Functional outcome and health-related quality of life after traumatic brain injury in the framework of the International Classification of Functioning, Disability and Health (ICF)

Traumatic brain injury (TBI) affects people of all ages and is a cause of long-term disability. In recent years, the epidemiological patterns of TBI have been changing. TBI is a heterogeneous disorder with different forms of presentation and highly individual outcome regarding functioning and health-related quality of life (HRQoL). The meaning of disability differs from person to person based on the individual s personality, value system, past experience, and the purpose he or she sees in life. Understanding of all these viewpoints is needed in comprehensive rehabilitation. This study examines the epidemiology of TBI in Finland as well as functioning and HRQoL after TBI, and compares the subjective and objective assessments of outcome. The frame of reference is the International Classification of Functioning, Disability and Health (ICF). The subjects of Study I represent the population of Finnish TBI patients who experienced their first TBI between 1991 and 2005. The 55 Finnish subjects of Studies II and IV participated in the first wave of the international Quality of life after brain injury (QOLIBRI) validation study. The 795 subjects from six language areas of Study III formed the second wave of the QOLIBRI validation study. The average annual incidence of Finnish hospitalised TBI patients during the years 1991-2005 was 101:100 000 in patients who had TBI as the primary diagnosis and did not have a previous TBI in their medical history. Males (59.2%) were at considerably higher risk of getting a TBI than females. The most common external cause of the injury was falls in all age groups. The number of TBI patients ≥ 70 years of age increased by 59.4% while the number of inhabitants older than 70 years increased by 30.3% in the population of Finland during the same time period. The functioning of a sample of 55 persons with TBI was assessed by extracting information from the patients medical documents using the ICF checklist. The most common problems were found in the ICF components of Body Functions (b) and Activities and Participation (d). HRQoL was assessed with the QOLIBRI which showed the highest level of satisfaction on the Emotions, Physical Problems and Daily Life and Autonomy scales. The highest scores were obtained by the youngest participants and participants living independently without the help of other people, and by people who were working. The relationship between the functional outcome and HRQoL was not straightforward. The procedure of linking the QOLIBRI and the GOSE to the ICF showed that these two outcome measures cover the relevant domains of TBI patients functioning. The QOLIBRI provides the patients subjective view, while the GOSE summarises the objective elements of functioning. Our study indicates that there are certain domains of functioning that are not traditionally sufficiently documented but are important for the HRQoL of persons with TBI. This was the finding especially in the domains of interpersonal relationships, social and leisure activities, self, and the environment. Rehabilitation aims to optimize functioning and to minimize the experience of disability among people with health conditions, and it needs to be based on a comprehensive understanding of human functioning. As an integrative model, the ICF may serve as a frame of reference in achieving such an understanding.

Social and material deprivation among youth in Finland : causes, consequences, and coping.

