Dominant negative ATM mutations in breast cancer families

BACKGROUND: The ATM gene encoding a putative protein kinase is mutated in ataxia-telangiectasia (A-T), an autosomal recessive disorder with a predisposition for cancer. Studies of A-T families suggest that female heterozygotes have an increased risk of breast cancer compared with noncarriers. However, neither linkage analyses nor mutation studies have provided supporting evidence for a role of ATM in breast cancer predisposition. Nevertheless, two recurrent ATM mutations, T7271G and IVS10-6T-->G, reportedly increase the risk of breast cancer. We examined these two ATM mutations in a population-based, case-control series of breast cancer families and multiple-case breast cancer families. METHODS: Five hundred twenty-five or 262 case patients with breast cancer and 381 or 68 control subjects, respectively, were genotyped for the T7271G and IVS10-6T-->G ATM mutations, as were index patients from 76 non-BRCA1/2 multiple-case breast cancer families. Linkage and penetrance were analyzed. ATM protein expression and kinase activity were analyzed in lymphoblastoid cell lines from mutation carriers. All statistical tests were two-sided. RESULTS: In case and control subjects unselected for family history of breast cancer, one case patient had the T7271G mutation, and none had the IVS10-6T-->G mutation. In three multiple-case families, one of these two mutations segregated with breast cancer. The estimated average penetrance of the mutations was 60% (95% confidence interval [CI] = 32% to 90%) to age 70 years, equivalent to a 15.7-fold (95% CI = 6.4-fold to 38.0-fold) increased relative risk compared with that of the general population. Expression and activity analyses of ATM in heterozygous cell lines indicated that both mutations are dominant negative. CONCLUSION: At least two ATM mutations are associated with a sufficiently high risk of breast cancer to be found in multiple-case breast cancer families. Full mutation analysis of the ATM gene in such families could help clarify the role of ATM in breast cancer susceptibility.

The impact of a streamlined funding application process on application time: Two cross-sectional surveys of Australian researchers

Objective: To examine if streamlining a medical research funding application process saved time for applicants. Design: Cross-sectional surveys before and after the streamlining. Setting: The National Health and Medical Research Council (NHMRC) of Australia. Participants: Researchers who submitted one or more NHMRC Project Grant applications in 2012 or 2014. Main outcome measures: Average researcher time spent preparing an application and the total time for all applications in working days. Results: The average time per application increased from 34 working days before streamlining (95% CI 33 to 35) to 38 working days after streamlining (95% CI 37 to 39; mean difference 4 days, bootstrap p value <0.001). The estimated total time spent by all researchers on applications after streamlining was 614 working years, a 67-year increase from before streamlining. Conclusions: Streamlined applications were shorter but took longer to prepare on average. Researchers may be allocating a fixed amount of time to preparing funding applications based on their expected return, or may be increasing their time in response to increased competition. Many potentially productive years of researcher time are still being lost to preparing failed applications.

Prediction of breeding values for average fruit weight in mango using a multivariate individual mixed model

Mango is an important horticultural fruit crop and breeding is a key strategy to improve ongoing sustainability. Knowledge of breeding values of potential parents is important for maximising progress from breeding. This study successfully employed a mixed linear model methods incorporating a pedigree to predict breeding values for average fruit weight from highly unbalanced data for genotypes planted over three field trials and assessed over several harvest seasons. Average fruit weight was found to be under strong additive genetic control. There was high correlation between hybrids propagated as seedlings and hybrids propagated as scions grafted onto rootstocks. Estimates of additive genetic correlation among trials ranged from 0.69 to 0.88 with correlations among harvest seasons within trials greater than 0.96. These results suggest that progress from selection for broad adaptation can be achieved, particularly as no repeatable environmental factor that could be used to predict G x E could be identified. Predicted breeding values for 35 known cultivars are presented for use in ongoing breeding programs.

