Epidemiological investigation of a Legionnaires' disease outbreak in Christchurch, New Zealand: the value of spatial methods for practical public health.

Between April and August 2005 Christchurch, New Zealand experienced an outbreak of Legionnaires' disease. There were 19 laboratory-confirmed case including three deaths. Legionella pneumophila serogroup 1 (Lpsg1) was identified as the causative agent for all cases. A case-control study indicated a geographical association between the cases but no specific common exposures. Rapid spatial epidemiological investigation confirmed the association and identified seven spatially significant case clusters. The clusters were all sourced in the same area and exhibited a clear anisotropic process (noticeable direction) revealing a plume effect consistent with aerosol dispersion from a prevailing southwesterly wind. Four out of five cases tested had indistinguishable allele profiles that also matched environmental isolates from a water cooling tower within the centre of the clusters. This tower was considered the most probable source for these clusters. The conclusion would suggest a maximum dispersal distance in this outbreak of 11·6 km. This work illustrated the value of geostatistical techniques for infectious disease epidemiology and for providing timely information during outbreak investigations.

Epistaxis: a contemporary evidence based approach.

This article provides a contemporary management protocol for adult epistaxis admissions, evidence based where possible, and otherwise based on the authors' own experience.

Changing epidemiological trends of legionellosis in New Zealand, 1979-2009.

This study evaluated the spatio-temporal variation of Legionella spp. in New Zealand using notification and laboratory surveillance data from 1979 to 2009 and analysed the epidemiological trends. To achieve this we focused on changing incidence rates and occurrence of different species over this time. We also examined whether demographic characteristics such as ethnicity may be related to incidence. The annual incidence rate for laboratory-proven cases was 2·5/100,000 and 1·4/100,000 for notified cases. Incidence was highest in the European population and showed large geographical variations between 21 District Health Boards. An important finding of this study is that the predominant Legionella species causing disease in New Zealand differs from that found in other developed countries, with about 30-50% of cases due to L. longbeachae and a similar percentage due to L. pneumophila for any given year. The environmental risk exposure was identified in 420 (52%) cases, of which 58% were attributed to contact with compost; travel was much less significant as a risk factor (6·5%). This suggests that legionellosis has a distinctive epidemiological pattern in New Zealand.

Rare structural variation of synapse and neurotransmission genes in autism.

Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci.

A review of outcomes following inferior turbinate reduction surgery in children for chronic nasal obstruction.

BACKGROUND: The surgical management of enlarged inferior turbinates in children is controversial. The evidence base for turbinate surgery is weak and surgeons empirically offer surgery where the predominant symptom was nasal obstruction. OBJECTIVE: To evaluate the evidence for inferior turbinate surgery in children suffering with chronic nasal congestion. METHODS: A structured review of the PubMed, EMBASE and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews) was undertaken, using the MeSH terms: nasal obstruction, turbinates, surgery and children. Only articles focusing on turbinate surgery with an exclusively paediatric cohort were included. RESULTS: Eleven studies fulfilled the inclusion criteria. The ages of the children ranged from 1 to 17 years at the time of surgery and were followed-up for a period of 3 months to 14 years. Surgical indication for all studies was chronic nasal congestion, resistant to a trial of medical treatment for 2-3 months preceding surgery. Of the 730 cases reviewed, 79.1% had turbinate surgery as the standalone procedure. The remaining 21.9% had other concurrent procedures performed, the most common being adeno-tonsillectomy. Although all studies generally supported the effectiveness of turbinate reduction surgery for inferior turbinate hypertrophy, the outcome measures used were varied and did not allow comparison across studies. CONCLUSIONS: There is currently little evidence to support turbinate reduction surgery in children. The role of surgery, if any, has not been properly examined. Furthermore, the long-term effects on nasal airflow dynamics, nasal physiology and long-term complications remain to be studied.

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.

The impact of endonasal dacryocystorhinostomy (DCR), on patient health status as assessed by the Glasgow benefit inventory.

