Assessing the Functionality and Biocompatibility of a Wireless Contact Lens Sensor for 24 hour-intraocular Pressure Monitoring in Volunteers: Preliminary Results

Purpose: In vitro studies in porcine eyes have demonstrated a good correlation between induced intraocular pressure variations and corneal curvature changes, using a contact lens with an embedded microfabricated strain gauge. Continuous 24 hour-intraocular pressure (IOP) monitoring to detect large diurnal fluctuation is currently an unmet clinical need. The aims of this study is to evaluate precision of signal transmission and biocompatibility of 24 hour contact lens sensor wear (SENSIMED Triggerfish®) in humans. Methods: After full eye examination in 10 healthy volunteers, a 8.7 mm radius contact lens sensor and an orbital bandage containing a loop antenna were applied and connected to a portable recorder. Best corrected visual acuity and position, lubrication status and mobility of the sensor were assessed after 5 and 30 minutes, 4, 7 and 24 hours. Subjective comfort was scored and activities documented in a logbook. After sensor removal full eye examination was repeated, and the registration signal studied. Results: The comfort score was high and did not fluctuate significantly, except at the 7 hour-visit. The mobility of the contact lens was minimal but its lubrication remained good. Best corrected visual acuity was significantly reduced during the sensor wear and immediately after its removal. Three patients developed mild corneal staining. In all but one participant we obtained a registration IOP curve with visible ocular pulse amplitude. Conclusions: This 24 hour-trial confirmed the functionality and biocompatibility of SENSIMED Triggerfish® wireless contact lens sensor for IOP-fluctuation monitoring in volunteers. Further studies with a range of different contact lens sensor radii are indicated.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

Perception and Interpretation of Advance Warning Signs on County Roads, HR-256, 1984

This research consisted of five laboratory experiments designed to address the following two objectives in an integrated analysis: (1) To discriminate between the symbol Stop Ahead warning sign and a small set of other signs (which included the word-legend Stop Ahead sign); and (2) To analyze sign detection, recognizability, and processing characteristics by drivers. A set of 16 signs was used in each of three experiments. A tachistoscope was used to display each sign image to a respondent for a brief interval in a controlled viewing experiment. The first experiment was designed to test detection of a sign in the driver's visual field; the second experiment was designed to test the driver's ability to recognize a given sign in the visual field; and the third experiment was designed to test the speed and accuracy of a driver's response to each sign as a command to perform a driving action. A fourth experiment tested the meanings drivers associated with an eight-sign subset of the 16 signs used in the first three experiments. A fifth experiment required all persons to select which (if any) signs they considered to be appropriate for use on two scale model county road intersections. The conclusions are that word-legend Stop Ahead signs are more effective driver communication devices than symbol stop-ahead signs; that it is helpful to drivers to have a word plate supplementing the symbol sign if a symbol sign is used; and that the guidance in the Manual on Uniform Traffic Control Devices on the placement of advance warning signs should not supplant engineering judgment in providing proper sign communication at an intersection.

Development of projections from auditory to visual areas in the cat.

In newborn kittens, cortical auditory areas (including AI and AII) send transitory projections to ipsi- and contralateral visual areas 17 and 18. These projections originate mainly from neurons in supragranular layers but also from a few in infragranular layers (Innocenti and Clarke: Dev. Brain Res. 14:143-148, '84; Clarke and Innocenti: J. Comp. Neurol. 251:1-22, '86). The postnatal development of these projections was studied with injections of anterograde tracers (wheat germ agglutinin-horseradish peroxidase [WGA-HRP]) in AI and AII and of retrograde tracers (WGA-HRP, fast blue, diamidino yellow, rhodamine-labeled latex beads) in areas 17 and 18. It was found that the projections are nearly completely eliminated in development, this, by the end of the first postnatal month. Until then, most of the transitory axons seem to remain confined to the white matter and the depth of layer VI; a few enter it further but do not appear to form terminal arbors. As for other transitory cortical projections the disappearance of the transitory axons seems not to involve death of their neurons of origin. In kittens older than 1 month and in normal adult cats, retrograde tracer injections restricted to, or including, areas 17 and 18 label only a few neurons in areas AI and AII. Unlike the situation in the kitten, nearly all of these are restricted to layers V and VI. A similar distribution of neurons projecting from auditory to visual areas is found in adult cats bilaterally enucleated at birth, which suggests that the postnatal elimination of the auditory-to-visual projection is independent of visual experience and more generally of information coming from the retina.

Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections.

OBJECTIVE: To identify disease causing mutation in three generations of a Swiss family with pattern dystrophy and high intrafamilial variability of phenotype. To assess the effect of intravitreal ranibizumab injections in the treatment of subfoveal choroidal neovascularization associated with pattern dystrophy in one patient. METHODS: Affected family members were ascertained for phenotypic and genotypic characterization. Ophthalmic evaluations included fundus photography, autofluorescence imaging, optical coherence tomography, and International Society for Clinical Electrophysiology of Vision standard full-field electroretinography. When possible family members had genetic testing. The proband presented with choroidal neovascularization and had intravitreal injections as needed according to visual acuity and optical coherence tomography. RESULTS: Proband had a multifocal type pattern dystrophy, and his choroidal neovascularization regressed after four intravitreal injections. The vision improved from 0.8 to 1.0, and optical coherence tomography showed complete anatomical restoration. A butterfly-shaped pattern was observed in her cousin, whereas a fundus pulverulentus pattern was seen in a second cousin. Aunt had a multifocal atrophic appearance, simulating geographic atrophy in age-related macular degeneration. The Y141C mutation was identified in the peripherin/RDS gene and segregated with disease in the family. CONCLUSION: This is the first report of marked intrafamilial variation of pattern dystrophy because of peripherin/RDS Y141C mutation. Intravitreal ranibizumab injections might be a valuable treatment for associated subfoveal choroidal neovascularization.

Remaining rod activity mediates visual behavior in adult Rpe65-/- mice.

Purpose: C57/Bl6, Cpfl1-/- (Cone photoreceptors function loss 1; pure rod function), Gnat1alpha-/- (rod alpha-transducin; pure cone function) and Rpe65-/-;Rho-/- double knock-out mice were studied in order to distinguish the respective contributions of the different photoreceptor (PR) systems that enable light perception and mediate a visual reflex in adult Rpe65-/- mice using a simple behavioural procedure. Methods: Visual function was estimated using a rotating automatized optomotor drum covered with vertical black and white stripes at spatial frequencies of 0.025 to 0.5 cycles per degree (cpd) in both photopic and scotopic conditions. To evaluate the contribution as well as the light intensity threshold of each PR system, we tested the mouse strains with different luminances. Results: Stripe rotation elicits head movements in wild-type (WT) animals in photopic and scotopic conditions depending on the spatial frequency, whereas Cpfl1-/- mice show a reduced activity in the photopic condition and Gnat1alpha-/- mice an almost absent response in the scotopic condition. Interestingly, a robust visual response is obtained with Rpe65-/- knockout mice at 0.075 cpd and 0.1 cpd in the photopic condition. The residual rod function in the Rpe65-/- animals was demonstrated by testing Rpe65-/-;Rho-/- mice that present no response in photopic conditions. Conclusions: The optomotor test is a simple method to estimate the visual function, and to evaluate the respective contributions of rod and cone systems. Using this test, we demonstrate that in Rpe65-/- mice, devoid of functional cones and of detectable 11-cis-retinal protein, rods mimic in part the cone function by mediating vision in photopic conditions.

Subtelomeric 6p deletion: clinical and array-CGH characterization in two patients

We report on two patients with de novo subtelomeric terminal deletion of chromosome 6p. Patient 1 is an 8-month-old female born with normal growth parameters, typical facial features of 6pter deletion, bilateral corectopia, and protruding tongue. She has severe developmental delay, profound bilateral neurosensory deafness, poor visual contact, and hypsarrhythmia since the age of 6 months. Patient 2 is a 5-year-old male born with normal growth parameters and unilateral hip dysplasia; he has a characteristic facial phenotype, bilateral embryotoxon, and moderate mental retardation. Further characterization of the deletion, using high-resolution array comparative genomic hybridization (array-CGH; Agilent Human Genome kit 244 K), revealed that Patient 1 has a 8.1 Mb 6pter-6p24.3 deletion associated with a contiguous 5.8 Mb 6p24.3-6p24.1 duplication and Patient 2 a 5.7 Mb 6pter-6p25.1 deletion partially overlapping with that of Patient 1. Complementary FISH and array analysis showed that the inv del dup(6) in Patient 1 originated de novo. Our results demonstrate that simple rearrangements are often more complex than defined by standard techniques. We also discuss genotype-phenotype correlations including previously reported cases of deletion 6p.

