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The purpose of this recommendation is to provide research organisations and their funders as well as other organisations operating in the interface of the civil society with principles and guidelines for promoting citizen science. The recommendation provides answers to questions on how to make citizen science projects more appealing to researchers and how citizen science methods give researchers recognition and merits. The recommendation concerns specific issues in citizen science and provides ways of establishing citizen science as an equal scientific method with other scientific methods in use. The aim of this recommendation is to provide a basis for ensuring the quality of citizen science research in the Finnish scientific community.

Syftet med denna rekommendation är att ge forskningsorganisationer och deras finansiärer samt andra organisationer som verkar i vetenskapssamfundets gränssnitt principer och anvisningar för att främja medborgarforskning. Rekommendationen ger svar på frågor om hur medborgarforskningsprojekt kan göras mer lockande för forskare och hur medborgarforskningsmetoder ger forskare erkännande och meriter. Rekommendationen behandlar specialfrågor inom medborgarforskning och erbjuder sätt att etablera medborgarforskning som en jämbördig vetenskaplig metoder. Syftet med denna rekommendation är att erbjuda en grund för säkerställande av kvaliteten på medborgarforskningen i det finländska vetenskapssamfundet.

Purpose: iCare tonometers are easy-to-use and portable devices for measuring the intraocular pressure (IOP). Purpose was to evaluate the IOP values measured by both novel iCare ic100 and conventional model TA01i devices in unselected population. Methods: IOP was measured with iCare ic100 and TA01i tonometers in 149 participants aged 32–33 years (born in 1985 or 1986) of the Northern Finland Birth Cohort Eye 2 study. The right eye of each participant was selected for analysis. We also collected data on axial length, corneal curvature and central corneal thickness (CCT). Bland-Altman plot was used for comparing the values obtained by these devices. Results: Mean IOP measured with the ic100 device was 13.8 (3.4) mmHg, with TA01i it was 12.5 (3.0) mmHg. The mean difference between these devices was 1.30 mmHg ( p 2 was 0.694. In Bland-Altman analysis, the agreement between the two tonometers ic100 and TA01i was constantly good (mean difference −1.30, ic100 device showing higher measures). There was a correlation between IOP and CCT ( r = 0.269, p Conclusion: In summary, we found ic100 rebound tonometry to be both reliable and effective, although CCT may influence IOP measurements with ic100 and TA01i. Therefore, iCare ic100 is suitable for IOP measurement in large cohort studies.

Purpose The aim of this study was to compare the measurements of intraocular pressure by two tonometers, the Icare rebound tonometer and the Goldmann applanation tonometer, in a randomised screening study. The influence of refraction and central corneal thickness on the measurements was also evaluated. Methods Intraocular pressure was measured with rebound tonometer and Goldmann applanation tonometer in 1266 participants; refraction and central corneal thickness were also determined. One randomised eye of each participant was selected for this report’s analysis. A Bland–Altman plot was used to compare the values obtained with the two devices. Results The correlation between rebound tonometer and Goldmann applanation tonometer was good: the intraclass correlation coefficient (r) between the two methods was 0.735 ( p Conclusion Measurements with rebound tonometer and Goldmann applanation tonometer are relatively uniform although rebound tonometer slightly overestimated intraocular pressure. Both rebound tonometer and Goldmann applanation tonometer and the difference between these devices were affected by central corneal thickness but not by refraction. Higher astigmatism affected Goldmann applanation tonometer more than rebound tonometer. It is concluded that rebound tonometer is a reliable method for measuring intraocular pressure in a population-based screening study.

Purpose: The optic nerve head (ONH) is a part of the brain that can be evaluated through the transparent medium of the eye. The purpose of this study was to explore the possible correlations among the properties of the optic nerve head, maternal factors during pregnancy and neonatal parameters in a randomized sample of a birth cohort. Methods: The Northern Finland 1966 Birth Cohort has been prospectively monitored since their antenatal period. Data on pregnancy and neonatal period were collected during gestation and right after birth in 1966. A randomized sample of 3070 subjects underwent an ophthalmic assessment at the age of 46–48 years. The examination protocol included scanning laser ophthalmoscopy with the Heidelberg Retina Tomograph. The ophthalmological parameters assessed were the disc area and the neuroretinal rim volume of the ONH. Results: We found that chronic pulmonary disease of the mother (p = 0.007), the number of gestational weeks (p = 0.030) and the mother’s highest measured systolic blood pressure (p = 0.035) during pregnancy had a statistically significant effect on the disc area. Smaller disc size was associated with pulmonary disease and early gestation. There was a significant difference in rim volume between genders (p

