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Hard-part microchemistry offers a powerful tool for inferring the environmental history and stock assignment of individual fishes. However, despite the applicability of this technique to a wide range of fisheries conservation and management issues, its use has been restricted to only a small fraction of North American species and inland waters. In this article, we provide freshwater fisheries professionals with an accessible review of methods and applications of hard-part microchemistry techniques. Our objectives are to (1) summarize the science of hard-part microchemistry; (2) provide guidelines for designing hard-part microchemistry studies, including sample sizes, laboratory analyses, statistical techniques, and inferential limitations; and (3) identify conservation and management applications where these techniques may be particularly useful. We argue that strategic use of hard-part microchemistry methods (specifically when they are used in concert with other indirect tracer techniques such as stable isotope chemistry and genetics) can advance fish management and conservation across all stages of fish life history. la microquímica de partes duras representa una herramienta poderosa para inferir la historia ambiental y la asignación de stocks en peces. No obstante, a pesar de la aplicabilidad de esta técnica a un amplio rango de aspectos de conservación y manejo de pesquerías, su utilización se ha restringido a sólo una pequeña fracción de especies de aguas continentales en Norte América. En este trabajo, se presenta una revisión accesible de los métodos y aplicaciones de técnicas de microquímica de partes duras, dirigida a los profesionales en pesquerías de aguas interiores. Los objetivos son: (1) resumir la ciencia de la microquímica de partes duras, (2) proporcionar guías para el diseño de estudios de microquímica de partes duras, incluyendo tamaños de muestra, análisis de laboratorio, técnicas estadísticas y limitaciones de orden inferencial, y (3) identificar aplicaciones para la conservación y manejo en las cuales estas técnicas puedan ser particularmente útiles. Se argumenta que la utilización estratégica de métodos de microquímica de partes duras (específicamente cuando éstos son usados en conjunto con otras técnicas de rastreo indirecto como química de isótopos estables y genética) puede abonar a la conservación y manejo de los peces durante todos los estadios de vida.

Surveillance for intussusception (IS) has been recommended in countries using rotavirus vaccine, but can be resource intensive. There is little data about the relative severity of rotavirus vaccine-associated IS compared with other IS cases. We collected detailed clinical data on all cases to evaluate the validity of ICD coding for IS in routinely collected data and case severity.

Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or block expression (>90%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.

Three bacteria—Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis—account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzaemeningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H influenzaemeningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the effect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt.

Pertussis or whooping cough, caused by Bordetella pertussis, remains a global concern. Following the availability of vaccines against pertussis from the mid-1940s, the reported pertussis incidence rate fell dramatically in countries with high vaccine coverage. However, countries with long-standing high pertussis vaccine coverage have, since the 1980s, increasingly identified pertussis in adolescents and adults. In adults ≥65 years of age, there is less data on morbidity but outbreaks in settings such as residential facilities have been associated with severe morbidity including death. The US FDA approved two different tetanus, diphtheria and pertussis vaccines in 2005 for booster vaccination of adolescents and adults, extending usage to adults 18–64 years of age in 2008. Following data demonstrating satisfactory immunogenicity, the FDA approved a single dose of tetanus, diphtheria and pertussis vaccine for use in adults 65 years or older in July 2011. This review will discuss the available data on the disease burden of pertussis in older adults (≥65 years of age) and the potential need for pertussis vaccination in the USA and comparable countries.

Two studies examined a matching hypothesis: Attitudes predict behaviors better when they both involve the same rather than different levels of attitude-relevant action activity. In Study 1, participants listed actions they might take toward gay men and immediately reported their attitudes. One to two weeks later, their reported attitudes were more predictive of behaviors that matched than mismatched the activity level of their listed actions. In Study 2, participants were randomly assigned to make decisions about either active or passive actions toward gay men just before they reported their attitudes. One to two weeks later, their reported attitudes better predicted behaviors that matched than mismatched the type of attitude-relevant action that had been made salient. The results support the importance to attitude–behavior consistency of matching attitude-relevant actions and behavioral measures on activity level, and the utility of considering both positivity and activity level in studies of attitude–behavior consistency.

