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1.
Nat Commun ; 11(1): 4161, 2020 08 19.
Article in English | MEDLINE | ID: mdl-32814777

ABSTRACT

Variability is a problem for the scalability of semiconductor quantum devices. The parameter space is large, and the operating range is small. Our statistical tuning algorithm searches for specific electron transport features in gate-defined quantum dot devices with a gate voltage space of up to eight dimensions. Starting from the full range of each gate voltage, our machine learning algorithm can tune each device to optimal performance in a median time of under 70 minutes. This performance surpassed our best human benchmark (although both human and machine performance can be improved). The algorithm is approximately 180 times faster than an automated random search of the parameter space, and is suitable for different material systems and device architectures. Our results yield a quantitative measurement of device variability, from one device to another and after thermal cycling. Our machine learning algorithm can be extended to higher dimensions and other technologies.

2.
Science ; 359(6371): 69-71, 2018 01 05.
Article in English | MEDLINE | ID: mdl-29302009

ABSTRACT

The 30 Doradus star-forming region in the Large Magellanic Cloud is a nearby analog of large star-formation events in the distant universe. We determined the recent formation history and the initial mass function (IMF) of massive stars in 30 Doradus on the basis of spectroscopic observations of 247 stars more massive than 15 solar masses ([Formula: see text]). The main episode of massive star formation began about 8 million years (My) ago, and the star-formation rate seems to have declined in the last 1 My. The IMF is densely sampled up to 200 [Formula: see text] and contains 32 ± 12% more stars above 30 [Formula: see text] than predicted by a standard Salpeter IMF. In the mass range of 15 to 200 [Formula: see text], the IMF power-law exponent is [Formula: see text], shallower than the Salpeter value of 2.35.

3.
Epidemiol Infect ; 142(8): 1713-21, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24534254

ABSTRACT

Our aim was to describe the epidemiology and incidence of community-onset invasive S. aureus disease in children presenting to our hospital, and to compare the clonal complexes and virulence genes of S. aureus strains causing invasive and non-invasive disease. The virulence gene repertoire of invasive disease isolates was characterized using DNA microarray and compared with the virulence gene repertoire of non-invasive S. aureus isolates. Over the study period, 163 children had an invasive S. aureus infection. There was no difference in the distribution of clonal complexes or in the prevalence of genes encoding virulence factors between invasive and non-invasive isolates. Future research should include a strong focus on identifying the host and environmental factors that, along with organism virulence factors, are contributing to the patterns of invasive S. aureus disease observed in New Zealand.


Subject(s)
Community-Acquired Infections/epidemiology , Community-Acquired Infections/pathology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/pathology , Staphylococcus aureus/classification , Staphylococcus aureus/genetics , Adolescent , Child , Child, Preschool , Cluster Analysis , Community-Acquired Infections/microbiology , Cross-Sectional Studies , Genotype , Humans , Incidence , Infant , Infant, Newborn , Microarray Analysis , Molecular Epidemiology , Molecular Typing , New Zealand/epidemiology , Retrospective Studies , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Virulence Factors/genetics
4.
Pediatr Pulmonol ; 48(8): 772-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22997178

ABSTRACT

Severe lower respiratory infection (LRI) is believed to be one precursor of protracted bacterial bronchitis, chronic moist cough (CMC), and chronic suppurative lung disease. The aim of this study was to determine and to describe the presence of respiratory morbidity in young children 1 year after being hospitalized with a severe LRI. Children aged less than 2 years admitted from August 1, 2007 to December 23, 2007 already enrolled in a prospective epidemiology study (n = 394) were included in this second study only if they had a diagnosis of severe bronchiolitis or of pneumonia with no co-morbidities (n = 237). Funding allowed 164 to be identified chronologically, 131 were able to be contacted, and 94 agreed to be assessed by a paediatrician 1 year post index admission. Demographic information, medical history and a respiratory questionnaire was recorded, examination, pulse oximetry, and chest X-ray (CXR) were performed. The predetermined primary endpoints were; (i) history of CMC for at least 3 months, (ii) the presence of moist cough and/or crackles on examination in clinic, and (iii) an abnormal CXR when seen at a time of stability. Each CXR was read by two pediatric radiologists blind to the individuals' current health. Results showed 30% had a history of CMC, 32% had a moist cough and/or crackles on examination in clinic, and in 62% of those with a CXR it was abnormal. Of the 81 children with a readable follow-up X-ray, 11% had all three abnormal outcomes, and 74% had one or more abnormal outcomes. Three children had developed bronchiectasis on HRCT. The majority of children with a hospital admission at <2 years of age for severe bronchiolitis or pneumonia continued to have respiratory morbidity 1 year later when seen at a time of stability, with a small number already having sustained significant lung disease.


