A journey access tool to facilitate mobility-related access for people with disabilities in low and middle income countries

People with disabilities (PWD) experience difficulties in accessing the transport system (including both infrastructure and services) to meet their needs for health care, employment and other activities. Our research shows that lack of access to the journeys needed for these purposes is a more significant barrier in low and middle income countries than in high income countries, and results in inadequate health care, rehabilitation and access to education and employment. At the same time, the existing transport system in low and middle income countries presents much higher road crash risks than in high income countries. By combining the principles and methods of Road Safety Audit and disability access, and adapting these Western approaches to a low/middle income country context, we have worked with Handicap International Cambodia to develop a Journey Access Tool (JAT) for use by disabled peoples’ organisations (DPOs), people with a disability and other key stakeholders. A key element of the approach is that it involves the participation of PWD on the journeys that they need to take, and it identifies infrastructure and service improvements that should be prioritised in order to facilitate access to these journeys. The JAT has been piloted in Cambodia with a range of PWD. This presentation will outline the design of the JAT and the results of the pilot studies. The information gained thus far strongly suggests that the JAT is a valuable and cost-effective approach that can be used by DPOs and professionals to identify barriers to access and prioritise the steps needed to address them.

Molecular Genetics of Age-related Macular Degeneration

Age-related macular degeneration (AMD; OMIM # 603075) is an eye disease of the elderly, signs of which appear after the age of 50. In the Western world it is a leading cause of permanent visual loss with a prevalence of 8.5% in persons under 54 years of age and of 37% in persons over 75 years of age. Early forms of AMD may be asymptomatic, but in the late forms usually a central scotoma in the visual field follows severely complicating daily tasks. Smoking, age, and genetic predisposition are known risk factors for AMD. Until recently no true susceptibility genes had been identified though the composition of drusen deposits, the hallmarks of AMD, has suggested that the complement system might play a role in the pathogenesis of AMD. When four groups reported in March 2005, that, on chromosome 1q32, a Y402H variant in the complement factor H (CFH) gene confers risk for AMD in independent Caucasian samples, a new period in the field of genetic research of AMD started. CFH is a key regulator of the complement system. Thus, it is logical to speculate, that it plays a role in the pathogenesis of AMD. We performed a case-control association study to analyse whether the CFH Y402H variant contain a risk for AMD in the Finnish population. Although the population of Finland represents a genetic isolate, the CFH Y402H polymorphism was associated with AMD also in our patient sample with similar risk allele frequencies as in the other Caucasian populations. We further evaluated the effects of this variant, but no association between lesion subtype (predominantly classic, minimally classic or occult lesion) or lesion size of neovascular AMD and the CFH Y402H variant was detected. Neither did the variant have an effect on the photodynamic therapy (PDT) outcome. The patients that respond to PDT carried the risk genotype as frequently as those who did not respond, and no difference was found in the number of PDT sessions needed in patients with or without the risk genotypes of CFH Y402H. Functional analyses, however, showed that the binding of C-reactive protein (CRP) to CFH was significantly reduced in patients with the risk genotype of Y402H. In the past two years, the LOC387715/ high-temperature requirement factor A1 (HTRA1) locus on 10q26 has also been repeatedly associated with AMD in several populations. The recent discovery of the LOC387715 protein on the mitochondrial outer membrane suggests that the LOC387715 gene, not HTRA1, is the true predisposing gene in this region, although its biological function is still unknown. In our Finnish patient material, patients with AMD carried the A69S risk genotype of LOC387715 more frequently than the controls. Also, for the first time, an interaction between the CFH Y402H and the LOC387715 A69S variants was found. The most recently detected susceptibilty gene of AMD, the complement component 3 (C3) gene, encodes the central component of the complement system, C3. In our Finnish sample, an additive gene effect for the C3 locus was detected, though weaker than the effects for the two main loci, CFH and LOC387715. Instead, the hemicentin-1 or the elongation of very long chain fatty acids-like 4 genes that have also been suggested as candidate genes for AMD did not carry a risk for AMD in the Finnish population. This was the first series of molecular genetic study of AMD in Finland. We showed that two common risk variants, CFH Y402H and LOC387715 A69S, represent a high risk of AMD also in the isolated Finnish population, and furthermore, that they had a statistical interaction. It was demonstrated that the CFH Y402H risk genotype affects the binding of CFH to CRP thus suggesting that complement indeed plays an important role in the pathogenesis of AMD.