Soil nitrogen—crop response calibration relationships and criteria for winter cereal crops grown in Australia

More than 1200 wheat and 120 barley experiments conducted in Australia to examine yield responses to applied nitrogen (N) fertiliser are contained in a national database of field crops nutrient research (BFDC National Database). The yield responses are accompanied by various pre-plant soil test data to quantify plant-available N and other indicators of soil fertility status or mineralisable N. A web application (BFDC Interrogator), developed to access the database, enables construction of calibrations between relative crop yield ((Y0/Ymax) × 100) and N soil test value. In this paper we report the critical soil test values for 90% RY (CV90) and the associated critical ranges (CR90, defined as the 70% confidence interval around that CV90) derived from analysis of various subsets of these winter cereal experiments. Experimental programs were conducted throughout Australia’s main grain-production regions in different eras, starting from the 1960s in Queensland through to Victoria during 2000s. Improved management practices adopted during the period were reflected in increasing potential yields with research era, increasing from an average Ymax of 2.2 t/ha in Queensland in the 1960s and 1970s, to 3.4 t/ha in South Australia (SA) in the 1980s, to 4.3 t/ha in New South Wales (NSW) in the 1990s, and 4.2 t/ha in Victoria in the 2000s. Various sampling depths (0.1–1.2 m) and methods of quantifying available N (nitrate-N or mineral-N) from pre-planting soil samples were used and provided useful guides to the need for supplementary N. The most regionally consistent relationships were established using nitrate-N (kg/ha) in the top 0.6 m of the soil profile, with regional and seasonal variation in CV90 largely accounted for through impacts on experimental Ymax. The CV90 for nitrate-N within the top 0.6 m of the soil profile for wheat crops increased from 36 to 110 kg nitrate-N/ha as Ymax increased over the range 1 to >5 t/ha. Apparent variation in CV90 with seasonal moisture availability was entirely consistent with impacts on experimental Ymax. Further analyses of wheat trials with available grain protein (~45% of all experiments) established that grain yield and not grain N content was the major driver of crop N demand and CV90. Subsets of data explored the impact of crop management practices such as crop rotation or fallow length on both pre-planting profile mineral-N and CV90. Analyses showed that while management practices influenced profile mineral-N at planting and the likelihood and size of yield response to applied N fertiliser, they had no significant impact on CV90. A level of risk is involved with the use of pre-plant testing to determine the need for supplementary N application in all Australian dryland systems. In southern and western regions, where crop performance is based almost entirely on in-crop rainfall, this risk is offset by the management opportunity to split N applications during crop growth in response to changing crop yield potential. In northern cropping systems, where stored soil moisture at sowing is indicative of minimum yield potential, erratic winter rainfall increases uncertainty about actual yield potential as well as reducing the opportunity for effective in-season applications.

Science, ICT and Mathematics Education in Rural and Regional Australia: The SiMERR National Survey

The SiMERR National Survey was one of the first priorities of the National Centre of Science, Information and Communication Technology and Mathematics Education for Rural and Regional Australia (SiMERR Australia), established at the University of New England in July 2004 through a federal government grant. With university based ‘hubs’ in each state and territory, SiMERR Australia aims to support rural and regional teachers, students and communities in improving educational outcomes in these subject areas. The purpose of the survey was to identify the key issues affecting these outcomes. The National Survey makes six substantial contributions to our understanding of issues in rural education. First, it focuses specifically on school science, ICT and mathematics education, rather than on education more generally. Second, it compares the different circumstances and needs of teachers across a nationally agreed geographical framework, and quantifies these differences. Third, it compares the circumstances and needs of teachers in schools with different proportions of Indigenous students. Fourth, it provides greater detail than previous studies on the specific needs of schools and teachers in these subject areas. Fifth, the analyses of teacher ‘needs’ have been controlled for the socio-economic background of school locations, resulting in findings that are more tightly associated with geographic location than with economic circumstances. Finally, most previous reports on rural education in Australia were based upon focus interviews, public submissions or secondary analyses of available data. In contrast, the National Survey has generated a sizable body of original quantitative and qualitative data.