Subject(s)
Health Status , Hospitalization , Respiratory Tract Infections/epidemiology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Morbidity/trends , New Zealand/epidemiology , Prognosis , Radiography, Thoracic , Respiratory Tract Infections/diagnostic imaging , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors
5.
Phys Rev Lett ; 108(17): 170503, 2012 Apr 27.
Article in English | MEDLINE | ID: mdl-22680846

ABSTRACT

We have investigated the driven dynamics of a superconducting flux qubit that is tunably coupled to a microwave resonator. We find that the qubit experiences an oscillating field mediated by off-resonant driving of the resonator, leading to strong modifications of the qubit Rabi frequency. This opens an additional noise channel, and we find that low-frequency noise in the coupling parameter causes a reduction of the coherence time during driven evolution. The noise can be mitigated with the rotary-echo pulse sequence, which, for driven systems, is analogous to the Hahn-echo sequence.

6.
J Chem Phys ; 134(21): 214704, 2011 Jun 07.
Article in English | MEDLINE | ID: mdl-21663372

ABSTRACT

A series of five alumina-supported palladium catalysts have previously been prepared and characterised by a combination of CO chemisorption and infrared spectroscopy. The reactive attributes of these catalysts are examined using the hydrogenation of crotonaldehyde as a test reaction, using a modified infrared gas cell as a batch reactor. Periodic scanning of the infrared spectrum of the gaseous phase present over the Pd/Al(2)O(3) catalysts was used to construct reaction profiles. Four of the catalysts were able to facilitate a 2-stage hydrogenation process (crotonaldehyde → butanal → butanol), whilst one catalyst was totally selective for the first stage hydrogenation process (crotonaldehyde → butanal). Rate coefficients for the first and second stage hydrogenation processes are normalised to the number of surface palladium atoms for the particular catalyst. Correlation of these kinetic parameters as a function of mean particle size indicates the first stage process to be structure insensitive, whilst the second stage hydrogenation is structure sensitive. Chlorine residues associated with the preparative process of one of the catalysts is seen to selectively poison the second stage hydrogenation process for that catalyst. Structure/activity relationships are considered to explain the observed trends.