Purpose: The purpose of the study was to assess and compare the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) parameters and image quality parameters obtained by Cirrus HD-OCT, GDxECC and HRT3 in a population-based screening study. Methods: This analysis examined 2566 subjects taking part in the Northern Finland Birth Cohort Eye study. Images with spectral domain OCT (Cirrus HD-OCT 4000), scanning laser ophthalmoscopy (HRT3) and scanning laser polarimetry (GDxECC) were obtained from each subject. The correlation of average and regional parameters of RNFL and ONH between devices was evaluated. Results: The RNFL thickness was 90.9 µm when measured with OCT, 24.6 µm with HRT and 48.1 µm with GDx. There was a high correlation between the disc and cup measurements with the HRT and OCT and the RNFL thickness of the OCT and GDx (r > 0.5). A statistically significant correlation was found between RNFL measurements of the HRT and OCT in the superior, temporal and inferior quadrants. Optical coherence tomography (OCT) signal strength correlated with the image quality parameters of the HRT and GDx. The percentage of good quality images was the lowest with the GDx. Conclusions: The RNFL thickness in Northern Finland birth cohort was at a lower level compared to other studies. The study confirms the difference in measuring ONH parameters between the imaging devices. However, significant correlations between devices were found in the cup volume and cup disc area ratio parameters of the OCT and HRT. The correlations between image quality parameters and glaucoma detection parameters were relatively low.

Purpose Next-generation sequencing (NGS) has made genetic testing of patients with epileptic encephalopathies easier – novel variants are discovered and new phenotypes described. Variants in the same gene – even the same variant – can cause different types of epilepsy and neurodevelopmental disorders. Our aim was to identify the genetic causes of epileptic encephalopathies in paediatric patients with complex phenotypes. Methods NGS was carried out for three patients with epileptic encephalopathies. Detailed clinical features, brain magnetic resonance imaging and electroencephalography were analysed. We searched the Human Gene Mutation Database for the published GABRG2 variants with clinical description of patients and composed a summary of the variants and their phenotypic features. Results We identified two novel de novo GABRG2 variants, p.P282T and p.S306F, with new phenotypes including neuroradiological evidence of neurodegeneration and epilepsy of infancy with migrating focal seizures (EIMFS). One patient carried previously reported p.P83S variant with autism spectrum disorder (ASD) phenotype that has not yet been described related to GABRG2 disorders and a more severe epilepsy phenotype than reported earlier. In all, the literature search yielded twenty-two articles describing 27 different variants that were divided into two categories: those with self-limiting epilepsies and febrile seizures and those with more severe drug-resistant epileptic encephalopathies. Conclusion This study further expands the genotypic and phenotypic spectrum of epilepsies associated with GABRG2 variants. More knowledge is still needed about the influence of the environment, genetic background and other epilepsy susceptibility genes on the phenotype of the specific GABRG2 variants.

Purpose: The optic nerve head (ONH) is a part of the brain that can be easily studied through the transparent medium of the eye. We explored the relationship between the properties of the optic nerve head, the retinal nerve fiber layer (RNFL) and cognitive function. Methods: Participants of the Northern Finland Birth Cohort (NFBC) 1966 underwent an ophthalmic and cognitive assessment after randomization at age 46. The ophthalmological parameters obtained were the disc area and the neuroretinal rim volume of the ONH and the average RNFL thickness. The surrogates used for cognitive function were the paired associates learning test (PAL), level of education, grade point average (GPA) and Humphrey 24–2 perimetric test time (HFA). We did exploratory research between the ophthalmological parameters and the surrogates for cognition and the correlations between the surrogates for cognition. Results: We found that a larger disc area was associated with a higher level of education, faster accomplishment of the HFA (R = −0.065) but a lower GPA (R = −0.084). An increase in neuroretinal rim volume was associated with fewer errors in the PAL test (R = −0.056), higher level of education, higher GPA (R = 0.072) and faster accomplishment of the HFA (R = −0.047). A thicker RNFL was associated with faster accomplishment of the HFA (R = −0.047). Conclusion: We were able to find statistically significant associations between the parameters of the optic nerve head, the RNFL and cognition in the NFBC Eye study. However, the correlations were negligible at best and of limited predictive value.

