Barriers, Borders, Boundaries: Program and Abstracts of the 2001 Australian Archaeological Association Annual Conference

Program and abstracts of the 2001 Australian Archaeological Association Annual Conference, 6-8 December 2001, Kondari Resort, Hervey Bay, Queensland. Includes a list of delegates and index

Cost and cost-eff ectiveness of newborn home visits: fi ndings from the Newhints cluster-randomised controlled trial in rural Ghana

Background Every year, 2·9 million newborn babies die worldwide. A meta-analysis of four cluster-randomised controlled trials estimated that home visits by trained community members in programme settings in Ghana and south Asia reduced neonatal mortality by 12% (95% CI 5–18). We aimed to estimate the costs and cost-eff ectiveness of newborn home visits in a programme setting. Methods We prospectively collected detailed cost data alongside the Newhints trial, which tested the eff ect of a homevisits intervention in seven districts in rural Ghana and showed a reduction of 8% (95% CI –12 to 25%) in neonatal mortality. The intervention consisted of a package of home visits to pregnant women and their babies in the fi rst week of life by community-based surveillance volunteers. We calculated incremental cost-eff ectiveness ratios (ICERs) with Monte Carlo simulation and one-way sensitivity analyses and characterised uncertainty with cost-eff ectiveness planes and cost-eff ectiveness acceptability curves. We then modelled the potential cost-eff ectiveness for baseline neonatal mortality rates of 20–60 deaths per 1000 livebirths with use of a meta-analysis of eff ectiveness estimates. Findings In the 49 zones randomly allocated to receive the Newhints intervention, a mean of 407 (SD 18) communitybased surveillance volunteers undertook home visits for 7848 pregnant women who gave birth to 7786 live babies in 2009. Annual economic cost of implementation was US$203 998, or$0·53 per person. In the base-case analysis, the Newhints intervention cost a mean of $10 343 (95$352 (95% CI 104 to –268) per discounted life-year saved, and had a 72% chance of being highly cost eff ective with respect to Ghana’s 2009 gross domestic product per person. Key determinants of cost-eff ectiveness were the discount rate, protective eff ectiveness, baseline neonatal mortality rate, and implementation costs. In the scenarios modelled with the meta-analysis results, the ICER increased from $127 per life-year saved at a neonatal mortality rate of 60 deaths per 1000 livebirths, to$379 per life-year saved at a rate of 20 deaths per 1000 livebirths. The strategy had at least a 99% probability of being highly cost eff ective for lower-middle-income countries in all neonatal mortality rate scenarios modelled, and at least a 95% probability of being highly cost eff ective for low-income countries at neonatal mortality rates of 30 or more deaths per 1000 livebirths. Interpretation Our fi ndings show that the seemingly modest mortality reductions achieved by a newborn home-visit strategy might in fact be cost eff ective. In Ghana, such strategies are also likely to be aff ordable. Our fi ndings support recommendations from WHO and UNICEF that low-income and middle-income countries implement newborn home visits

Whole-genome epidemiology links phage-mediated acquisition of a virulence gene to the clonal expansion of a pandemic Salmonella enterica serovar Typhimurium clone

Epidemic and pandemic clones of bacterial pathogens with distinct characteristics continually emerge, replacing those previously dominant through mechanisms that remain poorly characterized. Here, whole-genome-sequencing-powered epidemiology linked horizontal transfer of a virulence gene, sopE, to the emergence and clonal expansion of a new epidemic Salmonella enterica serovar Typhimurium (S. Typhimurium) clone. The sopE gene is sporadically distributed within the genus Salmonella and rare in S. enterica Typhimurium lineages, but was acquired multiple times during clonal expansion of the currently dominant pandemic monophasic S. Typhimurium sequence type (ST) 34 clone. Ancestral state reconstruction and time-scaled phylogenetic analysis indicated that sopE was not present in the common ancestor of the epidemic clade, but later acquisition resulted in increased clonal expansion of sopE-containing clones that was temporally associated with emergence of the epidemic, consistent with increased fitness. The sopE gene was mainly associated with a temperate bacteriophage mTmV, but recombination with other bacteriophage and apparent horizontal gene transfer of the sopE gene cassette resulted in distribution among at least four mobile genetic elements within the monophasic S. enterica Typhimurium ST34 epidemic clade. The mTmV prophage lysogenic transfer to other S. enterica serovars in vitro was limited, but included the common pig-associated S. enterica Derby (S. Derby). This may explain mTmV in S. Derby co-circulating on farms with monophasic S. Typhimurium ST34, highlighting the potential for further transfer of the sopE virulence gene in nature. We conclude that whole-genome epidemiology pinpoints potential drivers of evolutionary and epidemiological dynamics during pathogen emergence, and identifies targets for subsequent research in epidemiology and bacterial pathogenesis

NEWHINTS cluster randomised trial to evaluate the impact on neonatal mortality in rural Ghana of routine home visits to provide a package of essential newborn care interventions in the third trimester of pregnancy and the first week of life: trial protocol