Vertigo in children

Vertigo in children is more common than previously thought. However, only a small fraction of affected children meet a physician. The reason for this may be the benign course of vertigo in children. Most childhood vertigo is self-limiting, and the provoking factor can often be identified. The differential diagnostic process in children with vertigo is extensive and quite challenging even for otologists and child neurologists, who are the key persons involved in treating vertiginous children. The cause of vertigo can vary from orthostatic hypotension to a brain tumor, and thus, a structured approach is essential in avoiding unnecessary examinations and achieving a diagnosis. Common forms of vertigo in children are otitis media-related dizziness, benign paroxysmal vertigo of childhood, migraine-associated dizziness, and vestibular neuronitis. Orthostatic hypotension, which is not a true vertigo, is the predominant type of dizziness in children. Vertigo is often divided according to origin into peripheral and central types. An otologist is familiar with peripheral causes, while a neurologist treats central causes. Close cooperation between different specialists is essential. Sometimes consultation with a psy-chiatrist or an ophthalmologist can lead to the correct diagnosis. The purpose of this study was to evaluate the prevalence and clinical characteristics of vertigo in children. We prospectively collected general population-based data from three schools and one child wel-fare clinic located close to Helsinki University Central Hospital (HUCH). A simple questionnaire with mostly closed questions was given to 300 consecutive children visiting the welfare clinic. At the schools, entire classes that fit the desired age groups received the questionnaire. Of the 1050 children who received the questionnaire, 938 (473 girls, 465 boys) returned it, the response rate thus being 89% (I). In Study II, we evaluated the 24 vertiginous children (15 girls, 9 boys) with true vertigo and 12 healthy age- and gender-matched controls. A detailed medical history was obtained using a structured approach, and an otoneurologic examination, including audiogram, electronystagmography, and tympanometry, was performed at the HUCH ear, nose, and throat clinic for cooperative subjects. In Study III, we reviewed and evaluated the medical records of 119 children (63 girls, 56 boys) aged 0-17 years who had visited the ear, nose, and throat clinic with a primary complaint of vertigo in 2000-2004. We also wanted information about indications for imaging of the head in vertiginous children. To this end, we reviewed the medical records of 978 children who had undergone imaging of the head for various indications. Of these, 87 children aged 0-16 years were imaged because of vertigo. Subjects of interest were the 23 vertiginous children with an acute deviant finding in magnetic resonance images or com-puterized tomography (IV). Our results indicate that vertigo and other balance problems in children are quite common. Of the HUCH area population, 8% of the children had sometimes experienced vertigo, dizziness, or balance problems. Of these 23% had vertigo sufficiently severe to stop their activity (I). The structured data collection approach eased the evaluation of vertiginous children. More headaches and head traumas were observed in vertiginous children than in healthy controls (II). The most common diagnoses of ear, nose, and throat clinic patients within the five-year period were benign paroxysmal vertigo of child-hood, migraine-associated dizziness, vestibular neuronitis, and otitis media-related vertigo. Valuable diagnostic tools in the diagnostic process were patient history and otoneurologic examinations, includ-ing audiogram, electronystagmography, and tympanometry (III). If the vertiginous child had neurologi-cal deficits, persistent headache, or preceding head trauma, imaging of the head was indicated (IV).

