Analysis of traffic injury severity in Dhaka, Bangladesh

This research identifies roadway, traffic, and environmental factors that influence the injury severity of road traffic crashes in Dhaka. Dhaka provides a rather unusual driving risk environment to study, since virtually anyone can obtain a drivers’ license and very little traffic enforcement and fines are given when drivers violate traffic rules. To examine this city with presumed heightened crash severity risk, police reported crash data from 2007 to 2011 containing about 2714 road traffic crashes were collected. The injury severity of traffic crashes—recorded as either fatal, serious injury, or property damage only—were modeled using an ordered Probit model. Significant factors increasing the probability of fatal injuries include crashes along highways (65%), absence of a road divider (80%), crashes during night time (54%), and vehicle-pedestrian collisions (367%); whereas two-way traffic configuration (21%), and traffic police controlled schemes (41%) decrease the probability of fatalities. Both similarities and differences of the findings between crash risk in Dhaka and developed countries are discussed in policy relevant terms.

International juvenile (in)justice : penal severity and rights compliance

This article focuses on the anomalies and contradictions surrounding the notion of ‘international juvenile justice’, whether in its pessimistic (neoliberal penality and penal severity) or optimistic (universal children’s rights and rights compliance) incarnations. It argues for an analysis which recognises firstly, the uneven, multi-facetted and heterogeneous nature of the processes of globalisation and secondly, how the global, the international, the national and the local are not mutually exclusive but continually interact to re-constitute, re-make and challenge each other.

The impact of viral respiratory infection on the severity and recovery from an asthma exacerbation

Background Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown. Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma. Methods Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined. Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7,10, and 14. Results On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = 0.36, P = 0.025). By day 7 and 14, there was no difference between groups. Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA. Conclusions The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.

Correlates of foot pain severity in adults with hallux valgus : a cross-sectional study

Background Hallux valgus (HV) is highly prevalent and associated with progressive first metatarsophalangeal joint subluxation and osteoarthritis. The link between structural HV deformity and foot pain is unclear. This study investigated possible explanatory factors surrounding foot pain in HV, including radiographic HV angle and signs of joint degeneration. Methods Participants were 60 adults (53 female) with HV aged 20 to 75 years. Participant demographics and a range of radiographic, clinical and functional measures were considered potential correlates of foot pain. Self-reported foot pain (visual analogue scales and a dichotomous definition) was considered the dependent variable. Multivariate modelling was used to determine which characteristics and measures explained pain, with univariate analyses first used to screen potential variables. Results Approximately 20 to 30% of the variance in foot pain associated with HV could be explained by patient characteristics such as poorer general health status, lower educational attainment and increased occupational physical activity levels, in combination with some dynamic physical characteristics such as hallux plantarflexion weakness and reduced force-time integral under the second metatarsal during gait. Neither increasing lateral deviation of the hallux (HV angle) nor presence of first metatarsophalangeal joint osteoarthritis was associated with foot pain. Conclusions This study shows that passive structural factors, including HV angle, do not appear to be significant correlates of foot pain intensity in HV. Our data demonstrate the importance of considering patient characteristics such as general health and physical activity levels when assessing foot pain associated with HV.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.

The effect of deprivation and disease-severity on malnutrition risk in chronic obstructive pulmonary disease (COPD)

Deprivation has previously been shown to be an independent risk factor for the high prevalence of malnutrition observed in COPD (Collins et al., 2010). It has been suggested the socioeconomic gradient observed in COPD is greater than any other chronic disease (Prescott & Vestbo, 1999). The current study aimed to examine the infl uence of disease severity and social deprivation on malnutrition risk in outpatients with COPD. 424 COPD outpatients were screened using the ‘Malnutrition Universal Screening Tool’ (‘MUST’). COPD disease severity was recorded in accordance with the GOLD criteria and deprivation was established according to the patient’s geographical location (postcode) at the time of nutritional screening using the UK Government’s Index of Multiple Deprivation (IMD). IMD ranks postcodes from 1 (most deprived) to 32,482 (least deprived). Disease severity was posi tively associated with an increased prevalence of malnutrition risk (p < 0.001) both within and between groups, whilst rank IMD was negatively associated with malnutrition (p = 0.020), i.e. those residing in less deprived areas were less likely to be malnourished. Within each category of disease severity the prevalence of malnutrition was two-fold greater in those residing in the most deprived areas compared to those residing in the least deprived areas. This study suggests that deprivation and disease severity are independent risk factors for malnutrition in COPD both contributing to the widely variable prevalence of malnutrition. Consideration of these issues could assist with the targeted nutritional management of these patients.