AimTo assess the applicability of a structure–function (S-F) analysis combining spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP) in glaucoma screening in a middle-aged population.MethodsA randomised sample of 3001 Caucasian participants aged 45–49 years of the Northern Finland Birth Cohort Eye Study was examined. We performed an eye examination, including 24–2 SAP, optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and SD-OCT of the peripapillary RNFL. The S-F report was generated by Forum Glaucoma Workplace software. OCT, SAP and the S-F analysis were evaluated against clinical glaucoma diagnosis, that is, the positive ‘2 out of 3’ rule based on the clinician’s evaluation of ONH and RNFL photographs and visual fields (VFs).ResultsAt a specificity of 97.5%, the sensitivity for glaucomatous damage was 26% for abnormal OCT, 35% for SAP and 44% for S-F analysis. Estimated areas under the curve were 0.74, 0.85 and 0.76, and the corresponding positive predictive values were 8 %, 10% and 12%, respectively. By applying a classification tree approach combining OCT, SAP and defect localisation data, a sensitivity of 77% was achieved at 90% specificity. In a localisation analysis of glaucomatous structural and functional defects, the correlation with glaucoma increased significantly if the abnormal VF test points were located on borderline or abnormal OCT zones.ConclusionSAP performs slightly better than OCT in glaucoma screening of middle-aged population. However, the diagnostic capability can be improved by S-F analysis.

Diabetic retinopathy is a microvascular complication of hyperglycaemia. Little is known about the association of glucose metabolism and retinopathy signs in the non-diabetic middle-aged population. We studied prevalence of retinopathy in a subsample of Northern Finland Birth Cohort study (NFBC1966) of 1809 subjects, at 47 years of age, without previously diagnosed type 2 diabetes and/or blood pressure-lowering medication. All participants underwent clinical evaluations including an oral glucose tolerance test (glucose and insulin values measured at 0, 30, 60 and 120 min) and HbA1c. The retinopathy signs were diagnosed by fundus photographs and classified according to the Eurodiab classification scheme. The overall prevalence of newly diagnosed retinopathy was 1.4%. The retinopathy signs were significantly associated with increased 30 min, 1-h and 2-h glucose levels and 2-h insulin level in an OGTT. After adjustment with systolic blood pressure, only 30 min glucose, 1-h glucose and 2-h insulin levels were associated with retinopathy signs. Our findings show the potential role of 30 min and 1-h post-load glucose and 2-h insulin levels as risk factors for retinopathy lesions among the participants without previously diagnosed diabetes or hypertensive medication.

Background/AimThe aim of this study was to evaluate the effect of prediabetes and diabetes on macular thickness and retinal vascular calibres in our population-based cohort (Northern Finland Birth Cohort).MethodsThe population of 2005 individuals was divided into diabetes (n=57), prediabetes (n=1638) and normal glucose metabolism (NGM) groups (n=310). Total thickness of the macula was measured using Cirrus HD-OCT 4000. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) calibres were measured from the fundus images. The diagnosis of diabetes and prediabetes was made according to WHO 2006 diagnostic standards.ResultsSignificant macular thinning was observed in subjects with prediabetes (−2.69 μm (95% CI −4.29 to −1.09), p3 (95% CI −0.16 to −0.04), pConclusionWe detected significant thinning of the macula in subjects with prediabetes. The diameters of retinal arteries were decreased by impaired glucose metabolism. This study provides a new perspective since it revealed that the early and subtle changes caused by prediabetes as macular thinning had significant ACME on retinal vessels, therefore supporting the neurodegenerative theory of diabetes-induced changes in the retina.

To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenoma (PA) suprasellar extension (SSE), volume and the patients' age.Medical records of 47 patients with PA undergoing ETS were evaluated. VA, VF, preoperative visual impairment score (VISpre) and postoperative visual impairment score (VISpost) were determined. The PA SSE, volume, chiasmal contact, and their correlation with visual function were assessed preoperatively and postoperatively.The final cohort included 47 patients. VA improved in 54 of 76 eyes (71.0%) after ETS, and 69 of 76 eyes (90.7%) gained normal VA. Postoperative VF recovery occurred in 32 of 37 eyes (86.5%). The mean change in VIS was 12.0 (95% confidence interval [CI], 7.7-16.3) and improved in all patients with tumor-related visual impairment (n = 25). However, visual outcome was poorer when VISpre was greater than 40. When VISpre was 21-40, age linearly correlated with VIS improvement (P = 0.03); younger patients had satisfactory and older poorer visual outcome. The mean SSE in patients with VF defects (n = 20) was 16.6 mm (95% CI, 13.3-19.9). Mean SSE in patients with no VF defects (n = 23) was 6.6 mm (95% CI, 4.9-8.3; P 0.001), and the cutoff value for visual perturbations was 9.5 mm for SSE and 8.6 mL for PA volume (P0.001 for both).The visual outcome after ETS for PAs was excellent, and serious complications were rare. Severe preoperative visual impairment resulted in poorer postoperative visual outcomes. The SSE of the PA was the most important predictor of visual outcome after ETS.

