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1.
Psychiatr Psychol Law ; 28(2): 274-285, 2021.
Article in English | MEDLINE | ID: mdl-34712096

ABSTRACT

In March 2019, a mass shooting at two Christchurch mosques, livestreamed to Facebook, resulted in the deaths of 51 people. Psychologically, this served as a focusing event with high threat salience, shocking a country unused to gun violence despite its comparatively lax firearm legislation. The unprecedented reluctance by the New Zealand media to feature the shooter as a protagonist or even publish his name, concentrating instead on victims and societal issues, helped promote a sense of collective responsibility for change. This was strongly modeled by political leaders. Within weeks, new gun control laws were introduced with bipartisan support. We present this as a national case study, considering psychological and societal enablers for legislative reform in response to extreme gun violence. The shooting also raised the intractable problem of the internet allowing terrorists to promulgate violent content and extremist ideology with regulation in this area harder to achieve than gun control.

2.
Psychol Med ; : 1-9, 2021 Apr 20.
Article in English | MEDLINE | ID: mdl-33875022

ABSTRACT

BACKGROUND: Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors. METHODS: We used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender. RESULTS: For males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20-1.84] and self-harm (OR: 1.55, 95% CI: 1.45-1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32-1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94-1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93-1.80) and of self-harm (OR: 1.52, 95% CI: 1.43-1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98-1.75) and self-harm (OR: 1.32, 95% CI: 1.26-1.40). DISCUSSION: Exclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.

5.
J Hosp Infect ; 100(1): 60-64, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29864485

ABSTRACT

BACKGROUND: Gastric acid suppressants increase the risk of gastroenteritis by allowing ingested pathogens to survive passage through the stomach. It is not known whether the same mechanism affects transmission of Enterobacteriaceae. A case-control study was undertaken to answer this question. AIM: To determine whether use of proton pump inhibitors (PPIs) increases the risk of infection with Enterobacteriaceae in hospital patients. METHODS: Retrospective case-control study in a teaching hospital in South West England. Cases were 126 patients infected with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae between April 2014 and March 2015. Use of PPIs, H2 receptor antagonists or antacids at the time of admission or in the preceding six months was compared with 126 demographically matched controls infected with non-ESBL-producing Enterobacteriaceae and 126 uninfected controls, matched by primary diagnosis. FINDINGS: Sixty-six of 126 ESBL cases, 62 of 126 non-ESBL controls and 34 of 126 uninfected controls were prescribed PPIs on or within six months of admission. Multi-variable logistic regression analysis gave an odds ratio of 3.37 [95% confidence interval (CI) 1.84-6.18] for PPI exposure vs uninfected controls and 1.15 (95% CI 0.68-1.95) for ESBL infection vs non-ESBL infection. H2 receptor antagonists and antacids were not significantly associated with infection. CONCLUSION: PPI exposure within the previous six months is significantly associated with infection with both ESBL- and non-ESBL-producing bacteria. Reducing inappropriate use of PPIs may be a novel way to reduce transmission, which might reduce antibiotic use and help control antimicrobial resistance.


Subject(s)
Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae/isolation & purification , Proton Pump Inhibitors/adverse effects , Adult , Aged , Aged, 80 and over , Case-Control Studies , England/epidemiology , Enterobacteriaceae/enzymology , Female , Hospitals, Teaching , Humans , Inpatients , Male , Middle Aged , Retrospective Studies , Risk Assessment , beta-Lactamases/metabolism
6.
Scand J Med Sci Sports ; 27(12): 1824-1832, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28028836

ABSTRACT

In Australian government-funded primary schools, the responsibility for physical education (PE) falls mainly on general classroom teachers, many of whom possess limited PE training. This study sought to examine the impact of specialist-taught PE on eye-hand coordination (EHC) development. In this 4-year cluster-randomized intervention, participants were 187 boys and 172 girls initially in grade 2 in 29 primary schools, where no school employed university-trained specialist PE teachers. In 13 (intervention) schools, specialist PE teachers conducted 268 PE classes (two 45-minute sessions/wk) from grade 2 to grade 6. The intervention was based on traditional PE educational objectives, including fundamental motor skills, but did not specifically focus on EHC. The remaining 16 (control) schools continued with common-practice PE taught by general classroom teachers (30-60 min/wk). EHC was measured by a ball throw and wall-rebound catch test and recorded at ages 8, 10, and 12 (SD 0.3) at ends of grades 2, 4, and 6, respectively. There was steady yearly improvement of EHC in both groups, but no evidence of any intervention effect in boys (P=.88) or girls (P=.20). The introduction of specialist-taught PE during 4 years of primary school did not influence EHC development. Considering evidence that classroom teachers make little contribution to PE in this jurisdiction, together with the steady progression of EHC over the 4 years, other influences such as organized sport, after-school activities, natural development, and parental instruction are conceivably more influential factors in EHC development during primary school years.