7.
J Clin Microbiol ; 48(10): 3470-4, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20686081

ABSTRACT

Panton-Valentine leukocidin (PVL) has been linked to invasive community-acquired methicillin-resistant Staphylococcus aureus infections. However, the association between disease and PVL-positive methicillin-susceptible Staphylococcus aureus (MSSA) has not been widely reported. We aimed to examine the epidemiology of PVL in clinical MSSA isolates from patients presenting to Auckland City Hospital. Four hundred eleven MSSA clinical isolates and 93 nasal carriage isolates were collected and tested for the presence of the lukSF-PV genes using PCR. The results were examined in light of host and disease factors. Multilocus sequence typing (MLST) was performed on a random subset of isolates to ensure that there was no single PVL-positive MSSA clone responsible for disease in Auckland. The prevalence of the lukSF-PV genes in MSSA isolates associated with disease (124/335; 37%) was not significantly different from the prevalence of the lukSF-PV genes in MSSA nasal carriage isolates (29/93; 31% [P = 0.33]). PVL-positive MSSA isolates in Auckland are genetically diverse and come from a number of different clonal complexes. PVL-positive infections peaked at between 10 and 20 years of age, with a subsequent decline. Pacific ethnicity, age, diagnosis of skin and soft tissue infection (SSTI), community-onset infection, and the need for surgical intervention were found by multivariate analysis to be independently associated with PVL-positive MSSA infection. More than one-third of MSSA infections in our patient population are caused by PVL-positive strains. Those patients with PVL-positive MSSA infection were more likely to be of Pacific ethnicity, be younger in age, have community-onset infection, have SSTI, and need surgical intervention.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Toxins/biosynthesis , Exotoxins/biosynthesis , Leukocidins/biosynthesis , Methicillin/pharmacology , Staphylococcal Infections/epidemiology , Staphylococcus aureus/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Proteins/genetics , Bacterial Toxins/genetics , Carrier State/epidemiology , Carrier State/microbiology , Child , Child, Preschool , DNA, Bacterial/genetics , Exotoxins/genetics , Female , Humans , Incidence , Infant , Infant, Newborn , Leukocidins/genetics , Male , Middle Aged , New Zealand/epidemiology , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Risk Factors , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/pathogenicity , Treatment Outcome , Virulence Factors/biosynthesis , Virulence Factors/genetics , Young Adult
8.
Opt Express ; 17(7): 5193-204, 2009 Mar 30.
Article in English | MEDLINE | ID: mdl-19333283

ABSTRACT

SOI CMOS compatible Si waveguide photodetectors are made responsive from 1100 to 1750 nm by Si+ implantation and annealing. Photodiodes have a bandwidth of >35 GHz, an internal quantum efficiency of 0.5 to 10 AW-1, and leakage currents of 0.5 nA to 0.5 microA. Phototransistors have an optical response of 50 AW-1 with a bandwidth of 0.2 GHz. These properties are related to carrier mobilities in the implanted Si waveguide. These detectors exhibit low optical absorption requiring lengths from <0.3 mm to 3 mm to absorb 50% of the incoming light. However, the high bandwidth, high quantum efficiency, low leakage current, and potentially high fabrication yields, make these devices very competitive when compared to other detector technologies.


Subject(s)
Photometry/instrumentation , Silicon/chemistry , Transducers , Transistors, Electronic , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Infrared Rays , Microwaves , Reproducibility of Results , Sensitivity and Specificity , Silicon/radiation effects
9.
Arch Dis Child ; 94(10): 745-51, 2009 Oct.
Article in English | MEDLINE | ID: mdl-18838420

ABSTRACT

BACKGROUND: A tailor-made serogroup B outer membrane vesicle vaccine was evaluated in the context of a serogroup B meningococcal epidemic dominated by Neisseria meningitidis strain B:4:P1.7b,4. OBJECTIVE: To determine the safety, reactogenicity and immunogenicity in infants aged 6-8 months of a meningococcal B vaccine developed against the New Zealand epidemic strain. DESIGN, SETTING AND PARTICIPANTS: Observer-blind, randomised, controlled trial conducted in 296 healthy infants in Auckland, New Zealand. INTERVENTION: Infants were randomised 4:1 to receive three doses of New Zealand candidate vaccine (epidemic strain NZ98/254, B:4:P1.7b,4) or meningococcal C conjugate vaccine at 6-weekly intervals. MAIN OUTCOME MEASURES: Immune response was determined by human complement mediated serum bactericidal assay. Sero-response was a fourfold or greater rise in titre compared to baseline, with baseline titres <4 required to increase to >or=8. Blood samples were taken before vaccination, 6 weeks after dose two, and 4 weeks after dose three. Local and systemic reactions were recorded for 7 days following vaccination. RESULTS: Sero-response to the candidate vaccine strain, NZ98/254, was demonstrated in 74% of vaccinees (95% CI: 68% to 80% intention-to-treat; 67% to 79% per protocol) after three doses of New Zealand candidate vaccine. No meningococcal C conjugate vaccine recipients were sero-responders to NZ98/254 after three doses. Both vaccines were well tolerated with no vaccine related serious adverse events. CONCLUSIONS: Our data indicate that the New Zealand candidate vaccine administered in three doses to this group of 6-8-month-old infants was safe and immunogenic against the candidate vaccine strain NZ98/254 (Neisseria meningitidis B:4:P1.7b,4).