The pertussis epidemic experienced in NSW in 2008–2009 was likely to be in part due to changes in diagnostic practice since 2007, which amplified disease notifications. We used population-based seroepidemiology as a less biased means of interpreting age-specific pertussis infection patterns in NSW from three serosurveys undertaken in 1997–98 (during an epidemic), 2002 (post-epidemic) and 2007 (inter-epidemic), using a standardised pertussis toxin IgG enzyme-linked immunosorbent assay (ELISA). There was a decrease in the proportion of high anti-pertussis toxin IgG titres (>62.5ELISAUnits/mL) across all age groups in the 2007 serosurvey compared to the previous two serosurveys. In the 2007 serosurvey, the proportion of undetectable (<5ELISAUnits/mL) anti-pertussis toxin IgG titres increased in many age groups. The seroepidemiological profiles of the three serosurveys demonstrate fluctuating immunity profiles related to changes in vaccination schedules.

This annual report, the second in the series, documents trends in immunisation coverage in NSW for children, adolescents and the elderly, to the end of 2010. Methods: Data from the Australian Childhood Immunisation Register, the NSW School Immunisation Program and the NSW Population Health Survey were used to calculate various measures of population coverage, coverage for Aboriginal children and vaccination timeliness for all children. Results: Over 90% coverage has been reached for children at 12 and 24 months of age. For children at 5 years of age there was an improvement during 2010 in timeliness for vaccines due at 4 years and coverage almost reached 90%. Delayed receipt of vaccines is still an issue for Aboriginal children. For adolescents, there is good coverage for the first and second doses of human papillomavirus vaccine and the dose of diphtheria, tetanus and acellular pertussis. The pneumococcal vaccination rate in the elderly has been steadily rising, although it has remained lower than the influenza coverage estimates. Conclusion: Completion of the recommended immunisation schedule at the earliest appropriate age should be the next public health goal at both the state and local health district level. Official coverage assessments for ‘fully immunised’ should include the 7-valent pneumococcal conjugate and meningococcal C vaccines, and wider dissemination should be considered.

Postmarketing surveillance of heptavalent pneumococcal conjugate vaccine (7vPCV) has shown significant reductions in admissions coded as pneumonia in countries where a booster dose is given in the second year of life. In Australia, a 3-dose primary schedule at 2, 4, and 6 months of age without a booster has been funded nationally for non-Indigenous children since 2005.

Aims: This is the first in a series of annual immunisation coverage reports that document trends in NSW for a range of standard measures derived from Australian Childhood Immunisation Register data, including overall coverage at standard age milestones and for individual vaccines. This report includes data up to and including 2009. Methods: Data from the Australian Childhood Immunisation Register, the NSW Health Survey and the NSW School Immunisation Program were used to calculate various measures of population coverage relating to childhood vaccines, adult influenza and pneumococcal vaccines and adolescent vaccination, respectively. Results: Immunise Australia Program targets have been reached for children at 12 and 24 months of age but not for children at 5 years of age. Delayed receipt of vaccines is an issue for vaccines recommended for Aboriginal children. Pneumococcal vaccination in the elderly has been steadily rising, although it has remained lower than the influenza coverage estimates. For adolescents, there is better coverage for the first and second doses of human papillomavirus vaccine and the dose of dTpa than for varicella. Conclusion: This comprehensive analysis provides important baseline data for NSW against which future reports can be compared to monitor progress in improving immunisation coverage. Immunisation at the earliest appropriate age should be a public health goal for countries such as Australia where high levels of vaccine coverage at milestone ages have been achieved.