Subject(s)
Motor Skills , Physical Education and Training , Psychomotor Performance , Australia , Child , Child Development , Female , Humans , Longitudinal Studies , Male , Schools
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 17-20, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28268270

ABSTRACT

Multivariable intermittent control (MIC) combines stability with flexibility in the control of unstable systems. Using an underlying continuous-time optimal control design, MIC uses models of the physical system to generate multivariate open-loop control signals between samples of the observed state. Using accurate model values of physical system parameters, stability of the closed loop system is not dependent upon sample interval. Here we consider the sensitivity of MIC to inaccurate model values of system parameters. The high dimensionality of multiple parameters combined with an unstable open loop system ensures the ratio of hyper-volumes containing good to bad parameter combinations resembles a "needle in a haystack". Is this sensitivity a problem or an asset? Prediction error between open loop and observed states provides the basis for triggering a sampling event but is also sensitive to inaccurate model values. Investigation of the mapping between prediction error and model values of physical parameters illustrates the value of prediction error to identify combinations of parameters giving stable closed loop control with low state error, similar to that provided by accurate values. Sensitivity of prediction error to model inaccuracy is potentially an asset facilitating adaptation and supporting the rationale for MIC to combine control with flexibility.


Subject(s)
Models, Biological , Psychomotor Performance/physiology , Humans , Uncertainty
8.
Ghana Med J ; 49(3): 136-41, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26693187

ABSTRACT

BACKGROUND: The aims of this study were to characterize the patients seeking acute care for injury and non-injury complaints in an urban Emergency Department in Ghana in order to 1) inform the curriculum of the newly developed Emergency Medicine resident training program 2) improve treatment processes, and 3) direct future community-wide injury prevention policies. STUDY DESIGN: A prospective cross-sectional survey of patients 18 years or older seeking care in an urban Accident and Emergency Center (AEC) was conducted between 7/13/2009 and 7/30/2009. Questionnaires were administered by trained research staff and each survey took 10-15 minutes to complete. Patients were asked questions regarding demographics, overall health and chief complaint. RESULTS: 254 patients were included in the sample. Participants' chief complaints were classified as either medical or injury-related. Approximately one third (38%) of patients presented with injuries and 62% presented for medical complaints. The most common injury at presentation was due to a road traffic injury, followed by falls and assault/fight. The most common medical presentation was abdominal pain followed by difficulty breathing and fainting/ blackout. Only 13% arrived to AEC by ambulance and 51% were unable to ambulate at the time of presentation. CONCLUSION: Approximately one-third of non-fatal adult visits were for acute injury. Future research should focus on developing surveillance systems for both medical and trauma patients. Physicians that are specifically trained to manage both the acutely injured patient and the medical patient will serve this population well given the variety of patients that seek care at the AEC.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Abdominal Pain/epidemiology , Accidents, Traffic/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Ghana , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Surveys and Questionnaires , Wounds and Injuries/epidemiology , Young Adult
9.
Ir J Med Sci ; 184(2): 469-74, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25023126

ABSTRACT

INTRODUCTION: Venous thromboembolism (VTE) is a common complication of hospital admission. The incidence of hospital-acquired deep vein thrombosis is approximately 10-40% amongst medical and general surgical patients without prophylaxis. Pulmonary embolism accounts for 5-10% of deaths in hospitalised patients, making hospital-acquired VTE the most common preventable cause of in-hospital death. Studies suggest that prophylactic measures are widely under- and inappropriately used. AIMS: We hypothesised that the introduction of a medication chart with a dedicated VTE prophylaxis section would improve compliance with local guidelines. METHODS: Trial medication charts were piloted over a 4-week period in one surgical and two medical wards. Data on compliance with hospital guidelines were collected before and after introduction using a detailed chart review. The difference in prescribing compliance was assessed with the Chi-squared test. RESULTS: 70 patients were assessed before and 38 after the introduction of the new charts. Initially, only 58.6% (n = 41) of patients' prescriptions were in compliance with local guidelines. In 28.6% (n = 20) of patients, VTE prophylaxis was needed and not prescribed. 7.1% (n = 5) of patients were prescribed an inappropriately low dose of low molecular weight heparin (LMWH) prophylaxis. 2.9% (n = 2) of patients were prescribed inappropriately high dose of LMWH prophylaxis. After introduction of the new medication chart, compliance with guidelines rose to 71% (n = 27, p = 0.09). CONCLUSION: Compliance with VTE guidelines is inadequate. Medication charts with specific sections on VTE assessment and prophylaxis may increase compliance with guidelines.