Subject(s)
Antibodies, Bacterial/biosynthesis , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/immunology , Antibodies, Bacterial/blood , Female , Humans , Immunization Schedule , Infant , Male , Meningitis, Meningococcal/immunology , Meningococcal Vaccines/adverse effects , Single-Blind Method
10.
Opt Express ; 16(15): 11027-31, 2008 Jul 21.
Article in English | MEDLINE | ID: mdl-18648416

ABSTRACT

A broadband, Mach-Zehnder-interferometer based silicon optical modulator is demonstrated, with an electrical bandwidth of 26 GHz and V(pi)L of 4 V.cm. The design of this modulator does not require epitaxial overgrowth and is therefore simpler to fabricate than previous devices with similar performance.


Subject(s)
Interferometry/instrumentation , Optics and Photonics/instrumentation , Semiconductors , Signal Processing, Computer-Assisted/instrumentation , Silicon/chemistry , Telecommunications/instrumentation , Equipment Design , Equipment Failure Analysis
11.
Arch Dis Child ; 93(6): 474-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18337284

ABSTRACT

BACKGROUND: Rheumatic fever is a preventable chronic disease preceded by group A beta-haemolytic streptococcal (GABHS) pharyngitis. OBJECTIVE: To test the non-inferiority of once-daily (QD) oral amoxicillin to the recommended twice-daily (BID) oral penicillin V in GABHS pharyngitis. METHODS: This was a randomised non-inferiority trial carried out in a school-based clinic in New Zealand. Children presenting with GABHS pharyngitis were randomised to oral amoxicillin 1500 mg QD (or 750 mg if bodyweight was

Subject(s)
Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Penicillin V/administration & dosage , Pharyngitis/drug therapy , Rheumatic Fever/prevention & control , Streptococcal Infections/drug therapy , Acute Disease , Child , Child, Preschool , Drug Administration Schedule , Female , Humans , Male , Microbial Sensitivity Tests , New Zealand , Pharyngitis/microbiology , Rheumatic Fever/drug therapy , Streptococcal Infections/microbiology , Treatment Outcome
12.
Opt Express ; 15(25): 16886-95, 2007 Dec 10.
Article in English | MEDLINE | ID: mdl-19550979

ABSTRACT

CMOS compatible infrared waveguide Si photodiodes are made responsive from 1100 to 1750 nm by Si(+) implantation and annealing. This article compares diodes fabricated using two annealing temperatures, 300 and 475 degrees C. 0.25-mm-long diodes annealed to 300 degrees C have a response to 1539 nm radiation of 0.1 A W-(-1) at a reverse bias of 5 V and 1.2 A W(-1) at 20 V. 3-mm-long diodes processed to 475 degrees C exhibited two states, L1 and L2, with photo responses of 0.3 +/-0.1 A W(-1) at 5 V and 0.7 +/-0.2 A W(-1) at 20 V for the L1 state and 0.5 +/-0.2 A W(-1) at 5 V and 4 to 20 A W(-1)-1 at 20 V for the L2 state. The diodes can be switched between L1 and L2. The bandwidths vary from 10 to 20 GHz. These diodes will generate electrical power from the incident radiation with efficiencies from 4 to 10 %.

13.
Vaccine ; 24(9): 1395-400, 2006 Feb 27.
Article in English | MEDLINE | ID: mdl-16242221

ABSTRACT

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.


