**Landscape Sciences**

The eighth and final chapter takes us into the built environment and the concern with spatial variation in the landscape. Mapping of the engineered, or "built" landscape, is another important component of the ability to map and understand the spatial patterns of the human environment and their implications for humans' interactions with nature. "High-resolution Object-based Building Extraction Using PCA of LiDAR nDSM and Aerial Photos" by Alfred Cal presents a methodology by which LiDAR nDSM and aerial photos can be analyzed with principal components analysis (PCA) to generate a highly successful and highly accurate extraction of building footprints. The author demonstrates the manipulations that are needed to map human structures in a regional rural to semi-rural landscape in Belize. He demonstrates an approach that improves our capacity to assess the spatial variability of land cover and land uses in our natural environments.

It is our hope that these chapters provide interesting reading for students who are compelled by questions of spatial variability (or Geography) in the realms of diverse environments of our planet.

> **John P. Tiefenbacher** Texas State University, USA

**Davod Poreh** University of Naples Federico II, Italy

**IV**

not only for human health and welfare, but also for the security and safety of the ecological systems upon which we depend. Sulfur and nitrogen are two components of the atmospheric pollution regime that can have both human and ecological effects that are often determined by the molecular forms they take, but are also a function of concentrations, timing, and spatial distributions that effect exposure to harmful (if not toxic) levels of contamination. The authors study the phenomenon of deposition of these elements in the city of León, Mexico. They describe the methods used to compile and analyze data from regional monitoring networks and samplers. The implications of these contaminants for local and regional flora and ecosystem health is discussed. They demonstrate an approach to discerning the spatial variability of

Change in the environment poses certain hazards in certain places. The capacity to quickly and accurate assess the results of an extreme natural event is an ever-present desire. The coastal zone is one of the most dynamic environments on Earth as it is in constant flux due to the interactions between the land, the atmosphere, and the ocean. Evaluation of the impacts of storms on barrier islands presents certain challenges, but our fourth chapter, "Monitoring Storm Impacts on Sandy Coastlines with UAVs" by Alex Smith, Brianna Lunardi, Elizabeth George, and Chris Houser presents an effort to use unmanned aerial vehicles to do just that, with speed and precision as its goal. The authors describe the methods, challenges, and limitations of their new approach in the context of Prince Edward Island, Canada. Their study reveals the effectiveness of linear, aerial, and volumetric monitoring of the spatial changes of dunes after a storm using drone technology. They demonstrate an approach to

discerning the spatial variability of coastal geomorphological processes.

of the spatial variability of coastal geomorphology.

**Biological Sciences**

Similarly focused on the spatial variability of coastal geomorphology, our fifth chapter "Recent Advances in Coastal Survey Techniques: From GNSS to LiDAR and Digital Photogrammetry: Examples on the Northern Coast of France" examines the effectiveness of the technologies used to gather spatial data. Olivier Cohen and Arnaud Héquette discuss the benefits and limitations of several sensor technologies to gather land surface measurements from which digital terrain models (DTMs) can be derived. The authors employ these methods in case studies along France's northern coast. They demonstrate the implications of the selection of technologies on analysis

The sixth chapter of this volume is by João Carvalho, Manuela Magalhães, and Selma Pena and covers the analysis of forest ecology for landscape planning. In "Spatial and Temporal Variability Regarding Forest – From Tree to the Landscape," the authors discuss the ramifications of scale on the assessment of the integrity, biodiversity, and viability of forests in Portugal. An important lesson described in this chapter is that spatial variability varies with spatial scale. Or to put it differently, one could possibly not see the forest for the trees and that attention to scale is vitally important to assessment. Such mindfulness to spatial scale should guide the selection of the metrics (biodiversity, forest fire risk, disturbance, fragmentation, etc.) by which the conditions of a forest are judged. Interventions in using forested lands must focus on clearly stated management goals and those goals need to vary with spatial scale and

pollution in the lower atmosphere.

**Geological Sciences**

Section 1

Meteorological Sciences

**1**

Section 1


**Author details**

Articular cartilage damage is a persistent and increasing problem as the ageing population expands and treatments to achieve biological repair have been challenging [176]. Cartilage tissue engineering has been around for over 20 years. However, none of the approaches available so far have been able to achieve the consistency, effectiveness and reliability that are required for clinical applications. Tissue engineering of a mechanically resilient cartilage construct that meets the structural and functional criteria for effective functional integration into a defect site in the host is a difficult endeavour [177]. One of the fundamental weaknesses of all the models available to date is that none of them possess the normal zonal organization of chondrocytes that is seen *in vivo* (i.e. superficial, middle, deep and calcified zones) and the local composition of extracellular matrix in each zone. This structural organisation is a prerequisite for normal cartilage function and the success of any future clinical applications. The currently available 3-D models produce fairly homogeneous populations of cells without the ability to achieve any zonal organization *in vitro* [176]. The ability to produce a construct that recapitulates the zonal and structural architecture of the original tissue is currently lacking. Even the mechanically stable scaffolds that have been created so far do not allow regeneration of a sufficiently large mass of structurally and functionally competent cartilage construct especially if they were constructed and seeded with 2-D passaged (monolayer) chondrocytes in combination with a biomimetic carrier or scaffold [177]. This is one reason why future studies must begin with 3-D cultured chondrocytes maintained in a physiologically relevant microenvironment that replicates the ionic, osmotic and biomechanical milieu of cartilage. The 3-D and microenvironmental impact on cell phenotype is a significant factor creating cartilage

In summary, it may be difficult to imagine research being done without animal models but it is worth pointing out that *in vitro* models of joint and musculoskeletal tissues have been around for several decades and new researchers are increasingly adopting them for work on muscu‐ loskeletal diseases. Therefore, it is our optimistic view that in future many animal models could potentially be replaced with biomimetic and animal sparing alternatives in a variety of research

A. Mobasheri acknowledges the financial support of The Wellcome Trust, the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (grant number: Mobasheri.A.28102007), the Biotechnology and Biological Sciences Research Council (BBSRC) (grants BBSRC/S/M/2006/ 13141 and BB/G018030/1), the Engineering and Physical Sciences Research Council (EPSRC), Arthritis Research UK (ARUK) and the European Commission Framework 7 (EU FP7). M. Lewis acknowledges the financial support of the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the Engineering and Physical Sciences Research Council (EPSRC), Arthritis Research UK (ARUK), The Wellcome Trust, the National Centre for Sport and Exercise Medicine

constructs within biomimetic scaffold constructs [177].

disciplines and applications.