Subject(s)
Decision Support Techniques , Guideline Adherence , Medical Records , Pulmonary Embolism/prevention & control , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Anticoagulants/administration & dosage , Contraindications , Heparin, Low-Molecular-Weight/administration & dosage , Hospitalization , Humans , Medical Audit , Middle Aged , Pilot Projects , Practice Guidelines as Topic , Risk Assessment/methods
10.
J Hosp Infect ; 86(2): 155-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24440371

ABSTRACT

Proton pump inhibitor (PPI) use increases the risk of Clostridium difficile infection (CDI) despite C. difficile spores being acid resistant. Swallowed saliva contains nitrite which reacts with gastric acid, producing bactericidal nitrogen oxides. With 5mM nitrite at pH 2 (reflecting normal gastric conditions) all C. difficile spores were killed within 15 min. No reduction in count was seen with the same nitrite concentration at pH 5, representing gastric conditions in patients taking PPIs, even after 60 min. Reduced gastric acidification of salivary nitrite may explain the increased risk of CDI in patients taking PPIs.


Subject(s)
Anti-Bacterial Agents/metabolism , Clostridioides difficile/drug effects , Clostridioides difficile/immunology , Nitrites/metabolism , Nitrogen Oxides/metabolism , Spores, Bacterial/drug effects , Spores, Bacterial/immunology , Anti-Bacterial Agents/pharmacology , Humans , Hydrogen-Ion Concentration , Microbial Viability/drug effects , Nitrites/pharmacology , Nitrogen Oxides/pharmacology , Time Factors
11.
Pediatr Obes ; 9(6): 448-54, 2014 Dec.
Article in English | MEDLINE | ID: mdl-23943435

ABSTRACT

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The index of body mass related to stature, (body mass index, BMI, kgm(-2) ), is widely used as a proxy for percent body fat (%BF) in cross-sectional and longitudinal investigations. BMI does not distinguish between lean and fat mass and in children, the cross-sectional relationship between %BF and BMI changes with age and sex. WHAT THIS STUDY ADDS: While BMI increases linearly with age from age 8 to 12 years in both boys and girls, %BF plateaus off between 10 and 12 years. Repeated measures in children show a systematic decrease in %BF for any given BMI from age 8 to 10 to 12 years. Because changes in BMI misrepresent changes in %BF, its use as a proxy of %BF should be avoided in longitudinal studies in this age group. BACKGROUND: Body mass index (BMI, kgm(-2) ) is commonly used as an indicator of pediatric adiposity, but with its inability to distinguish changes in lean and fat mass, its use in longitudinal studies of children requires careful consideration. OBJECTIVE: To investigate the suitability of BMI as a surrogate of percent body fat (%BF) in pediatric longitudinal investigations. METHODS: In this longitudinal study, healthy Australian children (256 girls and 278 boys) were measured at ages 8.0 (standard deviation 0.3), 10.0 and 12.0 years for height, weight and percent body fat (%BF) by dual-energy X-ray absorptiometry. RESULTS: The patterns of change in the means of %BF and BMI were different (P < 0.001). While mean BMI increased linearly from 8 to 12 years of age, %BF did not change between 10 and 12 years. Relationships between %BF and BMI in boys and girls were curvilinear and varied with age (P < 0.001) and gender (P < 0.001); any given BMI corresponding with a lower %BF as a child became older. CONCLUSION: Considering the divergence of temporal patterns of %BF and BMI between 10 and 12 years of age, employment of BMI as a proxy for %BF in absolute or age and sex standardized forms in pediatric longitudinal investigations is problematical.