The challenges of maintaining high influenza vaccination rates in health care workers have focused worldwide attention on mandatory measures. In 2007, NSW Health issued a policy directive requiring health care workers to be screened/vaccinated for certain infectious diseases. Annual influenza vaccine continued to be recommended but not required. This paper describes the views of NSW Health administrators and clinical leaders about adding influenza vaccination to the requirements. Of 55 staff interviewed, 45 provided a direct response. Of these, 23 supported inclusion, 14 did not and eight were undecided. Analysis of interviews indicated that successfully adding influenza vaccination to the current policy directive would require four major issues to be addressed: (1) providing and communicating a solid evidence base supporting the policy directive; (2) addressing the concerns of staff about the vaccine; (3) ensuring staff understand the need to protect patients; and (4) addressing the logistical challenges of enforcing an annual vaccination.

In randomized controlled trials and postmarketing studies the heptavalent pneumococcal conjugate vaccine (7vPCV) has been shown to reduce myringotomy with ventilation tube insertion (MVTI) procedures in a 4-dose schedule. In Australia, a 3-dose schedule at 2, 4, and 6 months of age is routinely used in non-Indigenous children. Our aim was to determine if a reduction in MVTI comparable to that documented in the United States occurred in Australia despite the absence of the booster dose.

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low‐nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low‐nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature‐dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter. Bacteria and fungi contribute to the breakdown of leaf litter in rivers and floodplains. To break down leaf litter, these microbes need the nutrients nitrogen and phosphorus (P), and microbes can get nutrients either from the leaf litter itself or from the environment. Most leaf litter has low nutrient content and microbes must rely on the environment to supply nutrients. We studied microbial nutrient uptake from the environment during litter breakdown to determine whether it varies predictably across the globe and how it is influenced by changing climate and nutrient pollution. In 100 rivers and floodplains in 11 of Earth's major biomes we placed small strips of cotton as stand‐ins for leaf litter. Nutrient uptake was consistently greater on cotton strips that were submerged in the river compared to cotton on the floodplain. For microbes in the river, nutrient uptake was faster in instances where there was more P in the water. For microbes in the floodplain, nutrient uptake was faster where temperatures were warmer. Faster nutrient uptake by microbes was linked with faster cotton breakdown in rivers and floodplains. Our study shows that climate change and nutrient pollution can alter the activity of microbes in rivers and floodplains. Nitrogen (N) and phosphorus (P) immobilization was measured on organic matter (cotton) in 100 rivers and riparian zones representing 11 biomesElevated temperature in riparian zones and phosphate in rivers increased immobilization, and consequently accelerated decompositionN and P immobilization was strongly linked by microbial stoichiometry despite widely varied surface‐water nutrient ratios Nitrogen (N) and phosphorus (P) immobilization was measured on organic matter (cotton) in 100 rivers and riparian zones representing 11 biomes Elevated temperature in riparian zones and phosphate in rivers increased immobilization, and consequently accelerated decomposition N and P immobilization was strongly linked by microbial stoichiometry despite widely varied surface‐water nutrient ratios

Hydropower production is one of the greatest threats to fluvial ecosystems and freshwater biodiversity. Now that we have entered the Anthropocene, there is an opportunity to reflect on what might constitute a ‘sustainable’ Anthropocene in the context of hydropower and riverine fish populations. Considering elements of existing practices that promote favorable social-ecological outcomes (i.e., ‘bright spots’) is timely given that there are plans to expand hydropower capacity in previously undammed rivers, intensify dam development in some of the world's largest river systems, and re-license existing facilities. We approach this from a pragmatic perspective: for the foreseeable future, hydropower will likely remain an important source of renewable electricity. To offer support for moving toward a more ‘sustainable’ Anthropocene, we provide syntheses of best practices during the siting, design, construction, operation, and compensation phases of hydropower development to minimize impacts on inland fish. For each phase, we offer positive examples (or what might be considered ‘bright spots’) pertaining to some of the approaches described within our syntheses, acknowledging that these projects may not be viewed as without ecological and (or) societal detriment by all stakeholders. Our findings underscore the importance of protecting critical habitat and free-flowing river reaches through careful site selection and basin-scale planning, infrastructure designs that minimize reservoir effects and facilitate safe passage of fish, construction of hydropower plants using best practices that minimize long-term damage, operating guidelines that mimic natural flow conditions, and compensation that is lasting, effective, inclusive, and locally relevant. Learning from these ‘bright spots’ may require engagement of diverse stakeholders, professionals, and governments at scales that extend well beyond a given site, river, or even basin. Indeed, environmental planning that integrates hydropower development into broader discussions of conserving regional biodiversity and ecosystem services will be of utmost importance.