526 Regenerative Medicine and Tissue Engineering

**Acknowledgements**

(NCSEM).

Ali Mobasheri1 and Mark Lewis2

1 Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskele‐ tal Ageing Research, The University of Nottingham, Musculoskeletal Research Group, Divi‐ sion of Veterinary Medicine, School of Veterinary Medicine and Science, Faculty of Medicine and Health Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bo‐ nington, Leicestershire, UK

2 Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Musculoskeletal Biolo‐ gy Research Group, School of Sport, Exercise and Health Sciences, Loughborough Universi‐ ty, Loughborough, Leicestershire, UK


*Edited by Muhammad Salik Javaid and Shaukat Ali Khan*

The rock matrix and the fluids contained therein define the aquifer as a whole, the custodian of continuity of life on this planet Earth. Its sustainable development, equitable utilization, quality maintenance, and balanced discharge and recharge are the essential elements to ensure that the next generation receives the resource baton passed on by the current generation. Spanning across the political and regional frontiers, transboundary aquifers have the potential to provide a uniting platform to the participatory nations. The common good of water can be enhanced by synergized research, data and knowledge sharing, joint development ventures, and hazard mitigation.

Covering the multifarious facets of aquifers, this book will form an essential and interesting reading for all stakeholders—researchers, engineers, academia, intelligentsia, and the common consumer.

Published in London, UK © 2018 IntechOpen © Scott Rodgerson / unsplash

Aquifers - Matrix and Fluids

Aquifers

Matrix and Fluids

*Edited by Muhammad Salik Javaid*

*and Shaukat Ali Khan*


**5. Conclusion**

Soybean curd residue which is the residue of *Tofu* production was used for nutrients for production of a lipopeptide antibiotic, iturin A in solid state fermentation(SSF) using *Bacillus subtilis*. As the main carbon sources of soybean curd residue were insoluble fiber, we expected that *B. subtilis* produced the soybean curd residue-degrading enzymes. Among insoluble fibers in soybean curd residue, hemicellulose was mainly degraded by *B. subtilis* during SSF. Xylan, a major hemicellulose in plant cell wall was degraded by *B. subtilis*, and two enzymes which showed xylanase activity were purified and identified as endo-1,4-βxylanase and α-amylase. As productivity of iturin A in soybean curd residue was almost equivalent to that in glucose medium, this study gave a possible way to use soybean curd residue in higher and economical production of lipopeptides.


*3.1. Aim 1: Feasibility and Floor Effects*

Feasibility and floor effect indices for raw scores, percentile ranks, and/or standard scores (as appropriate) of the NEPSY-II Theory of Mind, NEPSY-II Affect Recognition, and SRS-2 are presented in Table 1. Two of the three measures evaluated in this study met the a priori criterion for feasibility: the NEPSY-II Theory of Mind (86.3–87.7%) and the SRS-2 (87.7%). NEPSY-II Affect Recognition fell below acceptable criterion for feasibility (71.2%) and therefore was investigated for Aim 3 as part of the post hoc analysis for low feasibility measures. Reasons for missing the NEPSY-II Affect Recognition subtest included not understanding the task (17.8%), behavioral noncompliance (3.4%), and verbal refusal (0.7%). A small portion of participants only completed the subtest at one time point (6.9%). Additionally, 15.4% of participants who completed the measure were described as exhibiting "acquiescence", defined as selecting responses without considering each response option. Floor effects followed the same pattern for the NEPSY-II raw scores and SRS-2 T-scores, with acceptable levels of floor effects for the NEPSY-II Theory of Mind (15.1–19.2%) and the SRS-2 (12.3%), and unacceptable levels for the NEPSY-II Affect Recognition (28.8%). Floor effects for percentile rank on the NEPSY-II Theory of Mind and standard scores on the NEPSY-II

Affect Recognition were both below a priori criteria. Specifically, of the participants who could complete the measures, 95% had the lowest percentile rank (<2%) on the NEPSY-II Theory of Mind Verbal, 97% had the lowest percentile rank (<2%) on the NEPSY-II Theory of Mind Total, and 39% had the lowest standard score (1) on the NEPSY-II Affect Recognition. Table 1 presents floor effects that include those with the lowest score on each measure and those who were unable to complete the task.

**Table 1.** Social cognition performance and feasibility at Time 1, *n* = 73.

a *n* at floor includes children who got the lowest score on the measure and those who could not complete the task; b Some descriptive statistics not reported for percentile ranks; c NEPSY-II Theory of Mind Total score percentile rank is not normed for 6-year-olds (*n* = 3); ToM = Theory of Mind; AR = Affect Recognition; SRS-2 = Social Responsiveness Scale, Second Edition; RRBI = Restricted, Repetitive Behaviors and Interests.


**Part 1**

**Tinnitus and Hearing Loss**

*Brasil*

**Tinnitus and Hearing Loss**

*University of Brasilia Medical School,*

*Brasilia -Distrito Federal,*

Fayez Bahmad Jr, Carlos Augusto C.P. Oliveira and Lisiane Holdefer

Tinnitus is a symptom present in approximately 15% of the world, and this proportion increases to 33% in individuals over 60 years Jastreboff and Hanzel, 1993). It carries a

May be associated with more than 300 diseases (Ganança et al, 1994), with a hearing loss of the most common (Hiller and Goebel, 2006). Only 80-10% of patients with tinnitus have normal hearing (Barnea et al, 1990), while 85 to 96% have some degree of hearing loss

The influence of hearing loss in the degree of suffering of tinnitus remains no consensus (Baskell and Coles, 1999). Findings relate tinnitus severity to hearing loss at high frequencies (Weisz et al, 2004). Mazurek et al (2010) found a significant correlation between the degree of hearing loss and tinnitus loudness. They found that patients with decompensated chronic tinnitus had more hearing loss than those with compensated tinnitus. The study concluded had evidence that indirectly support the hypothesis that the degree of hearing loss affects