Subject(s)
Absorptiometry, Photon , Adipose Tissue/pathology , Body Composition/physiology , Aging , Australia/epidemiology , Body Fat Distribution , Body Mass Index , Child , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Sex Factors
12.
Article in English | MEDLINE | ID: mdl-23789918

ABSTRACT

Spiramycin, tylosin, bacitracin and virginiamycin are among a group of antibiotic growth promoters that have been banned in the European Union since the 1999 Council. This was due to concerns over the development of resistant bacteria emerging between humans and animals with the threat of antibiotics no longer being able to be used effectively to treat human infections. A sensitive and fast immunochemical method is presented for the determination of these four antibiotic growth promoters simultaneously in poultry tissue. The method employs methanol extraction followed by sample clean-up by solid-phase extraction (SPE) with determination by enzyme-linked immunoabsorbant assay (ELISA). The limit of detection (LOD) was less than 1 ng g(-1) and the detection capability (CCß) was 3 ng g(-1) or less for all four antibiotic growth promoters. Validation was completed with both raw and cooked chicken, therefore either matrix could be used for the monitoring of these banned drugs. In a feeding trial no residues of either bacitracin or virginiamycin were found in medicated birds even without a withdrawal period. In the case of tylosin and spiramycin much higher residues level were detected immunochemically than was the case by mass spectrometry.


Subject(s)
Anti-Bacterial Agents/analysis , Growth Substances/analysis , Poultry Products/analysis , Animals , Enzyme-Linked Immunosorbent Assay , Limit of Detection
13.
Scand J Med Sci Sports ; 23(5): e263-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23614667

ABSTRACT

We investigated longitudinal and cross-sectional relationships between eye-hand coordination (EHC) and cardiorespiratory fitness (multistage run), physical activity (pedometers), percent body fat (%BF, dual energy x-ray absorptiometry), body image, and organized sport participation (questionnaires) in 406 boys and 384 girls at 8 and 10 years of age. EHC was measured by a throw and wall-rebound catch test involving 40 attempts of increasing difficulty. Median EHC improved during two years from 18 to 32 (boys) and 9 to 24 (girls), and gender differences and improvements were both significant (P < 0.001). Cross-sectional analyses showed that boys and girls with better EHC were fitter (P < 0.001), and a longitudinal relationship showed that girls who improved their EHC over the two years became fitter (P < 0.001). There was also evidence that children with better EHC possessed a more positive body image (P = 0.05 for combined sex data), but there was no evidence of any relationships between EHC and %BF or PA (both P > 0.3). Finally, even at age 8 years, boys and girls participating in organized sport possessed better EHC than non-participants. These data provide evidence for the premise that early acquisition of this single motor skill promotes the development of a child's fitness, body image, and participation in sport.


Subject(s)
Adipose Tissue , Eye Movements/physiology , Hand/physiology , Motor Skills/physiology , Physical Fitness , Sports/physiology , Australia , Body Image , Child , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Sex Distribution
14.
Trop Med Int Health ; 17(6): 775-81, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22519746

ABSTRACT

OBJECTIVE: To characterise the population that presents to the Accident and Emergency Centre (AEC) at Komfo Anokye Teaching Hospital (KATH) and to identify risk factors associated with bypassing proximal care facilities. METHODS: A structured questionnaire was verbally administered to patients presenting to the AEC over 2 weeks. The questionnaire focused on the use of health care resources and characteristics of current illness or injury. Measures recorded include demographics, socioeconomic status, chief complaint, transportation and mobility, reasons for choosing KATH and health care service utilisation and cost. RESULTS: The total rate of bypassing proximal care was 33.9%. On multivariate analysis, factors positively associated with bypassing included age older than 38 years (OR: 2.18, P 0.04) and prior visits to facility (OR 2.88, P 0.01). Bypassers were less likely to be insured (OR 0.31, P 0.01), to be seeking care due to injury (OR 0.42, P 0.03) and to have previously sought care for the problem (OR 0.10, P < 0.001). CONCLUSIONS: Patients who bypass facilities near them to seek care at an urban AEC in Ghana do so for a combination of reasons including familiarity with the facility, chief complaint and insurance status. Understanding bypassing behaviour is important for guiding health care utilisation policy decisions and streamlining cost-effective, appropriate access to care for all patients.


Subject(s)
Community Health Centers/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Population Surveillance , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Emergency Medicine/methods , Emergency Medicine/statistics & numerical data , Female , Ghana , Humans , Infant , Insurance Coverage/statistics & numerical data , Male , Middle Aged , Prospective Studies , Socioeconomic Factors , Surveys and Questionnaires , Urban Population/statistics & numerical data , Young Adult
15.
J Clin Microbiol ; 49(10): 3576-83, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21865429

