology, which resulted in the screening of all stools submitted for enteric investigations for G. duodenalis. Previous selection criteria were restricted to patients with a travel history to specific regions of the world, or on the basis of certain clinical details. In this report, clinical details were recorded from samples shown to be positive using two methods: an ELISA-based antigen detection assay and microscopy. Clinical details were assessed for a total of 28 laboratory-confirmed positive cases against the original selection criteria. Twenty-six cases (93%) would have been excluded from Giardia testing if the previous selection criteria had been applied. Although nine cases stated foreign travel, only two had been to regions deemed to be ‘high risk’. Therefore, those seven cases that travelled to perceived ‘low-risk’ regions would have been excluded from testing for this reason. This summary highlights the need for significant improvements to the selection criteria for Giardia testing. Laboratories should be encouraged towards the testing of all routinely submitted stools for this neglected pathogen to ensure cases that are acquired locally are properly identified and treated effectively.
The perception of dental and alveolar stops among speakers of Irish English and American English
Authors: KELLY NIAMH E.
Published: September 2017

Most speakers of Irish English use a dental stop for words containing , a sound that is generally pronounced as [θ] and [ð], in other varieties of English (Wells 1982; Ó hÚrdail 1997). Alveolar stops [t,d] and dental stops [,] are articulatorily and acoustically similar, and thus it is unusual for a language to use them contrastively (e.g. Ladefoged 2001). Despite this, Irish English contrasts them and speakers of this dialect have no trouble distinguishing them. This raises the question as to whether speakers of a dialect which does not use this contrast can distinguish them. To investigate this, speakers of Irish English and American English participated in an identification task involving words produced by an Irish English speaker. American English speakers had a high accuracy but did significantly worse than Irish English speakers, and both groups did significantly worse when the contrast was in final position than when it was in initial position. A small-scale production experiment examined words with this contrast and the vowel /a/, with the finding that for speakers of both dialects, the vowel is longer in words ending in  than . The findings are discussed in the context of linguistic experience, and the effect of surrounding consonants on vowel duration.
Adherence to dietary recommendations for Swedish adults across categories of greenhouse gas emissions from food
Authors: Sjörs Camilla , Hedenus Fredrik , Sjölander Arvid , Tillander Annika , Bälter Katarina
Published: September 2017

Objective

To explore associations between diet-related greenhouse gas emissions (GHGE), nutrient intakes and adherence to the Nordic Nutrition Recommendations among Swedish adults.

Design

Diet was assessed by 4d food records in the Swedish National Dietary Survey. GHGE was estimated by linking all foods to carbon dioxide equivalents, using data from life cycle assessment studies. Participants were categorized into quartiles of energy-adjusted GHGE and differences between GHGE groups regarding nutrient intakes and adherence to nutrient recommendations were explored.

Setting

Sweden.

Subjects

Women (n840) and men (n627) aged 18–80 years.

Results

Differences in nutrient intakes and adherence to nutrient recommendations between GHGE groups were generally small. The dietary intake of participants with the lowest emissions was more in line with recommendations regarding protein, carbohydrates, dietary fibre and vitamin D, but further from recommendations regarding added sugar, compared with the highest GHGE group. The overall adherence to recommendations was found to be better among participants with lower emissions compared with higher emissions. Among women, 27 % in the lowest GHGE group adhered to at least twenty-three recommendations compared with only 12 % in the highest emission group. For men, the corresponding figures were 17 and 10 %, respectively.

Conclusions

The study compared nutrient intakes as well as adherence to dietary recommendations for diets with different levels of GHGE from a national dietary survey. We found that participants with low-emission diets, despite higher intake of added sugar, adhered to a larger number of dietary recommendations than those with high emissions.
CDP138 silencing inhibits TGF-β/Smad signaling to impair radioresistance and metastasis via GDF15 in lung cancer
Authors: Lu Yanwei , Ma Jia , Li Yan , Huang Jing , Zhang Sheng , Yin Zhongyuan , Ren Jinghua , Huang Kai , Wu Gang , Yang Kunyu , Xu Shuangbing
Published: September 2017

CDP138, a CDK5 binding partner, regulates cell proliferation and migration. However, the mechanisms by which CDP138 functions in these processes remain unclear. In this study, we show that CDP138 is frequently overexpressed and that high levels of CDP138 are correlated with lymph node metastasis in lung cancer. Furthermore, we provide evidence that CDP138-depleted lung cancer cells exhibit enhanced radiosensitivity as well as reduced migration and invasion. Mechanistically, we identify GDF15, a member of the TGF-β superfamily, as a key downstream effector of CDP138. CDP138 silencing attenuates TGF-β/Smad signaling activation at least in part through the downregulation of GDF15. More importantly, the observed phenotypes caused by CDP138 knockdown are partially dependent on GDF15 inhibition. Together, our findings demonstrate that CDP138 positively modulates the TGF-β/Smad signaling pathway via GDF15 to promote radioresistance and metastasis, suggesting CDP138 as a potential oncogenic biomarker and a promising therapeutic target in the treatment of lung cancer.
Asymmetrically substituted triazenes as poor electron donor ligands in the precursor chemistry of iron(ii) for iron-based metallic and intermetallic nanocrystals
Authors: Soussi Khaled , Mishra Shashank , Jeanneau Erwann , Millet Jean-Marc M. , Daniele Stéphane
Published: September 2017

