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Background Junior doctors undertake a significant amount of prescribing; however, they are not well prepared for this, and report they would like more training in their undergraduate courses. To address this we tested a pharmacist-led prescribing program for final-year medical students. Methods Sixteen final-year students took part in the program. The program involved students writing prescriptions and getting feedback from clinical pharmacists, undertaking prescribing and calculation tutorials, and spending time in the pharmacy department. Evaluation included a pre- and post-assessment of their confidence and skills in prescribing, and a feedback session discussing the strengths and weakness of the program, and their perceptions about the role of pharmacists. Changes in the pre- and post-assessment of confidence and skills were examined with permutation and Mann-Whitney U tests. Results There was a significant improvement in students’ confidence in prescribing, and a small but consistent improvement in prescribing skills. Of note, no student prescribed inappropriately and potentially harmfully after the program. Participants were positive about the program, and indicated a better understanding about the pharmacists’ role and their ability to support them as junior doctors. Conclusions This study has shown the potential effect of a pharmacist-led prescribing program on the skills and confidence in prescribing by medical students. It provided an interprofessional teaching opportunity, preparing students for a team-based approach to patient management. Electronic supplementary material The online version of this article (10.1186/s12909-019-1486-1) contains supplementary material, which is available to authorized users.

Stem-cell-based therapies provide a biological basis for the regeneration of mineralised tissues. Stem cells isolated from adipose tissue (ADSCs), bone marrow (BMSCs) and dental pulp (DPSCs) have the capacity to form mineralised tissue. However, studies comparing the capacity of ADSCs with BMSCs and DPSCs for mineralised tissue engineering are lacking, and their ability to regenerate dental tissues has not been fully explored. Characterisation of the cells using fluorescence-activated cell sorting and semi-quantitative reverse transcription PCR for MSC markers indicated that they were immunophenotypically similar. Alizarin red (AR) staining and micro-computed tomography (µCT) analyses demonstrated that the osteogenic potential of DPSCs was significantly greater than that of BMSCs and ADSCs. Scanning electron microscopy and AR staining showed that the pattern of mineralisation in DPSC cultures differed from ADSCs and BMSCs, with DPSC cultures lacking defined mineralised nodules and instead forming a diffuse layer of low-density mineral. Dentine matrix components (DMCs) were used to promote dentinogenic differentiation. Their addition to cultures resulted in increased amounts of mineral deposited in all three cultures and significantly increased the density of mineral deposited in BMSC cultures, as determined by µCT analysis. Addition of DMCs also increased the relative gene expression levels of the dentinogenic markers dentine sialophosphoprotein and dentine matrix protein 1 in ADSC and BMSC cultures. In conclusion, DPSCs show the greatest potential to produce a comparatively high volume of mineralised matrix; however, both dentinogenesis and mineral volume was enhanced in ADSC and BMSC cultures by DMCs, suggesting that these cells show promise for regenerative dental therapies.

The different algorithms appropriate for point source photometry on data from the SPIRE instrument on-board the Herschel Space Observatory, within the Herschel Interactive Processing Environment (HIPE) are compared. Point source photometry of a large ensemble of standard calibration stars and dark sky observations is carried out using the 4 major methods within HIPE: SUSSEXtractor, DAOphot, the SPIRE Timeline Fitter and simple Aperture Photometry. Colour corrections and effective beam areas as a function of the assumed source spectral index are also included to produce a large number of photometric measurements per individual target, in each of the 3 SPIRE bands (250, 350, 500μm), to examine both the accuracy and repeatability of each of the 4 algorithms. It is concluded that for flux densities down to the level of 30mJy that the SPIRE Timeline Fitter is the method of choice. However, at least in the 250 and 350μm bands, all 4 methods provide photometric repeatability better than a few percent down to at approximately 100mJy. The DAOphot method appears in many cases to have a systematic offset of ∼8 % in all SPIRE bands which may be indicative of a sub-optimal aperture correction. In general, aperture photometry is the least reliable method, i.e. largest scatter between observations, especially in the longest wavelength band. At the faintest fluxes