Identification methods of key contributing factors in crashes with high numbers of fatalities and injuries in China

Objectives In China, “serious road traffic crashes” (SRTCs) are those in which there are 10-30 fatalities, 50-100 serious injuries or a total cost of 50-100 million RMB ($US8-16m), and “particularly serious road traffic crashes” (PSRTCs) are those which are more severe or costly. Due to the large number of fatalities and injuries as well as the negative public reaction they elicit, SRTCs and PSRTCs have become great concerns to China during recent years. The aim of this study is to identify the main factors contributing to these road traffic crashes and to propose preventive measures to reduce their number. Methods 49 contributing factors of the SRTCs and PSRTCs that occurred from 2007 to 2013 were collected from the database “In-depth Investigation and Analysis System for Major Road traffic crashes” (IIASMRTC) and were analyzed through the integrated use of principal component analysis and hierarchical clustering to determine the primary and secondary groups of contributing factors. Results Speeding and overloading of passengers were the primary contributing factors, featuring in up to 66.3% and 32.6% of accidents respectively. Two secondary contributing factors were road-related: lack of or nonstandard roadside safety infrastructure, and slippery roads due to rain, snow or ice. Conclusions The current approach to SRTCs and PSRTCs is focused on the attribution of responsibility and the enforcement of regulations considered relevant to particular SRTCs and PSRTCs. It would be more effective to investigate contributing factors and characteristics of SRTCs and PSRTCs as a whole, to provide adequate information for safety interventions in regions where SRTCs and PSRTCs are more common. In addition to mandating of a driver training program and publicisation of the hazards associated with traffic violations, implementation of speed cameras, speed signs, markings and vehicle-mounted GPS are suggested to reduce speeding of passenger vehicles, while increasing regular checks by traffic police and passenger station staff, and improving transportation management to increase income of contractors and drivers are feasible measures to prevent overloading of people. Other promising measures include regular inspection of roadside safety infrastructure, and improving skid resistance on dangerous road sections in mountainous areas.

Health-Related Quality of Life and Mental Disorders in Finland

Quality of life (QoL) and Health-related quality of life (HRQoL) are becoming one of the key outcomes of health care due to increased respect for the subjective valuations and well-being of patients and an increasing part of the ageing population living with chronic, non-fatal conditions. Preference-based HRQoL measures enable estimation of health utility, which can be useful for rational rationing, evidence-based medicine and health policy. This study aimed to compare the individual severity and public health burden of major chronic conditions in Finland, including and focusing on reliably diagnosed psychiatric conditions. The study is based on the Health 2000 survey, a representative general population survey of 8028 Finns aged 30 and over. Depressive, anxiety and alcohol use disorders were diagnosed with the Composite International Diagnostic Interview (M-CIDI). HRQoL was measured with the 15D and the EQ-5D, with 83% response rate. This study found that people with psychiatric disorders had the lowest 15D HRQoL scores at all ages, in comparison to other main groups of chronic conditions. Considering 29 individual conditions, three of the four most severe (on 15D) were psychiatric disorders; the most severe was Parkinson s disease. Of the psychiatric disorders, chronic conditions that have sometimes been considered relatively mild - dysthymia, agoraphobia, generalized anxiety disorder and social phobia - were found to be the most severe. This was explained both by the severity of the impact of these disorders on mental health domains of HRQoL, and also by the fact that decreases were widespread on most dimensions of HRQoL. Considering the public health burden of conditions, musculoskeletal disorders were associated with the largest burden, followed by psychiatric disorders. Psychiatric disorders were associated with the largest burden at younger ages. Of individual conditions, the largest burden found was for depressive disorders, followed by urinary incontinence and arthrosis of the hip and knee. The public health burden increased greatly with age, so the ageing of the Finnish population will mean that the disease burden caused by chronic conditions will increase by a quarter up to year 2040, if morbidity patterns do not change. Investigating alcohol consumption and HRQoL revealed that although abstainers had poorer HRQoL than moderate drinkers, this was mainly due to many abstainers being former drinkers and having the poorest HRQoL. Moderate drinkers did not have significantly better HRQoL than abstainers who were not former drinkers. Psychiatric disorders are associated with a large part of the non-fatal disease burden in Finland. In particular anxiety disorders appear to be more severe and have a larger public health burden than previously thought.