First as precursors: Heteroleptic FeII complexes derived from new asymmetric triazene ligands t-BuNN-NHR (R = Et, i-Pr, n-Bu) show interesting molecular and precursor chemistry.
Rational design and structure–activity relationship studies of quercetin–amino acid hybrids targeting the anti-apoptotic protein Bcl-xL
Authors: Kellici Tahsin F. , Chatziathanasiadou Maria V. , Lee Min-Sung , Sayyad Nisar , Geromichalou Elena G. , Vrettos Eirinaios I. , Tsiailanis Antonis D. , Chi Seung-Wook , Geromichalos George D. , Mavromoustakos Thomas , Tzakos Andreas G.
Published: September 2017

Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target.
Concepts for Prehospital and Initial In-hospital Therapy of Status Epilepticus
Authors: Strzelczyk Adam , Kay Lara , Kellinghaus Christoph , Knake Susanne , von Blomberg Anemone , Willems Laurent , Rosenow Felix
Published: September 2017

Status epilepticus is a major neurological emergency requiring immediate anticonvulsive treatment. Rapid and sufficient treatment is essential for optimizing outcome and reducing mortality. Here, we give an overview on concepts for acute prehospital and initial in-hospital treatment of status epilepticus. Options for initial therapy in settings without intensive care monitoring are presented in detail.
Eine schwierige Entscheidung
Authors: Komor Beate , Hoppe Andreas , Gouba Benjamin
Published: September 2017

NIV und Palliativmedizin – ein Widerspruch? Sollte bei einem Palliativpatienten mit Dyspnoe Nicht-invasive Ventilation zum Einsatz
kommen? Die Meinungen darüber sind geteilt. Wird das Sterben dadurch verlängert? Oder bedeutet es für den Patienten mehr Lebensqualität? –
Die Facharbeit der drei Autoren zu diesem Thema brachte ihnen beim Thieme intensiv-Pflegepreis 2015 den 2. Platz ein.
Hyper Suprime-Cam: System design and verification of image quality
Authors: Miyazaki Satoshi , Komiyama Yutaka , Kawanomoto Satoshi , Doi Yoshiyuki , Furusawa Hisanori , Hamana Takashi , Hayashi Yusuke , Ikeda Hiroyuki , Kamata Yukiko , Karoji Hiroshi , Koike Michitaro , Kurakami Tomio , Miyama Shoken , Morokuma Tomoki , Nakata Fumiaki , Namikawa Kazuhito , Nakaya Hidehiko , Nariai Kyoji , Obuchi Yoshiyuki , Oishi Yukie , Okada Norio , Okura Yuki , Tait Philip , Takata Tadafumi , Tanaka Yoko , Tanaka Masayuki , Terai Tsuyoshi , Tomono Daigo , Uraguchi Fumihiro , Usuda Tomonori , Utsumi Yousuke , Yamada Yoshihiko , Yamanoi Hitomi , Aihara Hiroaki , Fujimori Hiroki , Mineo Sogo , Miyatake Hironao , Oguri Masamune , Uchida Tomohisa , Tanaka Manobu M , Yasuda Naoki , Takada Masahiro , Murayama Hitoshi , Nishizawa Atsushi J , Sugiyama Naoshi , Chiba Masashi , Futamase Toshifumi , Wang Shiang-Yu , Chen Hsin-Yo , Ho Paul T P , Liaw Eric J Y , Chiu Chi-Fang , Ho Cheng-Lin , Lai Tsang-Chih , Lee Yao-Cheng , Jeng Dun-Zen , Iwamura Satoru , Armstrong Robert , Bickerton Steve , Bosch James , Gunn James E , Lupton Robert H , Loomis Craig , Price Paul , Smith Steward , Strauss Michael A , Turner Edwin L , Suzuki Hisanori , Miyazaki Yasuhito , Muramatsu Masaharu , Yamamoto Koei , Endo Makoto , Ezaki Yutaka , Ito Noboru , Kawaguchi Noboru , Sofuku Satoshi , Taniike Tomoaki , Akutsu Kotaro , Dojo Naoto , Kasumi Kazuyuki , Matsuda Toru , Imoto Kohei , Miwa Yoshinori , Suzuki Masayuki , Takeshi Kunio , Yokota Hideo
Published: September 2017