Clinically significant hearing loss in patients with tinnitus was associated with anxiety and depression as a reaction to hearing loss that could interfere with the impact of tinnitus (McKinney et al, 1999). However it is not possible to say whether the hearing loss is only one cause of tinnitus or whether it also influences the severity and handicap (Davis, 1996). Searches related to gender discomfort is inconclusive. While Davis (1983) observed higher scores for discomfort due to tinnitus in women compared with men (Davis and Cole, 1983 and Coelho et al, 2004), and Hiller and Goebel (2006) a higher intensity and severity of tinnitus annoyance in older men. Méric et al (1998) and Pinto et al (2010) assessed the impact of tinnitus on quality of life and found no correlation between age, sex or duration of

The subjectivity of tinnitus, its symptoms, the different characteristics of each patient and the many causes of tinnitus are issues that require investigation. It is known that hearing loss is one of the largest generators of tinnitus and its pathology and diagnostics must be studied and known to offer the patient the 'most successful treatment option in symptom remission. It is well established that after lesions of the peripheral auditory receptor, the cochlea, increased spontaneous activity (hyperactivity) develops in central auditory nuclei. This plasticity has been demonstrated in a wide range of animal models, using either mechanically, acoustically, or drug-induced cochlear lesions (Brozoski et al., 2007; Bauer et

**1. Introduction**

negative impact on quality of life for 20% of them.

(Fowler, 1994; Sanchez e Ferrari, 2002).

the severity of tinnitus (Mazurek et al, 2010).

tinnitus and the annoyance it causes.


**Author details**

**Figure 4.** The pathways of apoptosis. Interference with any of these steps may prevent the apoptosis cascade.

also from ischemia if the optic disc does not receive enough oxygen even without AION. This damage is added to the damage caused by the mechanical effect of optic disc compression.

Patients with glaucoma suffer loss of axons of the ganglion cells as they pass the optic disc. Two theories explain the axonal loss. The first one is mechanical. According to this theory, the force caused by the IOP impedes axonal transport (flow) (micro-strangulation) and this may trigger axonal apoptosis [7]. The second theory is vascular. This means that the IOP impedes vascular supply to the optic disc. This causes a relative ischemia to the optic disc and triggers apoptosis. It is probable that both mechanisms coexist and the mechanical force may have a greater influence. Nonetheless, apoptosis, and not degeneration/necrosis, is the mechanism of axonal death in glaucoma. Apoptosis is programmed cell death, while necrosis is a different process involving extracellular components of inflammation. It consists of several pathways initiated be certain extracellular ligands such as programmed death ligand 1 (PD-L1), Fas ligand (FasL), tumor necrosis factor (TNF), nerve growth factor (NGF), growth factors, and others (**Figure 4**) [8, 9]. These molecules attach to receptors on the cell wall such as tropomyosin kinase receptor (TRK), tyrosine kinase receptor (RTK), receptor of apoptosis signal factor (Fas), and tissue necrosis factor receptor (TNFR) that trigger intracellular cascades that involve multiple pathways and molecules including the caspase cascade. These processes

**8.5. Continuation of the neuronal apoptosis**

30 Causes and Coping with Visual Impairment and Blindness

Shimon Rumelt\* and Schachar Schreiber

\*Address all correspondence to<EMAIL_ADDRESS>
Department of Ophthalmology, Galilee Medical Center, Nahariya and Faculty of Medicine, Bar Ilan University, Zefat, Israel

### **References**

[1] World Health Organization. Visual Impairment and Blindness. Fact Sheet No. 282. August 2014

**Chapter 3**

**Provisional chapter**

**Visual Loss in Neuro-Ophthalmology**

**Visual Loss in Neuro-Ophthalmology**

DOI: 10.5772/intechopen.80682

Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells lead to characteristic features of optic neuropathy. The main symptom is loss of vision (visual acuity and visual field damages), with colors appearing subtly washed out in the affected eye. The diagnosis is made on clinical examination. The history often points to the possible etiology of the optic neuropathy. In most of the cases, one eye is affected but it could be both. A rapid onset is typical of demyelinating, inflammatory, ischemic, and traumatic causes. A gradual course points to compressive, toxic/nutritional, and hereditary causes. The classic clinical signs of optic neuropathy are visual acuity and field defects, dyschromatopsia, and abnormal pupillary response. There are ancillary investigations that can support the diagnosis of optic neuropathy. Visual field testing, neuroimaging of the brain and orbit are essential in many optic neuropathies including demyelinating and compressive. In the last decade, increase of use new technology for optic neuropathies evaluation including multifocal visual evoked potentials and optic coherence tomography. Long standing of optic neuropathy is described by pale optic disk or optic atrophy, which means damage and death of these nerve cells or neurons. **Keywords:** optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy (NAION), arteritic anterior ischemic optic neuropathy (AION), traumatic

Accurate medical history is very important information, helping to evaluate the etiology of visual loss. Rapid onset is characteristic of optic neuritis, ischemic optic neuropathy, inflammatory (non-demyelinating), and traumatic optic neuropathy. On the other hand, gradual onset over months or even years is typical of compressive toxic/nutritional optic neuropathy. A history over years is seen in compressive and hereditary optic neuropathies. The

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80682

Eitan Z. Rath

Eitan Z. Rath

**Abstract**

optic neuropathy

**1. Introduction**

#### **Visual Loss in Neuro-Ophthalmology Visual Loss in Neuro-Ophthalmology**

#### Eitan Z. Rath Eitan Z. Rath

**References**

August 2014

1999;**10**:474-482

2007;**35**:495-516

2000;**69**:217-245

2014;**23**:282-287

[1] World Health Organization. Visual Impairment and Blindness. Fact Sheet No. 282.

[2] Jorje J, Ramoa-Marques R, Lourenço S, et al. IOP variations in the sitting and supine

[3] Yoon D-Y. Effects of head elevation on intraocular pressure in healthy subjects: Raising

[4] Roy Chowdhury U, Fautch MP. Intracranial pressure and its relationship to glaucoma: Current understanding and future directions. Medical Hypothesis, Discovery and

[5] Berdahl JP, Allingham RR. Intracranial pressure and glaucoma. Current Opinion in

[6] Hayreh SS. Role of nocturnal arterial hypotension in the development of ocular manifestations of systemic arterial hypertension. Current Opinion in Ophthalmology.