Childhood atopic dermatitis : a cross-sectional study of relationships between child and parent factors, atopic dermatitis management, and disease severity

Background: Successful management of atopic dermatitis poses a significant and ongoing challenge to parents of affected children. Despite frequent reports of child behaviour problems and parenting difficulties, there is a paucity of literature examining relationships between child behaviour and parents' confidence and competence with treatment. Objectives: To examine relationships between child, parent, and family variables, parents' self-efficacy for managing atopic dermatitis, self-reported performance of management tasks, observed competence with providing treatment, and atopic dermatitis severity. Design: Cross-sectional study design. Participants A sample of 64 parent-child dyads was recruited from the dermatology clinic of a paediatric tertiary referral hospital in Brisbane, Australia. Methods: Parents completed self-report questionnaires examining child behaviour, parents' adjustment, parenting conflict, parents' relationship satisfaction, and parents' self-efficacy and self-reported performance of key management tasks. Severity of atopic dermatitis was assessed using the Scoring Atopic Dermatitis index. A routine home treatment session was observed, and parents' competence in carrying out the child's treatment assessed. Results: Pearson's and Spearman's correlations identified significant relationships (p< .05) between parents' self-efficacy and disease severity, child behaviour difficulties, parent depression and stress, parenting conflict, and relationship satisfaction. There were also significant relationships between each of these variables and parents' self-reported performance of management tasks. More profound child behaviour difficulties were associated with more severe atopic dermatitis and greater parent stress. Using multiple linear regressions, significant proportions of variation in parents' self-efficacy and self-reported task performance were explained by child behaviour difficulties and parents' formal education. Self-efficacy emerged as a likely mediator for relationships between both child behaviour and parents' education, and self-reported task performance. Direct observation of treatment sessions revealed strong relationships between parents' treatment competence and parents' self-efficacy, outcome expectations, and self-reported task performance. Less competent task performance was also associated with greater parent-reported child behaviour difficulties, parent depression and stress, parenting conflict, and relationship dissatisfaction. Conclusion: This study revealed the importance of child behaviour to parents' confidence and practices in the context of atopic dermatitis management. Children with more severe atopic dermatitis are at risk of presenting with challenging behaviour problems and their parents struggle to manage the condition successfully.

Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis

Dehydroepiandrosterone (DHEA) and its sulphate form (DHEA) are neuroactive steroids with antiglucocorticoid properties. An imbalance in the ratio of cortisol to DHEA(S) has been implicated in the pathophysiology of stress-related psychiatric disorders. This study prospectively investigated circulating cortisol, DHEAS and their ratio in first-episode psychosis (FEP) patients compared to healthy controls, and their relationship to perceived stress, psychotic, negative and mood symptoms. METHODS: Blood cortisol and DHEAS levels were obtained in 39 neuroleptic-naïve or minimally-treated FEP patients and 25 controls. Twenty-three patients and 15 controls received repeat assessments after 12 weeks. Perceived stress was assessed using the Perceived Stress Scale and symptoms were assessed in patients using standard rating scales. RESULTS: At baseline, no differences were observed in cortisol, DHEAS or the cortisol/DHEAS ratio between patients and controls. There were also no group differences in the change in these biological variables during the study period. Within FEP patients, decreases in cortisol and the cortisol/DHEAS ratio over time were directly related to the improvement in depression (r = 0.45; p = 0.031, r = 0.52; p = 0.01), negative (r = 0.51; p = 0.006, r = 0.55; p = 0.008) and psychotic symptoms (cortisol only, r = 0.53; p = 0.01). Perceived stress significantly correlated with DHEAS (r = 0.51; p = 0.019) and the cortisol/DHEAS ratio (r = -0.49; p = 0.024) in controls, but not patients, possibly reflecting an impaired hormonal response to stress in FEP patients. CONCLUSIONS: These findings further support the involvement of the stress system in the pathophysiology of psychotic disorders, with implications for treatment strategies that modulate these neurosteroids.