Gene expression profiling during Forskolin induced differentiation of BeWo cells by differential display RT-PCR

The differentiation of cytotrophoblasts into syncytiotrophoblasts in the placenta has been employed as a model to investigate stage specific expression as well as regulation of genes during this process. While the cytotrophoblasts are highly invasive and proliferative with relatively less capacity to synthesize pregnancy related proteins, the multinucleated syncytiotrophoblasts are non-proliferative and non-invasive. However, syncytiotrophoblasts are the site of synthesis of a variety of protein, peptide and steroid hormones as well as several growth factors. Both the freshly isolated cytotrophoblasts from human placenta as well as the BeWo cell, a choriocarcinoma cell line model which retain several characteristic of cytotrophoblasts has been employed by us to study regulation of differentiation. In the present study, we have employed the differential display RT-PCR analysis (DD-RT-PCR) to evaluate gene expression changes during Forskolin induced in vitro differentiation of BeWo cells. We have identified several genes which are differentially expressed during differentiation and the differential expression of 10 transcripts was confirmed by Northern blot analysis. Based on the identity of the transcripts an attempt has been made to relate the known function of the gene products, to changes observed during differentiation. Of the several transcripts, one of the transcripts, namely Secretory Leukocyte Protease Inhibitor (SLPI) which is known to have multiple functions was found to increase 15-fold in the syntiotrophoblast.

The effects of the 2004 reduction in the price of alcohol on alcohol-related harm in Finland : A natural experiment based on register data

Changes in alcohol pricing have been documented as inversely associated with changes in consumption and alcohol-related problems. Evidence of the association between price changes and health problems is nevertheless patchy and is based to a large extent on cross-sectional state-level data, or time series of such cross-sectional analyses. Natural experimental studies have been called for. There was a substantial reduction in the price of alcohol in Finland in 2004 due to a reduction in alcohol taxes of one third, on average, and the abolition of duty-free allowances for travellers from the EU. These changes in the Finnish alcohol policy could be considered a natural experiment, which offered a good opportunity to study what happens with regard to alcohol-related problems when prices go down. The present study investigated the effects of this reduction in alcohol prices on (1) alcohol-related and all-cause mortality, and mortality due to cardiovascular diseases, (2) alcohol-related morbidity in terms of hospitalisation, (3) socioeconomic differentials in alcohol-related mortality, and (4) small-area differences in interpersonal violence in the Helsinki Metropolitan area. Differential trends in alcohol-related mortality prior to the price reduction were also analysed. A variety of population-based register data was used in the study. Time-series intervention analysis modelling was applied to monthly aggregations of deaths and hospitalisation for the period 1996-2006. These and other mortality analyses were carried out for men and women aged 15 years and over. Socioeconomic differentials in alcohol-related mortality were assessed on a before/after basis, mortality being followed up in 2001-2003 (before the price reduction) and 2004-2005 (after). Alcohol-related mortality was defined in all the studies on mortality on the basis of information on both underlying and contributory causes of death. Hospitalisation related to alcohol meant that there was a reference to alcohol in the primary diagnosis. Data on interpersonal violence was gathered from 86 administrative small-areas in the Helsinki Metropolitan area and was also assessed on a before/after basis followed up in 2002-2003 and 2004-2005. The statistical methods employed to analyse these data sets included time-series analysis, and Poisson and linear regression. The results of the study indicate that alcohol-related deaths increased substantially among men aged 40-69 years and among women aged 50-69 after the price reduction when trends and seasonal variation were taken into account. The increase was mainly attributable to chronic causes, particularly liver diseases. Mortality due to cardiovascular diseases and all-cause mortality, on the other hand, decreased considerably among the-over-69-year-olds. The increase in alcohol-related mortality in absolute terms among the 30-59-year-olds was largest among the unemployed and early-age pensioners, and those with a low level of education, social class or income. The relative differences in change between the education and social class subgroups were small. The employed and those under the age of 35 did not suffer from increased alcohol-related mortality in the two years following the price reduction. The gap between the age and education groups, which was substantial in the 1980s, thus further broadened. With regard to alcohol-related hospitalisation, there was an increase in both chronic and acute causes among men under the age of 70, and among women in the 50-69-year age group when trends and seasonal variation were taken into account. Alcohol dependence and other alcohol-related mental and behavioural disorders were the largest category in both the total number of chronic hospitalisation and in the increase. There was no increase in the rate of interpersonal violence in the Helsinki Metropolitan area, and even a decrease in domestic violence. There was a significant relationship between the measures of social disadvantage on the area level and interpersonal violence, although the differences in the effects of the price reduction between the different areas were small. The findings of the present study suggest that that a reduction in alcohol prices may lead to a substantial increase in alcohol-related mortality and morbidity. However, large population group differences were observed regarding responsiveness to the price changes. In particular, the less privileged, such as the unemployed, were most sensitive. In contrast, at least in the Finnish context, the younger generations and the employed do not appear to be adversely affected, and those in the older age groups may even benefit from cheaper alcohol in terms of decreased rates of CVD mortality. The results also suggest that reductions in alcohol prices do not necessarily affect interpersonal violence. The population group differences in the effects of the price changes on alcohol-related harm should be acknowledged, and therefore the policy actions should focus on the population subgroups that are primarily responsive to the price reduction.