OBJECTIVE: To measure the effect of Endonasal DCR on the health status of patients, using a validated outcomes measure, the Glasgow Benefit Inventory. METHOD: Postal questionnaire with telephone follow up of patients undergoing Endonasal DCR in two institutions in Scotland. The same surgical technique is used in both centres. Patients were identified from prospectively collected data on consecutive patients undergoing this procedure. All adult patients, a minimum of twelve months post-intervention, were included. RESULTS: Ninety two of 123 patients (75%) completed the questionnaire, the mean age was 59 years and the sex ratio m:f was 1:1.8. The mean overall GBI for this intervention was + 32.7 (95% confidence intervals 27.8 - 37.6). The patients were grouped according to the indication for intervention: Obstruction of lacrimal system GBI + 32.7 (26.3-37.1), mucoecele + 40.1 (28.7-51.4), dacryocystitis + 19.4 (10.0-28.9). CONCLUSION: The GBI provides a measure of the effect of an ORL intervention on the health of a patient. Endonasal DCR scores highly when compared with a number of other rhinological procedures including rhinoplasty (GBI + 20), endoscopic sinus surgery (GBI + 23), and septal surgery (mean ranges from + 6 to + 24). Endonasal DCR is a successful intervention with demonstrable health benefits to the patient.

Measuring competence in endoscopic sinus surgery.

BACKGROUND: Competence based education is currently being introduced into higher surgical training in the UK. Valid and reliable performance assessment tools are essential to ensure competencies are achieved. No such tools have yet been reported in the UK literature. OBJECTIVE: We sought to develop and pilot test an Endoscopic Sinus Surgery Competence Assessment Tool (ESSCAT). The ESSCAT was designed for in-theatre assessment of higher surgical trainees in the UK. METHODS: The ESSCAT rating matrix was developed through task analysis of ESS procedures. All otolaryngology consultants and specialist registrars in Scotland were given the opportunity to contribute to its refinement. Two cycles of in-theatre testing were used to ensure utility and gather quantitative data on validity and reliability. Videos of trainees performing surgery were used in establishing inter-rater reliability. RESULTS: National consultation, the consensus derived minimum standard of performance, Cronbach's alpha = 0.89 and demonstration of trainee learning (p = 0.027) during the in vivo application of the ESSCAT suggest a high level of validity. Inter-rater reliability was moderate for competence decisions (Cohen's Kappa = 0.5) and good for total scores (Intra-Class Correlation Co-efficient = 0.63). Intra-rater reliability was good for both competence decisions (Kappa = 0.67) and total scores (Kendall's Tau-b = 0.73). CONCLUSION: The ESSCAT generates a valid and reliable assessment of trainees' in-theatre performance of endoscopic sinus surgery. In conjunction with ongoing evaluation of the instrument we recommend the use of the ESSCAT in higher specialist training in otolaryngology in the UK.

Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas.

Neuroblastomas are characterized by 1p deletions, suggesting that a tumor suppressor gene (TSG) resides in this region. We have mapped the smallest region of deletion (SRD) to a 2 Mb region of 1p36.31 using microsatellite and single nucleotide polymorphisms. We have identified 23 genes in this region, and we have analysed these genes for mutations and RNA expression patterns to identify candidate TSGs. We sequenced the coding exons of these genes in 30 neuroblastoma cell lines. Although rare mutations were found in 10 of the 23 genes, none showed a pattern of genetic change consistent with homozygous inactivation. We examined the expression of these 23 genes in 20 neuroblastoma cell lines, and most showed readily detectable expression, and no correlation with 1p deletion. However, 7 genes showed uniformly low expression in the lines, and 2 genes (CHD5, RNF207) had virtually absent expression, consistent with the expected pattern for a TSG. Our mutation and expression analysis in neuroblastoma cell lines, combined with expression analysis in normal tissues, putative function and prior implication in neuroblastoma pathogenesis, suggests that the most promising TSG deleted from the 1p36 SRD is CHD5, but TNFRSF25, CAMTA1 and AJAP1 are also viable candidates.