Background: Social and material deprivation is associated with poor health, decreased subjective well-being, and limited opportunities for personal development. To date, little is known about the lived experiences of Finnish low-income youths and the general purpose of this study is to fill this gap. Despite the extensive research on socioeconomic income disparities, only a few scholars have addressed the question of how low socioeconomic position is experienced by disadvantaged people themselves. Little is known about the everyday social processes that lead to decreased well-being of economically and socially disadvantaged citizens. Data: The study is based on the data of 65 autobiographical essays written by Finnish low-income youths aged 14-29 (M=23.51, SD=3.95). The research data were originally collected in a Finnish nationwide writing contest “Arkipäivän kokemuksia köyhyydestä” [Everyday Experiences of Poverty] between June and September of 2006. The contest was partaken by 850 Finnish writers. Methods and key concepts: Autobiographical narratives (N=65) of low-income youths were analyzed based on grounded theory methodology (GTM). The analysis was not built on specific pre-conceived categorizations; it was guided by the paradigm model and so-called “sensitizing concepts”. The concepts this study utilized were based on the research literature on socioeconomic inequalities, resilience, and coping. Socioeconomic inequalities refer to unequal distribution of resources, such as income, social status, and health, between social groups. The concept of resilience refers to an individual’s capacity to cope despite existing risk factors and conditions that are harmful to health and well-being. Coping strategies can be understood as ways by which a person tries to cope with psychological stress in a situation where internal or externals demands exceed one’s resources. The ways to cope are cognitive or behavioral efforts by which individual tries to relieve the stress and gain new resources. Lack of material and social resources is associated with increased exposure to health-related stressors during the life-course. Aims: The first aim of this study is to illustrate how youths with low socioeconomic status perceive the causes and consequences of their social and material deprivation. The second aim is to describe what kind of coping strategies youths employ to cope in their everyday life. The third aim is to build an integrative conceptual framework based on the relationships between causes, consequences, and individual coping strategies associated with deprivation. The analysis was carried out through systematic coding and orderly treatment of the data based on the grounded theory methodology. Results: Finnish low-income youths attributed the primary causes of deprivation to their family background, current socioeconomic status, sudden life changes, and contextual factors. Material and social deprivation was associated with various kinds of negative psychological, social, and material consequences. Youths used a variety of coping strategies that were identified as psychological, social, material, and functional-behavioral. Finally, a conceptual framework was formulated to link the findings together. In the discussion, the results were compared and contrasted to the existing research literature. The main references of the study were: Coping: Aldwin (2007); Lazarus & Folkman (1984); Hobfoll (1989, 2001, 2002). Deprivation: Larivaara, Isola, & Mikkonen (2007); Lister (2004); Townsend (1987); Raphael (2007). Health inequalities: Dahlgren & Whitehead (2007); Lynch. et al. (2000); Marmot & Wilkinson (2006); WHO (2008). Methods: Charmaz (2006); Flick (2009); Strauss & Corbin (1990). Resilience: Cutuli & Masten (2009); Luthar (2006).

Nitrogen and carbon flows through Belandur lake - Role of Bellandur lake as a natural wetland treating Bangalore wastewater

Much of the Bangalore sewage is treated in three streams namely Bellandur (K&C Valley),Vrishabhavati and Hebbal-Nagavara stream systems. Among these it is estimated that out of a total of about 500MLD of partially treated sewage is let into the Bellandur tank. We estimate that a total of about 77t N non-industrial anthropogenic nitrogen efflux (mainly urine and excreta) in Bangalore city. This is distributed between that handled by the three sewage streams, soak-pits and land deposition. About 17-24.5t N enters the Bellandur tank daily. This has been happening over few decades and our observations suggest that this approximately 380ha tank is functioning as a C and N removal system with reasonable efficiency. The ammoniacal and nitrate nitrogen content of the water at the discharge points were estimated and found that over 80% of the nitrogen influx and over 75% of the C influx is removed by this tank system. We observed that there are three nitrogen sinks namely bacterial, micro-algal and macrophytes. The micro-algal fraction is dominated by Microcystis and Euglenophyceae members and they appear to constitute a significant fraction. Water hyacinth represents the single largest representative of the macrophytes. This tank has been functioning in this manner for over three decades. We attempt to study this phenomenon from a material balance approach and show that it is functioning with a reasonable degree of satisfaction as a natural wetland. As the population served and concomitant influx into this wetland increases, there is a potential for the system to be overloaded and to collapse. Therefore a better understanding of its function and the need for maintenance is discussed in the paper.

Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy

Purpose: Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentation defects of the eye, skin, and hair. It is caused by mutations in one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3), SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10). Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. The purpose of this study was to identify the genetic causes of WS and DMD in an Indian family with two patients: one affected with WS and DMD, and another one affected with only WS. Methods: Blood samples were collected from individuals for genomic DNA isolation. To determine the linkage of this family to the eight known WS loci, microsatellite markers were selected from the candidate regions and used to genotype the family. Exon-specific intronic primers for EDN3 were used to amplify and sequence DNA samples from affected individuals to detect mutations. A mutation in DMD was identified by multiplex PCR and multiplex ligation-dependent probe amplification method using exon-specific probes. Results: Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. Haplotype analysis suggested linkage of the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense mutation p.T98M in EDN3. A deletion mutation was identified in DMD. Conclusions: This study reports a novel missense mutation in EDN3 and a deletion mutation in DMD in the same Indian family. The present study will be helpful in genetic diagnosis of this family and increases the mutation spectrum of EDN3.