[7] Quigly HA. Ganglion cell death in glaucoma: Pathology recapitulates ontogeny.

[8] Elmore S. Apoptosis: A Review of programmed cell death. Toxicologic Pathology.

[9] Strasser A, O'connor L, Dixit VM. Apoptosis signaling. Annual Review of Biochemistry.

[10] Lazzaro EC, Mallick A, Singh M, et al. The effect of positional changes on intraocular pressure during sleep in patients with and without glaucoma. Journal of Glaucoma.

Australian and New Zealand Journal of Ophthalmology. 1995;**23**:85-91

positions. Journal of Glaucoma. 2010;**19**:609-612

Innovation in Ophthalmology. 2015;**4**:71-78

Ophthalmology. 2010;**21**:106-111

32 Causes and Coping with Visual Impairment and Blindness

bed head vs. using multiple pillows. Eye. 2014;**28**:1328-1333

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80682

#### **Abstract**

Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells lead to characteristic features of optic neuropathy. The main symptom is loss of vision (visual acuity and visual field damages), with colors appearing subtly washed out in the affected eye. The diagnosis is made on clinical examination. The history often points to the possible etiology of the optic neuropathy. In most of the cases, one eye is affected but it could be both. A rapid onset is typical of demyelinating, inflammatory, ischemic, and traumatic causes. A gradual course points to compressive, toxic/nutritional, and hereditary causes. The classic clinical signs of optic neuropathy are visual acuity and field defects, dyschromatopsia, and abnormal pupillary response. There are ancillary investigations that can support the diagnosis of optic neuropathy. Visual field testing, neuroimaging of the brain and orbit are essential in many optic neuropathies including demyelinating and compressive. In the last decade, increase of use new technology for optic neuropathies evaluation including multifocal visual evoked potentials and optic coherence tomography. Long standing of optic neuropathy is described by pale optic disk or optic atrophy, which means damage and death of these nerve cells or neurons.

DOI: 10.5772/intechopen.80682

**Keywords:** optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy (NAION), arteritic anterior ischemic optic neuropathy (AION), traumatic optic neuropathy

### **1. Introduction**

Accurate medical history is very important information, helping to evaluate the etiology of visual loss. Rapid onset is characteristic of optic neuritis, ischemic optic neuropathy, inflammatory (non-demyelinating), and traumatic optic neuropathy. On the other hand, gradual onset over months or even years is typical of compressive toxic/nutritional optic neuropathy. A history over years is seen in compressive and hereditary optic neuropathies. The

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ophthalmologist or neurologist can make the differential diagnosis according the symptoms, the age of onset, and the gender. Young age group (15–45 years) for optic neuritis women gender and pain on eye movement are more typical for optic neuritis versus. Elderly patients (older than 50 years), painless loss of vision without gender predisposition are typical for ischemic optic neuropathy. Additionally, in a young patient, history of neurological symptoms such as parenthesis, limb weakness, and ataxia is suggestive of demyelinating optic neuritis.

frequent in Caucasians, no gender predisposition, and mean age at onset in most studies is from 57 to 65 years. No clinically effective treatment exists because little is known about its pathophysiology, and there are only few histopathological studies of the acute condition.

Visual Loss in Neuro-Ophthalmology http://dx.doi.org/10.5772/intechopen.80682 35

NAION [1, 2] typically presents suddenly upon awakening the painless patient notes seeing poorly in one eye. Vision in that eye is obscured by a dark shadow, often involving just the upper or lower half of vision. On examination, the patient is found with visual acuity reduction from 20/25 down to hand movement only, relative afferent pupillary defect (RAPD), swollen disk (segmental or diffuse) with splinter hemorrhages (see **Figure 1**), absent of large cup, and contralateral disk is small and crowded in 20–40% of the patents [4]. In approximately 6 months following the infarct visual acuity improves by 3 or more lines of vision on the Snellen chart in 42.7% of patients. In addition, vision had worsened by 3 lines or more in 12.4% of patients; some clinicians use the term "progressive ischemic optic neuropathy". Second eye involvement occurs in approximately 20% of patients with NAION within 5 years. Furthermore, most cases of NAION involve the loss of an altitudinal hemifield (**Figure 2**) (either the upper or mostly lower half of the visual field, but not both), and visual acuity

**Figure 2** shows a few cases of NAION, which involve almost total loss of vision. The mechanism of injury for NAION is used to be controversial. Experts have come to a consensus that most cases involve two main risk factors. The first is a predisposition in the form of a type of optic disk shape named crowded disk [4, 5] or "disk at risk," where the cup/disk ratio is low (0.0–0.1), and secondly, cardiovascular risk factors as diabetes mellitus, hypertension, hypercholesterolemia, and coagulation deficits. Laboratory examinations at the presentation to differentiate between NAION and AAION include (erythrocyte sedimentation rate [ESR] that should be less than 40 mm/h) and C-reactive protein (CRP). It is advised to draw complete blood count and serum chemistry especially glucose, serum cholesterol and triglycerides, coagulophatic state, antitrombin III antiphospholipid antibody, and serum fibrinogen. Analysis of brain MRI suggests an increasing number of ischemic white matter lesions.

remains almost normal or slightly reduced.

**Figure 1.** Disk appearance in nonarteritic ischemic optic neuropathy.

In an elderly patient (more than 60 years mostly 70–80 years) with signs of severe optic neuropathy and the presence of preceding transient visual loss, temporal pain, jaw claudication, fatigue, fever, anemia, weight loss and myalgia, an arteritic ischemic optic neuropathy (AION) due to giant cell arteritis (GCA) should be suspected.

In children, a history of recent flu-like illness or vaccination days or weeks before vision loss points to a para-infectious or postvaccinia optic neuritis, respectively.

Transient visual obscurations, transient diplopia, and headache should raise the suspicion of increased intra-cranial pressure.