Subject(s)
Meningococcal Infections/prevention & control , Meningococcal Vaccines/adverse effects , Meningococcal Vaccines/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Human Experimentation , Humans , Meningococcal Vaccines/administration & dosage , Middle Aged , New Zealand , Single-Blind Method , Species Specificity
14.
Phys Chem Chem Phys ; 7(16): 3093-101, 2005 Aug 21.
Article in English | MEDLINE | ID: mdl-16186915

ABSTRACT

The industrially important interaction of methanol with an eta-alumina catalyst has been investigated by a combination of infrared spectroscopy (diffuse reflectance and transmission) and inelastic neutron scattering (INS) spectroscopy. The infrared and INS spectra together show that chemisorbed methoxy is the only surface species present. Confirmation of the assignments was provided by a periodic DFT calculation of methoxy on eta-alumina (110). The thermal conversion of adsorbed methoxy groups to form dimethylether was also followed by INS, with DFT calculations assisting assignments. An intense feature about 2600 cm(-1) was observed in the diffuse reflectance spectrum. This band is poorly described in the extensive literature on the alumina/methanol adsorption system and its observation raised the possibility of a new surface species existing on this particular catalyst surface. INS measurements established that the 2600 cm(-1) feature could be assigned to a combination band of the methyl rock with the methyl deformation modes. This assignment was reinforced by an analysis of the neutron scattering intensity at a particular energy as a function of momentum transfer, which confirmed this particular adsorbed methoxy feature to arise from a second order transition. Similar behaviour was observed in the model compound Al(OCH3)3. The anomalous infrared intensity of the 2600 cm(-1) peak in the diffuse reflectance spectrum is a consequence of the different absorption coefficients of the C-H stretch and the combination mode. The implications for catalyst studies are discussed.


Subject(s)
Aluminum Oxide/chemistry , Methanol/chemistry , Models, Chemical , Models, Molecular , Neutron Diffraction/methods , Spectrophotometry, Infrared/methods , Aluminum Oxide/analysis , Computer Simulation , Elasticity , Methanol/analysis
15.
J Bone Joint Surg Am ; 85-A Suppl 2: 93-100, 2003.
Article in English | MEDLINE | ID: mdl-12721350

ABSTRACT

BACKGROUND: Progenitor cells in mesenchymal tissues are important in the maintenance of tissue homeostasis and regeneration capacity. Articular cartilage is a tissue with a very low capacity for repair. One explanation could be the lack of chondrogenic progenitor cells within the adult tissue. As a test of chondrogenic differentiation potential, we examined the ability of isolated chondrocytes to take on several phenotypic identities within the mesenchymal lineage by applying culture techniques and markers used in the study of the phenotypic plasticity of marrow-derived mesenchymal stem cells (MSCs). METHODS: Culture-expanded human articular chondrocytes were analyzed for chondrogenic, adipogenic, and osteogenic capacity in defined in vitro culture systems. The osteochondrogenic potential of cells loaded into porous calcium-phosphate ceramic cubes implanted into mice was also determined. RESULTS: The different assays demonstrated that culture-expanded chondrocytes have the potential to form cartilage in pellet mass cultures, to form adipose cells in dense monolayer cultures, and to form a calcium-rich matrix in an osteogenic assay. In the in vitro assays, a variability of phenotypic plasticity was demonstrated among the donors. In contrast with MSCs, chondrocytes formed cartilage only (and not bone) in the in vivo osteochondrogenic assay. CONCLUSIONS: These results suggest that, within articular cartilage, there are chondrogenic cells that exhibit a level of phenotypic plasticity that is comparable with that of MSCs. However, there was a difference in the expression of bone in the in vivo assay.