The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the three putative functional IL6 promoter variants, -174G>C, -572G>C and -6331T>C, two complementary techniques, allele-specific chromatin immunoprecipitation and allele-specific formaldehyde-assisted isolation of regulatory elements, were carried out using unrelated lymphoblast cell lines of known genotype. There were no allele-specific effects for all three single-nucleotide polymorphisms (SNPs) under basal conditions. Upon IL-1β stimulation, however, allele-specific effects were seen for the -6331 allele, which showed both increased RNA polymerase II loading (56%, P=0.001) and increased open chromatin (59%, P=0.004) for the T allele, which is in line with previous reports of this SNP and the effects from acute inflammation. These studies highlight the importance of examining chromatin under different environmental conditions when studying the functionality of regulatory polymorphisms.

Following 35 years of persistent groundwater rise beneath northern Ivanhoe Plain in the Ord River Irrigation Area, northern Australia, the water table appears to have stabilized near the base of the irrigation surface-drain network. Hydrometric evidence indicates that intersection of the deepest surface drains by the rising water table simultaneously reduced aquifer recharge from surface-water infiltration and increased aquifer discharge by groundwater exfiltration. Water-table analysis supports the working hypothesis that the largest irrigation drain D4 on north Ivanhoe Plain has been receiving a significant amount of groundwater discharge since the mid-1990s. The rate of groundwater discharge to surface drains on north Ivanhoe Plain was estimated to be around 15–20 million (M)L/day based on groundwater-flow modelling. Groundwater tracing using radon and electrical conductivity indicated that groundwater discharge to drain D4 was ∼6–12 ML/day in August 2007. The rate of groundwater discharge was significantly larger where the drain traverses a very-permeable sand and gravel palaeochannel. Relatively modest exfiltration rates of order of magnitude tens to hundreds of mm/day into the drain were estimated to mitigate 0.5 m/year groundwater accretion for a land area of order of magnitude hundreds to thousands of ha.

Understanding outcomes of the interaction between a dental material and tooth tissue is important in terms not only of biocompatibility but also of the potential for the material to modulate the response of the tissue. This interaction is influenced by many factors, including the chemistry of the material and any of its eluted components or degradation products, and the manner in which the tissue responds to these agents. Past studies of this interaction have primarily been aimed at identifying cytotoxic effects. More recently, investigations have focused on specific cellular responses, and in particular, on understanding how the materials themselves actually may contribute to regenerative processes in the tooth. Recent work has demonstrated the solubilization of proteins from dentin exposed to certain materials, such as calcium hydroxide, mineral trioxide aggregate, and acidic solutions that relate to those used in dentin bonding agents, with the subsequent modulation by these proteins of gene expression in odontoblast-like cells. This work suggests that dentin bridge formation under such materials may be stimulated through this process. Thus, there is much merit in examining both how new dental materials can be developed and how more traditional ones can be modified to preferentially stimulate regenerative processes when preferred. This review summarizes current knowledge about the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex, as well as potential future developments in this exciting field.

We have recently reported the induction of dental pulp stem cells (DPSCs) into dentin-secreting odontoblast-like cells after stimulation by isolated dentin matrix components, thus mimicking the nature of tissue regeneration seen after tooth disease and injury. After confluency, the cells were further cultured for 21 d in the 10% fetal bovine serum (FBS) Dulbecco's modified Eagle's medium (DMEM) (control), and in this medium, with the addition of dentin extract (DE) and the mineralization supplement (MS) of ascorbic acid and beta-glycerophosphate (treatment). To identify genes associated with this process, specimens were analyzed with a HG-U133A human gene chip and Arrayassist software. A total of 425 genes, among them 21 matrix and eight TGF-beta-related genes, were either up- or downregulated in the experimental group in which the cells showed odontoblast-like differentiation and mineralization. Expression of selected genes was further confirmed by real-time polymerase chain reaction (PCR) analysis. Of the extracellular matrix (ECM)-related genes, two types of collagen genes were upregulated and seven others downregulated. Other ECM-related genes, for example fibulin-1, tenascin C, and particularly thrombospondin 1, were upregulated, and fibulin-2 was downregulated. Most noticeably, the matrix metalloproteinase 1 was induced by the treatment. In the TGF-beta superfamily, upregulation of the type II receptor, endoglin, and growth/differentiation factor 5 was coordinated with the downregulation of activin A, TGF-beta2, and TGF-beta1 itself. This study identifies the matrix and TGF-beta-related gene profiles during the DPSC cell mineralization in which several genes are reported for the first time to be associated with this process, thus greatly expanding our molecular knowledge of the induced disease repair process.

