The Convective Transport of Active Species in the Tropics (CONTRAST) Experiment.

The Convective Transport of Active Species in the Tropics (CONTRAST) experiment was conducted from Guam (13.5° N, 144.8° E) during January-February 2014. Using the NSF/NCAR Gulfstream V research aircraft, the experiment investigated the photochemical environment over the tropical western Pacific (TWP) warm pool, a region of massive deep convection and the major pathway for air to enter the stratosphere during Northern Hemisphere (NH) winter. The new observations provide a wealth of information for quantifying the influence of convection on the vertical distributions of active species. The airborne in situ measurements up to 15 km altitude fill a significant gap by characterizing the abundance and altitude variation of a wide suite of trace gases. These measurements, together with observations of dynamical and microphysical parameters, provide significant new data for constraining and evaluating global chemistry climate models. Measurements include precursor and product gas species of reactive halogen compounds that impact ozone in the upper troposphere/lower stratosphere. High accuracy, in-situ measurements of ozone obtained during CONTRAST quantify ozone concentration profiles in the UT, where previous observations from balloon-borne ozonesondes were often near or below the limit of detection. CONTRAST was one of the three coordinated experiments to observe the TWP during January-February 2014. Together, CONTRAST, ATTREX and CAST, using complementary capabilities of the three aircraft platforms as well as ground-based instrumentation, provide a comprehensive quantification of the regional distribution and vertical structure of natural and pollutant trace gases in the TWP during NH winter, from the oceanic boundary to the lower stratosphere.

Kinetic evaluation of glucose 1-phosphate analogues with a thymidylyltransferase using a continuous coupled enzyme assay.

Cps2L, a thymidylytransferase, is the first enzyme in Streptococcus pneumoniae L-rhamnose biosynthesis and an antibacterial target. We herein report the evaluation of six sugar phosphate analogues selected to further probe Cps2L substrate tolerance. A modified continuous spectrophotometric assay was employed for facile detection of pyrophosphate (PPi) released from nucleotidylyltransfase-catalysed condensation of sugar 1-phosphates and nucleoside triphosphates to produce sugar nucleotides. Additionally, experiments using waterLOGSY NMR spectroscopy were investigated as a complimentary method to evaluate binding affinity to Cps2L.

Children on long-term ventilatory support: 10 years of progress.

OBJECTIVES: To identify the number and current location of all children receiving long-term ventilation (LTV) in the UK, and to establish their underlying diagnoses and ventilatory requirements. DESIGN: Single time-point census completed by members of the UK LTV working party using an electronic-based questionnaire SUBJECTS: All children in the UK at home or in hospital who, when medically stable, continue to need a mechanical aid for breathing following a failure to wean beyond a 3-month period. RESULTS: 933 children under the age of 17 years in 30 regional centres were identified as receiving LTV. 88 children (9.5%) required continuous positive pressure ventilation by tracheostomy over 24 h, while 658 received ventilation while asleep only. Most children are ventilated by a non-invasive mask (n=704; 75%) or tracheostomy (n=206; 22%). Underlying conditions included neuromuscular disease (n=402; 43%), chronic respiratory (n=343; 37%) and central nervous system conditions (n=168; 18%). 129 (14%) children were aged 16 or over. 844 (91%) children were cared for at home with only 49 children listed as being in acute hospital units (n=34) or paediatric intensive care units/high dependency units (n=15). CONCLUSIONS: The last 10 years has seen a very significant increase in the number of children requiring LTV in the UK with an increasing number cared for at home. This reflects both improving technology and increasing clinical expertise in paediatric non-invasive ventilatory support, and a continuing change in attitude towards long-term support, particularly in children with neuromuscular diseases. There are a substantial number of children who soon will require transition to adult services, yet few such services currently exist.

Effect of high versus low initial doses of L-thyroxine for congenital hypothyroidism on thyroid function and somatic growth.