Transcriptome analysis and characterisation of gill-expressed carbonic anhydrase and other key osmoregulatory genes in freshwater crayfish Cherax quadricarinatus

The pH and salinity balance mechanisms of crayfish are controlled by a set of transport-related genes. We identified a set of the genes from the gill transcriptome from a freshwater crayfish Cherax quadricarinatus using the Illumina NGS-sequencing technology. We identified and characterized carbonic anhydrase (CA) genes and some other key genes involved in systematic acid-base balance and osmotic/ionic regulation. We also examined expression patterns of some of these genes across different sublethal pH levels [1]. A total of 72,382,710 paired-end Illumina reads were assembled into 36,128 contigs with an average length of 800 bp. About 37% of the contigs received significant BLAST hits and 22% were assigned gene ontology terms. These data will assist in further physiological-genomic studies in crayfish.

Essays on Managing Knowledge and Work Related Wellbeing

This study explores the relationship between Intellectual Capital and Maintenance of Work Ability. Intellectual Capital is the central framework for analysing the increasing knowledge-intensiveness of business life. It is characteristic of Intellectual Capital that the intersection of human capital, internal structures and external structures is essential. Maintenance of Work Ability, on the other hand, has been the leading paradigm for Finnish occupational health and safety activities since the late 1980s. It is also a holistic approach that emphasises the interdependence of competence, work community, work environment and health as the key to work-related wellbeing. This thesis consists of five essays that scrutinise the focal phenomena both theoretically and empirically. The conceptual model that results from the first research essay provides a general framework for the whole thesis. The case study in the second essay supports a division of intangible assets into generative and commercially exploitable intangibles introduced in the first essay and further into the primary and secondary dimension of generative intangibles. Further scrutiny of the interaction of generative intangible assets in essay three reveals that employees’ wellbeing enhances the readiness to contribute to the knowledge creation process. The fourth essay shows that the MWA framework could benefit knowledge-intensive work but this would require a different approach than has been commonly adopted in Finland. In essay five, deeper analysis of the MWA framework shows that its potential results from comprehensive support of the functioning of an organisation. The general conclusion of this thesis is that organisations must take care of their employees’ wellbeing in order to secure innovativeness that is the key to surviving in today’s competitive business environment.

Differential regulation of MRN (Mre11-Rad50-Nbs1) complex subunits and telomerase activity in cancer cells

Several lines of evidence suggest that cancer progression is associated with up-regulation or reactivation of telomerase and the underlying mechanism remains an active area of research. The heterotrimeric MRN complex, consisting of Mre11, Rad50 and Nbs1, which is required for the repair of double-strand breaks, plays a key role in telomere length maintenance. In this study, we show significant differences in the levels of expression of MRN complex subunits among various cancer cells and somatic cells. Notably, siRNA-mediated depletion of any of the subunits of MRN complex led to complete ablation of other subunits of the complex. Treatment of leukemia and prostate cancer cells with etoposide lead to increased expression of MRN complex subunits, with concomitant decrease in the levels of telomerase activity, compared to breast cancer cells. These studies raise the possibility of developing anti-cancer drugs targeting MRN complex subunits to sensitize a subset of cancer cells to radio- and/or chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.