The Hyper Suprime-Cam (HSC) is an 870 megapixel prime focus optical imaging camera for the 8.2 m Subaru telescope. The wide-field corrector delivers sharp images of 0${^{\prime\prime}_{.}}$2 (FWHM) in the HSC-i band over the entire 1${^{\circ}_{.}}$5 diameter field of view. The collimation of the camera with respect to the optical axis of the primary mirror is done with hexapod actuators, the mechanical accuracy of which is a few microns. Analysis of the remaining wavefront error in off-focus stellar images reveals that the collimation of the optical components meets design specifications. While there is a flexure of mechanical components, it also is within the design specification. As a result, the camera achieves its seeing-limited imaging on Maunakea during most of the time; the median seeing over several years of observing is 0${^{\prime\prime}_{.}}$67 (FWHM) in the i band. The sensors use p-channel, fully depleted CCDs of 200 μm thickness (2048 × 4176 15 μm square pixels) and we employ 116 of them to pave the 50 cm diameter focal plane. The minimum interval between exposures is 34 s, including the time to read out arrays, to transfer data to the control computer, and to save them to the hard drive. HSC on Subaru uniquely features a combination of a large aperture, a wide field of view, sharp images and a high sensitivity especially at longer wavelengths, which makes the HSC one of the most powerful observing facilities in the world.
Association Between Mode of Delivery and Risk of Infection in Early Childhood
Authors: Christensen Nikolas , Søndergaard Jens , Christesen Henrik Thybo , Fisker Niels , Husby Steffen
Published: September 2017

Background:

Infections are the leading cause of morbidity and mortality in children. Caesarean section as a potential risk factor for infection has recently gained interest. Delivery by caesarean section has increased greatly, with nonmedical reasons playing an increasing role. We aimed to analyze the association between mode of delivery and hospitalizations because of infection and symptoms of infection at home in early childhood.

Methods:

A cohort study, based on the Odense Child Cohort, following infants from gestation until a mean age of 3.5 years. Data on hospitalization because of infections were collected from the Danish National Patient Registry. Data on symptoms of infection at home were collected via a text message–based questionnaire.

Results:

A total of 1921 children were born by vaginal delivery, 283 by elective caesarean section and 227 by acute caesarean section. An adjusted regression model showed an incidence rate ratio for hospitalizations because of infection in children born by elective caesarean section compared with children born by vaginal delivery of 1.45 (95% confidence interval: 1.16–1.80; P = 0.001). The analyses on symptoms of infection at home found no associations between any symptom of infection and mode of delivery. Symptom-specific subanalyses showed contrasting results.

Conclusions:

Mode of delivery showed a strong association to hospitalization because of infectious disease during early childhood. Overall, no association was present between rate of symptoms of infection at home and mode of delivery.
Outcomes of Abdominal Surgery in Patients With Mechanical Ventricular Assist Devices
Authors: Leung Krystle M. , Kiely Maria X. , Kimbrell Ashlee , Asban Ammar , Kelley Rosemary , Bleday Ronald , Davids Jennifer S. , Melnitchouk Nelya
Published: September 2017

Objective:

The aim of this study was to examine the outcomes of elective and emergent abdominal operations performed in end-stage heart failure patients supported with ventricular assist devices (VADs).

Summary of Background Data:

With the growing volume of end-stage heart failure patients receiving VADs, an increasing number of these patients require surgery for noncardiac pathology. There is a paucity of studies on the safety of abdominal operations in this population.

Methods:

We performed a retrospective chart review across 3 hospitals of patients with VADs who underwent abdominal surgeries between 2003 and 2015. We used Chi-square, Fisher exact, and Mann-Whitney U tests for comparison of elective and emergent cases.

Results:

Fifty-seven patients underwent 63 operations, of which 23 operations were elective, 24 were emergent, and 16 were emergently performed in the same admission as VAD placement and analyzed separately. Patients undergoing elective versus emergent procedures had similar comorbidities (Charlson score 2.9 vs 3.0). 43% versus 32% of patients had VADs as a destination therapy. Although perioperative anticoagulation approach was variable, holding warfarin and starting heparin/enoxaparin/bivalirudin bridge was most common (65% vs 54%). Although 2-fold higher in the emergent group (50 vs 100 mL, P = 0.06), median estimated blood loss was low. Postoperative bleeding requiring transfusion was not very common (13% vs 8%), whereas rate of ischemic cerebrovascular accident (4% each) and venous thromboembolism was low (0% vs 13%, P = 0.23). Thirty-day mortality rate was 4% versus 17%, P = 0.19.

Conclusion:

VAD patients have an acceptable risk profile for abdominal surgery.
Identification of senescent cell surface targetable protein DPP4
Authors: Kim Kyoung Mi , Noh Ji Heon , Bodogai Monica , Martindale Jennifer L. , Yang Xiaoling , Indig Fred E. , Basu Sandip K. , Ohnuma Kei , Morimoto Chikao , Johnson Peter F. , Biragyn Arya , Abdelmohsen Kotb , Gorospe Myriam
Published: September 2017

Senescent cell accumulation in aging tissues is linked to age-associated diseases and declining function, prompting efforts to eliminate them. Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts. Importantly, the differential presence of DPP4 allowed flow cytometry-mediated isolation of senescent cells using anti-DPP4 antibodies. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) assays revealed that the cell surface DPP4 preferentially sensitized senescent, but not dividing, fibroblasts to cytotoxicity by natural killer cells. In sum, the selective expression of DPP4 on the surface of senescent cells enables their preferential elimination.
Editorial: challenges in the development of a magnetic resonance imaging index for fistulising Crohn's disease
Authors: Lung P. F. C. , Ng S. C.
Published: September 2017