The aim of the study was to identify patients with NTRKfusion-positive or RETfusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were ‘pre-screened’ with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were ‘screened’ for NTRKfusions and RETfusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3).A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAFand RASmutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with NTRKfusions and 4 patients with RETfusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an NTRKfusion, 1 patient with a RETfusion, and 30 patients with BRAFmutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an NTRKfusion and 1 with aRETfusion (4/11, 36% of analyzed patients).Our findings indicate a higher rate of NTRKfusions and RETfusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.

In January 2005, Australia became the first country to introduce a publicly funded pneumococcal vaccination program for persons 65 years and older which is free at point of service, although the vaccine cost had previously been partially subsidised. Hospitalisation in this age group is an important indicator of risk of invasive pneumococcal disease but vaccine uptake has been suboptimal. To determine vaccination rates and predictors of vaccination in the elderly hospitalised patients before and after January 2005. We validated vaccination status against general practitioner (GP) records for patients aged ≥65 years admitted to a large teaching hospital in Sydney between 16th of May 2005 and the 20th of February 2006 and examined predictors of vaccinationCommencement of the new program resulted in a significant increase in vaccination uptake from 39% of inpatients prior to the free program to 73% in the same cohort of inpatients post January 2005. We found that patient recall of vaccination status was not reliable. Self-report of pneumococcal vaccination had a sensitivity of 0.53 and a specificity of 0.55, highlighting that validation of vaccination status is required. Age over 80 years and dementia significantly predicted under-vaccination.This highlights the importance of integrating free vaccine supply and delivery in primary care to achieve high vaccination coverage. However, demented patients and the very elderly remain under-vaccinated, despite being admitted to hospital for active management of acute conditions.

Without a preservative, such as thiomersal (known as thimerosal in the US), multi-dose liquid presentations of vaccine are vulnerable to bacteriological contamination that can result in death or serious illness of the recipient. Concerns about levels of mercury exposure from thiomersal-containing vaccines were first raised in the US during 1999 in the context of Hepatitis B vaccine for newborns. Since then, a large body of evidence from animal and epidemiological studies has accumulated on the safety of thiomersal. Ironically, these data have become largely irrelevant in wealthy countries, where mono-dose, thiomersal-free vaccines have been introduced as a precautionary measure in almost all childhood vaccines, in part related to residual public scepticism. In poor countries, multi-dose vials remain important for vaccine delivery. There is a real danger that this controversy may result in the loss to the world of thiomersal as a preservative, simply from popular pressure. In reality, it would be impossible to cease overnight using thiomersal and maintain the supply of vital vaccines. This paper reviews and summarises the data available from published studies on mercury toxicity, and thiomersal in vaccines in particular, that overwhelmingly indicate continued use of thiomersal is safe in those countries where it is most needed.

Australia experienced a resurgence of pertussis in the 1990s despite improved vaccine coverage. Although much of the increase was attributable to increased detection of cases in older persons with waning immunity by serology, vaccine changes or alterations in circulating Bordetella pertussis strains may also have contributed. We determined the frequency of variants of B. pertussis pertactin (prn), and pertussis toxin subunit 1 (ptxS1) genes, restriction fragment length polymorphism (RFLP) types and fimbrial serotypes prevalent in Australia prior to, and during the 1990s. Ampoules of the whole-cell vaccine in use prior to 1999 and 84 B. pertussis isolates stored between 1967 and 1998 by laboratories around Australia were analysed. One pertactin allele, Prn3, not detected before 1985, was found in 24 out of 57 (42%) isolates between 1989 and 1998 (P&lt;0·0001). PtxS1A was found in all isolates. IS1002 type 29, found in 17 out of 31 (55%) isolates tested, was the predominant RFLP type. The only difference in fimbrial serotype distribution between the time-periods was an increase in serotype 3 (P=0·054). The whole-cell vaccine contained only the alleles prn1 and ptxS1A. Antigenic shift in B. pertussis may have contributed to the re-emergence of pertussis in Australia. Monitoring these trends will be important as acellular vaccines are introduced and changes are made to pertussis vaccine schedules.