Differences based on fine motor behaviour in Parkinson's patients compared to an age matched control group in proprioceptive and visuo-proprioceptive test conditions

Personality differences based on fine motor precision performance were studied in early stage Parkinson's patients and an age-matched control group under two different test conditions: proprioceptive + visual information and proprioceptive information alone. A comparative data analysis for deviations of three measured movement types (transversal, frontal and sagittal) was done for both hands (dominant and non-dominant) with relation to personality dimensions. There were found significant differences between the two groups in decision making dimension and emotionality. After splitting the data for gender subgroups, some significant differences were found for men but not for women. The differences in fine motor task performance varied, being better in some directions for the Parkinson"s patients and worse in others. The findings may suggest that medication has both positive and negative effects on motor performance and provoke personality changes, being more pronounced in men.

Effectiveness of pharmacist care in the improvement of adherence to antidepressants: a systematic review and meta-analysis

BACKGROUND: Pharmacists can play a decisive role in the management of ambulatory patients with depression who have poor adherence to antidepressant drugs. OBJECTIVE: To systematically evaluate the effectiveness of pharmacist care in improving adherence of depressed outpatients to antidepressants. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. RCTs were identified through electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, Institute for Scientific Information Web of Knowledge, and Spanish National Research Council) from inception to April 2010, reference lists were checked, and experts were consulted. RCTs that evaluated the impact of pharmacist interventions on improving adherence to antidepressants in depressed patients in an outpatient setting (community pharmacy or pharmacy service) were included. Methodologic quality was assessed and methodologic details and outcomes were extracted in duplicate. RESULTS: Six RCTs were identified. A total of 887 patients with an established diagnosis of depression who were initiating or maintaining pharmacologic treatment with antidepressant drugs and who received pharmacist care (459 patients) or usual care (428 patients) were included in the review. The most commonly reported interventions were patient education and monitoring, monitoring and management of toxicity and adverse effects, adherence promotion, provision of written or visual information, and recommendation or implementation of changes or adjustments in medication. Overall, no statistical heterogeneity or publication bias was detected. The pooled odds ratio, using a random effects model, was 1.64 (95% CI 1.24 to 2.17). Subgroup analysis showed no statistically significant differences in results by type of pharmacist involved, adherence measure, diagnostic tool, or analysis strategy. CONCLUSIONS: These results suggest that pharmacist intervention is effective in the improvement of patient adherence to antidepressants. However, data are still limited and we would recommend more research in this area, specifically outside of the US.

MAP2 Isoforms in Developing Cat Cerebral Cortex and Corpus Callosum.

The microtubule-associated protein MAP2 was studied in the developing cat visual cortex and corpus callosum. Biochemically, no MAP2a was detectable in either structure during the first postnatal month; adult cortex revealed small amounts of MAP2a. MAP2b was abundant in cortical tissue during the first postnatal month and decreased in concentration towards adulthood; it was barely detectable in corpus callosum at all ages. MAP2c was present in cortex and corpus callosum at birth; in cortex it consisted of three proteins of similar molecular weights between 65 and 70 kD. The two larger, phosphorylated forms disappeared after postnatal day 28, the smaller form after day 39. In corpus callosum, MAP2c changed from a phosphorylated to an unphosphorylated variant during the first postnatal month and then disappeared. Immunocytochemical experiments revealed MAP2 in cell bodies and dendrites of neurons in all cortical layers, from birth onwards. In corpus callosum, in the first month after birth, a little MAP2, possibly MAP2c, was detectable in axons. The present data indicate that MAP2 isoforms differ in their cellular distribution, temporal appearance and structural association, and that their composition undergoes profound changes during the period of axonal stabilization and dendritic maturation.

