The authors would like to thank Rabih Dow, Padma Rajagopal, Molly Connors and the staff of the Carroll Center for the Blind (Newton MA, USA) for their support in carrying out this research. This work was supported by the NIH/NEI grant: RO1 EY019924.

1. Participant Demographics
This is an on-going study that recruits blind male and female participants aged between 18-45 years. All participants are legally blind of early onset (documented prior to the age of 3) and of varying ocular etiologies. None of the study participants were previously familiar with the spatial layout of the target physical building.
2. Preparation and Familiarization with AbES
<ol>
	<li> Provide the participant with a blindfold and headphon...

<ol>
	<li>Loomis, J. M., Klatzky, R. L., Golledge, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Navigating+without+vision:+basic+and+applied+research.">Navigating without vision: basic and applied research.</a> Optom. Vis. Sci. 78, 282-289 (2001).</li><li>Siegel, A. W., White, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+development+of+spatial+representations+of+large-scale+environments.">The development of spatial representations of large-scale environments.</a> Adv. Child Dev. Behav. 10, 9-55 (1975).</li><li>Strelow, E. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+is+needed+for+a+theory+of+mobility:+direct+perception+and+cognitive+maps--lessons+from+the+blind.">What is needed for a theory of mobility: direct perception and cognitive maps--lessons from the blind.</a> Psychol. Rev. 92, 226-248 (1985).</li><li>Giudice, N. A., Bakdash, J. Z., Legge, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wayfinding+with+words:+spatial+learning+and+navigation+using+dynamically+updated+verbal+descriptions.">Wayfinding with words: spatial learning and navigation using dynamically updated verbal descriptions.</a> Psychol. Res. 71, 347-358 (2007).</li><li>Ashmead, D. H., Hill, E. W., Talor, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Obstacle+perception+by+congenitally+blind+children.">Obstacle perception by congenitally blind children.</a> Percept. Psychophys. 46, 425-433 (1989).</li><li>Dede, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immersive+interfaces+for+engagement+and+learning.">Immersive interfaces for engagement and learning.</a> Science. 323, 66-69 (2009).</li><li>Bavelier, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brains+on+video+games.">Brains on video games.</a> Nat. Rev. Neurosci. 12, 763-768 (2011).</li><li>Bavelier, D., Green, C. S., Dye, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Children,+wired:+for+better+and+for+worse.">Children, wired: for better and for worse.</a> Neuron. 67, 692-701 (2010).</li><li>Lange, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Designing+informed+game-based+rehabilitation+tasks+leveraging+advances+in+virtual+reality.">Designing informed game-based rehabilitation tasks leveraging advances in virtual reality.</a> Disabil. Rehabil. , (2012).</li><li>Merabet, L., S&#225;nchez, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Audio-based+Navigation+Using+Virtual+Environments:+Combining+Technology+and+Neuroscience.">Audio-based Navigation Using Virtual Environments: Combining Technology and Neuroscience.</a> AER Journal: Research and Practice in Visual Impairment and Blindness. 2, 128-137 (2009).</li><li>Kalia, A. A., Legge, G. E., Roy, R., Ogale, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+Indoor+Route-finding+Technology+for+People+with+Visual+Impairment.">Assessment of Indoor Route-finding Technology for People with Visual Impairment.</a> J. Vis. Impair. Blind. 104, 135-147 (2010).</li><li>Lahav, O., Schloerb, D. W., Srinivasan, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Newly+blind+persons+using+virtual+environment+system+in+a+traditional+orientation+and+mobility+rehabilitation+program:+a+case+study.">Newly blind persons using virtual environment system in a traditional orientation and mobility rehabilitation program: a case study.</a> Disabil. Rehabil. Assist Technol. , (2011).</li></ol>

We describe an interactive audio-based virtual environment simulator designed to improve general spatial awareness and navigation skills in the blind. We demonstrate that interacting with AbES provides accurate cues that describe the spatial relationships between objects and the overall layout of the target environment. Blind users can generate accurate spatial cognitive maps based on this auditory information and by interacting with the immersive virtual environment. Furthermore, interacting with AbES within the context...