Objective: To estimate immunisation coverage for routinely administered vaccines among children using receipt of a particular Hib vaccine (PRP‐OMP) as a proxy for Indigenous status. Methods: Until May 2000, PRP‐OMP was provided only for Indigenous children in all jurisdictions except the Northern Territory. In three one‐year ACIR‐derived birth cohorts, any child recorded on the ACIR as receiving one or more doses of PRP‐OMP as the only Hib vaccine was presumed to be Aboriginal and Torres Strait Islander. Using this proxy, estimated numbers of Indigenous children were compared with Australian Bureau of Statistics estimates, and immunisation status for recommended vaccines was estimated at 12 and 24 months by jurisdiction and remoteness compared with children who received other Hib vaccines (presumed non‐Indigenous). Results: The numbers of Aboriginal and Torres Strait Islander children estimated using this ‘proxy method’ are approximately 42% of those estimated by the ABS. Immunisation coverage (among proxy Indigenous children) at 12 months (72–76%) and 24 months (64–73%) was considerably lower than others (90–94% and 81–88%, respectively). These children had significantly lower coverage when living in accessible areas than remote areas. Conclusions and Implications: These data provide the first national measure of immunisation status and are likely to be a valid measure among those identified. Aboriginal and Torres Strait Islander immunisation coverage is 17% lower with the biggest gaps in urban areas, indicating the need for better quality data informing appropriate interventions.

Australia introduced a fifth dose of pertussis vaccine at 4 to 5 years of age in 1994, the first country to do so for some 40 years. We report trends in national pertussis notifications from 1993 to 2001.

Objective: To assess the level of underreporting to the Australian Childhood Immunisation Register (ACIR) and the resulting underestimation of national immunisation coverage using ACIR data, and to correct national immunisation estimates for under‐reporting. Methods: A national population‐based telephone survey was conducted in May‐July 2001 of two random samples of children born in 1998 and 1999 who were recorded on the ACIR as incompletely immunised at either 12 months or 24 months of age. Parents were asked whether and when their child had received the vaccinations required to qualify as fully immunised. Survey data were then used to correct ACIR‐derived coverage estimates at 12 and 24 months of age. Results: Of 640 surveyed children in the 12‐month group, 258 (40%) met the study definition of ‘definitely immunised’. This adjusted the ACIR coverage estimate upwards by 2.7% to 94% (95% CI 93.6–94.1). Of 698 surveyed children in the 24‐month group, 387 (55%) met the study definition of ‘definitely immunised’ at the second birthday. Adjusted coverage for doses due by 24 months was 89.8% (95% CI 89.6–90.1), 5% higher than recorded on the ACIR. Conclusions: Immunisation coverage in Australia for all scheduled vaccines due by 12 months of age is 94% and for all vaccines due by two years of age is almost 90%. The ACIR underestimates coverage by up to 5%. As the ACIR database relies on provider notification, published estimates of immunisation coverage are unlikely to rise significantly above current levels, unless mechanisms are put in place to further improve notification to the ACIR.