Iowa Cultural Leadership Partners 2013 Interview Highlights, September 2013

The Cultural Leadership Partners Program of the Iowa Arts Council and Iowa Department of Cultural Affairs (IAC/DCA) engages leaders in Iowa’s arts and cultural community that have demonstrated an exemplary record of programming and managerial excellence, as well as exceptional community service to the citizens of Iowa on a year-round basis. After a rigorous application process, organizations selected to become Cultural Leadership Partners (CLPs) receive annual operating support from IAC/DCA. This document will not only serve to communicate to CLPs what the IAC/DCA has learned from these conversations, but that it will act as a catalyst for further development of the program and inform how IAC/DCA can support, challenge, connect, and partner with Iowa’s leading arts and cultural institutions.

Assigning and combining probabilities in single-case studies

There is currently a considerable diversity of quantitative measures available for summarizing the results in single-case studies. Given that the interpretation of some of them is difficult due to the lack of established benchmarks, the current paper proposes an approach for obtaining further numerical evidence on the importance of the results, complementing the substantive criteria, visual analysis, and primary summary measures. This additional evidence consists of obtaining the statistical significance of the outcome when referred to the corresponding sampling distribution. This sampling distribution is formed by the values of the outcomes (expressed as data nonoverlap, R-squared, etc.) in case the intervention is ineffective. The approach proposed here is intended to offer the outcome"s probability of being as extreme when there is no treatment effect without the need for some assumptions that cannot be checked with guarantees. Following this approach, researchers would compare their outcomes to reference values rather than constructing the sampling distributions themselves. The integration of single-case studies is problematic, when different metrics are used across primary studies and not all raw data are available. Via the approach for assigning p values it is possible to combine the results of similar studies regardless of the primary effect size indicator. The alternatives for combining probabilities are discussed in the context of single-case studies pointing out two potentially useful methods one based on a weighted average and the other on the binomial test.

Pupil responses derived from outer and inner retinal photoreception are normal in patients with hereditary optic neuropathy.

We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary optic neuropathy (HON, n = 8) and healthy controls (n = 8). Three different testing protocols were used. For the first two protocols, a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction, the half-max intensity, was determined. For the third protocol, the pupil size after light offset, the re-dilation rate and re-dilation amplitude were calculated to assess the post-light stimulus response. Patients with HON had bilateral, symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod, cone or melanopsin activity between patients and controls. In patients, there was a significant correlation between the half-max intensity of the red light sequence and visual field loss. In conclusion, pupil responses derived from outer or inner retinal photoreception in HON patients having mild-to moderate visual dysfunction are not quantitatively different from age-matched controls. However, an association between the degree of visual field loss and the half-max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes.

Authorship in scientific publications: analysis and recommendations.

In 2008, a Swiss Academies of Arts and Sciences working group chaired by Professor Emilio Bossi issued a "Memorandum on scientific integrity and the handling of misconduct in the scientific context", together with a paper setting out principles and procedures concerning integrity in scientific research. In the Memorandum, unjustified claims of authorship in scientific publications are referred to as a form of scientific misconduct - a view widely shared in other countries. In the Principles and Procedures, the main criteria for legitimate authorship are specified, as well as the associated responsibilities. It is in fact not uncommon for disputes about authorship to arise with regard to publications in fields where research is generally conducted by teams rather than individuals. Such disputes may concern not only the question who is or is not to be listed as an author but also, frequently, the precise sequence of names, if the list is to reflect the various authors' roles and contributions. Subjective assessments of the contributions made by the individual members of a research group may differ substantially. As scientific collaboration - often across national boundaries - is now increasingly common, ensuring appropriate recognition of all parties is a complex matter and, where disagreements arise, it may not be easy to reach a consensus. In addition, customs have changed over the past few decades; for example, the practice of granting "honorary" authorship to an eminent researcher - formerly not unusual - is no longer considered acceptable. It should be borne in mind that the publications list has become by far the most important indicator of a researcher's scientific performance; for this reason, appropriate authorship credit has become a decisive factor in the careers of young researchers, and it needs to be managed and protected accordingly. At the international and national level, certain practices have therefore developed concerning the listing of authors and the obligations of authorship. The Scientific Integrity Committee of the Swiss Academies of Arts and Sciences has collated the relevant principles and regulations and formulated recommendations for authorship in scientific publications. These should help to prevent authorship disputes and offer guidance in the event of conflicts.