Linked Content

This article is linked to Samaan et al paper. To view this article visit https://doi.org/10.1111/apt.14190.
Not all phonological awareness deficits are created equal: evidence from a comparison between children with Otitis Media and poor readers
Authors: Carroll Julia M. , Breadmore Helen L.
Published: September 2017

Children with reading difficulties and children with a history of repeated ear infections (Otitis Media, OM) are both thought to have phonological impairments, but for quite different reasons. This paper examines the profile of phonological and morphological awareness in poor readers and children with OM. Thirty‐three poor readers were compared to individually matched chronological age and reading age controls. Their phonological awareness and morphological awareness skills were consistently at the level of reading age matched controls. Unexpectedly, a significant minority (25%) of the poor readers had some degree of undiagnosed mild or very mild hearing loss. Twenty‐nine children with a history of OM and their matched controls completed the same battery of tasks. They showed relatively small delays in their literacy and showed no impairment in morphological awareness but had phonological awareness scores below the level of reading age matched controls. Further analysis suggested that this weakness in phonological awareness was carried by a specific weakness in segmenting and blending phonemes, with relatively good performance on phoneme manipulation tasks. Results suggest that children with OM show a circumscribed deficit in phoneme segmentation and blending, while poor readers show a broader metalinguistic impairment which is more closely associated with reading difficulties.
Sensitivity to auditory‐tactile colocation in early infancy
Authors: Thomas Rhiannon L. , Misra Reeva , Akkunt Emine , Ho Cristy , Spence Charles , Bremner Andrew J.
Published: September 2017

An ability to detect the common location of multisensory stimulation is essential for us to perceive a coherent environment, to represent the interface between the body and the external world, and to act on sensory information. Regarding the tactile environment “at hand”, we need to represent somatosensory stimuli impinging on the skin surface in the same spatial reference frame as distal stimuli, such as those transduced by vision and audition. Across two experiments we investigated whether 6‐ (n = 14; Experiment 1) and 4‐month‐old (n = 14; Experiment 2) infants were sensitive to the colocation of tactile and auditory signals delivered to the hands. We recorded infants’ visual preferences for spatially congruent and incongruent auditory‐tactile events delivered to their hands. At 6 months, infants looked longer toward incongruent stimuli, whilst at 4 months infants looked longer toward congruent stimuli. Thus, even from 4 months of age, infants are sensitive to the colocation of simultaneously presented auditory and tactile stimuli. We conclude that 4‐ and 6‐month‐old infants can represent auditory and tactile stimuli in a common spatial frame of reference. We explain the age‐wise shift in infants’ preferences from congruent to incongruent in terms of an increased preference for novel crossmodal spatial relations based on the accumulation of experience. A comparison of looking preferences across the congruent and incongruent conditions with a unisensory control condition indicates that the ability to perceive auditory‐tactile colocation is based on a crossmodal rather than a supramodal spatial code by 6 months of age at least.
Habitat structural complexity metrics improve predictions of fish abundance and distribution
Authors: Ferrari Renata , Malcolm Hamish A. , Byrne Maria , Friedman Ariell , Williams Stefan B. , Schultz Arthur , Jordan Alan R. , Figueira Will F.
Published: September 2017

Habitat structural complexity influences biotic diversity and abundance, but its influence on marine ecosystems has not been widely addressed. Recent advances in computer vision and robotics allow quantification of structural complexity at higher‐resolutions than previously achieved. This provides an important opportunity to determine the ecological role of habitat structural complexity in marine ecosystems. We used high‐resolution three‐dimensional (3D) maps to test multiple structural complexity metrics, depth and benthic biota as surrogates of fish assemblages across hundreds of meters on subtropical reefs. Non‐parametric multivariate statistics were used to determine the relationship between these surrogates and the entire fish assemblage. Fish were divided into functional groups, which were used to further investigate the relationship between surrogates and fish abundance using generalized linear models. Fish community composition and abundance were strongly related to habitat complexity metrics, benthic biota and depth. Surface rugosity and its variance had a significant positive influence on the abundance of piscivores and sediment infauna predators, and a negative effect on the abundance of predators, herbivores, planktivores and cleaners. Final models for fish functional groups explained up to 68% of the variance. The best metrics to explain the variance in fish abundance were benthic biota (25 ±7.5% of variance explained, mean ± SE) and complexity metrics (16 ±6.6%, mean ± SE). Our results show that high‐resolution 3D maps and derived metrics can predict a large percentage of variance in fish abundance and potentially serve as useful surrogates of fish abundance across all functional groups in spatially dynamic reefs.
To pay or not to pay: affective and cognitive response to a bribe situation
Authors: Gopinath C. , Choudhury Muntakim M.
Published: September 2017

