Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration

For geographic atrophy (GA) due to age-related macular degeneration (AMD) there is so far no approved treatment option. Usually, increased autofluorescence (AF) levels of different patterns adjacent to the atrophic area indicate lipofuscin-laden retinal pigment epithelium (RPE) cells at a high risk for apoptosis. Herein, SRT was used to selectively treat these cells to stimulate RPE proliferation, in order to reduce or ideally stop further growth of the atrophic area.

A Distributed Outstar Network for Spatial Pattern Learning

The distributed outstar, a generalization of the outstar neural network for spatial pattern learning, is introduced. In the outstar, signals from a source node cause weights to learn and recall arbitrary patterns across a target field of nodes. The distributed outstar replaces the outstar source node with a source field of arbitrarily many nodes, whose activity pattern may be arbitrarily distributed or compressed. Learning proceeds according to a principle of atrophy due to disuse, whereby a path weight decreases in joint proportion to the transmitted path signal and the degree of disuse of the target node. During learning, the total signal to a target node converges toward that node's activity level. Weight changes at a node are apportioned according to the distributed pattern of converging signals. Three synaptic transmission functions, by a product rule, a capacity rule, and a threshold rule, are examined for this system. The three rules are computationally equivalent when source field activity is maximally compressed, or winner-take-all. When source field activity is distributed, catastrophic forgetting may occur. Only the threshold rule solves this problem. Analysis of spatial pattern learning by distributed codes thereby leads to the conjecture that the unit of long-term memory in such a system is an adaptive threshold, rather than the multiplicative path weight widely used in neural models.

Spatial Pattern Learning, Catastophic Forgetting and Optimal Rules of Synaptic Transmission

It is a neural network truth universally acknowledged, that the signal transmitted to a target node must be equal to the product of the path signal times a weight. Analysis of catastrophic forgetting by distributed codes leads to the unexpected conclusion that this universal synaptic transmission rule may not be optimal in certain neural networks. The distributed outstar, a network designed to support stable codes with fast or slow learning, generalizes the outstar network for spatial pattern learning. In the outstar, signals from a source node cause weights to learn and recall arbitrary patterns across a target field of nodes. The distributed outstar replaces the outstar source node with a source field, of arbitrarily many nodes, where the activity pattern may be arbitrarily distributed or compressed. Learning proceeds according to a principle of atrophy due to disuse whereby a path weight decreases in joint proportion to the transmittcd path signal and the degree of disuse of the target node. During learning, the total signal to a target node converges toward that node's activity level. Weight changes at a node are apportioned according to the distributed pattern of converging signals three types of synaptic transmission, a product rule, a capacity rule, and a threshold rule, are examined for this system. The three rules are computationally equivalent when source field activity is maximally compressed, or winner-take-all when source field activity is distributed, catastrophic forgetting may occur. Only the threshold rule solves this problem. Analysis of spatial pattern learning by distributed codes thereby leads to the conjecture that the optimal unit of long-term memory in such a system is a subtractive threshold, rather than a multiplicative weight.

Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac diseases. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immunoreactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

Single nucleotide polymorphisms in the APCS gene influence geographic atrophy secondary to VEGF inhibition therapy in neovascular macular degeneration.

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly mostly due to the development of neovascular AMD (nAMD) or geographic atrophy (GA). Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are an effective therapeutic option for nAMD. Following anti-VEGF treatments, increased atrophy of the retinal pigment epithelium (RPE) and choriocapillaries that resembles GA has been reported. We sought to evaluate the underlying genetic influences that may contribute to this process. Methods: We selected 68 single nucleotide polymorphisms (SNPs) from genes previously identified as susceptibility factors in AMD, along with 43 SNPs from genes encoding the VEGF protein and its cognate receptors as this pathway is targeted by treatment. We enrolled 467 consecutive patients (Feb 2009 to October 2011) with nAMD who received anti-VEGF therapy. The acutely presenting eye was designated as the study eye and retinal tomograms graded for macular atrophy at study exit. Statistical analysis was performed using PLINK to identify SNPs with a P value < 0.01. Logistic regression models with macular atrophy as dependent variable were fitted with age, gender, smoking status, common genetic risk factors and the identified SNPs as explanatory variables. Results: Grading for macular atrophy was available in 304 study eyes and 70% (214) were classified as showing macular atrophy. In the unadjusted analysis we observed significant associations between macular atrophy and two independent SNPs in the APCS gene: rs6695377: odds ratio (OR) = 1.98; 95% confidence intervals (CI): 1.23, 3.19; P = 0.004; rs1446965: OR = 2.49, CI: 1.29, 4.82; P = 0.006 and these associations remained significant after adjustment for covariates. Conclusions: VEGF is a mitogen and growth factor for choroidal blood vessels and the RPE and its inhibition could lead to atrophy of these key tissues. Anti-VEGF treatment can interfere with ocular vascular maintenance and may be associated with RPE and choroidal atrophy. As such, these medications, which block the effects of VEGF, may influence the development of GA. The top associated SNPs are found in the APCS gene, a highly conserved glycoprotein that encodes Serum amyloid P (SAP) which opsonizes apoptotic cells. SAP can bind to and activate complement components via binding to C1q, a mechanism by which SAP may remove cellular debris, affecting regulation of the three complement pathways.

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rapid Atrophy of the Lumbar Multifidus Follows Experimental Disc or Nerve Root Injury.