AimsStudying the relationship between retinal vessel diameter (RVD) with (1) macular thickness and volume, (2) retinal nerve fibre layer (RNFL), (3) ganglion cell-inner plexiform layer (GC-IPL) and (4) optic nerve head (ONH) in a population cohort of middle-aged Caucasians.MethodsWe collected data from 3070 individuals. We used a semiautomated computer-assisted programme to measure central retinal arteriolar equivalent and central retinal venular equivalent. Macular and ONH parameters were assessed by optical coherence tomography.ResultsData from 2155 persons were analysed. A larger RVD was associated with a thicker macula and increased macular volume; each SD increase in average macular thickness and volume was associated with a 3.28 µm and a 3.19 µm increase in arteriolar diameter and a 5.10 µm and a 5.08 µm increase in venular diameter, respectively (pConclusionsIncreased macular thickness, macular volume, GC-IPL thickness, RNFL thickness and optic nerve rim area were associated with larger RVDs in all subjects. This study clarified the anatomical correlations between both macular and ONH parameters with RVD for middle-aged Caucasians; these can represent a basis for further studies investigating the vascular aetiology of eye diseases.

AimTo evaluate the applicability of imaging devices (spectral-domain optical coherence tomography (Cirrus SD-OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph, HRT3)) for glaucoma screening in a middle-aged unselected population.MethodsParticipants of the population-based Northern Finland Birth Cohort Eye Study, aged 45 to 49 years, underwent a comprehensive eye examination including modern imaging with five methods (retinal nerve fibre layer (RNFL) and macular ganglion cell layer +inner plexiform layer (GCIPL) analysis and their combination with SD-OCT, GDx and HRT). The performance of the automated classification of the imaging devices was assessed using a clinical glaucoma diagnosis as reference, that is, the ‘2 out of 3’ rule based on the evaluation of optic nerve head and RNFL photographs and visual fields.ResultsWe examined 6060 eyes of 3039 subjects; in the clinical evaluation, glaucomatous damage was found in 33 subjects (1.1%) in 43 eyes. The following sensitivities were obtained; RNFL analysis (53%), GCIPL analysis (50%), OCT combination analysis (61%), GDx (56%) and HRT (31%) with corresponding specificities of 95%, 92%, 90%, 88% and 96%. The area under the curve values were 0.76, 0.73, 0.75, 0.75 and 0.73, respectively. Post-test probabilities of glaucoma after positive imaging finding with each of these methods in this unselected population were 11%, 7%, 6%, 5% and 7%, respectively.ConclusionScreening capabilities of the OCT, GDx and HRT were rather similar. The accuracy of all evaluated parameters was only moderate and thus screening with these parameters alone is not reliable.

Solution sellers increasingly use value-based selling and pricing strategies to market and monetize their offerings. Performance-based contracts constitute a key component of value-based pricing strategies. The present study explores solutions to the challenges solution sellers may encounter while developing value-based selling processes and implementing value-based pricing. The research design builds on the explorative action research methodology. While our study confirms earlier research on barriers to value-based selling and pricing, we also identify legal-technical contract design issues as an important but previously unknown barrier. We further identify integration as the appropriate theoretical framework for conceptualizing the barriers. Finally, we identify functional contracting as a solution for value-based sellers to overcome the barriers arising from deficient precontractual integration. The study highlights the role of contracts as barriers to be overcome by legal sales efforts when implementing value-based selling and pricing strategies. Further, the study stresses the utility of functional contracting in pre-contractual integration.

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. This phase 2, randomized, double-blind (fluoxetine vs. placebo), multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n=22) or placebo (n=20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. There was no significant difference in treatment efficacy between the groups. Visual acuity at the primary endpoint had significantly improved over baseline in both the fluoxetine (-0.167 logMAR) and placebo (-0.194 logMAR) groups (both p < 0.001). Because patching alone is not effective in adults, the visual acuity improvement likely resulted from perceptual training. There was a positive correlation between visual acuity improvement and the perceptual training time. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support the usefulness of perceptual training for vision improvement in adults with amblyopia. Clinical trial registration ID #EudraCT 2010-023216-14.