Objectives:To (i) assess under‐reporting of measles‐mumps‐rubella (MMR) vaccinations to the Australian Childhood Immunisation Register (ACIR); (ii) estimate MMR coverage among five‐year‐old children and the proportion immune to measles infection; (iii) identify factors related to non‐uptake of MMR vaccination. Methods:We analysed ACIR data for a birth cohort of approximately 64,000 children aged five years. The parents of a sample of 506 children with no ACIR record for the second MMR vaccination (MMR2), due at four years of age, were interviewed by telephone to assess under‐reporting to the ACIR and reasons for non‐uptake of MMR vaccination. Results:Parents reported that 22% (n=111) of the surveyed 506 children had received MMR2 before their fifth birthday, and 42% (n=214) by ˜5.5 years of age. After correcting for this level of underreporting to the ACIR, MMR2 coverage for the entire cohort at five years of age was 52.9% (95% CI 52.3–53.4), and increased to 84.1% (95% CI 83.4–84.8) by ˜5.5 years of age. This was 4.3% and 8.2%, respectively, higher than ACIR coverage estimates at the two ages. Based on the corrected MMR coverage estimates, 93% of the cohort was immune to measles due to vaccination. The most common parent‐reported reason for incomplete vaccination was lack of knowledge about the MMR vaccination schedule. Conclusions:Measles elimination in Australia will require continued effort in vaccination coverage and timeliness among pre‐school children. School‐entry requirements are important for MMR2 uptake. Strategies are needed to improve reporting to the ACIR for more accurate measurement of coverage.

• Childhood pneumococcal disease is associated with substantial morbidity and mortality, but total disease burden is more difficult to measure than for invasive disease caused by Haemophilus influenzaetype b (Hib). • A safe, effective seven‐valent conjugate pneumococcal vaccine will be available in Australia by early 2001, and will certainly be indicated for high‐risk groups and purchased in the private sector, as was Hib vaccine. • The status of this vaccine on the Australian Standard Vaccination Schedule will require more detailed consideration of the burden and serotype distribution of pneumococcal disease in Australian children and the vaccine's likely cost‐effectiveness. • Postmarketing surveillance will be particularly important.

Objectives: To describe the serotypes, incidence and morbidity of invasive pneumococcal disease in urban New South Wales. Design: Prospective laboratory surveillance. Setting: Microbiology laboratories and hospitals in the Sydney, Hunter and lllawarra Statistical Divisions of NSW, June 1997 to May 1999. Results: 1270 cases were identified in two years. Incidence of disease was highest in those aged < 2 years (96.4 per 100000; 95% CI, 83.7–107.9) and ≥ 85 years (100.1 per 100000; 95% CI, 81.8–121.3). Incidence of disease increased significantly from the age of 60 years, compared with low rates in those aged 5–59 years. Underlying diseases predisposing to pneumococcal infection increased with age, from 4% (<2 years) to 60% (≥ 65 years). A seven‐valent conjugate vaccine would have covered 84.8% of serotypes in those aged 0–14 years, falling to 69% in those ≥ 15 years. Penicillin resistance was significantly higher in the < 5 years group (19.0%) than in older people (14.6%). Conclusions: Incidence of invasive pneumococcal disease was higher in this study using active surveillance than in previous Australian studies. An effective seven‐valent conjugate pneumococcal vaccine could prevent more than 80% of cases in children aged < 5 years.