Cannibalism can drive the evolution of behavioural phase polyphenism in locusts

During outbreaks, locust swarms can contain millions of insects travelling thousands of kilometers while devastating vegetation and crops. Such large-scale spatial organization is preceded locally by a dramatic density-dependent phenotypic transition in multiple traits. Behaviourally, low-density solitarious individuals avoid contact with one another; above a critical local density, they undergo a rapid behavioural transition to the gregarious phase whereby they exhibit mutual attraction. Although proximate causes of this phase polyphenism have been widely studied, the ultimate driving factors remain unclear. Using an individual-based evolutionary model, we reveal that cannibalism, a striking feature of locust ecology, could lead to the evolution of density-dependent behavioural phase-change in juvenile locusts. We show that this behavioural strategy minimizes risk associated with cannibalistic interactions and may account for the empirically observed persistence of locust groups during outbreaks. Our results provide a parsimonious explanation for the evolution of behavioural plasticity in locusts.

On the basin-scale detection and attribution of human-induced climate change in monsoon precipitation and streamflow

Detecting and quantifying the presence of human-induced climate change in regional hydrology is important for studying the impacts of such changes on the water resources systems as well as for reliable future projections and policy making for adaptation. In this article a formal fingerprint-based detection and attribution analysis has been attempted to study the changes in the observed monsoon precipitation and streamflow in the rain-fed Mahanadi River Basin in India, considering the variability across different climate models. This is achieved through the use of observations, several climate model runs, a principal component analysis and regression based statistical downscaling technique, and a Genetic Programming based rainfall-runoff model. It is found that the decreases in observed hydrological variables across the second half of the 20th century lie outside the range that is expected from natural internal variability of climate alone at 95% statistical confidence level, for most of the climate models considered. For several climate models, such changes are consistent with those expected from anthropogenic emissions of greenhouse gases. However, unequivocal attribution to human-induced climate change cannot be claimed across all the climate models and uncertainties in our detection procedure, arising out of various sources including the use of models, cannot be ruled out. Changes in solar irradiance and volcanic activities are considered as other plausible natural external causes of climate change. Time evolution of the anthropogenic climate change ``signal'' in the hydrological observations, above the natural internal climate variability ``noise'' shows that the detection of the signal is achieved earlier in streamflow as compared to precipitation for most of the climate models, suggesting larger impacts of human-induced climate change on streamflow than precipitation at the river basin scale.

Evaluation of polyvinylidene fluoride nasal sensor to assess deviated nasal septum in comparision with peak nasal inspiratory flow measurements

Background: Deviated nasal septum (DNS) is one of the major causes of nasal obstruction. Polyvinylidene fluoride (PVDF) nasal sensor is the new technique developed to assess the nasal obstruction caused by DNS. This study evaluates the PVDF nasal sensor measurements in comparison with PEAK nasal inspiratory flow (PNIF) measurements and visual analog scale (VAS) of nasal obstruction. Methods: Because of piezoelectric property, two PVDF nasal sensors provide output voltage signals corresponding to the right and left nostril when they are subjected to nasal airflow. The peak-to-peak amplitude of the voltage signal corresponding to nasal airflow was analyzed to assess the nasal obstruction. PVDF nasal sensor and PNIF were performed on 30 healthy subjects and 30 DNS patients. Receiver operating characteristic was used to analyze the DNS of these two methods. Results: Measurements of PVDF nasal sensor strongly correlated with findings of PNIF (r = 0.67; p < 0.01) in DNS patients. A significant difference (p < 0.001) was observed between PVDF nasal sensor measurements and PNIF measurements of the DNS and the control group. A cutoff between normal and pathological of 0.51 Vp-p for PVDF nasal sensor and 120 L/min for PNIF was calculated. No significant difference in terms of sensitivity of PVDF nasal sensor and PNIF (89.7% versus 82.6%) and specificity (80.5% versus 78.8%) was calculated. Conclusion: The result shows that PVDF measurements closely agree with PNIF findings. Developed PVDF nasal sensor is an objective method that is simple, inexpensive, fast, and portable for determining DNS in clinical practice.

Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a `footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by similar to 50% in generator potentials, to similar to 3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

Modeling non-stationarity in intensity, duration and frequency of extreme rainfall over India

Significant changes are reported in extreme rainfall characteristics over India in recent studies though there are disagreements on the spatial uniformity and causes of trends. Based on recent theoretical advancements in the Extreme Value Theory (EVT), we analyze changes in extreme rainfall characteristics over India using a high-resolution daily gridded (1 degrees latitude x 1 degrees longitude) dataset. Intensity, duration and frequency of excess rain over a high threshold in the summer monsoon season are modeled by non-stationary distributions whose parameters vary with physical covariates like the El-Nino Southern Oscillation index (ENSO-index) which is an indicator of large-scale natural variability, global average temperature which is an indicator of human-induced global warming and local mean temperatures which possibly indicate more localized changes. Each non-stationary model considers one physical covariate and the best chosen statistical model at each rainfall grid gives the most significant physical driver for each extreme rainfall characteristic at that grid. Intensity, duration and frequency of extreme rainfall exhibit non-stationarity due to different drivers and no spatially uniform pattern is observed in the changes in them across the country. At most of the locations, duration of extreme rainfall spells is found to be stationary, while non-stationary associations between intensity and frequency and local changes in temperature are detected at a large number of locations. This study presents the first application of nonstationary statistical modeling of intensity, duration and frequency of extreme rainfall over India. The developed models are further used for rainfall frequency analysis to show changes in the 100-year extreme rainfall event. Our findings indicate the varying nature of each extreme rainfall characteristic and their drivers and emphasize the necessity of a comprehensive framework to assess resulting risks of precipitation induced flooding. (C) 2014 Elsevier B.V. All rights reserved.

Raman Spectroscopic Studies on Screening of Myopathies

Myopathies are among the major causes of mortality in the world. There is no complete cure for this heterogeneous group of diseases, but a sensitive, specific, and fast diagnostic tool may improve therapy effectiveness. In this study, Raman spectroscopy is applied to discriminate between muscle mutants in Drosophila on the basis of associated changes at the molecular level. Raman spectra were collected from indirect flight muscles of mutants, upheld1 (up1), heldup(2) (hdp(2)), myosin heavy chain7 (Mhc7), actin88F(KM88) (Act88F(KM88)), upheld101 (up101), and Canton-S (CS) control group, for both 2 and 12 days old flies. Difference spectra (mutant minus control) of all the mutants showed an increase in nucleic acid and beta-sheet and/or random coil protein content along with a decrease in a-helix protein. Interestingly, the 12th day samples of up1 and Act88F(KM88) showed significantly higher levels of glycogen and carotenoids than CS. A principal components based linear discriminant analysis classification model was developed based on multidimensional Raman spectra, which classified the mutants according to their pathophysiology and yielded an overall accuracy of 97% and 93% for 2 and 12 days old flies, respectively. The up1 and Act88F(KM88) (nemaline-myopathy) mutants form a group that is clearly separated in a linear discriminant plane from up101 and hdp2 (cardiomyopathy) mutants. Notably, Raman spectra from a human sample with nemaline-myopathy formed a cluster with the corresponding Drosophila mutant (up1). In conclusion, this is the first demonstration in which myopathies, despite their heterogeneity, were screened on the basis of biochemical differences using Raman spectroscopy.

Regional hydrological impacts of climate change: implications for water management in India

Climate change is most likely to introduce an additional stress to already stressed water systems in developing countries. Climate change is inherently linked with the hydrological cycle and is expected to cause significant alterations in regional water resources systems necessitating measures for adaptation and mitigation. Increasing temperatures, for example, are likely to change precipitation patterns resulting in alterations of regional water availability, evapotranspirative water demand of crops and vegetation, extremes of floods and droughts, and water quality. A comprehensive assessment of regional hydrological impacts of climate change is thus necessary. Global climate model simulations provide future projections of the climate system taking into consideration changes in external forcings, such as atmospheric carbon-dioxide and aerosols, especially those resulting from anthropogenic emissions. However, such simulations are typically run at a coarse scale, and are not equipped to reproduce regional hydrological processes. This paper summarizes recent research on the assessment of climate change impacts on regional hydrology, addressing the scale and physical processes mismatch issues. Particular attention is given to changes in water availability, irrigation demands and water quality. This paper also includes description of the methodologies developed to address uncertainties in the projections resulting from incomplete knowledge about future evolution of the human-induced emissions and from using multiple climate models. Approaches for investigating possible causes of historically observed changes in regional hydrological variables are also discussed. Illustrations of all the above-mentioned methods are provided for Indian regions with a view to specifically aiding water management in India.