Subject(s)
Cartilage, Articular/cytology , Cell Differentiation , Chondrocytes/cytology , Stem Cells/cytology , Adipose Tissue , Alkaline Phosphatase/analysis , Animals , Bone and Bones/cytology , Calcium/analysis , Cells, Cultured , Chondrocytes/chemistry , Chondrogenesis , DNA/analysis , Humans , Mice , Mice, SCID , Osteogenesis , Phenotype
16.
J Paediatr Child Health ; 39(1): 40-5, 2003.
Article in English | MEDLINE | ID: mdl-12542811

ABSTRACT

OBJECTIVES: To determine the current management of bronchiolitis by five major New Zealand hospitals and to identify areas for improvement. METHODS: Lists of infants under 1 year of age admitted with bronchiolitis during 1998 were obtained from the casemix offices of the five largest New Zealand hospitals with paediatric services. Hospital records from a random sample of these admissions were reviewed. RESULTS: Out of the 409 infants admitted overnight, 8% had been born less than or=32 weeks gestation and 53% were aged younger than 6 months. Overall, 59% received oxygen, 21% had nasogastric fluids, 22% had intravenous fluids, 34% were prescribed antibiotics, 42% received bronchodilators and 60% had a chest radiograph. Respiratory secretions were collected for viral studies from 58% of infants and, in 59%, respiratory syncytial virus was detected. Significant variations in management were detected between hospitals. The overall proportion of infants requiring oxygen, intravenous or nasogastric fluids (65%) was significantly higher than that found in a 1986-1988 Christchurch study where only 25% received one or more of these interventions (P < 0.001). CONCLUSIONS: Opportunities exist to rationalize bronchiolitis management in New Zealand with potential cost savings, particularly by reducing the number of chest radiographs and prescribing of unnecessary antibiotics and bronchodilators.


Subject(s)
Bronchiolitis/therapy , Hospitals, Community/standards , Infant Care/standards , Anti-Bacterial Agents/therapeutic use , Bronchiolitis/diagnostic imaging , Bronchiolitis/drug therapy , Bronchodilator Agents/therapeutic use , Evidence-Based Medicine , Female , Fluid Therapy , Guideline Adherence , Humans , Infant , Infant, Newborn , Length of Stay , Male , New Zealand , Oxygen Inhalation Therapy , Radiography , Risk Factors , Severity of Illness Index
17.
J Paediatr Child Health ; 38(6): 550-4, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12410864

ABSTRACT

Palivizumab prophylaxis significantly reduces hospitalization for respiratory syncytial virus (RSV) disease in preterm infants. However, palivizumab is very expensive. Data from a New Zealand cost-effectiveness analysis were considered by representatives of the Infectious Diseases and Immunisation, Fetus and Newborn, and Respiratory Committees of the Paediatric Society of New Zealand. Prophylaxis in all high-risk groups was associated with net cost. The consensus panel recommends that the priority for palivizumab be given to babies discharged on home oxygen with chronic lung disease, followed by babies born at 28 weeks or less gestation.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Infant, Premature , Respiratory Syncytial Virus Infections/prevention & control , Antibodies, Monoclonal/economics , Antibodies, Monoclonal, Humanized , Antiviral Agents/economics , Cost-Benefit Analysis , Drug Costs , Humans , Infant , Infant, Newborn , New Zealand , Palivizumab , Patient Readmission/statistics & numerical data , Premedication/economics , Risk Factors
18.
J Paediatr Child Health ; 38(4): 352-7, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12173995

ABSTRACT

OBJECTIVE: To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab. METHODS: The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization. RESULTS: Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those " 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants " 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings. CONCLUSION: If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less.


Subject(s)
Antibodies, Monoclonal/economics , Antiviral Agents/economics , Hospital Costs , Infant, Premature , Intensive Care Units, Neonatal/economics , Respiratory Syncytial Virus Infections/prevention & control , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , Humans , Infant, Newborn , Models, Econometric , New Zealand/epidemiology , Palivizumab , Patient Readmission/economics , Respiratory Syncytial Virus Infections/epidemiology , Risk
19.
J Paediatr Child Health ; 38(3): 272-7, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12047696

