Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2sigma;2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2sigma;2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca<inf>o</inf>²⁺) homeostasis. To elucidate the role of AP2sigma;2 in Ca<inf>o</inf>²⁺ regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2sigma;2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2sigma;2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2sigma;2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2sigma;2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2sigma;2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Estudio exploratorio del impacto del feedback en el PLE

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Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors.

Women primary principals in independent schools : creativity and inspiration

The purpose of my research is to reinvigorate educational leadership through improved understandings of women primary principals in Independent schools, thereby rethinking the current directions. By 'reinvigorate' I mean investigate what serves as inspiration for current women primary leaders and explore how this might be better used to generate the kinds of educational change that lead to more dynamic primary school leadership. These 'improved understandings' are expected to suggest a reconceptualizing of primary school leadership by, what I coin 'response-ability'. By 'response-ability' I mean to expose untapped potentials in primary leadership performance so that the leader utilizes the full range of their knowledge, skills and values.

There are acknowledged gaps in the primary school Independent sector concerning women in leadership both theory and practice and in this instance the Victorian context. Considerable research surrounds educational leadership [Peter Hill (2003), Neil Cranston (2001), Frances Townsend (1999),Helen Telford.(1996) and Caldwell & Spinks (1992)]. In particular Jill Blackmore's, (1999) research analysed a number of projects focusing on women secondary principals. As a critique of leadership her research exposed the gendered influences reinforced through culture, values and language

However there has been limited research into women in primary leadership and the implications for the Independent sector. In summary this research aims to understand women in primary educational leadership and investigate the significance of their untapped knowledge, skills, attitudes and values. Furthermore to propose what may constitute 'Response-able' leadership that could serve to highlight ethical principles, authenticity and creativity.

Ethical tensions and academic leaders

Internationally universities have been characterized by shrinking government funding, fierce competition for student enrolments, and greater pressures to become commercially viable. It is against this complex background that academic leaders have been required to confront and resolve a magnitude of conflicting interests as they seek to balance a variety of values in their decision-making processes. In this article we put forward a model of ethical decision-making developed from empirical research and literature. To test the efficacy of the model, a case scenario is posed. The article concludes by raising a number of implications for academic leaders regarding ongoing professional learning needed in this area.

An exploratory study of ethical dilemmas faced by academic leaders in three Australian universities

Being an academic in universities today is characterised by change and increasing complexity in response to a multitude of factors impacting on the university sector. Among the consequences of such changes are that many academics, and academic leaders in particular, are subjected to both increasing stress and scrutiny in many of the decisions they make. Some of these decisions require critical choices that involve contestation of values (including personal, professional, institutional, and community), resulting in ethical dilemmas for the decision makers. This article reports on an exploratory study into ethical dilemmas faced by middle-level academic leaders, drawing on the results of an on-line survey distributed to relevant academics in three universities in Australia. Here, middle-level academic leaders are defined as those holding course coordination roles, locating them between senior university staff and other academics on the one hand, and students on the other hand. As a consequence, these diverse groups of staff and students potentially have an array of conflicting interests in, and expectations on, middle-level academics’ decision-making processes. The findings of the study are clear: ethical dilemmas are evident, and commonly so, for many middle-level academic leaders. While exploratory in nature, the findings of this study suggest that much more attention to ethics and ethical dilemmas is needed in our universities.

(Un)ethical practices and ethical dilemmas in universities : academic leaders’ perceptions

In this paper we report on the qualitative component of a study that explored middle-level academic leaders’ experiences of (un)ethical practices and ethical dilemmas in their daily work. An electronic survey was distributed to academic leaders from universities across three Australian states. There are three major findings in this study. First, the messy context of universities is providing a fertile ground for ethical dilemmas to flourish. Second, the two main categories of unethical practices identified by participants were academic dishonesty and inappropriate behaviour towards staff and students. Third, the ethical dilemmas that emerged focused on the academic leaders’ strong sense of professional ethics that were in conflict with an ethic of care, supervisors’ directives, and the rules and policies of the organisation.

Factors influencing students’ decisions about post-year 10 education

This paper reports pilot data from an instrument devised as part of a large ARC funded project that aims, among other things, to investigate factors that influence the decisions of students in rural and/or disadvantaged areas to continue their schooling beyond Year 10. One section of the pilot student questionnaire comprised 42 items designed to reflect dimensions believed to influence these decisions. Participants responded on 5-point Likert scales indicating the extent of their agreement from Strongly Disagree to Strongly Agree with each of the items. We were interested in the extent to which the data supported the theoretical structure that underpinned the structure of the questionnaire and in testing the appropriateness of the language used. The large scale data collection will survey students from Years 5 to 11 with as few adaptations for differences in literacy levels across that range as possible. To this end, the pilot questionnaire was administered to Year 5 (n = 44) and Year 9/10 students (n = 50) with identical wording for both grade levels. A factor analysis of the complete data set (n = 94) provided initial evidence that being happy at school; having family support to continue with education, and appropriate curriculum options and extra-curricular activities, perceiving oneself as a high achiever both in general and in relation to mathematics, having teacher and peer support to continue, being positive about English, planning to be an apprentice, and having a job type in mind are dimensions worthy of further exploration in the larger study.