Bribery is ubiquitous in most developing countries. The negative impact of corruption on macro variables such as economic growth and foreign investments has been widely studied. In this study, we take a micro perspective to examine the effects of bribery on the individual's emotions. We analysed two sets of post‐event self‐reports of individuals who bribed or did not bribe for government services in India to explore their cognitive and affective response. We identified the revealed basic emotions along with the justifications provided for their action when faced with a bribe situation. We find that affective response appears to dominate the reports of those who bribed, while cognitive response dominates those who did not bribe. Understanding individual emotional responses to corruption provides new avenues for researching the moral aspects of corruption and we derive implications for further research and practice.
Aflibercept in neovascular age related macular degeneration previously refractory to standard intravitreal therapy: An Irish perspective to compare against international trends
Authors: Mccloskey C. , Mongan A.M. , Chetty S. , McAteer D. , Quinn S.
Published: September 2017

Purpose

To determine visual and anatomical outcomes of Age‐Related Macular Degeneration (ARMD) patients, in a tertiary centre, following conversion to Aflibercept having been refractory to previous treatment with Bevacizumab and/or Ranibizumab and to make international comparisons.

Methods

A retrospective chart review of patients with a diagnosis of neovascular AMD (nvAMD) undergoing Aflibercept intravitreal therapy for at least six months who had previous treatment with three consecutive Bevacizumab ± Ranibizumab injections prior to switch. Exclusion criteria included any other procedures affecting visual outcome performed within the treatment period. Outcomes measured included visual acuity (VA), central macular thickness (CMT) and injection frequency.

Results

Sixty eyes of 52 patients were included, 25 of which were male. Mean BCVA pre‐switch was 55 ± 15 letters and CMT was 285 μm ± 77. Eyes received a mean of 14 ± 8 prior Bevacizumab/Ranibizumab. The mean follow up post switch was 13.2 months (SD = 5.5). Mean BCVA improved by two letters at six months (SD = 6.6, p < 0.05), by four letters at 12 months (SD = 6, p < 0.01). The mean VA at 18 and 24 months was unchanged from baseline VA. The mean CMT decreased by 44 μm at six months (SD = 73.5, p < 0.0001), 48.4 μm at 12 months (SD = 88.1, p < 0.01), 48 μm at 18 months (SD = 22.39, p < 0.001). The mean number of injections in the six months pre‐switch was 2.8 (SD = 0.8), this increased to a mean of 4 injections (SD = 0.94) in first six months post switch then decreased to 2 injections (SD = 1) in each six month period thereafter (p = 0.002).There were no significant systemic or ocular adverse events.

Conclusions

Switching to Aflibercept in patients with treatment resistant AMD produces statistically significant improvements in visual and anatomical outcomes with eventual maintenance of visual acuity levels at one year post switch.
Automated gonioscopy photography for iridocorneal angle grading
Authors: Teixeira F. , Sousa D. , Leal I. , Marques‐Neves C. , Abegão‐Pinto L.
Published: September 2017

Purpose

This study aims to assess inter‐device and inter‐observer agreement of iridocorneal angle grading using automatic gonio‐photography and dynamic gonioscopy.

Methods

Cross sectional single‐center observational study. Consecutive patients from Glaucoma Clinic were recruited to perform two types of gonioscopy. Manual gonioscopy (MG) was performed using a dynamic gonio lens, while the automatic Gonio‐Photography (AG) was done using a contact‐gonioscope prototype (from NIDEK). AG images were graded by two masked observers (glaucoma specialist and resident). Criteria for classification was similar in both methods. An eye was classified with angle closure when the posterior trabecular meshwork couldn't be seen in two or more quadrants. Inter‐device agreement (AG vs MG) was ascertained by κ statistic and comparison of area under receiver operating characteristic curves (AUC). Agreement among raters was ascertained by Fleiss’ κ statistic and intraclass correlation coefficient (ICC).

Results

Forty‐eight eyes were analyzed. Mean age was 63 ± 16 years. Angle closure was detected in 11 eyes (23.4%) with MG in comparison with 2 eyes (4.3%) using AG images grading. The agreement for angle closure diagnosis between MG and AG was poor (κ=0.09 ± 0.10; p = 0.18). The AUC for detecting eyes with gonioscopic angle closure showed poor accuracy between automated and manual methods (AUC=0.53 ± 0.05, confidence interval (CI) 95%: 0.44‐0.62). The ICC for iridocorneal angle grading between the two raters was 0.34 [CI 95%: 0.10‐0.51] and Fleiss’ kappa coefficient for opening status was 0.13 [CI 95%: 0.04‐0.30].

Conclusions

Only slight agreement was found when comparing automated with manual dynamic gonioscopy and also when comparing two raters. Manual dynamic gonioscopy is the gold standard and further technological development is desired for promising automated gonioscopy.
Interest of analysis of circumpapillary retinal nerve fibers layer thickness at different measurement diameters
Authors: El Chehab H. , Agard E. , Loria O. , Théo L. , Dot C.
Published: September 2017

Purpose

The analysis of the circumpapillary retinal nerve fiber layer (RNFL) is a major data in structural analysis in glaucoma. Since OCT development, analysis is on a circle of 3.4 mm diameter. This study evaluates the diagnostic capability of an RNFL analysis with different diameter measurements.