The use of any medications should be carefully noted, since some are either directly or indirectly toxic to the optic nerve. These include drugs as ethambutol, methanol, isoniazid, tobacco alcohol, and more. History of diabetes mellitus, systemic hypertension, hypercholesterolemia, coagulation deficit, and smoking is more common in patients with nonarteritic ischemic optic neuropathy (NAION). Patients who have history of malignancy may have infiltrative or para-neoplastic optic neuropathy. It is important to inquire into the patient's general health, eating, and social habits (drinking and smoking) in suspected nutritional optic neuropathy (complex B–vitamins). In addition, a detailed family history is inquired in diagnosing hereditary autosomal and mitochondrial optic neuropathies.

This chapter addresses the major diseases neuropathies accompanied by rapid visual loss: nonarteritic and arteritic optic neuropathy, traumatic optic neuropathy, and optic neuritis.


2. Trends in the labor income share and basic drivers of the change

As summarized by Brada [2] and Young and Tackett [3], we find that labor income shares of world economies have shown a downward trend since the 1980s (especially since the 1990s), and this decline trend is shared by developed and developing countries equally. This chapter focuses on the period from 1995 to 2011 for which related data are available. The ratio of labor income share in 2011 to that in 1995 for developed countries (32 OECD countries) is 0.956 on average, and 0.932 for 23 developing countries (data source is Penn World Table Ver.9.0).

Theoretically, the key parameters that influence the factor shares of income are the elasticity of substitution between capital and labor, the accumulation of production factors, and labor- and capital-augmenting technology or directed technological changes [4]. If capital and labor are gross complements, as most empirical evidence suggests, and if the directed technological changes are not taken into account, then the labor income share increases as long as a relative cost of capital to labor decreases, as would be the case in many economies. However, this is not reality. The evolution of income shares thus depends especially on the above two factors: factor-augmenting technological changes and the rate of capital deepening. According to Alvarez-Cuadrado et al. [5], the basic theoretical overview is as follows.

Assuming that the elasticity of substitution within each sector is constant, the output for sector i is produced using the production function

globalization (the expansion of international trade and capital flows), technological change, capital deepening (the amount of real capital present in relation to labor increases), product and labor market institutions, and the bargaining power of labor, among others. This chapter focuses on the global value chains (GVCs) as an important determinant of changes in the labor income share and indicates the mechanism responsible for the share decline under GVCs, which has never been documented in prior studies. We analyze the mechanism by measuring

The important point is that the amount of services input for nonservices production increases in developing countries where the nonservices production has started to be conducted by multinational enterprises (MNEs) from developed countries in GVCs. As a result, the services sector in developing countries actively accumulates capital to supply quality services to the nonservices sector effectively while the nonservices sector also promotes capital accumulation under severe international competition. The consequent macro-based capital deepening decreases labor income share in developing countries. In developed countries, on the other hand, many tasks of the nonservices sector with low elasticity of substitution between capital and labor are offshored to developing countries and the remaining nonservices sectors with relatively high elasticity of substitution accumulate capital at a rapid pace in an environment of

This mechanism of worldwide labor share changes can be analyzed by utilizing the data of sectoral labor income shares of developing and developed countries. Preceding studies have rarely used this kind of comprehensive dataset and rarely discussed intersectoral linkages between services and nonservices sectors as important determinants of the changes in macro-

As summarized by Brada [2] and Young and Tackett [3], we find that labor income shares of world economies have shown a downward trend since the 1980s (especially since the 1990s), and this decline trend is shared by developed and developing countries equally. This chapter focuses on the period from 1995 to 2011 for which related data are available. The ratio of labor income share in 2011 to that in 1995 for developed countries (32 OECD countries) is 0.956 on average, and 0.932 for 23 developing countries (data source is Penn World Table Ver.9.0).

Theoretically, the key parameters that influence the factor shares of income are the elasticity of substitution between capital and labor, the accumulation of production factors, and labor- and capital-augmenting technology or directed technological changes [4]. If capital and labor are gross complements, as most empirical evidence suggests, and if the directed technological changes are not taken into account, then the labor income share increases as long as a relative cost of capital to labor decreases, as would be the case in many economies. However, this is not reality. The evolution of income shares thus depends especially on the above two factors: factor-augmenting technological changes and the rate of capital deepening. According to

Alvarez-Cuadrado et al. [5], the basic theoretical overview is as follows.

2. Trends in the labor income share and basic drivers of the change

the labor income share at the sectoral level in developing and developed countries.

low local relative cost of capital.

24 Globalization

economic labor income shares in developing countries.

$$Y\_{it} = \left[ \alpha\_i (B\_{it} K\_{it})^{\frac{\sigma\_i - 1}{\sigma\_i}} + (1 - \alpha\_i) (A\_{it} L\_{it})^{\frac{\sigma\_i - 1}{\sigma\_i}} \right]^{\frac{\sigma\_i}{\sigma\_i - 1}} \tag{1}$$

where αi governs the relative importance of the two inputs, Kit and Lit are capital and labor used in sector i at time t, and σi is the elasticity of substitution between these two inputs. Ait and Bit are the levels of labor- and capital-augmenting productivity, respectively. With this production function, the ratio of the factor income shares in sector i is given by

$$\frac{KIS\_{it}}{LIS\_{it}} = \frac{\alpha\_i}{1 - \alpha\_i} \left( \frac{B\_{it}}{A\_{it}} \frac{K\_{it}}{L\_{it}} \right)^{\frac{\sigma\_i - 1}{\sigma\_i}} \tag{2}$$

if the factor markets are competitive and firms choose inputs optimally. Here, KISit and LISit represent the capital and labor income shares, respectively, in sector i at time t.