ABSTRACT

The laboratory diagnostic strategy used to determine the etiology of encephalitis in 203 patients is reported. An etiological diagnosis was made by first-line laboratory testing for 111 (55%) patients. Subsequent testing, based on individual case reviews, resulted in 17 (8%) further diagnoses, of which 12 (71%) were immune-mediated and 5 (29%) were due to infection. Seventy-five cases were of unknown etiology. Sixteen (8%) of 203 samples were found to be associated with either N-methyl-d-aspartate receptor or voltage-gated potassium channel complex antibodies. The most common viral causes identified were herpes simplex virus (HSV) (19%) and varicella-zoster virus (5%), while the most important bacterial cause was Mycobacterium tuberculosis (5%). The diagnostic value of testing cerebrospinal fluid (CSF) for antibody was assessed using 139 samples from 99 patients, and antibody was detected in 46 samples from 37 patients. Samples collected at 14 to 28 days were more likely to be positive than samples taken 0 to 6 days postadmission. Three PCR-negative HSV cases were diagnosed by the presence of virus-specific antibody in the central nervous system (CNS). It was not possible to make an etiological diagnosis for one-third of the cases; these were therefore considered to be due to unknown causes. Delayed sampling did not contribute to these cases. Twenty percent of the patients with infections with an unknown etiology showed evidence of localized immune activation within the CNS, but no novel viral DNA or RNA sequences were found. We conclude that a good standard of clinical investigation and thorough first-line laboratory testing allows the diagnosis of most cases of infectious encephalitis; testing for CSF antibodies allows further cases to be diagnosed. It is important that testing for immune-mediated causes also be included in a diagnostic algorithm.


Subject(s)
Algorithms , Clinical Laboratory Techniques/methods , Encephalitis/diagnosis , Encephalitis/etiology , Adolescent , Adult , Antibodies/cerebrospinal fluid , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Cerebrospinal Fluid/immunology , Child , Child, Preschool , Cohort Studies , Diagnosis, Differential , England , Female , Humans , Immune System Diseases/diagnosis , Male , Middle Aged , Prospective Studies , Virus Diseases/diagnosis , Virus Diseases/virology , Young Adult
16.
Ir J Med Sci ; 180(2): 615, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20963509
17.
Br J Biomed Sci ; 68(4): 174-80, 2011.
Article in English | MEDLINE | ID: mdl-22263430

ABSTRACT

Otitis externa is a ubiquitous inflammatory disease; although it arises most commonly from an infection, there is no consensus in the UK for the reporting of ear swab culture results. This study aims to review current microbiology laboratory reporting of ear swab specimens to primary care and reach an evidence-based consensus for a reporting policy. Fifty consecutive ear swab reports were reviewed from each of 12 laboratories in the South West region to determine and discuss reporting practice. The Health Protection Agency (HPA) GP Microbiology Laboratory Use Group reviewed the underlying evidence and worked towards a consensus of expert microbiology opinion for laboratory reporting of ear swab results using a modified version of the Delphi technique. A total of 487 reports from primary care were reviewed (54% female; 46% male). Cultures most commonly yielded Pseudomonas species (36%), Staphylococcus species (21%), Streptococcus species (15%) and fungi (11%). Five reporting policies were agreed: Policy 1: Common pathogens such as group A beta-haemolytic streptococci, Streptococcus pneumoniae, Staphylococcus aureus - Always reported by name with antibiotic susceptibilities. Policy 2: Pseudomonas species - Always reported, but antibiotic susceptibilities only reported in severe disease. Policy 3: Aspergillus, Candida, coliforms and Proteus species, as well as non-group A streptococci and anaerobes - Only reported if moderate numbers of colonies and it is the predominant organism present; if appropriate report antibiotic susceptibilities. Policy 4: Coagulase-negative staphylococci, diphtheroids and enterococci - Not reported by name; generic terms used and antibiotic susceptibilities not reported. Policy 5: When antibiotic susceptibilities reported these must include susceptibility to a topical antibiotic. It is suggested that laboratories should consider adopting this evidence-based reporting consensus for ear swab culture results from primary care patients with otitis externa.