Methods

60 glaucomatous and 58 control patients had a complete ophthalmological exam to exclude patients with papillary morphological abnormalities (coloboma, dysversion …). Others had an OCT Spectralis (Heidelberg Engineering, Germany) of RNFL on 4 circles of different diameters: 3.4, 3.5, 4.1 and 4.7 mm. Only one eye per patient was randomly included. The diagnostic capabability of each of these circles was analyzed for global mean thickness and for each sector (temporal, temporal‐superior, nasal‐superior, nasal, nasal‐inferior and temporal‐inferior) by calculating areas under ROC curve (AUROC).

Results

Patients were comparable for clinical characteristics. In glaucomatous patient group, 58.9% of the patients were early glaucoma (MD> ‐6 dB) and 21.4% of the patients were severe (MD <‐12 dB). For conventional RNFL measurement (3.4 mm), the temporal‐inferior sector had the highest diagnostic capability with an AUROC of 0.916. For the 3.5 mm measurement, the global mean thickness of the RNFL had the highest diagnostic capability (AUROC = 0.909). For the 4.1 mm measurement, the global mean thickness of the RNFL had the highest diagnostic capability (AUROC = 0.915). For the 4.7 mm measurement, the average thickness of the temporal‐inferior sector had the highest diagnostic capability (AUROC = 0.909). There was no statistically significant difference between these 4 AUROC.

Conclusions

Regardless of the diameter of RNFL analysis, the diagnostic capability remains very good with no significant difference in patients with normal papillary morphology.
Screening for glaucoma progression by using non‐parametric tests
Authors: Pantalon A. , Chiselita D. , Feraru C.
Published: September 2017

Purpose

Automated perimetry still represents the gold standard in long term glaucoma monitoring.Early detection of progression tendency in glaucoma patients is crucial. Purpose of this study was to assess an alternative fast and convenient method compared to GPA (Humphrey Perimeter, Carl Zeiss®) for detecting glaucoma progression shortly after diagnosis‐24 months.

Methods

We studied in a longitudinal manner 41 eyes from 41 patients with early open angle glaucoma forms, followed in the first 24 months after diagnosis. Glaucoma was defined according to EGS criteria and a minimum of 5 valid visual fields were required form each patient. All specific glaucoma clinical data were recorded and progression was verified by two distinctive methods: Glaucoma Progression Analysis (GPA) software from Hymphrey Visual Field Analyzer and a non parametric analysis (NPA) according to Wesselink protocol.

Results

In GPA analysis, a positive „event” (progression) was detected in 11/ 41 eyes, 26.82%. NPA confirmed progression in all GPA cases, but additionally detected 8 moreprogression cases (46.34% eyes). The concordance between tests was good (k = 0.596, p = 0.000), with positive correlation (Mc Nemar test r = 0.652, p = 0.008). In the first 2 years after diagnosis, GPA sensitivity was 26.82% and a specificity of 73.33%, whereas NPA sensitivity was 46.34% and comparable specificity 72.41% to GPA. Likelihood ratio for progression (LR) in GPA was 1.00 vs 1.51 for NPA analysis.

Conclusions

NPA tends to overestimate progressor number in a cohort, but its purpose is to allert and orient the clinician on the progression profile of the followed patients. In the first years, the GPA analysis can be highly inaccurate, therefore combining two methods with similar specificity might aid this purpose and ease the glaucoma care management.
Signs and symptoms of uveitis
Authors: Neri P. , Calamita R. , Pelliccioni P. , Gorgoni F. , Lassandro N. , Pirani V.
Published: September 2017

Uveitis can be a sight‐threatening disease. In ammation of uveal tract can be divided into: anterior, intermediate, posterior, and panuveitis. Blurred vision, ocular pain, photophobia and oaters are some of the symptoms complained by those who are a ected by uveitis. e onset of uveitis can be either acute or insidious, bilateral rather than unilateral. Posterior uveitis is usually associated with vitritis. Anterior chamber cells and are should be graded according to standardized uveitis nomenclature (SUN) working group. Binocular indirect ophthalmoscopy (BIO) score is used to evaluate the severity of vitritis. Vitreous changes may comprehend: vitreous hemorrhage, vitreous strands, and vitreous traction. A further classi cation of posterior uveitis depends on the primary site of in ammation, which can identify: retinitis, choroiditis, retinochoroiditis, and chorioretinitis. Posterior pole uveal involvement can be: focal, multifocal, and placoid. Retinal vasculitis can be present. Uveitis might be complicated by anterior and posterior synechiae, which can lead to uveitic glaucoma, cystoid macular oedema, retinal and choroidal neovascularizations, and retinal ischemia.
Bioinformatic analysis of experimental and clinical proteomic data
Authors: Nättinen J.
Published: September 2017

Proteomics, along with other omics, can be utilized as a tool of personalized medicine in order to understand the individual needs of patients better based on their expression levels of proteins. This type of personalized approaches are likely to be much more common in the future, since new diagnostic and therapeutic methods are constantly being developed and there is already currently a great need to select the most cost‐effective ones for each patient. For these reasons, a lot of effort is currently going into finding potential biomarkers through discovery studies. In addition to sample processing and advanced equipment, proteomic research also requires the work of statisticians and bioinformaticians as the research methods produce a growing amount of statistical data. Hence, methods of analyzing big data are also increasingly important and therefore researchers in bioinformatics field are both developing new methods and utilizing old ones in order to tackle the growing data. This course will focus on some of the most basic aspects of bioinformatics analysis of proteomic data and is aimed to provide clinicians and other researchers alike better understanding of the aspects important to the analysis.
Do we need to treat?
Authors: Meier‐Gibbons F.
Published: September 2017