Groundwater discharge rates were estimated from borehole groundwater temperature and pore water temperature under the seabed to be 0.92–3.6 cm/day in Cockburn Sound, Western Australia. Automated and manual seepage meters measured larger groundwater discharge rates of 13.7–16.3 cm/day. This difference may be because the observed seepage rates measured by seepage meters include not only terrestrial fresh groundwater discharge but also recirculated salt water. On the other hand, the discharge rates estimated from subsurface temperature may consist of only terrestrial fresh groundwater discharge.

Submarine groundwater discharge (SGD) into Cockburn Sound Western Australia was quantified by applying a distributed groundwater flow model to estimate the inshore aquifer water balance. Spatially averaged SGD along the coast was estimated to be 2.5–4.8 ± 0.9 m3 day−1 m−1. The range in estimated average SGD reflected low and high estimates of average groundwater recharge, which ranged from 0.13 to 0.24 m year−1 (15–28% of average annual rainfall). The error ±0.9 m3 day−1 m−1 was calculated by assuming arbitrary ±20% errors in groundwater pumping and inflow across boundaries. SGD varied spatially along the coastal boundary due to variation in hydraulic connection between the coastal aquifers and ocean, and spatial variability in recharge, transmissivity and pumping. Under assumptions of low and high groundwater recharge, SGD along the coastline varied in the ranges 1.4–4.6 m3 day−1 m−1 and 2.4–7.9 m3 day−1 m−1, respectively.

This study aimed to characterize fluoride-induced alterations in dentin mineralization within a dentin-pulp organ culture system. Tooth sections derived from male Wistar rat incisors were cultured in Trowel-type culture for 14 days, in the presence of 0 mM, 1 mM, 3 mM and 6 mM sodium fluoride. Tooth sections were processed and analyzed for uptake of fluoride, its subsequent effect on dentin mineralization by tetracycline hydrochloride incorporation and mineral composition, expressed as calcium/phosphorous (Ca/P) ratios. Tetracycline hydrochloride incorporation was demonstrated to decrease with increased fluoride exposure, accompanied by significant increases in both Ca/P ratios and fluoride incorporation. These findings provide further evidence that the established alterations in dentin formation during fluorosis are a consequence of disruption to the mineralization process, and provide a model system with which to investigate further the potential role the extracellular matrix plays in inducing the apparent changes in mineral composition.

OBJECTIVES: (1) To determine the extent to which Australian general practitioners (GPs) restrict the numbers of agents they prescribe within a drug class ('personal formularies'); (2) To assess concordance of these drug choices with standards based on established guidelines or recognised good prescribing practices; (3) To assess the potential of these measures as indicators of the quality of prescribing. METHODS: Australian Health Insurance Commission (HIC) prescription data (1994 1997) for around 15,400 GPs providing 1500 or more Medicare services per year were analysed. Measures of an individual GP's use of a personal formulary (determined by number of agents) and concordance with prescribing criteria based on specified drugs for five classes of commonly prescribed drugs were derived. RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs): GP concordance was higher with a non-specified personal formulary (any five NSAIDs) than with a list of specified drugs (five NSAIDs of 'low' or 'medium' risk of gastrointestinal toxicity), and concordance with both increased over time. In 1997, around 70% of GPs used five or fewer NSAIDs for 90% of their prescribing; 47% of GPs had 90% of prescribing from five selected agents. Angiotensin converting enzyme inhibitors/angiotensin-II receptor antagonists: The introduction of new agents appeared to increase the size of the GPs' personal formularies, and concordance with defined standards decreased over time. Antibacterial agents: Concordance with a specified drug standard (nine drugs listed in the Australian Antibiotic Guidelines) increased substantially over time but was largely due to increased prescribing of two heavily promoted drugs. Beta-blocking agents: Over time, GPs restricted most prescribing to two agents, atenolol and metoprolol. Calcium channel blockers: GPs did not appear to restrict prescribing of these drugs; most GPs prescribed all five agents available. CONCLUSIONS: Australian GPs use 'personal formularies'. Formulary size varies with the drug class, can change over time as new agents become available, and its contents can be influenced by promotional activities. Prescribing standards based on numbers of drugs used may not always reflect rational prescribing choices. Criteria based on specified drugs provide more rigorous prescribing standards, but may give a misleading picture of prescribing quality in the absence of information on patients and the indications for treatment. Personal formulary measures are potentially useful prescribing indicators but need to be carefully defined and interpreted. GPs should be encouraged to identify their personal formularies and review the drugs included in them.