Changes in nasal aesthetics following nasal bone manipulation.

Nasal bone fractures are the commonest type of bony facial injury causing aesthetic deformity. The aim of this study was to identify the effect of nasal trauma and fracture manipulation on the aesthetic proportions of the nose, by comparing pre- and post-treatment nasal aesthetics. Thirty-two patients (26 men and 6 women) underwent aesthetic assessment prior to treatment of the injury by closed nasal manipulation, 7 to 10 days after the initial injury. Standard facial aesthetic photographic assessments were performed prior to and following manipulation. Assessment involved measurement of standard nasal aesthetic parameters. In the nasal trauma cohort, the main anomalies in nasal aesthetics were nasal deviation and differences in the nasal aesthetic profile. Nasal fracture manipulation successfully reduced deviation from an average of 35 degrees pre-manipulation to an average of 9 degrees post-manipulation.

Repair of inner canthus surgical wound using superior palpebral artery based advancement flap.

BACKGROUND: Small defects of the inner canthus can be difficult to repair with an aesthetically satisfactory result, due to the difficulty in matching skin types and the resulting donor site scars. METHODS: We describe a technique which we have employed for repairing skin defects around the inner canthus, using a cutaneous advancement flap from the upper eyelid, based on the superior palpebral artery. RESULTS: Complete excision of the lesion was possible, and a cosmetically acceptable result was obtained. CONCLUSIONS: By using this technique, skin is moved within one aesthetic unit, thus maximising skin type matching and cosmetic results. In addition, the technique creates a donor site which can be easily hidden within the natural creases of the upper lid, and the arterial supply maximises the chances of flap survival.

Endoscopic control of the sphenopalatine artery for epistaxis: long-term results.

The aim of this study was to prospectively evaluate post-operative cessation of bleeding and late recurrence of epistaxis in a cohort of patients treated by endoscopic ligation of the sphenopalatine artery. Participants comprised patients undergoing sphenopalatine artery ligation for posterior epistaxis at three east Scotland hospitals. Main outcome measures were recurrence of epistaxis in the immediate post-operative period and at long-term follow up (minimum nine months). Forty-three patients (30 men and 13 women) underwent 45 procedures; two patients underwent bilateral ligation. Two patients suffered recurrence as in-patients. Two patients experienced subsequent epistaxis requiring medical treatment. Two further patients suffered minor late epistaxis not requiring treatment. Success in preventing significant recurrence was 93 per cent. All recurrences requiring intervention occurred within one month of surgery. None of the patients in this series reported nasal complications. We found sphenopalatine artery ligation to be an effective means of achieving long-term control of posterior epistaxis.

A comparison of aesthetic proportions between the Oriental and Caucasian nose.

Differences in aesthetics between the Oriental and Caucasian nose were examined from a cohort of 118 healthy volunteers of which 61 had an Oriental and 57 had a Caucasian racial origin. The oriental nose projected less from the face, and was broader at the intercanthal level (P < 0.001) and the alar base (P < 0.001), but not at the bony base. The oriental nose projected less at all levels: nasion projection (P < 0.001) and tip projection (P < 0.001). The naso-labial angles for the Orientals in this study exhibited a wider range of variation than the Caucasians, with the oriental male exhibiting the most acute angle (average 86.2 degrees ), because of the forward angulation of the upper lip. Many of the average aesthetic parameters obtained from these two cohorts of healthy subjects did not conform to the published aesthetic standards, set out as the ideal goals for rhinoplasty.

A combined linkage-physical map of the human genome.

We have constructed de novo a high-resolution genetic map that includes the largest set, to our knowledge, of polymorphic markers (N=14,759) for which genotype data are publicly available; that combines genotype data from both the Centre d'Etude du Polymorphisme Humain (CEPH) and deCODE pedigrees; that incorporates single-nucleotide polymorphisms; and that also incorporates sequence-based positional information. The position of all markers on our map is corroborated by both genomic sequence and recombination-based data. This specific combination of features maximizes marker inclusion, coverage, and resolution, making this map uniquely suitable as a comprehensive resource for determining genetic map information (order and distances) for any large set of polymorphic markers.