The gold standard for treating glaucoma patients has always been a reduction of the intraocular pressure with medical therapy, laser or surgery. But despite reaching a defined target intraocular pressure, many glaucoma patients still progress and show a deterioration of their optic nerve or their visual field. Using examples of glaucoma patients, we will discuss if we should treat patients with other therapeutic options besides intraocular pressure control.
B27‐associated uveitis, Fuchs uveitis
Authors: Xxxx Xxxx
Published: September 2017

B27‐associated uveitis is a very frequent form of non infectious intraocular inflammation which account for approximately 50% of acute anterior uveitis. Its main clinical features, natural history and association with seronegative arthritis are well known. Fuchs uveitis is another frequent cause of anterior and intermediate uveitis. Its natural history is well characterised as well as its association with intraocular production of anti‐rubella antibodies. Both diseases are thus often considered as easy diagnosis. However, several aspects of those diseases remain challenging and debated. In this interactive course, based on clinical cases, we will insist on those difficult aspects as well as on the more recent issues discussed in the literature.
Behçet's disease, VKH, sarcoidosis
Authors: khairallah M. , Ksiaa I. , Jelliti B.
Published: September 2017

Ocular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agents in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. Treatment for acute VKH disease relies on systemic corticosteroids for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease. Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis is challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis relies on corticosteroids and immunosuppressive agents, in severe cases.
Choroiditis (non‐infectious)
Authors: Herbort C.P.
Published: September 2017

Choroiditis (non‐infectious) Non‐infectious choroiditis is classically subdivided into at least two main categories, including choriocapillaritis and stromal choroiditis. In the latter, the site of inflammation is situated in the choroidal stroma. When inflammation exclusively originates from the choroidal stroma which is the target of an immune reaction such as in Vogt‐Koyanag‐Harada disease (VKH), sympathetic Ophthalmia (SO) or birdshot retinochoroiditis (BRC), the term of primary stromal choroiditis is used. When the choroidal stroma is a chance and random location of a systemic disease such as sarcoidosis, the term of secondary stromal choroiditis is used. In the choriocapillaritis group the lesion process is an inflammatory non perfusion of the choriocapillaris, a mechanism occurring or suspected to occur in diseases such as multiple evanescent white dots syndrome (MEWDS), (idiopathic) multifocal choroiditis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The difference of these two mechanism will be further presented with the help of practical examples presented in the same fashion as the “viva voce” EBO examination.
Loss of Nrf‐2 and PGC1‐alpha genes changes macromorphology of the eye and evokes microstructural and pigmentation pattern changes of the retinal pigmented epithelium
Authors: Felszeghy S. , Viiri J. , Koskela A. , Paterno J. , Kettunen M. , Jokivarsi K. , Kaarniranta K.
Published: September 2017

Purpose

Nrf2 (NF‐E2‐related factor 2) and PGC1‐ α (peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha) regulate oxidative stress response in cells. Nrf‐2 and PGC1‐alpha double‐knock‐out (dKO) mice were used to monitor macro and morphological changes of eye, retina and retinal pigmented epithelium (RPE), respectively.

Methods

The mMRI and mCT imaging were carried out for mice aged at 6 weeks (mCT), 12 weeks and 12 months (mMRI). The retinal and RPE microanatomy and pigmentation were studied from HE‐stained thin wax and toluidine blue‐stained epoxy sections. Finally, cellular proliferation and pigmentation patterns were studied in the primary cell cultures.

Results

The dKO samples showed smaller body parameters and weight. mMRI, mCT assays indicated size differences and dysmorphic body features in the dKO mice. Moreover, dKOs exhibited reduced retinal full tickness joined with retained RPE morphology. The melanosomes of dKO RPEs were heterogeneous in shape morphology, but comparable in size to aged matched wild type melanosomes, respectively. However, there was a striking trend of increase in the density of melanosomes in RPE of dKOs that was convinced by the primary RPE cultures.

Conclusions

Nrf‐2/PGC‐1α knockout mice provide a novel model to study degenerative changes in retina and RPE.
Effects of HSP90 inhibitor TAS‐116 on the inflammasome activation in ARPE‐19 cells
Authors: RANTA‐AHO S. , Piippo N. , Korhonen E. , Hytti M. , Kinnunen K. , Kaarniranta K. , Kauppinen A.
Published: September 2017

Purpose

Chronic inflammation is one of the key characters of Age‐Related Macular Degeneration (AMD), the leading cause of blindness in the Western countries. The NLRP3 inflammasome contributes to the induction of inflammation. The heat shock protein, Hsp90 protects NLRP3 prior to its activation, and its removal releases the receptor protein for degradation. In this study, we tested the effect of the Hsp90 inhibition on the regulation of NLRP3 inflammasome in human ARPE‐19 cells.