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in human bone; And causes varying phenotypic severity of osteogenesis imperfecta type V

Background The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C > T) in the 5' untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V. Methods Sanger sequencing of the IFITM5 5' UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5. Results: All nine subjects with OI type V were heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone. Conclusions The c.-14C > T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.

The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis

Objective. To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). Methods. Three hundred sixty- three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. Results. A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10-4 among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10-6 among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class H associations with disease severity or with different clinical manifestations of AS were found. Conclusion. The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.

Is disease severity in ankylosing spondylitis genetically determined?

Objective. To assess the role of genes and the environment in determining the severity of ankylosing spondylitis. Methods: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components Contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models. Results. Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10-4], BASFI familiality 0,68 [P = 3 × 10-7]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0,36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI. Conclusion. This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

Antibody reactivity to the transmembrane protein of the caprine arthritis encephalitis virus correlates with severity of arthritis: No evidence for the involvement of epitope mimicry

Serum and synovial antibody reactivities of caprine arthritis encephalitis virus (CAEV) infected goats were assessed by Western blotting against purified CAEV antigen and the greatest intensity of reactivity in the serum of arthritic goats was to the gp45 transmembrane protein (TM). The extracytoplasmic domain of the TM gene was cloned into a pGEX vector and expressed in Escherichia coil as a glutathione S transferase fusion protein (GST-TM). This clone was found to be 90.5 and 89.2% homologous to published sequences of CAEV TM gene. Serum of 16 goats naturally infected with CAEV were examined by Western blotting for reactivity to the fusion protein. Antibody reactivity to the GST-TM correlated with clinically detectable arthritis (R = 0.642, P ≤ 0.007). The hypothesis that the immune response to the envelope proteins of the CAEV contributes to the severity of arthritis in goats naturally infected with CAEV via epitope mimicry was tested. Antibodies from 5 CAEV infected goats were affinity purified against the GST-TM fusion protein and tested for cross-reactivity with a series of goat synovial extracts and proteogylcans. No serum antibody response or cross-reactivity of affinity purified antibodies could be detected. Peptides of the CAEV SU that were predicted to be linear epitopes and a similar heat shock protein 83 (HSP) peptide identified by database searching, were synthesized and tested for reactivity in CAEV goats using ELISA, in vitro lymphocyte proliferation and delayed type hypersensitivity (DTH) assays. Peripheral blood lymphocytes from 10 of 17 goats with long term natural CAEV infections proliferated in vitro in response to CAEV and in vivo 3 of 7 CAEV infected goats had a DTH reaction to CAEV antigen. However, none of the peptides elicited significant cell mediated immune responses from CAEV infected goats. No antibody reactivity to the SU peptides or HSP peptide was found. We observed that the antibody reactivity to the CAEV TM protein associated with severity of arthritis however epitope mimicry by the envelope proteins of CAEV is unlikely to be involved.

Genetic aspects of susceptibility, severity, and clinical expression in ankylosing spondylitis

While twin studies have previously demonstrated high heritability of susceptibility to ankylosing spondylitis (AS), it is only recently that the involvement of genetic factors in determining the severity of the disease has been demonstrated. The genes involved in determining the rate of ankylosis in AS are likely to be different from those involved in the underlying immunologic events, and represent important potential targets for treatment of AS. This article will describe the progress that has been made in the genetic epidemiology of AS, and in identifying the genes involved.