Finding one's way in an unfamiliar environment presents as a significant challenge for the blind. Navigating successfully requires an understanding of the spatial relationships that exist between one's self and objects in the environment1,2. The mental representation that describes surrounding space is referred to as a spatial cognitive map3. Blind individuals can gather relevant spatial information regarding their surrounding environment through other sensory channels (such as hearing) allowing for the generation of an accurate spatial cognitive map for the purposes of real world navigation tasks4,5. 
Considerable interest has arisen regarding the educative potential of virtual environments and action video games as a means to learn and master skills6-9. Indeed, many strategies and approaches have been developed for the blind for this purpose (see 4,10-12). We have developed Audio-based Environment Simulator (AbES); a user-centered audio-based virtual environment that allows for simulated navigation and exploration of an existing physical building. Drawing from original architectural floor plans, a virtual rendering of a modern two-story building (located at the Carroll Center for the Blind; Newton, MA) was generated with the AbES software (Figures 1A and B). AbES incorporates an action game metaphor with a premise designed to promote full exploration of the building space. Using simple key strokes and spatialized sound cues, users navigate and explore the entire building to collect a maximum number of jewels hidden in various rooms. Users must avoid roving monsters that can take them away and hide them elsewhere in the building (Figure 1C).
We demonstrate that interacting with AbES allows a blind user to generate an accurate spatial cognitive map of a target building based on auditory information acquired within the context of an action game metaphor. This is confirmed by a series of post-training behavioral performance tests designed to assess the transfer of acquired spatial information from a virtual environment to a real-world and large scale indoor navigation task (see Figure 2 for overall study design). Our results show that blind users are able to successfully navigate throughout a building for which they were previously unfamiliar, despite the fact that at no time were they informed of the overall purpose of the study, nor were they instructed to recall the spatial layout of the building while playing the game.

<table border="1">
<tbody>
 <tr>
 <td>Name of Equipment</td>
 <th >Comments</td>
 </tr>
 <tr>
 <td>Laptop computer</td>
 <td >Laptop used exclusively for training participants and collecting data</td>
 </tr>
 <tr>
 <td>Stereo Head phones (fully enclosed circumaural design)</td>
 <td >Worn by all participants during training</td>
 </tr>
 <tr>
 <td>Blindfold</td>
 <td >Worn by all participants during training and testing</td>
 </tr>
 </tbody>
</table>

development of an audio-based virtual gaming environment to assist with navigation skills in the blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building's layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals.

Results from three early blind participants (aged between 19 and 22 years) are shown (see Table 1 for participant characteristics). In summary, all three participants showed a high level of success on all three navigation tasks following game play with the AbES software. This was confirmed by the performance scores (group mean and individual) on all three behavioral tasks (see Figure 6). The percentage correct performance for the virtual (mean: 90%) followed by the physical (mean: 88.7%)...

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Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind.

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio ...

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14.2K Views.  Massachusetts Eye and Ear Infirmary, Harvard Medical School. Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind.

Video: Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the...

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Using Quantitative Real-time PCR to Determine Donor Cell Engraftment in a Competitive Murine Bone Marrow Transplantation Model

Murine bone marrow transplantation models provide an important tool in measuring hematopoietic stem cell (HSC) functions and determining genes/molecules that regulate HSCs. In these transplant model systems, the function of HSCs is determined by the ability of these cells to engraft and reconstitute lethally irradiated recipient mice. Commonly, the donor cell contribution/engraftment is measured by antibodies to donor- specific cell surface proteins using flow cytometry. However, this method heavily depends on the specificity and the ability of the cell surface marker to differentiate donor-derived cells from recipient-originated cells, which may not be available for all mouse strains. Considering the various backgrounds of genetically modified mouse strains in the market, this cell surface/ flow cytometry-based method has significant limitations especially in mouse strains that lack well-defined surface markers to separate donor cells from congenic recipient cells. Here, we reported a PCR-based technique to determine donor cell engraftment/contribution in transplant recipient mice. We transplanted male donor bone marrow HSCs to lethally irradiated congenic female mice. Peripheral blood samples were collected at different time points post transplantation. Bone marrow samples were obtained at the end of the experiments. Genomic DNA was isolated and the Y chromosome specific gene, Zfy1, was amplified using quantitative Real time PCR. The engraftment of male donor-derived cells in the female recipient mice was calculated against standard curve with known percentage of male vs. female DNAs. Bcl2 was used as a reference gene to normalize the total DNA amount. Our data suggested that this approach reliably determines donor cell engraftment and provides a useful, yet simple method in measuring hematopoietic cell reconstitution in murine bone marrow transplantation models. Our method can be routinely performed in most laboratories because no costly equipment such as flow cytometry is required.

Determining donor cell engraftment presents a challenge in mouse bone marrow transplant models that lack well-defined phenotypical markers. We described a methodology to quantify male donor cell engraftment in female transplant recipient mice. This method can be used in all mouse strains for the study of HSC functions.

Murine bone marrow transplantation models provide an important tool in measuring hematopoietic stem cell (HSC) functions and determining genes/molecules ...

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Lipoxygenase (LOX) isozymes can generate products that may increase or decrease neuroinflammation and neurodegeneration.&#160;A gene-environment interaction study could identify LOX isozyme-specific effects. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of nigrostriatal damage in two LOX isozyme-deficient transgenic lines allows for comparison of the contribution of LOX isozymes on dopaminergic integrity and inflammation.