Spectral Invariance of SG Pseudo-Differential Operators on L-P(R-n)

We prove the spectral invariance of SG pseudo-differential operators on L-P(R-n), 1 < p < infinity, by using the equivalence of ellipticity and Fredholmness of SG pseudo-differential operators on L-p(R-n), 1 < p < infinity. A key ingredient in the proof is the spectral invariance of SC pseudo-differential operators on L-2(R-n).

A differential-geometric analysis of singularities of point trajectories of serial and parallel manipulators

In this paper, we present a differential-geometric approach to analyze the singularities of task space point trajectories of two and three-degree-of-freedom serial and parallel manipulators. At non-singular configurations, the first-order, local properties are characterized by metric coefficients, and, geometrically, by the shape and size of a velocity ellipse or an ellipsoid. At singular configurations, the determinant of the matrix of metric coefficients is zero and the velocity ellipsoid degenerates to an ellipse, a line or a point, and the area or the volume of the velocity ellipse or ellipsoid becomes zero. The degeneracies of the velocity ellipsoid or ellipse gives a simple geometric picture of the possible task space velocities at a singular configuration. To study the second-order properties at a singularity, we use the derivatives of the metric coefficients and the rate of change of area or volume. The derivatives are shown to be related to the possible task space accelerations at a singular configuration. In the case of parallel manipulators, singularities may lead to either loss or gain of one or more degrees-of-freedom. For loss of one or more degrees-of-freedom, ther possible velocities and accelerations are again obtained from a modified metric and derivatives of the metric coefficients. In the case of a gain of one or more degrees-of-freedom, the possible task space velocities can be pictured as growth to lines, ellipses, and ellipsoids. The theoretical results are illustrated with the help of a general spatial 2R manipulator and a three-degree-of-freedom RPSSPR-SPR parallel manipulator.

Efficient Key Management and Distribution for MANET

Ad hoc networks are being used in applications ranging from disaster recovery to distributed collaborative entertainment applications. Ad hoc networks have become one of the most attractive solution for rapid deployment of interconnecting large number of mobile personal devices. The user community of mobile personal devices are demanding a variety of value added multimedia entertainment services. The popularity of peer group is increasing and one or some members of the peer group need to send data to some or all members of the peer group. The increasing demand for group oriented value added services is driving for efficient multicast service over ad hoc networks. Access control mechanisms need to be deployed to provide guarantee that the unauthorized users cannot access the multicast content. In this paper, we present a topology aware key management and distribution scheme for secure overlay multicast over MANET to address node mobility related issues for multicast key management. We use overlay approach for key distribution and our objective is to keep communication overhead low for key management and distribution. We also incorporate reliability using explicit acknowledgments with the key distribution scheme. Through simulations we show that the proposed key management scheme has low communication overhead for rekeying and improves the reliability of key distribution.

Mobile node authentication using key distribution scheme in wireless sensor networks

We consider the problem of secure communication in mobile Wireless Sensor Networks (WSNs). Achieving security in WSNs requires robust encryption and authentication standards among the sensor nodes. Severe resources constraints in typical Wireless Sensor nodes hinder them in achieving key agreements. It is proved from past studies that many notable key management schemes do not work well in sensor networks due to their limited capacities. The idea of key predistribution is not feasible considering the fact that the network could scale to millions. We prove a novel algorithm that provides robust and secure communication channel in WSNs. Our Double Encryption with Validation Time (DEV) using Key Management Protocol algorithm works on the basis of timed sessions within which a secure secret key remains valid. A mobile node is used to bootstrap and exchange secure keys among communicating pairs of nodes. Analysis and simulation results show that the performance of the DEV using Key Management Protocol Algorithm is better than the SEV scheme and other related work.

Differential Action of Glycoprotein Hormones: Significance in Cancer Progression

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.