Findings from a pilot study into student retention beyond Year 10

This paper reports on early findings from a pilot study into student retention beyond Year 10. Located in rural, regional and disadvantaged communities in Tasmania, the research has implications at State, national and international levels. It is being funded by a nationally competitive Australian Research Council Linkage grant and the Tasmanian Department of Education across three years. The paper begins by providing a conceptual overview of the research, including the background to the study, and then reports on trends that have emerged during the initial phase of data collection. Preliminary findings resulting from pilot data analysis of responses to questionnaires by students in Years 5 and 9/10 are discussed. The paper concludes with a discussion about what these early findings suggest in regard to factors impacting on student retention.

Interstitial-water geochemistry of Kerguelen Plateau sediments

This report synthesizes all of the interstitial-water chemistry studies associated with the Kerguelen Plateau phase of ODP Leg 119. Sediments were cored at six sites (49°24'S to 59°36'S) in water depths ranging from 564 to 4082 m. A total of 77 interstitial-water samples was recovered as part of the routine sampling protocol. In addition, a novel, highresolution pore-water sampling program was tested during Leg 119 that enabled us to pinpoint reaction zones and extend our data base to deeper, drier levels that were heretofore inaccessible. Data collected include interstitial-water sodium, potassium, calcium, magnesium, pH, alkalinity, sulfate, ammonia, phosphate, aqueous silica, salinity, chloride, oxidation-reduction potentials, and sediment chemistry. The northern sector (Sites 736 and 737) is characterized by the highest sedimentation rates (up to 140 m/m.y.) and thermal gradients (70°-98°C/km) encountered on the Kerguelen Plateau during Leg 119. Site 737 represents the most reactive sediment column cored on the Kerguelen Plateau. Major cation fluxes at Site 737 are the strongest measured during Leg 119. High dissolved calcium concentrations (141.5 mM) were encountered near the bottom of Hole 737B. Elevated temperatures promote silica diagenesis and the alteration of volcanic material below 300 mbsf, and a diagenetic front was discovered near 370 mbsf at Site 737. The southern portion of the Kerguelen Plateau (Sites 738 and 744) records the lowest sedimentation rates (less than 5 m/m.y.) and thermal gradients (43°C/km) of the three study areas. Major cation fluxes at the southern sites are the lowest that we measured on the Kerguelen Plateau. High-resolution sampling provided evidence for significant silica release to the pore waters during the weathering of basement basalt. The relatively low thermal gradient does not appear to be sufficient for the formation of the opal-CT and quartz chert beds and nodules that were encountered below 120 mbsf at Site 738. Sediment-accumulation rates on the Eastern Kerguelen Sediment Ridge (Sites 745 and 746) are intermediate to those of the northern and southern sites. Deposition below the regional CCD accounts for the nearly carbonate-free, siliceous sediments. Despite their low organic carbon contents (mean = 0.15%), sediments on the Eastern Kerguelen Sediment Ridge exhibit the highest pore-water alkalinity (6.77 mM), ammonium (0.50 mM), and phosphate (23 µM) concentrations measured on the Kerguelen Plateau. Major cation fluxes are intermediate to those calculated for the northern and southern sites. The Eastern Kerguelen Sediment Ridge interstitial waters are unusual, however, in that the downward flux of magnesium is greater than the upward flux of calcium.

Interstitial-water chemistry of ODP Leg 119 sites

Ocean Drilling Program inorganic geochemistry procedures routinely overlook more than 99% of the sediment column. Present and past biogeochemical reactions alter the sediment record; however, most of these reaction zones are bypassed by the normal methods where samples are collected every 30 m. A new approach to increase resolution was introduced during Leg 119. Ten milliliters of sediment provided interstitial-water samples for ammonia, silica, sulfate, magnesium, and calcium analyses. The new method introduced some systematic differences in concentrations, as well as some decrease in precision. A number of advantages, however, may warrant using the method in some instances. In cases where routine interstitial-water data showed anomalous results, core sections were retrieved from the storage facility and resampled. The new high-resolution procedure was used to provide water samples in cases were water contents were low and routine squeezing could not recover pore water.