Comite National de Secours Aux Refugies 1933-1934

Materials on the founding and organizational structure of the Comite. Lists of board members, reports, minutes of meetings. Correspondence and other materials from HIAS-JCA-EMIGDIRECT, Government of France. List of German Jewish students at Lucien de Hirsch school in Paris. List of German Jewish refugees.

National Council of Jewish Women, New York Section records, undated, 1895-2004.

These records document New York Section’s early history to the present, representing a significant portion of its work in community programming and advocacy, as well as its supporting administrative, fundraising, membership, and public relations activities. As a section of the National Council, its records also include a substantial amount of material regarding the National Organization’s programs, events, publications, and reports, dating from 1896 through 1999.

Achieving a national sample of nursing homes: Balancing probability techniques and practicalities

Sampling design is critical to the quality of quantitative research, yet it does not always receive appropriate attention in nursing research. The current article details how balancing probability techniques with practical considerations produced a representative sample of Australian nursing homes (NHs). Budgetary, logistical, and statistical constraints were managed by excluding some NHs (e.g., those too difficult to access) from the sampling frame; a stratified, random sampling methodology yielded a final sample of 53 NHs from a population of 2,774. In testing the adequacy of representation of the study population, chi-square tests for goodness of fit generated nonsignificant results for distribution by distance from major city and type of organization. A significant result for state/territory was expected and was easily corrected for by the application of weights. The current article provides recommendations for conducting high-quality, probability-based samples and stresses the importance of testing the representativeness of achieved samples.

Identifying advanced practice: A national survey of a nursing workforce

Background The size and flexibility of the nursing workforce has positioned nursing as central to the goals of health service improvement. Nursing's response to meeting these goals has resulted in proliferation of advanced practice nursing with a confusing array of practice profiles, titles and roles. Whilst numerous models and definitions of advanced practice nursing have been developed there is scant published research of significant scope that supports these models. Consequently there is an ongoing call in the literature for clarity and stability in nomenclature, and confusion in the health industry on how to optimise the utility of advanced practice nursing. Objectives To identify and delineate advanced practice from other levels of nursing practice through examination of a national nursing workforce. Design A cross-sectional electronic survey of nurses using the validated Advanced Practice Role Delineation tool based on the Strong Model of Advanced Practice. Participants Study participants were registered nurses employed in a clinical service environment across all states and territories of Australia. Methods A sample of 5662 registered nurses participated in the study. Domain means for each participant were calculated then means for nursing position titles were calculated. Position titles were grouped by delineation and were compared with one-way analysis of variance on domain means. The alpha for all tests was set at 0.05. Significant effects were examined with Scheffe post hoc comparisons to control for Type 1 error. Results The survey tool was able to identify position titles where nurses were practicing at an advanced level and to delineate this cohort from other levels of nursing practice, including nurse practitioner. The results show that nurses who practice at an advanced level are characterised by high mean scores across all Domains of the Strong Model of Advanced Practice. The mean scores of advanced practice nurses were significantly different from nurse practitioners in the Direct Care Domain and significantly different from other levels of nurse across all domains. Conclusions The study results show that the nurse practitioner, advanced practice nurse and foundation level registered nurse have different patterns of practice and the Advanced Practice Role Delineation tool has the capacity to clearly delineate and define advanced practice nursing. These findings make a significant contribution to the international debate and show that the profession can now identify what is and what is not advanced practice in nursing.