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: −0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (−0.167 logMAR; 95% CI: −0.226 to −0.108; p

Purpose: The evaluation of visual acuity (VA) and refraction in the Northern Finland Birth Cohort Eye study was performed using the Nidek AR-360A autorefractometer. The accuracy of the method for this population-based screening study was assessed. Methods: Measurements of the refractive error were obtained from the right eyes of 1238 subjects (mean age 47), first objectively with the AR-360A and then subjectively by an optometrist. Agreement with the subjective refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE), cylindrical vectors J₄₅ and J₀ and presbyopic correction (add). Visual acuity (VA) was measured using an ETDRS chart and the autorefractometer. Results: The refractive error measured with the AR-360A was higher than the subjective refraction performed by the optometrist for sphere (0.007 D ± 0.24 D p = 0.30) and also for cylinder (−0.16 D ± 0.20 D p < 0.0005). The bias between the measurements of MSE, J₄₅ and J₀ was low: −0.07 D ± 0.22 D (p = 0.002), 0.01 D ± 0.43 D (p = 0.25) and −0.01 D ± 0.42 D (p = 0.43), respectively. The amount of add measured by the autorefractometer was higher than the subjective 0.35 D ± 0.29 D (p < 0.0005). There was a statistically significant correlation between VA (p < 0.0005) and the difference between the subjective and objective refraction. In 99.2% of the measurements, visual values were within one decimal line of each other. Conclusion: The Nidek AR-360A autorefractometer is an accurate tool for determining the refraction and VA in a clinical screening trial.

Being a solution provider differs significantly from being an industrial product manufacturer, as solution sales necessitate value-based selling techniques. In order to succeed in solution sales, sellers have to change their way of doing business by seeking to understand customer problems and communicating how their solution generates higher profits for the customer. The findings show that companies lack the tools and managerial capabilities to transform their organization into one that solves customer problems. We present a value-based sales approach to enable industrial companies to address customer problems and enhance customer certainty in that added value. Design thinking was applied to guide the process of identifying, co-creating and confirming customer-perceived value. The sales process and its relevant tools were developed in collaboration with our company partners in the DIMECC REBUS program.

Creating and sustaining solutions business networks pose considerable challenges to lead firms. These challenges, in our contention, often stem from inadequate integration. In this chapter, we introduce a functional-contracting approach to facilitate the necessary integration process. The functional-contracting tool was co-designed with a case company trying to create a new business network for an industrial solution with value-based selling and pricing models. The tool builds on integration and functional-contracting theory and deploys contracts as relational integration tools capable of creating and sustaining trust-based networks.

To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration.Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months.Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P0.001) correlated with less visual acuity gain.The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Objective Ascending aortic aneurysms result from a degenerative process in the aortic wall, characterized by the loss of smooth muscle cells and elastic fibers. We hypothesized that there would be changes in plasma protein and aortic tissue messenger RNA levels of osteopontin, matrix metalloproteinase type 2, matrix metalloproteinase type 9, and tissue inhibitor of matrix metalloproteinases type 1 in ascending aortic aneurysm samples. Methods Plasma, aortic tissue, and aortic mRNA samples were collected from patients with an ascending aortic aneurysm or an abdominal aortic aneurysm and from control individuals. Plasma protein levels of osteopontin, matrix metalloproteinase (MMP) types 2 and 9, and tissue inhibitor of matrix metalloproteinases type 1 were determined by quantitative sandwich enzyme-linked immunosorbent assay. Aortic mRNA levels of these same proteins were analyzed with the quantitative real-time polymerase chain reaction (RT-PCR) method and protein levels from the aortic tissues were assayed by immunostaining. Quantitative RT-PCR results were estimated by the normalized expression method (ΔΔCt). Results Plasma protein levels were significantly elevated for osteopontin, MMP-2, and MMP-9 in the samples of ascending and abdominal aortic aneurysm group compared with controls. Plasma protein levels of MMP-9 were higher in the nonoperated compared with the operated ascending aortic aneurysm group. Aortic osteopontin, MMP-2, and MMP-9 mRNA levels were increased for ascending aortic aneurysm samples. Conclusions This study reveals an important role of osteopontin, MMP-2 and MMP-9 in the development of ascending and abdominal aortic aneurysm.

Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p=0.001), and 76.1 (48.2) for NoDR (p=0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p=0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p>0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.

Purpose: Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia-induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9), angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor-β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker. Methods: Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006–2008. Vitreous samples were collected before the start of the conventional 3-ppp vitrectomy. Vitreous MMP-2 and MMP-9, Ang-1 and Ang-2, VEGF, EPO and TGFβ1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls. Results: Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP-2 (p = 0.0015), totalMMP-2 (p = 0.0011), proMMP-9 (p = 0.00001), totalMMP-9 (p < 0.00001), Ang-2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFβ1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang-2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9). Conclusion: The main new finding is that the intravitreal concentrations of Ang-2 correlated significantly with MMP-9, VEGF, EPO and TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.

Background: Asthenopic symptoms associated with convergence insufficiency (CI) may compromise a person's ability to work or study. We investigated the effectiveness of orthoptic exercises in relieving symptoms related to CI and long-time results in adults and children. Methods: The data were retrospectively gathered from the patient clinical files. A total of 135 patients met the inclusion criteria of suffering asthenopic symptoms and CI but had not received prior strabismus surgery or orthoptic exercises. Results: The mean age was 26 ± 17 years, 74% of them were female. The patients (N = 135) suffered from CI and had at least one of the following symptoms: eyestrain, blurring of vision, problems in reading and while doing work-up at close distance or headache. In the two-year follow-up time, 4% of the patients needed to be retreated and 3% of the patients required strabismus surgery. There were no significant differences between adults and children in near point of convergence (NPC), number of visits needed or fusional vergence at the end of treatment nor did the outcome depend on the number of visits. 59.5% of children vs. 51.9% of adults were free of symptoms when completing the exercises. Conclusions: In conclusion orthoptic exercises are effective in relieving asthenopic symptoms in adults and children. The effects of orthoptic exercises on NPC and fusional vergence were equal in adults and in children and not dependent on the number of visits needed for successful outcome. With orthoptic exercises it is possible to achieve longstanding relief on the symptoms of CI.

PurposeIt has been argued that systems integration plays a central role when a company supplies complex technical and engineering intensive industrial projects. The purpose of this paper is to highlight the importance of customer integration as part of systems integration in industrial project business.Design/methodology/approachThis paper develops the understanding of systems integration based on an empirical study, in two phases, of a global company providing large and complex solutions including demanding strategic and operational efforts, within the power and marine sectors. The paper analyzes the technical and social dimensions and describes how to systematically manage them.FindingsThe social dimension of integration can be achieved by making a direct change in policy towards the six supplier capabilities or integration mechanisms found critical: showing interest in the customer's needs and business requirements; promptly responding to and solving customer needs; having knowledge concerning the latest technical development; having the ability to listen to the customer and to reflect on what has been said; taking responsibility for the delivered installation after handing it over and having logistics competence to guarantee availability of parts.Practical implicationsThe benefits of understanding and managing the social dimension, in terms of customer integration, of systems integration properly have a considerable financial impact on the project company's business.Originality/valueAddressing the social dimension of systems integration is beneficial to a project company's business because the company can decrease its level of risk and uncertainty, and at the same time develop market opportunities by increasing the value of the offerings.

Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL(2) and HDL(3) (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries.