BACKGROUND: Tackling neonatal mortality is essential for the achievement of the child survival millennium development goal. There are just under 4 million neonatal deaths, accounting for 38% of the 10.8 million deaths among children younger than 5 years of age taking place each year; 99% of these occur in low- and middle-income countries where a large proportion of births take place at home, and where postnatal care for mothers and neonates is either not available or is of poor quality. WHO and UNICEF have issued a joint statement calling for governments to implement "Home visits for the newborn child: a strategy to improve survival", following several studies in South Asia which achieved substantial reductions in neonatal mortality through community-based approaches. However, their feasibility and effectiveness have not yet been evaluated in Africa. The Newhints study aims to do this in Ghana and to develop a feasible and sustainable community-based approach to improve newborn care practices, and by so doing improve neonatal survival. METHODS: Newhints is an integrated intervention package based on extensive formative research, and developed in close collaboration with seven District Health Management Teams (DHMTs) in Brong Ahafo Region. The core component is training the existing community based surveillance volunteers (CBSVs) to identify pregnant women and to conduct two home visits during pregnancy and three in the first week of life to address essential care practices, and to assess and refer very low birth weight and sick babies. CBSVs are supported by a set of materials, regular supervisory visits, incentives, sensitisation activities with TBAs, health facility staff and communities, and providing training for essential newborn care in health facilities.Newhints is being evaluated through a cluster randomised controlled trial, and intention to treat analyses. The clusters are 98 supervisory zones; 49 have been randomised for implementation of the Newhints intervention, with the other 49 acting as controls. Data on neonatal mortality and care practices will be collected from approximately 15,000 babies through surveillance of women of child-bearing age in the 7 districts. Detailed process, cost and cost-effectiveness evaluations are also being carried out. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier NCT00623337)

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial

BACKGROUND: AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified. METHODS/DESIGN: An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose. DISCUSSION: An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00832208

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety

The principle of situated practice in literacy learning: students’ perspectives

O artigo resulta de uma investigação realizada no âmbito de uma iniciativa governamental destinada a melhorar os níveis de literacia nas séries iniciais do ensino fundamental em Portugal. A investigadora estudou as representações dos alunos sobre essa experiência por meio da realização de entrevistas em grupo. Este artigo analisa os dados referentes às representações dos alunos sobre uma das dimensões pedagógicas centrais da aprendizagem da literacia, nomeadamente a constituída pela prática situada. A análise qualitativa revela representações muito positivas sobre a prática que situou a aprendizagem, tendo os alunos expressado opiniões e sentimentos extremamente favoráveis sobre a prática de aprendizagem de literacia que experimentaram. A análise dos dados desvelou ainda que o contexto que situou a aprendizagem foi ativo, lúdico, colaborativo e mediado pelas TIC. Esses resultados fundamentam, do ponto de vista único dos próprios aprendentes, uma redefinição do entendimento atual do princípio da prática situada da literacia nas séries iniciais do ensino fundamental, no sentido do reconhecimento da centralidade da ludicidade nessa aprendizagem.This article derives from research developed in the context of the implementation of a governmental initiative aimed to enhance literacy learning in primary education in Portugal. The researcher studied students’ representations about their learning experience through group interviews. This article focuses on data concerning students’ representations about one of the central pedagogical dimensions of literacy learning, namely situated practice. Qualitative analysis revealed students’ very positive representations about the practice which situated their learning, as they expressed extremely favourable opinions and feelings. Data analysis further unveiled that the context of learning was active, playful, collaborative, and mediated by ICT. Such results provide foundations for a theoretical redefinition of current conceptions of situated practice by evidencing the centrality of playfulness as learning practice in the education of the first grades of primary education. This is an original contribution made from the perspectives of learners themselves(undefined)info:eu-repo/semantics/publishedVersio

Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP

Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI $80$1 infections compared with 23.3% of 355 patients receiving an IDI of,80% (odds ratio, 1.61; 95% confidence interval, 1.15-2.25; P 5 .006). An increased risk of infection-related admission was independently associated with IDI .80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score $6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin .36 g/L, CIRS-G score,6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial

Lake salinization drives consistent losses of zooplankton abundance and diversity across coordinated mesocosm experiments

Human-induced salinization increasingly threatens inland waters; yet we know little about the multifaceted response of lake communities to salt contamination. By conducting a coordinated mesocosm experiment of lake salinization across 16 sites in North America and Europe, we quantified the response of zooplankton abundance and (taxonomic and functional) community structure to a broad gradient of environmentally relevant chloride concentrations, ranging from 4 to ca. 1400 mg Cl- L-1. We found that crustaceans were distinctly more sensitive to elevated chloride than rotifers; yet, rotifers did not show compensatory abundance increases in response to crustacean declines. For crustaceans, our among-site comparisons indicate: (1) highly consistent decreases in abundance and taxon richness with salinity; (2) widespread chloride sensitivity across major taxonomic groups (Cladocera, Cyclopoida, and Calanoida); and (3) weaker loss of functional than taxonomic diversity. Overall, our study demonstrates that aggregate properties of zooplankton communities can be adversely affected at chloride concentrations relevant to anthropogenic salinization in lakes.Peer reviewe