BACKGROUND AND AIMS: The optimal dose of thyroxine (T4) in congenital hypothyroidism (CH) during infancy is controversial. Higher doses lead to improvement in cognitive scores, but have been linked to later behavioural difficulties. We have examined the effects of initial T4 dosage on somatic growth--a putative surrogate marker of overtreatment. METHODS: 314 CH children (214 girls, 100 boys) were analysed according to initial daily dose of T4: Group 1 (25 mug, n = 152), Group 2 (30-40 mug, n = 63) and Group 3 (50 mug, n = 99). Thyroid function and weight, length and occipito-frontal head circumference (OFC) standard deviation score (SDS) were compared at 3, 6, 12, 18, 24 and 36 months of age. Linear growth SDS was compared between the three groups using a regression adjustment model at 12 and 18 months of age using birth weight and 3-month data as baselines. Thyroid function was also compared at diagnosis (T 0), and 7-21 days after the start of treatment (T1). RESULTS: At T1 median thyroid stimulating hormone (TSH) for Groups 1, 2 and 3 was 58, 29 and 4.1 mU/l, respectively (p<0.001), Group 3 values remaining significantly lower at 3 and 6 months. Median free T4 (fT4) was within or just above the reference range in all groups at T1, but 7.4% of Group 1 had values <9 pmol/l compared with 5.1% and 0% for Groups 2 and 3, respectively. At 3 months weight, length and OFC SDS values were -0.39, -0.35, 0.09; -0.30, -0.47, 0.32; and -0.03, -0.13, 0.18 for Groups 1, 2 and 3, respectively, indicating relatively large OFC in all infants. A regression adjustment model showed no significant difference in growth rate from baseline and 12 or 18 months of age, between the three groups. CONCLUSION: An initial T4 dose of 50 mug daily, normalises thyroid function several months earlier than lower-dose regimes, with no evidence of sustained somatic overgrowth between 3 months and 3 years.

Children admitted with acute wheeze/asthma during November 1998-2005: a national UK audit.

OBJECTIVE: To report 8 years' data from a UK-wide audit of acute wheeze/asthma management in children carried out annually since 1998. DESIGN: Paediatricians were invited to complete a simple form based on British Thoracic Society (BTS) asthma guidelines for any child over 1 year of age admitted with acute wheeze/asthma each November from 1998 to 2005. Information was collected about patient demographics, initial hospital severity assessment, in-hospital treatment, asthma education and emergency planning, discharge treatment and follow-up. RESULTS: Data on 9429 admissions were available, with between 53 and 67 centres participating each year. The majority of children were under 5 years of age (median age 3 years). Nearly all were treated with bronchodilators, and around 90% received systemic steroids. Vital signs (pulse and respiratory rate) and oxygen saturation on admission remained stable over the audit period. However, the proportion of admitted children given bronchodilators exclusively by spacer increased from 7% to 44% between 1998 and 2005. The proportion discharged with written asthma plans increased from 24% to 41%. Wide variations were noted between centres in the proportions of children receiving chest x rays and written asthma plans. Children admitted under the care of a respiratory specialist were more likely to have documentation that they had been given written asthma information and a written asthma plan and had had their inhaler device technique checked than if under the care of a general paediatrician. CONCLUSIONS: In many areas, hospital treatment closely followed published guidance. However, some important deficiencies were noted and variations remain. As well as monitoring guideline implementation, national audit can highlight opportunities for research and improving care locally and nationally.

Comparison of work of breathing using drawover and continuous flow anaesthetic breathing systems in children.