Methods

The experiments were carried out using IL‐1α‐primed ARPE‐19 cells. Proteasomal degradation and autophagy were blocked with MG‐132 and Bafilomycin A, respectively. TAS‐116 was used as an Hsp90 inhibitor. The cytokine levels of IL‐1β, IL‐6, IL‐8, and MCP‐1 were measured from cell culture medium using the ELISA method. In addition, the activity of caspase‐1 was measured by a commercial assay, and the levels of Hsp70 and Hsp90 were determined by the western blot technique from cell lysates. The toxicity of TAS‐116 was assessed by measuring lactate dehydrogenase (LDH) levels from cell culture medium and using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay.

Results

According to our data, TAS‐116 showed no toxic effects on ARPE‐19 cells. TAS‐116 decreased the secretion of IL‐1β and IL‐8 from IL‐1a‐primed RPE cells with dysfunctional intracellular clearance. The caspase 1 activity decreased along with the IL‐1β levels. No changes were seen in the levels of IL‐6 and MCP‐1.

Conclusions

Our results suggest that TAS‐116 is capable of reducing the NLRP3 inflammasome activation and the subsequent release of IL‐1β and IL‐8 in human RPE cells.
Deep learning to screen for referable diabetic retinopathy
Authors: De Boever P. , Malik R. , Afifi N. , Elen B.
Published: September 2017

Purpose

Diabetes patients worldwide are at risk for diabetic retinopathy (DR). High performance informatics technologies, such as deep learning, are envisioned to achieve acceptable sensitivity for detecting referable retinopathy and appear to be cost‐effective alternatives to manual scoring, allowing for large‐scale, cost‐effective DR screening. The purpose of this work was to develop a deep learning computer model and evaluate its performance.

Methods

An ensemble of two deep convolutional neural networks (resp. 25 and 26 layers; high resolution (512 × 512 pixels); different filter sizes) was trained to detect the presence of signs of DR using labeled fundus images from the Kaggle dataset. The computer model has been evaluated with the public Messidor‐2 dataset for referable DR. Next, the model has been evaluated “in the field” in the context of the Qatar Biobank initiative. Study participants undergo fundus imaging. These images have been graded by retinal specialists in the context of this study.

Results

All 190 patients in the Messidor‐2 database with referable DR (moderate non‐proliferative DR or worse) have been detected by the trained computer model (sensitivity 100%, 95% CI: 98,1%‐100%). The software labeled 444 of the 684 diabetes patients without referable DR accordingly (specificity 64.9%, 95% CI: 61.2–68.5%). A total of 385 participants of the Qatar Biobank were examined, with 23 individuals having referable DR. The model identified them with 100% sensitivity (90% CI: 85.2–100%) and 88% specificity (95% CI: 84.3–91.3%).

Conclusions

The deep learning network obtains high sensitivity combined with a good specificity. The model is conservative while screening for the presence of referable DR, allowing users to focus their attention on patients in which signs of referable DR are detected by the automated screening.
Cross‐sectional static retinal vessel analysis in routine optometric practice
Authors: French C. , Heitmar R.
Published: September 2017

Purpose

Do retinal vessel calibres provide the same conclusions regardless of which eye was assessed?

Methods

A cross‐sectional sample of patients seen in routine optometric practice [n=225] underwent a standard eye examination including subjective refraction and slit‐lamp biomicroscopy. Undilated optic nerve‐centred fundus photographs were obtained (camera angle: 50 degrees). Red‐free photographs were analysed using iFlexis software (Vito, Belgium) to give objective retinal vessel calibre measurements (central retinal artery/vein equivalents; CRAE/CRVE), as described by Knudtson et al.

Results

The mean age of the cohort was 59 years (range: 16‐90 years ±15) and comprised of 137 women and 88 men. BMI ranged between 17.6 – 37.3 kg/m2. Average systolic blood pressure (BP) was 131mmHg ±20 and diastolic BP was 82mmHg ±12. Refractive error (MSE) ranged from ‐10.00 to +7.00D. CRAE was found to be 142AU ±16 (RE) and 143AU ±18 (LE). CRVE was 210AU ±23 (RE) and 209AU ±22 (LE). Paired t‐test showed no difference between RE and LE calibres. There was good agreement of both vessel calibres in both eyes, as shown by Bland‐Altman plots. (CRAE: bias: ‐0.88; upper/lower limits: 27.81/‐29.57; CRVE: bias: 0.08; upper/lower limits: 33.43/‐33.26). Stepwise forward multiple regression analysis found a significant (all p<0.001) decrease in both CRAE and CRVE with increasing myopia and age; CRVE also increased with increasing BMI. Analysis was run on all RE, all LE and randomly selected eyes to test if the same conclusion could be drawn regardless of eye selected.

Conclusions

Established associations between age, refractive error and BMI with retinal calibres were in agreement with the sample used. The impact of refractive error on retinal vessel calibre measurements highlights its importance as a co‐variate in larger studies, especially when assessing systemic vascular disease.