Subject(s)
Infections/diagnosis , Infections/epidemiology , Microbiology/statistics & numerical data , Otitis Externa/diagnosis , Otitis Externa/epidemiology , Primary Health Care/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Consensus , Female , Humans , Infant , Infant, Newborn , Male , Mandatory Reporting , Microbiology/standards , Middle Aged , Practice Guidelines as Topic , Primary Health Care/standards
18.
Epidemiol Infect ; 138(6): 783-800, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20388231

ABSTRACT

Defining the causal relationship between a microbe and encephalitis is complex. Over 100 different infectious agents may cause encephalitis, often as one of the rarer manifestations of infection. The gold-standard techniques to detect causative infectious agents in encephalitis in life depend on the study of brain biopsy material; however, in most cases this is not possible. We present the UK perspective on aetiological case definitions for acute encephalitis and extend them to include immune-mediated causes. Expert opinion was primarily used and was supplemented by literature-based methods. Wide usage of these definitions will facilitate comparison between studies and result in a better understanding of the causes of this devastating condition. They provide a framework for regular review and updating as the knowledge base increases both clinically and through improvements in diagnostic methods. The importance of new and emerging pathogens as causes of encephalitis can be assessed against the principles laid out here.


Subject(s)
Encephalitis/etiology , Acute Disease , Amebiasis/complications , Amebiasis/diagnosis , Bacterial Infections/complications , Bacterial Infections/diagnosis , Encephalitis/diagnosis , Encephalitis/microbiology , Humans , Rickettsia Infections/complications , Rickettsia Infections/diagnosis , Toxoplasmosis/complications , Toxoplasmosis/diagnosis , United Kingdom/epidemiology , Virus Diseases/complications , Virus Diseases/diagnosis
19.
Genes Immun ; 11(6): 467-78, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20200544

ABSTRACT

Natural killer (NK) cells are lymphocytes of the innate immune system. In humans, NK cell activities are partly controlled by the diverse killer immunoglobulin-like receptor (KIR) gene family. The importance of NK cells in both immunity to infection and reproduction makes KIR strong candidates for genes undergoing dynamic evolution in the human genome. Using high-resolution allelic typing, we investigated the potential role of natural selection in the diversification of KIR in the Irish population. Higher diversity than expected is observed at several loci, consistent with a history of balancing selection acting to maintain several allelic variants at high frequency in the population. KIR diversity is enhanced further at the haplotype level with functional polymorphisms at KIR2DL4, KIR3DL1 and KIR2DS4 defining nine 'core' haplotypes. Analysis of these core haplotypes in combination with human leukocyte antigen (HLA) class I ligands revealed several nonrandom associations. In particular, the KIR:HLA association for the core haplotype defined by KIR3DL1(*)01502 was female specific and a likely consequence of negative selection acting against KIR3DL1(*)01502 on an HLA-C1/C1 background. Many of the associations between KIR and HLA in the Irish differ from those previously reported, which argues against universal selective pressures for specific KIR:HLA combinations in diverse human populations.


Subject(s)
Evolution, Molecular , Gene Expression Profiling , Genes, MHC Class I/genetics , Multigene Family/immunology , Receptors, KIR/genetics , Selection, Genetic/genetics , Cohort Studies , Female , Gene Expression Profiling/methods , Genetic Linkage/genetics , Haplotypes/genetics , Humans , Male , Receptors, KIR2DL4/genetics , Receptors, KIR3DL1/genetics
20.
Genes Immun ; 11(1): 67-78, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19693090

ABSTRACT

Natural killer (NK) cells are components of the innate immune system that function in identifying and destroying aberrant or pathogen-infected cells. These functions are largely controlled by killer cell immunoglobulin-like receptors (KIRs). KIRs inhibit and activate NK cell functions through interactions with their ligands, epitopes encoded by human leukocyte antigen (HLA) class I genes (HLA-C1, C2 and Bw4). Genes that encode KIR and their HLA ligands vary in frequency across human populations. Here, we characterize two Irish populations for KIR and HLA and determine the spatial distribution of functionally important KIR:HLA systems in Europe, a region known for its considerable underlying genetic stratification. We find that Southern Europe is a region characterized by higher frequencies of activatory KIR and strong inhibitory HLA ligand systems (2DL1:HLA-C2 and 3DL1:Bw4). A lower frequency of activatory KIR and the predominance of a comparatively weaker inhibitory ligand system (2DL3:HLA-C1) are observed northwards. Despite contrasting KIR:HLA systems in Northern and Southern Europe, there is a clear balance between inhibitory and activatory repertoires, and their ligands in both regions. These findings show 'functional stratification' of the epistatic KIR:HLA receptor system in Europe, the presence of which will likely affect NK cell-mediated immunity across different populations.


Subject(s)
Epistasis, Genetic/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , Killer Cells, Natural , Receptors, KIR/genetics , Epistasis, Genetic/immunology , Female , HLA-B Antigens/immunology , HLA-C Antigens/immunology , Humans , Immunity, Cellular/genetics , Immunity, Cellular/immunology , Male , Receptors, KIR/immunology
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