Study Design. Experimental study of muscle changes after lumbar spinal injury. Objectives. To investigate effects of intervertebral disc and nerve root lesions on cross-sectional area, histology and chemistry of porcine lumbar multifidus. Summary of Background Data. The multifidus cross-sectional area is reduced in acute and chronic low back pain. Although chronic changes are widespread, acute changes at 1 segment are identified within days of injury. It is uncertain whether changes precede or follow injury, or what is the mechanism. Methods. The multifidus cross-sectional area was measured in 21 pigs from L1 to S1 with ultrasound before and 3 or 6 days after lesions: incision into L3 - L4 disc, medial branch transection of the L3 dorsal ramus, and a sham procedure. Samples from L3 to L5 were studied histologically and chemically. Results. The multifidus cross-sectional area was reduced at L4 ipsilateral to disc lesion but at L4 - L6 after nerve lesion. There was no change after sham or on the opposite side. Water and lactate were reduced bilaterally after disc lesion and ipsilateral to nerve lesion. Histology revealed enlargement of adipocytes and clustering of myofibers at multiple levels after disc and nerve lesions. Conclusions. These data resolve the controversy that the multifidus cross-sectional area reduces rapidly after lumbar injury. Changes after disc lesion affect 1 level with a different distribution to denervation. Such changes may be due to disuse following reflex inhibitory mechanisms.

Contrast sensitivity changes due to glaucoma and normal aging: low-spatial-frequency losses in both magnocellular and parvocellular pathways

PURPOSE: To explore the effects of glaucoma and aging on low-spatial-frequency contrast sensitivity by using tests designed to assess performance of either the magnocellular (M) or parvocellular (P) visual pathways. METHODS: Contrast sensitivity was measured for spatial frequencies of 0.25 to 2 cyc/deg by using a published steady- and pulsed-pedestal approach. Sixteen patients with glaucoma and 16 approximately age-matched control subjects participated. Patients with glaucoma were tested foveally and at two midperipheral locations: (1) an area of early visual field loss, and (2) an area of normal visual field. Control subjects were assessed in matched locations. An additional group of 12 younger control subjects (aged 20-35 years) were also tested. RESULTS: Older control subjects demonstrated reduced sensitivity relative to the younger group for the steady (presumed M)- and pulsed (presumed P)-pedestal conditions. Sensitivity was reduced foveally and in the midperiphery across the spatial frequency range. In the area of early visual field loss, the glaucoma group demonstrated further sensitivity reduction relative to older control subjects across the spatial frequency range for both the steady- and pulsed-pedestal tasks. Sensitivity was also reduced in the midperipheral location of "normal" visual field for the pulsed condition. CONCLUSIONS: Normal aging results in a reduction of contrast sensitivity for the low-spatial-frequency-sensitive components of both the M and P pathways. Glaucoma results in a further reduction of sensitivity that is not selective for M or P function. The low-spatial-frequency-sensitive channels of both pathways, which are presumably mediated by cells with larger receptive fields, are approximately equivalently impaired in early glaucoma.

Variations in MIMO-OFDM channel capacity due to random human movement in an indoor environment

Channel measurements and simulations have been carried out to observe the effects of pedestrian movement on multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) channel capacity. An in-house built MIMO-OFDM packet transmission demonstrator equipped with four transmitters and four receivers has been utilized to perform channel measurements at 5.2 GHz. Variations in the channel capacity dynamic range have been analysed for 1 to 10 pedestrians and different antenna arrays (2 × 2, 3 × 3 and 4 × 4). Results show a predicted 5.5 bits/s/Hz and a measured 1.5 bits/s/Hz increment in the capacity dynamic range with the number of pedestrian and the number of antennas in the transmitter and receiver array.

Increase in particle number emissions from motor vehicles due to interruption of steady traffic flow

We assess the increase in particle number emissions from motor vehicles driving at steady speed when forced to stop and accelerate from rest. Considering the example of a signalized pedestrian crossing on a two-way single-lane urban road, we use a complex line source method to calculate the total emissions produced by a specific number and mix of light petrol cars and diesel passenger buses and show that the total emissions during a red light is significantly higher than during the time when the light remains green. Replacing two cars with one bus increased the emissions by over an order of magnitude. Considering these large differences, we conclude that the importance attached to particle number emissions in traffic management policies be reassessed in the future.

Numerical analyses of crack spacing due to shrinkage in reinforced concrete slabs

Shrinkage cracking is commonly observed in concrete flat structures such as highway pavements, slabs, and bridge decks. Crack spacing due to shrinkage has received considerable attention for many years [1-3]. However, some aspects concerning the mechanism of crack spacing still remain un-clear. Though it is well known that the interval of the cracks generally falls with a range, no satisfactory explanation has been put forward as to why the minimum spacing exists.

Determinants of health costs due to farmers’ exposure to pesticides : an empirical analysis

It is now well known that pesticide spraying by farmers has an adverse impact on their health. This is especially so in developing countries where pesticide spraying is undertaken manually. The estimated health costs are large. Studies to date have examined farmers’ exposure to pesticides, the costs of ill-health and their determinants based on information provided by farmers. Hence, some doubt has been cast on the reliability of such studies. In this study, we rectify this situation by conducting surveys among two groups of farmers. Farmers who perceive that their ill-health is due to exposure to pesticides and obtained treatment and farmers whose ill-health have been diagnosed by doctors and who have been treated in hospital for exposure to pesticides. In the paper, cost comparisons between the two groups of farmers are made. Furthermore, regression analysis of the determinants of health costs show that the quantity of pesticides used per acre per month, frequency of pesticide use and number of pesticides used per hour per day are the most important determinants of medical costs for both samples. The results have important policy implications.