The bias of technical change is given by g Bð Þ it=Ait , where gðÞ denotes a growth rate. If the bias is positive (negative), technical change is labor-biased (capital-biased) in the sense that it increases (decreases) the marginal product of labor (W) relative to that of capital (R) as indicated from Eq. (3).

$$\frac{R}{W} = \frac{\alpha\_i}{1 - \alpha\_i} \left(\frac{K\_{it}}{L\_{it}}\right)^{-\frac{1}{\sigma\_i}} \left(\frac{B\_{it}}{A\_{it}}\right)^{\frac{\sigma\_i - 1}{\sigma\_i}} \tag{3}$$

The expression of Eq. (2) is potentially consistent with observed trends: if capital and labor are gross complements, that is, σi < 1 as most empirical evidence suggests, then the labor income share in sector i decreases as long as technical change in that sector is sufficiently capital-biased relative to the rate of capital accumulation, that is, g Bð Þ it=Ait < 0 < g Kð Þ it=Lit and the absolute value of g Bð Þ it=Ait is larger than that of g Kð Þ it=Lit .

As Acemoglu [4] has noted, from about the 1980s, when the labor share started a decline, the capital-augmenting technical change has dominated the labor-augmenting technical change. Using this theory and empirical evidence, one could predict that the high growth rate of capital accumulation coupled with capital-augmenting technical improvement may contribute to a downward trend of the worldwide labor income share.

Economic global integration, in terms of trade, finance, and international fragmentation of production, is widely viewed as a significant determinant of the evolution of labor shares. How is this global integration related to the abovementioned theoretical framework of the labor income share?

The Heckscher-Ohlin model predicts that trade integration will lead labor-abundant developing economies to specialize in the production of labor-intensive goods, leading to a rise in the labor income share in developing countries and a decrease of the share in developed countries. This model is at odds with the decline in labor shares of developing economies.

Financial integration, on the other hand, may play a major role in the evolution of the labor income share. Dao et al. [6] describe two distinct channels through which labor income share declines. First, capital mobility lowers labor's bargaining power. This is because globalization has made capital much more mobile internationally, while labor remains trapped behind national borders. The greater international mobility of capital has reduced the bargaining power of workers and increased that of the owners of capital. Second, financial integration lowers the cost of capital in capital-scarce countries, facilitating capital deepening and inducing greater substitution of capital for labor.

The economic globalization-based explanation for falling labor shares in developing countries thus rests on the relative size of the impact that trade and capital flows have on labor shares because increases in trade between developed and developing countries would increase labor income shares in the developing countries.

Financial integration includes two important capital flows: portfolio investment and foreign direct investment (FDI). Between them, FDI is closely related to the GVCs organized by MNEs that have been actively investing in developing countries through international fragmentation of production since the 1990s. The relation between labor income shares and international fragmentation of production through GVCs is discussed in detail in the next section.

To assess the contribution of these globalization factors to the evolutions of labor income shares, we present some stylized evidence of the relation between them (Figures 1–3). In the following analyses, the growth rates of two different variables are compared in each figure because the main objective of this study is to identify the cause of labor income share changes. Moreover, variables used in this study, such as economic globalization, labor income share, capital deepening, and intersectoral production linkages, show that most variations are seen not over time but across countries and industries (fixed effects attributable to countries and

industries). Thus, it is reasonable to compare growth rates of these variables to detect causal

Figure 3. Changes in the external assets and liabilities GDP ratio (x-axis) and changes in labor income share (y-axis) for

Figure 2. Changes in import GDP ratio (x-axis) and changes in labor income share (y-axis) for developed and developing

The Declining Labor Income Shares Revisited: Intersectoral Production Linkage in Global Value Chains

http://dx.doi.org/10.5772/intechopen.81316

27

Figure 1 illustrates the relation between changes in export GDP ratios (horizontal axis, gross rate between 1995 and 2011) and changes in labor income share (vertical axis, gross rate between 1995 and 2011) for 55 countries. These 55 countries include 32 developed and 23 developing countries. We can find significant negative relation between the two variables in

relationships. The available data cover the years 1995–2011.

developed and developing countries.

countries.

Figure 1. Changes in export GDP ratio (x-axis) and changes in labor income share (y-axis) for developed and developing countries.

The Declining Labor Income Shares Revisited: Intersectoral Production Linkage in Global Value Chains http://dx.doi.org/10.5772/intechopen.81316 27

Financial integration, on the other hand, may play a major role in the evolution of the labor income share. Dao et al. [6] describe two distinct channels through which labor income share declines. First, capital mobility lowers labor's bargaining power. This is because globalization has made capital much more mobile internationally, while labor remains trapped behind national borders. The greater international mobility of capital has reduced the bargaining power of workers and increased that of the owners of capital. Second, financial integration lowers the cost of capital in capital-scarce countries, facilitating capital deepening and induc-

The economic globalization-based explanation for falling labor shares in developing countries thus rests on the relative size of the impact that trade and capital flows have on labor shares because increases in trade between developed and developing countries would increase labor

Financial integration includes two important capital flows: portfolio investment and foreign direct investment (FDI). Between them, FDI is closely related to the GVCs organized by MNEs that have been actively investing in developing countries through international fragmentation of production since the 1990s. The relation between labor income shares and international

To assess the contribution of these globalization factors to the evolutions of labor income shares, we present some stylized evidence of the relation between them (Figures 1–3). In the following analyses, the growth rates of two different variables are compared in each figure because the main objective of this study is to identify the cause of labor income share changes. Moreover, variables used in this study, such as economic globalization, labor income share, capital deepening, and intersectoral production linkages, show that most variations are seen not over time but across countries and industries (fixed effects attributable to countries and

Figure 1. Changes in export GDP ratio (x-axis) and changes in labor income share (y-axis) for developed and developing

fragmentation of production through GVCs is discussed in detail in the next section.

ing greater substitution of capital for labor.

26 Globalization

income shares in the developing countries.

countries.

Figure 2. Changes in import GDP ratio (x-axis) and changes in labor income share (y-axis) for developed and developing countries.

Figure 3. Changes in the external assets and liabilities GDP ratio (x-axis) and changes in labor income share (y-axis) for developed and developing countries.

industries). Thus, it is reasonable to compare growth rates of these variables to detect causal relationships. The available data cover the years 1995–2011.

Figure 1 illustrates the relation between changes in export GDP ratios (horizontal axis, gross rate between 1995 and 2011) and changes in labor income share (vertical axis, gross rate between 1995 and 2011) for 55 countries. These 55 countries include 32 developed and 23 developing countries. We can find significant negative relation between the two variables in developed countries; however, we cannot find any relation in the case of developing countries. The same conclusion is obtained in Figure 2, which compares the import GDP ratio and labor income share changes.