Mycobacterium tuberculosis RecG Protein but Not RuvAB or RecA Protein Is Efficient at Remodeling the Stalled Replication Forks IMPLICATIONS FOR MULTIPLE MECHANISMS OF REPLICATION RESTART IN MYCOBACTERIA

Aberrant DNA replication, defects in the protection, and restart of stalled replication forks are major causes of genome instability in all organisms. Replication fork reversal is emerging as an evolutionarily conserved physiological response for restart of stalled forks. Escherichia coli RecG, RuvAB, and RecA proteins have been shown to reverse the model replication fork structures in vitro. However, the pathways and the mechanisms by which Mycobacterium tuberculosis, a slow growing human pathogen, responds to different types of replication stress and DNA damage are unclear. Here, we show that M. tuberculosis RecG rescues E. coli Delta recG cells from replicative stress. The purified M. tuberculosis RecG (MtRecG) and RuvAB(MtRuvAB) proteins catalyze fork reversal of model replication fork structures with and without a leading strand single-stranded DNA gap. Interestingly, single-stranded DNA-binding protein suppresses the MtRecG- and MtRuvAB-mediated fork reversal with substrates that contain lagging strand gap. Notably, our comparative studies with fork structures containing template damage and template switching mechanism of lesion bypass reveal that MtRecG but not MtRuvAB or MtRecA is proficient in driving the fork reversal. Finally, unlike MtRuvAB, we find that MtRecG drives efficient reversal of forks when fork structures are tightly bound by protein. These results provide direct evidence and valuable insights into the underlying mechanism of MtRecG-catalyzed replication fork remodeling and restart pathways in vivo.

The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

A detailed chemistry multi-cycle simulation of a gasoline fueled HCCI engine operated with NVO

A previously developed Stochastic Reactor Model (SRM) is used to simulate combustion in a four cylinder in-line four-stroke naturally aspirated direct injection Spark Ignition (SI) engine modified to run in Homogeneous Charge Compression Ignition (HCCI) mode with a Negative Valve Overlap (NVO). A portion of the fuel is injected during NVO to increase the cylinder temperature and enable HCCI combustion at a compression ratio of 12:1. The model is coupled with GT-Power, a one-dimensional engine simulation tool used for the open valve portion of the engine cycle. The SRM is used to model in-cylinder mixing, heat transfer and chemistry during the NVO and main combustion. Direct injection is simulated during NVO in order to predict heat release and internal Exhaust Gas Recycle (EGR) composition and mass. The NOx emissions and simulated pressure profiles match experimental data well, including the cyclic fluctuations. The model predicts combustion characteristics at different fuel split ratios and injection timings. The effect of fuel reforming on ignition timing is investigated along with the causes of cycle to cycle variations and unstable operation. A detailed flux analysis during NVO unearths interesting results regarding the effect of NOx on ignition timing compared with its effect during the main combustion. © 2009 SAE International.

Experimental investigation of a control method for SI-HCCI-SI transition in a multi-cylinder gasoline engine

In HCCI engines, the Air/Fuel Ratio (AFR) and Residual Gas Fraction (RGF) are difficult to control during the SI-HCCI-SI transition, and this may result in incomplete combustion and/or high pressure raise rates. As a result, there may be undesirably high engine load fluctuations. The objectives of this work are to further understand this process and develop control methods to minimize these load fluctuations. This paper presents data on instantaneous AFR and RGF measurements, both taken by novel experimental techniques. The data provides an insight into the cyclic AFR and RGF fluctuations during the switch. These results suggest that the relatively slow change in the intake Manifold Air Pressure (MAP) and actuation time of the Variable Valve Timing (VVT) are the main causes of undesired AFR and RGF fluctuations, and hence an unacceptable Net IMEP (NIMEP) fluctuation. We also found large cylinder-to-cylinder AFR variations during the transition. Therefore, besides throttle opening control and VVT shifting, cyclic and individual cylinder fuel injection control is necessary to achieve a smooth transition. The control method was developed and implemented in a test engine, and the result was a considerably reduced NIMEP fluctuation during the mode switch. The instantaneous AFR and RGF measurements could furthermore be adopted to develop more sophisticated control methods for SI-HCCI-SI transitions. © 2010 SAE International.