Dissolved organic matter (DOM) is a complex mixture of many compounds and its composition dictates numerous reactions in the environment. Large lakes and marine coastlines receive DOM from watersheds that differ widely in their land cover, with potential implications for both the quantity and composition of carbon inputs. Seasonal variation in DOM quantity and composition may also differ among tributaries and be mediated by land cover. Here, we quantify spatially (i.e., among tributary) and seasonal variation in DOM concentration, DOM composition based on ultraviolet‐visible spectroscopy, and alkalinity across 101 tributaries of Lake Michigan, one of the world's largest lakes, using a synoptic sampling approach. Wetland land cover has the largest effect on DOM, producing high concentrations of DOM that are more aromatic and larger in apparent molecular weight. Seasonal variation is also pronounced, with concentrations and aromaticity of DOM peaking in fall across most tributaries. Watershed lithology and land cover both affect alkalinity, with higher values associated with the geography of carbonate bedrock and urbanized watersheds. Watershed land cover has a larger effect than season on all organic carbon parameters. However, seasonal variation is especially important for DOM composition. This disparity suggests that the environmental processing of DOM within river channels mediates its composition more than its concentrations. Considering the wide range of land cover and lithology around Lake Michigan and other large water bodies, accounting for both spatial and seasonal dynamics is essential for understanding controls on DOM delivery. Tributaries carry important inputs of water, nutrients, and contaminants to the Great Lakes. We sampled >100 tributaries of Lake Michigan in each season to determine how the type of land surrounding each tributary affects the carbon it brings to Lake Michigan. We considered organic carbon concentration and composition, as well as alkalinity. Wetlands had the largest effect on organic carbon with tributaries from wetland‐dominated areas having a higher concentration of organic carbon and organic carbon composition consistent with that originating from the land. Both land cover and geology impact alkalinity with the amount of carbonate species underlying the watershed increasing the alkalinity in the tributary. The season of sample collection is significant for organic carbon but not for alkalinity. Additionally, the season of sample collection has a greater impact on organic carbon composition than it does on concentration. These results yield information about how the broader carbon cycle may be affected as a result of changing landscape types. Concentrations of dissolved organic matter (DOM) range widely among tributaries of Lake Michigan, peaking in wetland‐dominated watersheds and during the fall seasonDOM is smaller in molecular weight and less aromatic in watersheds with little wetland land cover type and in the spring season, whereas alkalinity is positively correlated to urban land cover as well as underlying carbonate geologyDOM composition varies more in time (i.e., among seasons) than does either organic carbon concentrations or alkalinity Concentrations of dissolved organic matter (DOM) range widely among tributaries of Lake Michigan, peaking in wetland‐dominated watersheds and during the fall season DOM is smaller in molecular weight and less aromatic in watersheds with little wetland land cover type and in the spring season, whereas alkalinity is positively correlated to urban land cover as well as underlying carbonate geology DOM composition varies more in time (i.e., among seasons) than does either organic carbon concentrations or alkalinity

Objective:To determine the incidence of childhood cerebral tuberculosis (tuberculous meningitis [TBM] and tuberculoma) in a defined population. Design:Retrospective, population‐based study. Setting and participants:All resident children aged up to 14 years in New South Wales diagnosed with cerebral tuberculosis, from 1982 to 1996. Main outcome measure:Population‐based incidence of childhood TBM. Results:10 children with TBM and one with tuberculoma were identified in the 15 years. The incidence of TBM was 0.053 (95% CI, 0.025–0.097) per 100 000. Eight of the 10 TBM patients were born in Australia and five were of white European origin. Only one had been vaccinated with BCG vaccine. Three of the children died. Conclusions:The incidence of childhood TBM in New South Wales is low, and comparable with that in other First World countries.

Members of the Sydney Blood Bank Cohort (SBBC) have been infected with an attenuated strain of HIV-1 with a natural nef/LTR mutation and have maintained relatively stable CD4+ T lymphocyte counts for 14-18 years. Flow cytometric analysis was used to examine the phenotype of CD4+ and CD8+ T lymphocytes in these subjects, including the immunologically important naive (CD45RA+ CD62L+), primed (CD45RO +), and activated (CD38+ HLA-DR+ and CD28-) subsets. The median values were compared between the SBBC and control groups, comprising age-, sex-, and transfusion-matched HIV-1-uninfected subjects; transfusion-acquired HIV-1-positive LTNPs; and sexually acquired HIV-1-positive LTNPs. Members of the SBBC not only had normal levels of naive CD4+ and CD8+ T lymphocytes, but had primed CD45RO+ CD4+ T lymphocytes at or above normal levels. Furthermore, these primed cells expressed markers suggesting recent exposure to specific antigen. SBBC members exhibited variable activation of CD8+ T lymphocytes. In particular, SBBC members with undetectable plasma HIV-1 RNA had normal levels of activated CD8+ T lymphocytes. Therefore, the result of long-term infection with natural nef/LTR mutant HIV-1 in these subjects suggests a decreased cytopathic effect of attenuated HIV-1 on susceptible activated CD4+ T lymphocyte subsets in vivo, and minimal activation of CD8+ T lymphocytes.