We compared the work of breathing under general anaesthesia in children using drawover and continuous flow anaesthetic systems. A pilot study was conducted in four children weighing > 20 kg in whom it would usually be considered appropriate to use breathing systems designed for adult anaesthesia. The pilot study compared work of breathing using the Mapleson D breathing system and the Triservice Anaesthetic Apparatus (TSAA). Work of breathing was calculated using the modified Campbell technique that calculates work using a pressure volume loop derived from oesophageal pressure and airway gas volume measurements. We found no difference in the work of breathing when comparing the Mapleson D and the TSAA in children > 20 kg. Following completion of the pilot study, we conducted a study on 10 children weighing between 10 and 20 kg comparing work of breathing using the Mapleson F breathing system and the TSAA. We found no significant difference in the work of breathing between the Mapleson F and the TSAA for these children. The TSAA can therefore be recommended for use down to a lower weight limit of 10 kg.

Improvement in screening performance and diagnosis of congenital hypothyroidism in Scotland 1979-2003.

AIM: To assess the Scottish newborn screening programme for congenital hypothyroidism from 1994 to 2003 (period 2) for performance and compare with an initial audit covering 1979 to 1993 (period 1). DESIGN: Performance data-age at blood spot sampling, notification by screening laboratory, start of treatment, and the prevalence of late testing, notification or treatment-were compared, together with the incidence of congenital hypothyroidism. RESULTS: Comparing data for period 2 with period 1, the mean annual incidence of true congenital hypothyroidism was 1:3655 live births v 1:4363. Median age for Guthrie sampling (all referrals) was 6 v 7 days (p<0.0001). Late sampling (>10 days) had fallen from 10.7% to 7%. For infants requiring repeat sampling before notification, the median (range) interval between initial and final repeat samples was 11 (1 to 52) compared with 14 (3 to 73) days. Median age at notification for true congenital hypothyroidism was 10 v 12 days (p <0.0001). Late notification (>15 days) was justifiable (mild TSH elevation) in 10 of 13 patients in period 2. Median age at start of treatment for true congenital hypothyroidism had improved to 11 days from 13.5 days. For true congenital hypothyroidism, late treatment (>16 days) occurred in 7% of patients compared with 19% (p<0.0001). CONCLUSIONS: There has been an improvement in performance measures for the congenital hypothyroidism screening programme in Scotland. However, late sampling, occurring primarily in inpatients and which is never justified, remains a problem, while the interval between initial and recall sampling is a further source of delay.

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Contraceptive responses of mice immunized with purified recombinant mouse zona pellucida subunit 3 (mZP3) proteins.

Mouse zona pellucida subunit 3 (mZP3) was tested for efficacy as an immunocontraceptive antigen by comparing the fertility of mice immunized with recombinant mZP3 proteins. Recombinant protein was expressed using either the vaccinia virus T7 mammalian (vmZP3 protein) or baculovirus insect cell (bmZP3 protein)-expression systems. Female BALB/c or wild mice were immunized by i.p. injection using Freund's complete adjuvant and boosted three times with affinity purified recombinant proteins in Freund's incomplete adjuvant. Most mice developed antibodies that crossreacted to the respective mZP3 antigens by ELISA or western blot. In BALB/c mice immunized with vmZP3, fertility and mean litter size were reduced transiently to 25% and 10%, respectively, of those of control mice. However, immunization with bmZP3 did not affect either the fertility or mean litter sizes in BALB/c or wild mice immunized with bmZP3. The results demonstrate that reduction in fertility can be achieved in female BALB/c mice immunized using Freund's adjuvants and recombinant mZP3 protein produced in a mammalian, but not an insect, cell-expression system. Arguments are presented for the likely role of glycosylation of the mZP3 antigen in inducing contraceptive immune responses.

Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox.

Genetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is characterized by an effective natural killer (NK) response and the early onset of a strong CD8(+) cytotoxic T-lymphocyte (CTL) response in resistant mice. We have investigated the influence of virus-expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4-expressing virus developed symptoms of acute mousepox accompanied by high mortality, similar to the disease seen when genetically sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mousepox. These data therefore suggest that virus-encoded IL-4 not only suppresses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.

Sporadic acute hepatitis E in the united kingdom: an underdiagnosed phenomenon?