Purpose To evaluate the role of vascular endothelial growth factor (VEGF) gene polymorphisms in exudative age-related macular degeneration (AMD). Design Retrospective, comparative case series. Participants Patients with recent exudative AMD (n = 162) and age-matched subjects without AMD (n = 85). Methods Fluorescein angiography (FA), clinical examination, and single nucleotide polymorphism (SNP) genotyping. Main Outcome Measures The frequencies of 3 VEGF gene SNPs were analyzed, 1 at the promoter site (rs699947, A→C) and 2 intronic SNPs (rs2146323, A→C, and rs3025033, A→G), in relation to the risk of AMD, to choroidal neovascular (CNV) lesion size and configuration, and to the anatomic response to photodynamic therapy (PDT). These SNPs were chosen to cover all the haploblocks of the VEGF gene. The 86 patients who had undergone PDT were classified as either PDT responders or PDT nonresponders based on the outcome of PDT after the last treatment session. For the PDT responders, the treating physician had deemed the lesion to be clinically dry and without leakage from CNV in FA at a visit scheduled at least 12 weeks after the last PDT treatment. For the PDT nonresponders, the PDT sessions had been discontinued by the treating retina specialist because of an apparently poor response and a still exudative lesion after several PDT sessions. Results The presence of exudative AMD or lesion size or configuration was not associated with the SNPs studied here. The frequencies of the rs699947 were significantly different in PDT nonresponders and PDT responders. The AA, AC, and CC genotypes were 14%, 39%, and 46%, respectively, in PDT nonresponders, compared with 40%, 48%, and 12%, respectively, in the PDT responders ( P = 0.0008). The corresponding frequencies for the rs2146323 AA, AC, and CC genotypes were 4%, 32%, and 64%, respectively, in nonresponders and 24%, 38%, and 38%, respectively, in responders ( P = 0.0369). The genotypes of the rs3025033 SNP were distributed evenly between the responders and nonresponders. Conclusions The VEGF gene polymorphic SNPs at rs699947 and rs2146323 are strong determinants of the anatomic outcome after PDT, but the SNPs studied were not associated with the presence of exudative AMD or with the CNV lesion size or configuration. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background: In diabetic retinopathy, the vascular endothelium is damaged due to oxidative stress and inflammation, and vitreous VEGF concentration becomes elevated. The association of diabetic retinopathy with single nucleotide polymorphisms (SNPs) was studied on two genes: VEGF, an important mediator of neovascularisation, and MnSOD, a major antioxidant enzyme. Methods: The study population was 755 individuals consisting of 131 diabetic (type 1 or type 2) patients with diabetic retinopathy (DR group), 98 diabetic controls without retinopathy (DC group) and 526 non-diabetic controls. VEGF SNPs rs699947, rs2010963, rs2146232, rs3025033, rs3025039 and Ala16Val polymorphism of the MnSOD gene were genotyped. Results: The frequencies of allele and genotype of the single genotyped VEGF SNPs or reconstructed haplotypes of these single SNPs did not differ between DR and DC groups. A higher frequency of the AlaAla genotype (p = 0.03) and Ala16 allele (p = 0.04) of the MnSOD gene in the DR group was found when compared with the DC group. Conclusions: In conclusion, the studied VEGF SNPs were not associated with the risk of diabetic retinopathy, and so it is unlikely that the VEGF gene is a major locus determining the risk of diabetic retinopathy. A statistically significant association of MnSOD Ala16Val polymorphism with diabetic retinopathy was found.

Purpose: Tafluprost is a new prostaglandin F2α (PGF2α) derivative in development for the treatment of glaucoma. Tafluprost is the first PGF2α analogue with a preservative-free formulation. Methods: This randomized, investigator-masked, multicentre, crossover phase III study evaluated the pharmacodynamics and safety of preserved and preservative-free tafluprost 0.0015% eyedrops administered for 4 weeks in 43 patients with open-angle glaucoma or ocular hypertension. The primary variable was change from baseline in overall diurnal intraocular pressure (IOP) at 4 weeks. Adverse events and other safety parameters were also analysed. Results: Decreased IOP was clearly observed with both formulations at week 1 and was sustained until week 4. The overall treatment difference (preservative-free versus preserved formulations) at week 4 was 0.01 mmHg (95% confidence interval − 0.46 to 0.49; p = 0.96). There were no unexpected safety-related findings. Both formulations were well tolerated and most adverse events were ocular and mild in severity. Conclusions: The reduction in IOP achieved by preservative-free tafluprost is equivalent to that obtained with the preserved formulation. The preservative-free formulation was generally well tolerated.

Purpose A clinical evaluation of the Nidek AR-360A autorefractometer was performed to examine its accuracy in measuring refraction and visual acuity, in a pilot study for a clinical screening trial (the Northern Finland Birth Cohort Eye Study). Methods Measurements of the refractive error were obtained from 160 eyes of 80 subjects (mean age 48.9), first objectively with the AR-360A and then subjectively by an optometrist. Agreement with the subjective refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE), cylindrical vectors J45 and J0, and presbyopic correction (add). Visual acuity was measured using an ETDRS chart and the autorefractometer. The central corneal thickness (CCT) was measured with pachymetry. Results The refractive error measured with the AR-360A was lower than the subjective refraction performed by the optometrist for sphere (−0.13D ± 0.31D p

The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttrans-lational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholestetyl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p < cOm), but without significant difference between the apo E groups. In conclusion, alcohol abuse does not cause major changes in the electric charge of apo E in humans. Heavy alcohol intake seems to have a beneficial effect on plasma lipids and lipoproteins, regardless of the apo E phenotype, but the modulation of the alcohol-induced increase in HDL by apo E phenotype should be taken into consideration in future studies. Key Words: Alcohol, Apolipoprotein E, HDL, LDL, VLDL.