ABSTRACT

OBJECTIVE: To determine in New Zealand infants the attack rates, risk factors, preventive policies, strain serotype and antibiotic susceptibilities of early-onset neonatal group B streptococcus (GBS) infection. METHOD: A 2-year prospective active surveillance study was conducted in New Zealand's 19 neonatal units. Cases had to present within 48 h of delivery, be unwell, possess abnormal haematological indices and have GBS isolated from sterile sites. RESULTS: Of the 112 402 infants born in New Zealand during 1998-1999, 56 had early-onset GBS infection, an attack rate of 0.5 per 1000 live births (95% confidence interval [CI] 0.38, 0.65). Seven had meningitis and there was one death (case fatality rate of 1.8%; upper 95% CI 9.5%). Univariate analysis identified young maternal age, parity, preterm labour, prolonged membrane rupture, maternal fever and assisted delivery as risk factors. Preventive policies for GBS were reported by 14 (74%) obstetric centres associated with neonatal units. Of the 56 cases, five (9%) were born to mothers receiving intrapartum antibiotics, 32 (57%) had mothers with risk factors but were not treated with antibiotics, and 19 (34%) were born to mothers without identifiable risk factors for GBS prevention. Serotypes Ia and III predominated, while two isolates were resistant to erythromycin and/or clindamycin. CONCLUSIONS: Rates of early-onset GBS infection are similar to other countries following the introduction of prevention policies. Further reductions are possible with full implementation of these guidelines. Meanwhile, emergence of antibiotic resistance complicates the management of women with penicillin allergy. Vaccine development therefore remains a priority.


Subject(s)
Drug Resistance, Microbial , Streptococcal Infections/epidemiology , Streptococcus agalactiae/isolation & purification , Adult , Analysis of Variance , Anti-Bacterial Agents/administration & dosage , Cohort Studies , Confidence Intervals , Cross Infection/diagnosis , Cross Infection/epidemiology , Female , Health Care Surveys , Humans , Incidence , Infant, Newborn , Intensive Care Units, Neonatal , Male , Maternal Age , Microbial Sensitivity Tests , Middle Aged , New Zealand/epidemiology , Obstetric Labor, Premature , Parity , Pregnancy , Risk Factors , Severity of Illness Index , Streptococcal Infections/drug therapy , Streptococcal Infections/prevention & control , Streptococcus agalactiae/drug effects , Time Factors
20.
J Virol ; 75(21): 10090-105, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11581377

ABSTRACT

The 192-kb linear DNA genome of vaccinia virus has covalently closed hairpin termini that are extremely AT rich and contain 12 extrahelical bases. Vaccinia virus telomeres have previously been implicated in the initiation of viral genome replication; therefore, we sought to determine whether the telomeres form specific protein-DNA complexes. Using an electrophoretic mobility shift assay, we found that extracts prepared from virions and from the cytoplasm of infected cells contain telomere binding activity. Four shifted complexes were detected using hairpin probes representing the viral termini, two of which represent an interaction with the "flip" isoform and two with the "flop" isoform. All of the specificity for protein binding lies within the terminal 65-bp hairpin sequence. Viral hairpins lacking extrahelical bases cannot form the shifted complexes, suggesting that DNA structure is crucial for complex formation. Using an affinity purification protocol, we purified the proteins responsible for hairpin-protein complex formation. The vaccinia virus I1 protein was identified as being necessary and sufficient for the formation of the upper doublet of shifted complexes, and the vaccinia virus I6 protein was shown to form the lower doublet of shifted complexes. Competition and challenge experiments confirmed that the previously uncharacterized I6 protein binds tightly and with great specificity to the hairpin form of the viral telomeric sequence. Incubation of viral hairpins with extracts from infected cells also generates a smaller DNA fragment that is likely to reflect specific nicking at the apex of the hairpin; we show that the vaccinia virus K4 protein is necessary and sufficient for this reaction. We hypothesize that these telomere binding proteins may play a role in the initiation of vaccinia virus genome replication and/or genome encapsidation.


Subject(s)
DNA-Binding Proteins/metabolism , Telomere , Vaccinia virus/genetics , Viral Core Proteins/metabolism , Viral Proteins/metabolism , Amino Acid Sequence , Animals , DNA Probes , DNA Replication , Mice , Molecular Sequence Data , Protein Structure, Secondary , Virus Replication
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