BACKGROUND: Hepatitis E (HEV) is the primary cause of enterically transmitted non-A non-B hepatitis worldwide. Case reports of HEV in individuals in the United Kingdom relate to travel to endemic areas or contact with individuals who have visited these areas. CASE REPORTS: Four individuals presented with acute hepatitis to a hepatology clinic in a teaching hospital. Serology confirmed acute hepatitis E in all four. Investigation by the Communicable Disease Control Department established no links between the cases, no travel to an endemic area, and no contacts. CONCLUSION: Contrary to current belief, community acquired hepatitis E virus infection occurs sporadically in the United Kingdom and should be considered as a cause of seronegative hepatitis.

Cloning and characterization of the cDNA encoding the PH20 protein in the European red fox Vulpes vulpes.

The PH20 protein is thought to play a crucial role in mammalian fertilization. The fox PH20 homologue has been cloned from a testis cDNA library and the deduced protein sequence shows high levels of homology to PH20 proteins isolated from other species. Unlike other PH20 proteins the fox protein does not appear to be membrane associated through a GPI-linkage nor does it show the presence of a transmembrane domain at the C-terminus of the protein. It is in this region that the proteins appear to be least conserved. Immunolocalization studies on fox sperm show that the PH20 protein is located on the inner acrosomal membrane. Transcription of PH20 in the fox is seasonally regulated, with the mRNA expressed during those months when spermatogenesis is at its peak. The PH20 sequence described in this paper has been submitted to the Genbank database and has the accession number U41412.

Community outbreak of psittacosis in a rural Australian town.

BACKGROUND: Health authorities in Victoria, Australia were notified of three men from a rural town with atypical pneumonia, admitted to hospital over 8 days. Initial serological testing suggested Chlamydia psittaci as the cause. We did a case-control study to find risk factors for psittacosis. METHODS: We searched for cases of pneumonia or severe flu-like illness through family physicians and the regional hospital. We selected three controls per case from the region's electoral roll. We collected blood for serological tests and administered questionnaires to all cases and controls. FINDINGS: We found 16 cases of psittacosis and one died. Most cases were clustered within a small geographical area, with a median age of 58 years (range 23-76), 15 (94%) of whom were male. Keeping, handling, or feeding domestic or wild birds was not associated with illness. Cases spent a median of 17.5 h per week in their garden, compared with a median of 5.2 h for controls (p=0.04) and were more likely to have mowed lawns during the 3 weeks before onset of illness than controls (odds ratio 4.81 [95% CI 1.08-33.37]). INTERPRETATION: We showed that psittacosis outbreaks are not limited to direct contact with birds and pose new challenges for disease control. Modifications may be needed to work outdoors to decrease the risk of psittacosis.

Generic nursing outcome objectives for use in long-term care facilities.

Twenty-two registered nurses employed in four long-term care facilities generated data for a study about nursing diagnoses in long-term care (N = 360). Generic outcome objectives were developed as an integral part of the project. The research team also specified exceptions to the outcomes: instances where meeting outcome objectives might not be possible. The outcome objectives and exceptions for the sample's 20 most frequently occurring nursing diagnoses are presented as working statements. The authors expect that these outcome objectives and exceptions will be revised by nurses who use them in practice, basic and continuing education, and research.

Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds.