Figure 3 indicates the relation between the external assets and liabilities GDP ratio (financial globalization index) and labor income share in the same manner as in Figures 1 and 2 (data source is [7]). In this case, we cannot find any significant relationship. These three figures are a very simple analysis that just compare one economic globalization-related variable and labor income share. One reason to take such a simple method is that it is difficult to consider these variables as distinct drivers of labor shares. In reality, the effects of these three factors on labor shares cannot be fully isolated. More elaborate studies should be conducted in the future. At this moment, it can be concluded that trade and financial integrations as economic globalization factors do not affect labor income share evolution with the exception of trade (export and import) in developed countries. The negative relation between changes in trade GDP ratios and those in labor income shares is consistent with the prediction of Heckscher-Ohlin model as mentioned earlier in this section.


**9. References**

72 Materials Science and Technology

minimum weight. The number of leaves is reduced one by one, without changing any of the dimensions, and found out results for same full bump load. The results are shown in Table 10. From the FEM results in Table 10, it is understood that the leaf spring with 3 leaves violates the constraints of deection and stress. Therefore, further optimization is terminated at this point. It is evident that only 4 leaves (2 full length leaves and 2 graduated leaves) are sufcient to withstand the applied load. The composite leaf spring with 4 leaves

175

To provide ride comfort to passenger, leaf spring has to be designed in such a way that its natural frequency is maintained to avoid resonant condition with respect to road frequency. The road irregularities usually have the maximum frequency of 12 Hz(Yu&Kim,1988). Therefore, leaf spring should be designed to have a natural frequency, which is away from 12 Hz to avoid the resonance. Stiffness is more and weight is lower of CLS than that of SLS. Therefore, first natural frequency of CLS (14.3 Hz) will be higher (126.98%) than that of SLS (6.3 Hz). First natural frequency of CLS is nearly 1.2 times the maximum road frequency and therefore resonance will not occur, and it provides improved ride comfort. After optimization, CLS has a fundamental natural frequency of 41.5 Hz, which is 3.46 times the maximum road frequency, which ensures that resonance

Design and experimental analysis of composite multi leaf spring using glass bre reinforced polymer are carried out. Compared to steel spring, the composite leaf spring is found to have 67.35% lesser stress, 64.95% higher stiffness and 126.98% higher natural frequency than that of existing steel leaf spring. The conventional multi leaf spring weighs about 13.5 kg whereas the E-glass/Epoxy multi leaf spring weighs only 4.3 kg. Thus the weight reduction of 68.15% is achieved. Besides the reduction of weight, the performance of the leaf spring is also increased. Compared to the steel leaf spring (13.5 kg), the optimised composite leaf spring weighs nearly 76.4% less than the steel spring. Ride comfort and life of CLS are also more when compared to SLS. Therefore, it is concluded that composite multi leaf spring is an effective replacement for the existing steel leaf

6 97 324 5 104 409 4 150 607 3 308 1079

ANSYS Allowable ANSYS Allowable

217

**Maximum direct stress along the length of leaf spring (MPa)**

610

weighs about 3.18 kg only. It gives a weight reduction of 76.4%.

**No.of Leaves Maximum Deflection (mm)**

Table 10. Results of optimization of number of leaves.

7 61

**6. Ride comfort**

will not occur.

**7. Conclusion**

spring in light passenger vehicles.

ANSYS 7.1. Manual, (1997). Ansys Inc, New York

**1. Introduction**

Beyond the assembling of components laser welding procedures are also increasingly applied in steel manufacturing. Reasons for this trend are: high joining velocities, concentrated heat input resulting in extremely thin heating zones, and nearly constant seam geometries along the welding line. So, for example, welding aggregates are installed at the beginning of electrolytic or hot-galvanizing manufacturing lines to join coils of different thickness or grade for continuous production, cf. Figure 1. To minimize shutdowns welding must be extremely reliable, since the joining zone of the 'endless strip' has to resist high thermal and mechanical loads, such subsequent annealing, bending and tension. Failures lead to technical breakdowns, repairs, and loss of production, which should be avoided as much as possible. Moreover, the welding process must be such robust that material with imperfections, such as oxidations or materials ripples, would be also accurately joined. Welding defects, for instances cracks, pores or seam shrinkages, cf. Figure 2, lead to reduction of the cross-sectional area and, therefore, represent critical regions w. r. t. damage and failure. From the engineering point-of-view it is essential to know, whether residual stresses or heat-induced degradations of the materials strength following from joining become critical or not. This question can be answered by e.g. extensive experimental investigations, during which material combinations, geometries (i.e., thickness) and welding parameters such as joining velocity, welding power or laser caustic are varied. Subsequent tensile tests of the different seams yield the critical

**Modeling, Simulation and Experimental**

**of As-Rolled Steels**

*3Department Research and Development,*

*Thyssen Krupp Steel Europe AG, Duisburg \*Formerly with ThyssenKrupp Steel Europe AG*

**Hydrogen Diffusion During Laser Welding**

*1Freudenberg-Schwab Vibration Control GmbH & Co. KG, Velten b Berlin*

*2Strip Processing Lines Division, SMS Siemag AG, Hilden*

**Studies of Distortions, Residual Stresses and**

T. Böhme1,\*, C. Dornscheidt2,\*, T. Pretorius3, J. Scharlack3 and F. Spelleken3

**5**

*Germany*

strength, which is compared with the loading conditions of the production line.

However, such experiments are time-consuming and, therefore, expensive. Moreover, the derived predictions only hold for the used materials, geometries and investigated process parameters; extrapolations of the results beyond these conditions are not possible. Consequently, it is desirable to have a general framework, which allows for the prediction of the thermal and mechanical material response following from an arbitrary choice of


**2.2 Construction of the VZV BAC (VZVBAC)**

Generally, BAC vectors can be directly inserted into viral genomes via homologous recombination. However, this method cannot be used to construct the VZVBAC because the virus' highly cell-associated nature makes isolation of the VZV genome and purification of recombinant plaques difficult (Nagaike et al., 2004). Instead, VZVBAC clones are constructed using a set of four overlapping cosmids spanning the entire VZV genome (Fig. 2).