Molecular, forensic and haplotypic inconsistencies regarding the identity of the Ekaterinburg remains.

BACKGROUND: A set of human remains unearthed near Ekaterinburg, Russia has been attributed to the Romanov Imperial Family of Russia and their physician and servants. That conclusion was officially accepted by the Russian government following publication of DNA tests that were widely publicized. The published study included no discussion of major forensic discrepancies and the information regarding the burial site and remains included irregularities. Furthermore, its conclusion of Romanov identity was based on molecular behaviour that indicates contamination rather than endogenous DNA. The published claim to have amplified by PCR a 1223 bp region of degraded DNA in a single segment for nine individuals and then to have obtained sequence of PCR products derived from that segment without cloning indicates that the Ekaterinburg samples were contaminated with non-degraded, high molecular weight, 'fresh' DNA. AIM: Noting major violations of standard forensic practices, factual inconsistencies, and molecular behaviours that invalidate the claimed identity, we attempted to replicate the findings of the original DNA study. SUBJECT: We analysed mtDNA extracted from a sample of the relic of Grand Duchess Elisabeth, sister of Empress Alexandra. RESULTS: Among clones of multiple PCR targets and products, we observed no complete mtDNA haplotype matching that reported for Alexandra. The consensus haplotype of Elisabeth differs from that reported for Alexandra at four sites. CONCLUSION: Considering molecular and forensic inconsistencies, the identity of the Ekaterinburg remains has not been established. Our mtDNA haplotype results for Elisabeth provide yet another line of conflicting evidence regarding the identity of the Ekaterinburg remains.

Retrospective characterization of Newcastle Disease Virus Antrim '73 in relation to other epidemics, past and present.

In November 1973 Newcastle disease suddenly appeared in Northern Ireland, where the viscerotropic disease had not been seen in 3 1/2 years and the two Irelands had been regarded as largely disease free for 30 years. It was successfully controlled with only 36 confirmed affected layer flocks, plus 10 more slaughtered as 'dangerous contacts'. Contemporary investigations failed to reveal the source of the Irish epidemic. Using archival virus samples from most of the affected flocks, RT PCR was conducted with primers selected for all six NDV genes. Phylogenetic analyses of three genes, HN, M and F, confirmed vaccine as the cause of one of the outbreaks. The other six samples were identical and closely related to previous outbreaks in the United States and western Europe initiated by infected imported Latin American parrots. The probable cause of the epidemic followed from the importation from The Netherlands of bulk feed grains contaminated with infected pigeon faeces.

Using human reliability analysis to detect surgical error in endoscopic DCR surgery.

The aim of this study was to describe the nature of active skill-based errors occurring in endoscopic dacrocystorhinostomy (DCR) surgery. A human reliability analysis methodology was used to assess surgical error from observational capture data. Twelve endoscopic DCR operations performed by three different surgical trainees were video recorded. The steps (subtasks) of each operation were carefully analysed and common errors were documented. Specific errors that resulted in trauma to the nasal mucosa were noted. Execution errors were common, with errors of grasping being most frequent (67% of all execution errors). Most of these involved the Blakesley forceps. In total, there were 69 mucosal trauma hits. Inserting instruments into or withdrawing them from the nasal cavity with too much force or speed caused more than half of these. Incising with too much force resulting in 'overshoot' caused 34% of mucosal trauma. Trainee ENT surgeons should take particular care when inserting or withdrawing instruments from the nasal cavity and also when performing lacrimal sac or nasal mucosa incisions. Performance of these tasks with too much force was identified as a common and potentially avoidable cause of mucosal trauma. Further research is needed into the design and use of endoscopic sinus surgery instruments with the aim of avoiding the errors that were encountered.