Purpose To study the association of potential key single-nucleotide polymorphisms with the short-term anatomic response to bevacizumab treatment in exudative age-related macular degeneration (AMD). Methods Clinical data of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months. Representative single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes were analysed. Results Interleukin 8 promoter polymorphism −251A/T,conferring a more acitve interleuking-8 system, was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of −251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted a poorer outcome. Conclusion The interleukin -8 pathway may modulate the early anatomic response to anti-VEGF treatment in AMD. A possible activation of interleukin -8 production in patients may represent a compensatory mechanism to chronic blockade of VEGF signalling in AMD lesions

Vascular endothelial growth factor (VEGF) plays an important role in the development of diabetic retinopathy. Previous studies have suggested that angiotensin-converting enzyme (ACE) inhibitor therapy may reduce vitreous VEGF concentration in diabetic retinopathy. Also HMG CoA reductase inhibitors (statins), known for their beneficial effects on vascular endothelium, might influence vitreous VEGF concentration in diabetic retinopathy.Vitreous VEGF concentration of diabetic patients with proliferative retinopathy using statin therapy and/or ACE inhibitor therapy was studied.Fifty diabetic patients with proliferative diabetic retinopathy, 21 diabetic control patients without proliferative retinopathy, and 43 non-diabetic control subjects underwent vitrectomy. Vitreous samples were collected at the beginning of surgery, and VEGF concentration was assessed using a chemiluminescent VEGF immunoassay.Vitreous VEGF concentration was significantly higher in diabetic patients with proliferative retinopathy using statins than in those not using statins. The diabetic patients with proliferative retinopathy were divided into subgroups according to use of ACE inhibitor and/or statin medication. These groups did not differ significantly in concentration of vitreous VEGF.Statin therapy is associated with high vitreous VEGF concentration in diabetic patients with proliferative retinopathy. In contrast to previous reports, ACE inhibitor use did not significantly influence vitreous VEGF concentration in these patients.

Aims: Alcohol consumption reduces the carbohydrate content of some glycoproteins, e.g. carbohydrate-deficient transfer- rin. The aim of this study was to investigate if there is such an alcohol-induced glycosylation defect in plasma cholesteryl ester transfer protein (CETP). A defect in the posttranslational glycosylation of CETP may affect its structure and electrical charge and may therefore affect its function. CETP activity is low in alcohol abusers. Methods: We studied the effect of alcohol consumption on CETP properties in 10 alcohol abusers and 10 control subjects. CETP was partially purified from lipoprotein-free plasma by FPLC using a Phenyl- Sepharose column. Isoelectric focusing, polyacrylamide gel electrophoresis, and western blotting were performed for partially purified CETP. Results: CETP had a lower molecular weight in the alcohol abusers than in the controls (range 50.6-84.0 kDa in the alcohol abusers vs 51.3-85.0 kDa in the controls).CETP purified from alcohol abusers had a higher isoelectric point, indicating a lower negative charge on the surface of the protein than in the controls' CETP. A similar effect was observed when control CETP was incubated with neuraminidase, an enzyme which is known to remove sialic acid from glycoproteins. Conclusions: We conclude that CETP from alco- hol abusers may have a glycosylation defect due to defective sialylation caused posttranslationally by alcohol itself or its metabolite acetaldehyde. The defective glycosylation of CETP associated with altered binding to lipoproteins may lead to the low CETP activity observed previously in alcoholic subjects.

This article presents results from a four-year study of various integration mechanisms in industrial project business. The projects analysed are complex solutions, which include demanding efforts in both engineering and organisation. Mechanisms for combining products and the processes needed to deliver projects are described and categorised according to the impact that they have on the management of knowledge and information. The design, commissioning and operations phases have been studied in particular and the entire project life cycles have been addressed to obtain an understanding that is as comprehensive as possible of the integration needs in different project phases. The results are summarised in a framework describing two dimensions of integration that are fundamental for knowledge integration when the logic is determined by how the project is delivered and what is the final outcome. The results provide support for project companies delivering solutions to their customers: to develop technical and social capabilities for integration of knowledge and information and to ensure their competitiveness.