Fig. 2. Schematic diagram the VZV genome and four-cosmid system. The VZV clinical strain, p-Oka, consists of a 125-kb genome with unique long (UL) and unique short (US) segments. Four cosmids with overlapping VZV genomic segments are shown. The BAC vector-containing plasmid, pUSF-6, was inserted between ORF60-61.

First, the pUSF-6 vector was inserted into VZV cosmid pvSpe23, between ORF60 and ORF61 (Fig. 2), via homologous recombination (Yu et al., 2000). The BAC-containing cosmid was then co-transfected with three complementary cosmids (Niizuma et al., 2003) into human melanoma (MeWo) cells. Because each of the four cosmids contains an overlapping sequence, the cosmids can recombine into one large circular virus genome via homologous recombination to create the recombinant virus. Our use of the GFP selectable marker in the pUSF-6 vector allowed for visualization of the recombinant VZVBAC in plaques that form post-transfection (Fig. 3C). Finally, the VZVBAC DNA from the infected cells was purified and transformed into *E. coli*. Chloramphenicol-resistant colonies were selected for and used to isolate the desired VZVBAC DNA (Zhang et al., 2007).

We used restriction enzyme digestion and DNA sequencing to verify the integrity and stability of the VZVBAC DNA. VZVBAC DNA was digested by HindIII, yielding the predicted digestion pattern with a sum of ~130 kb (Fig. 3G), thus indicating that no large deletions and rearrangements were present. In addition, the ORF62/71 gene was sequenced to check for base-pair changes in the VZVBAC genome after synthesis in *E. coli*. This large duplicated gene, encoding an immediate-early transactivating protein (Perera et al, 1992), was amplified via PCR and cloned into a pGEM-T vector for sequencing. Because the ORF62/71 sequences in the VZVBAC were identical to those of the published p-Oka strain, we can conclude that the BAC DNA in *E. coli* is stable.

Fig. 3. Construction of VZV BAC. (A) The BAC-containing cosmid was co-transfected with the three complementary cosmids into MeWo cells. (B) Homologous recombination between cosmids formed a circular, full-length VZVBAC genome. (C) The recombinant BAC was replicated, and produced a plaque visualized with the GFP marker. (D) Circular DNA was isolated from infected cells, (E) transformed into *E. coli*, and selected for cmR colonies. (F) The VZVBAC DNA was isolated from *E. coli* and (G) verified by restriction digestion and partial sequencing. (H) The infectivity and integrity of the VZVBAC were tested by transfecting BAC DNA into MeWo cells to generate the VZV virus.

The GFP marker in the viral genome was also tested; MeWo cells were infected with VZVBAC and continuously passed four times (1:10 dilution) over two weeks. On examination of the plaques under a fluorescent microscope, all VZVBAC-infected cells fluoresced green,

then co-transfected with three complementary cosmids (Niizuma et al., 2003) into human melanoma (MeWo) cells. Because each of the four cosmids contains an overlapping sequence, the cosmids can recombine into one large circular virus genome via homologous recombination to create the recombinant virus. Our use of the GFP selectable marker in the pUSF-6 vector allowed for visualization of the recombinant VZVBAC in plaques that form post-transfection (Fig. 3C). Finally, the VZVBAC DNA from the infected cells was purified and transformed into *E. coli*. Chloramphenicol-resistant colonies were selected for and used

We used restriction enzyme digestion and DNA sequencing to verify the integrity and stability of the VZVBAC DNA. VZVBAC DNA was digested by HindIII, yielding the predicted digestion pattern with a sum of ~130 kb (Fig. 3G), thus indicating that no large deletions and rearrangements were present. In addition, the ORF62/71 gene was sequenced to check for base-pair changes in the VZVBAC genome after synthesis in *E. coli*. This large duplicated gene, encoding an immediate-early transactivating protein (Perera et al, 1992), was amplified via PCR and cloned into a pGEM-T vector for sequencing. Because the ORF62/71 sequences in the VZVBAC were identical to those of the published p-Oka strain, we can

Fig. 3. Construction of VZV BAC. (A) The BAC-containing cosmid was co-transfected with the three complementary cosmids into MeWo cells. (B) Homologous recombination between cosmids formed a circular, full-length VZVBAC genome. (C) The recombinant BAC was replicated, and produced a plaque visualized with the GFP marker. (D) Circular DNA was isolated from infected cells, (E) transformed into *E. coli*, and selected for cmR colonies. (F) The VZVBAC DNA was isolated from *E. coli* and (G) verified by restriction digestion and partial sequencing. (H) The infectivity and integrity of the VZVBAC were tested by

The GFP marker in the viral genome was also tested; MeWo cells were infected with VZVBAC and continuously passed four times (1:10 dilution) over two weeks. On examination of the plaques under a fluorescent microscope, all VZVBAC-infected cells fluoresced green,

transfecting BAC DNA into MeWo cells to generate the VZV virus.

to isolate the desired VZVBAC DNA (Zhang et al., 2007).

conclude that the BAC DNA in *E. coli* is stable.

signifying the stability of the GFP marker in the viral genome. Lastly, the infectivity and integrity of the VZVBAC were confirmed by transfecting BAC DNA into MeWo cells to produce the virus. A summary of the process to construct a VZV BAC and verify its integrity is illustrated in Fig. 3.


*2.3.1 Compressive strength test*

Cube specimens were subjected to compressive axial load applied at the rate of 1.2 N/mm2 to 2.4 N/mm2 in accordance with IS code 5816:1999 [12] (**Figure 4**). The load was applied in such a way that the fracture plane crosses the trowel surface.


*2.2.7 HCPs may not value or use the data collected by patients in apps whose provenance and pedigree is not known or established*

It is important that HCPs understand how the app was designed, who was involved in the design and what evidence was used to guide its development. More importantly, this information will be more credible and trustworthy if they hear it from their peers and key opinion leaders they look to for knowledge about new products in their field. If HCPs are convinced about the benefits of the app for themselves and their patients, based on reports from opinion leaders who have already tested the app in their own practices, the more likely it is that they will be the ones to recommend it to patients in the first place, obviating this barrier.