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The catheter of a telemetry device is implanted into the abdominal aorta in order to continuously collect beat-by-beat hemodynamic data from animals pre and post-high thoracic spinal cord transection. A novel JAVA software was employed to analyze hemodynamic parameters as well as frequency and intensity of spontaneous episodes of autonomic dysreflexia.

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This protocol shows the measurement of the apoptotic activity neutralization of TNF&#945; in a mouse fibroblast cell model (WEHI 164) using an anti-TNF&#945; mAb. In addition, this protocol can be used to evaluate other anti-TNF&#945; molecules, such as fusion proteins. The cellular model employed here is sensitive to TNF&#945;-mediated apoptosis when an additional stress factor is induced in cell culture conditions (e.g., serum deprivation). This procedure exemplifies how to execute this analytical assay, highlighting the key operations relating to the sample preparation, cell dilution, apoptosis induction, and spectrophotometric measurements that are critical to ensure successful results. This protocol reveals the best-performance conditions relating to apoptosis induction and efficient signal recording, leading to low uncertainty values.

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method

A protocol for the determination of the relative anti-apoptotic activity of an anti-TNF&#945; mAb using a neutralization mechanism with WEHI 164 cells is presented here. This protocol is useful for comparing the neutralization strength of different molecules with the same biological functionality.

This protocol shows the measurement of the apoptotic activity neutralization of TNF&#945; in a mouse fibroblast cell model (WEHI 164) using an ...

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Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy

Here, a protocol involving re-arterialized rat partial liver transplantation is presented. Specifically, 70% liver was resected in vivo by using an updated technique of vessel-oriented hepatectomy. The hepatic artery was reconstructed in an end-to-side manner. The cuff technique was modified to shorten the anastomosis time of the infrahepatic vena cava.

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. ...

Assessment of the Efficacy of An Osteopathic Treatment in Infants with Biomechanical Impairments to Suckling

Breastfeeding can be challenging for mother-infant dyads experiencing biomechanical suckling difficulties. Although lactation consultants (LCs) all over the world have increased their skills in this field and can provide support to help position the infant at the breast, the impact of their intervention might be limited in the presence of stiff structures in the infants. Here we present a protocol for a randomized controlled trial to assess the efficacy of osteopathic treatment, coupled with lactation consultation, for infants&#39; biomechanical suckling difficulties. It proposes a set-up and a sequence of actions to ensure an optimal context for treatment, as well as a blinding of parents and LCs to the intervention. Data such as the infant&#39;s latch ability measured with the LATCH Assessment Tool, the mother&#39;s nipple pain with a visual analog scale (VAS), and the mother&#39;s perceptions are collected by LCs four times over a 10-day period. Osteopathic lesions are documented by the osteopath, using a standardized assessment grid. Structures of interest are coherent with the anatomical zones involved in latching onto the breast. This protocol also proposes a strategy to document systematically an osteopathic profile of infants with biomechanical suckling difficulties in their first weeks of life. The implementation of this protocol confirms its feasibility for osteopathic assessment and treatment and paves the way for future trials to further explore the efficacy of osteopathic techniques for infants with biomechanical suckling difficulties.

Osteopathy is an emerging field of clinical research. Here we present a protocol to assess the efficacy of an osteopathic intervention coupled with lactation consultation, in infants with biomechanical issues impeding breastfeeding.

Breastfeeding can be challenging for mother-infant dyads experiencing biomechanical suckling difficulties. Although lactation consultants (LCs) all over ...

Today, many functional skills are technology-based, so development of a technology-based training program has broad importance. Here we present a computerized functional skills training program that was paired in half of the participants with a commercially available cognitive training (CCT) program.
Non-impaired older individuals (NC) aged 60+ (n=45) and similarly aged individuals with mild cognitive impairment (MCI; n=50) were randomized to receive 12 weeks of twice-weekly computerized functional skills training (CFST) or 12 weeks of twice-weekly sessions split between CCT and CFST. Skills trained were use of an ATM; internet banking; ticket kiosk; telephone and internet prescription refill; medication management; and internet shopping. As with previous functional capacity assessments, we focus on completion time for each simulation.
51 participants completed the training program, either by mastering all 6 tasks (34) or completing 12 weeks of training. 44 more participants completed 4 or more training sessions so they were also analyzed for improvement up to their last training session. Completion time for all 6 tests significantly improved from the baseline assessment to the final training session in both groups of participants (all p&#60;0.001 with an average improvement in task completion time of 45%). Further, there was no differential improvement in MCI and NC in the 6 tests from baseline to end of training (all t&#60;1.66, all p&#62;0.12). Finally, combined CCT plus CFST did not differ from CSFT alone on any of the percent-change score measures (all t&#60;1.64, all p&#62;0.11).
Both NC and MCI groups evidenced substantial improvements in performance. CCT supplementation led to similar functional gains with half as many training sessions. The NC participants proceeded through the training fairly rapidly even without CCT supplementation; MCI participants required more training but learned equivalently. These findings suggest that even in cases with memory impairments, functional skills can be efficiently learned with training.