A pilot education on heart failure self-management and introduction of the teach-back method to cardiac nurses in Vietnam

It is recognised that patients with chronic disease are unable to remembercorrectly information provided by health care profesionals. The teach-back method is acknowledgedas a technique to improve patients’ understanding. Yet it is not used in nursing practice in Vietnam. Objectives This study sought to examine knowledge background of heart failure among cardiac nurses, introduce a education about heart failure self-management and the teach-back method to assist teaching patients on self-care. The study also wanted to explore if a short education could benefit nurses’ knowledge so they would be qualified to deliver education to patients. Methods A pre/post-test design was employed. Cardiac nurses from 3 hospitals (Vietnam National Heart Institute, E Hospital, Huu Nghi Hospital) were invited to attend a six-hour educational session which covered both the teach-back method and heart failure self-management. Role-play with scenarios were used to reinforce educational contents. The Dutch Heart Failure Knowledge Scale was used to assess nurses’ knowledge of heart failure at baseline and after the educational session. Results 20 nurses from3 selected hospitals participated. Average age was 34.5±7.9 years and years of nursing experience was 11.6±8.3. Heart failure knowledge score at the baseline was 12.7±1.2 and post education was 13.8±1.0. There was deficiency of nurses knowledge regarding fluid restriction among heart failure people, causes of worsening heart failure. Heart failure knowledge improved significantly following the workshop (p < 0.001). All nurses achieved an overall adequate knowledge score (≥11 of the maximum 15) at the end. 100% of nurses agreed that the teach-back method was effective and could be used to educate patients about heart failure self-management. Conclusions The results of this study have shown the effectiveness of the piloteducaiton in increasing nurses’ knowledge of heart failure. The teach-back method is accepted for Vietnamese nurses to use in routine cardiac practice.

Cost-effectiveness of a national initiative to improve hand hygiene compliance using the outcome of healthcare associated staphylococcus aureus bacteraemia

Background The objective is to estimate the incremental cost-effectiveness of the Australian National Hand Hygiene Inititiave implemented between 2009 and 2012 using healthcare associated Staphylococcus aureus bacteraemia as the outcome. Baseline comparators are the eight existing state and territory hand hygiene programmes. The setting is the Australian public healthcare system and 1,294,656 admissions from the 50 largest Australian hospitals are included. Methods The design is a cost-effectiveness modelling study using a before and after quasi-experimental design. The primary outcome is cost per life year saved from reduced cases of healthcare associated Staphylococcus aureus bacteraemia, with cost estimated by the annual on-going maintenance costs less the costs saved from fewer infections. Data were harvested from existing sources or were collected prospectively and the time horizon for the model was 12 months, 2011–2012. Findings No useable pre-implementation Staphylococcus aureus bacteraemia data were made available from the 11 study hospitals in Victoria or the single hospital in Northern Territory leaving 38 hospitals among six states and territories available for cost-effectiveness analyses. Total annual costs increased by $2,851,475 for a return of 96 years of life giving an incremental cost-effectiveness ratio (ICER) of $29,700 per life year gained. Probabilistic sensitivity analysis revealed a 100% chance the initiative was cost effective in the Australian Capital Territory and Queensland, with ICERs of $1,030 and $8,988 respectively. There was an 81% chance it was cost effective in New South Wales with an ICER of $33,353, a 26% chance for South Australia with an ICER of $64,729 and a 1% chance for Tasmania and Western Australia. The 12 hospitals in Victoria and the Northern Territory incur annual on-going maintenance costs of $1.51M; no information was available to describe cost savings or health benefits. Conclusions The Australian National Hand Hygiene Initiative was cost-effective against an Australian threshold of $42,000 per life year gained. The return on investment varied among the states and territories of Australia.

Global Media and National Policies : The Return of the State

Conventional wisdom views globalization as a process that heralds the diminishing role or even 'death' of the state and the rise of transnational media and transnational consumption, that defy state control or regulation. This book questions these assumptions and shows that the nation-state never left and is still a force to be reckoned with.

National media regulations in an age of convergent media: Beyond globalisation, neo-liberalism and internet freedom theories

There is a widely held view that the nation-state has become less central to media and communications policy over the last two decades. As Jan van Cuilenberg and Denis McQuail (2003, p. 181) observed in their overview of trends in communications policy-making, 'the old normative media policies have been challenged and policy-makers are searching for a new communications policy paradigm'. There are characteristically five factors put forward as to why the nation-state has become less central to media in the twenty-first century