CDKN2A (9p21) and CDK4 (12q13) have been identified as melanoma susceptibility genes in certain familial melanoma (FM) kindreds. There remain other FM families, however, for which there is little or no evidence for linkage of melanoma to these loci. Other loci may be involved in susceptibility to this malignancy. Chromosome 6 is deleted or rearranged in 66% of melanomas and has been targeted by several studies in an attempt to identify chromosomal regions associated with initiation or progression of melanoma. Previous studies of familial melanoma and chromosome arm 6p reported evidence suggestive of linkage for markers flanking the HLA complex. We have carried out genetic linkage analysis in 14 Australian familial melanoma kindreds using 16 short tandem repeat polymorphism (STRP) markers spanning 6p23-6q27. Analysis by maximum likelihood and non-parametric (affected pedigree member) techniques showed no evidence of linkage of melanoma in this family set to chromosome 6 (two-point Zmax = 0.5 at theta = 0.2 for D6S285). Lod scores > 1.0 were obtained for the loci D6S285, D6S105, D6S265, D6S292, and D6S311 in three individual kindreds but these were insufficiently strong for formal heterogeneity testing to confirm that a chromosome 6-linked subset of families exists. These data imply little or no role for a major chromosome 6 melanoma susceptibility locus; however the possibility of such a locus remains open and warrants further investigation.

A case of human anthrax in Victoria.

A human case of anthrax was identified through surveillance of knackery workers who had been exposed to infected cattle. The outbreak in cattle has affected 38 herds in the Stanhope/Tatura area of central northern Victoria. The human case, a 39 year old male, was treated in hospital and is recovering. Surveillance of other knackery workers has now been completed, and no other cases were found. Public health measures are in place to prevent further human cases.

Non-toxigenic Corynebacterium diphtheriae biovar gravis: evidence for an invasive clone in a south-eastern Australian community.

OBJECTIVE: To determine the prevalence and clonality of non-toxigenic Corynebacterium diphtheriae biovar gravis in a community with two cases of endocarditis caused by this organism. SETTING: A Koorie (Aboriginal) community in Gippsland, eastern Victoria, in 1994. METHODS: Nose and throat swabs were collected from 359 community contacts of the cases and cultured for C. diphtheriae. Strains isolated from the contacts were compared by pulsed-field gel electrophoresis (after digestion with Sma1, Not1 and Sfi1) with those from the invasive cases in the same community, another invasive case in Victoria, a cluster of invasive cases in New South Wales (NSW) (1990-1991), and other stored strains isolated from skin ulcers and sore throats. RESULTS: Non-toxigenic strains of C. diphtheriae biovar gravis were isolated from throat swabs of five of the case contacts. Uniform DNA patterns were found for the two community cases, the other Victorian case, nine of ten isolates from NSW, and the five throat isolates from case contacts. CONCLUSION: An invasive clone of C. diphtheriae biovar gravis appears to have been responsible for the three Victorian cases of endocarditis. It was also present among case contacts and responsible for previous invasive cases in NSW. Prophylactic treatment should be considered for clearly defined contacts in all instances where C. diphtheriae is isolated from a normally sterile site, regardless of the toxigenic nature of the strain.

Analysis of the p16 gene, CDKN2, in 17 Australian melanoma kindreds.

CDKN2 has been implicated as a melanoma susceptibility gene in some kindreds with a family history of this disease. Mutation analysis of CDKN2 in 17 familial melanoma Australian kindreds revealed a paucity of exon mutations and none of the previously described disease-related mutations. One novel germline mutation was found in exon one, Arg24Pro, which segregates with melanoma in 1/17 kindreds. Two previously described polymorphisms, Ala148Thr and a base change at nucleotide 540 were detected and one novel polymorphism in the untranslated region of exon 3 (nucleotide 580) was also found. Together with other recent reports, these findings provide support for CDKN2 as a susceptibility locus for familial melanoma but suggest that other loci are involved in some hereditary melanoma kindreds.

Alterations in erythrocyte band 3 organization induced by the photosensitizer, hematoporphyrin derivative.

Photosensitization of erythrocytes in the presence of hematoporphyrin derivative causes cross-linking of membrane proteins. This cross-linking is associated with partial lysis of the cells and an increased susceptibility to heat-induced membrane fragmentation. The effect of photosensitization on the organization of erythrocyte band 3 was monitored using the technique of time-resolved phosphorescence anisotropy. Band 3 rotational diffusion was somewhat restricted upon photooxidation, indicating aggregation of this major integral membrane protein.