This training protocol uses computerized training to teach technology-related everyday functional skills. These skills include financial skills, travel and transit, as well as medication management.

Today, many functional skills are technology-based, so development of a technology-based training program has broad importance. Here we present a ...

The newborn rabbit is a useful animal model for various pathologies and procedures. Airway management of the rabbit is complex due to its anatomical characteristics, which is further complicated in the case of the newborn. Of the different methods of advanced airway management, endotracheal intubation is less aggressive than tracheostomy, and is more feasible than supraglottic management given the lack of supraglottic devices of such a small size. As direct glottis visualization is very difficult in animals this size, this blind intubation model is presented as an effective alternative, especially for experiments requiring prolonged anesthesia. Using this method, we performed blind intubations with a 90% success rate.

We describe a technique of endotracheal intubation in newborn rabbits after esophageal catheterization with a gastric tube.

The newborn rabbit is a useful animal model for various pathologies and procedures. Airway management of the rabbit is complex due to its anatomical ...

Real-Time Dynamic Navigation System for the Precise Quad-Zygomatic Implant Placement in a Patient with a Severely Atrophic Maxilla

Zygomatic implants (ZIs) are an ideal way to address cases of a severely atrophic edentulous maxilla and maxilla defects because they replace extensive bone augmentation and shorten the treatment cycle. However, there are risks associated with the placement of ZIs, such as penetration of the orbital cavity or infra-temporal fossa. Furthermore, the placement of multiple ZIs makes this surgery risky and more difficult to perform. Potential intraoperative complications are extremely dangerous and may cause irreparable losses. Here, we describe a practical, feasible, and reproducible protocol for a real-time surgical navigation system for precisely placing quad-zygomatic implants in the severely atrophic maxilla of patients with residual bone that does not meet the requirements of conventional implants. Hundreds of patients have received ZIs at our department based on this protocol. The clinical outcomes have been satisfactory, the intraoperative and postoperative complications have been low, and the accuracy indicated by infusion of the designed image and postoperative three-dimensional image has been high. This method should be utilized during the entire surgical procedure to ensure ZI placement safety.

Here, we present a protocol to achieve precise quad-zygomatic implant placement in patients with severely atrophic maxilla using a real-time dynamic navigation system.

Zygomatic implants (ZIs) are an ideal way to address cases of a severely atrophic edentulous maxilla and maxilla defects because they replace extensive ...

Dynamic Navigation in Endodontics: Guided Access Cavity Preparation by Means of a Miniaturized Navigation System

In the case of teeth with pulp canal calcification (PCC) and apical pathology or pulpitis, root canal treatment can be very challenging. PCC are common sequelae of dental trauma but can also occur with stimuli such as caries, bruxism, or after placing a restoration. In order to access the root canal as minimally invasive as possible in case of a necessary root canal treatment, dynamic navigation has recently been introduced in endodontics in addition to static navigation. The use of a dynamic navigation system (DNS) requires pre-operative cone-beam computed tomography (CBCT) imaging and a digital surface scan. If necessary, reference markers must be placed on the teeth before the CBCT scan; with some systems, these can also be planned and created digitally afterward. By means of a stereo camera connected to the planning software, the drill can now be coordinated with the help of reference markers and virtual planning. As a result, the position of the drill can be displayed on the monitor in real-time during preparation in different planes. In addition, the spatial displacement, the angular deviation, and the depth position are also displayed separately. The few commercially available DNS mostly consist of relatively large camera-marker-systems. Here, the DNS contains miniaturized components: a low-weight camera (97 g) mounted on the micromotor of the electric handpiece utilizing a manufacturer-specific connecting mechanism and a small marker (10 mm x 15 mm), which can be easily attached to an individually manufactured intraoral tray. For research purposes, a post-operative CBCT scan can be matched with the pre-operative one, and the volume of tooth structure removed can be calculated by the software. This work aims to present the technique of guided access cavity preparation by means of a miniaturized navigation system from imaging to clinical implementation.

Dynamic navigation systems (DNS) provide real-time visualization and guidance to the operator during endodontic access cavities preparation. The planning of the procedure requires three-dimensional imaging utilizing cone beam computed tomography and surface scans. After the export of the planning data to the DNS, access cavities can be prepared with minimal invasion.

In the case of teeth with pulp canal calcification (PCC) and apical pathology or pulpitis, root canal treatment can be very challenging. PCC are common ...