To examine the ability of interns to prescribe appropriately for common clinical conditions at the commencement and completion of the intern year. Interns' perceptions of their ability to prescribe and the perceived influences on their practices were also assessed. The study was conducted at a teaching hospital in urban New South Wales, Australia. A self-complete questionnaire was administered to 56 interns at the beginning and end of internship. At the beginning of the year respondents were asked to identify how equipped they felt they were to perform specific functions related to prescribing practice. Interns were also asked to write hospital prescriptions for four common clinical cases scenarios: post-operative pain, urinary tract infection, asthma, and community-acquired pneumonia. At the end of the year interns were asked to prescribe for the same clinical scenarios and also asked to identify the main influences on their practice. At the beginning of the year 54% of interns felt equipped to choose an appropriate drug for common clinical conditions, however, few felt they were able to determine the appropriate dose (23% of respondents) or dose frequency (25%). A previously validated four-point rating scale was used by two assessors to judge appropriateness of prescribing [Kappa = 0.6]. At the beginning of the year at least two-thirds of interns were prescribing 'inappropriately' for all clinical conditions. By the end of the year 75% were prescribing 'appropriately' for all conditions. The main perceived influences on prescribing practices were registrars, consultants, books and pharmacists.The use of hypothetical clinical cases to explore prescribing ability has shown that doctors are ill-equipped to perform various aspects of prescribing on graduating from medical school. Although our findings may not translate into practice directly they highlight the existence of a potential problem that warrants further study, especially in the areas of actual practice and the influences on it in the early postgraduate years.

Blood pressure self-measurement is increasing in most communities and yet its role in the management of hypertension is poorly understood. This study was devised to evaluate the behaviour of doctors in general practice when treating patients with poorly controlled essential hypertension who use self-measurement. Patients, most of whom were already taking antihypertensive medications were commenced on perindopril or indapamide at their doctor's discretion and were randomly allocated to self-measurement (SM) using an OMRON HEM706 oscillometric device or a continuation of their usual care (UC) over an 8-week period. This was an observational study without any specific or set treatment goals for the doctor to follow. Sixty of 62 subjects completed the study and the two groups were equally matched for age, body mass index, gender, and blood pressure (BP). While additional perindopril or indapamide produced a significant fall in BP in both groups over the study period, the systolic pressure remained significantly higher in the SM group (sitting 148 +/- 3 compared with 142 +/- 3; 145 +/- 3 compared with 138 +/- 3 mm Hg respectively; P < 0.05). Twenty-four hour and daytime ambulatory monitor systolic pressures were also significantly higher in the SM group. Differences in diastolic BP were not statistically significant. Furthermore, SM patients were less likely to have their medications increased and more likely to have them reduced or ceased. Doctors and patients found self-measurement convenient and useful. This study suggests that doctors prescribing decisions are influenced by evidence from self-measurement of BP with consequential increases in office BP related to reduced drug use. While self-BP measurement can offer reassurance about adequacy of control when away from a physicians office, our best evidence of understanding target blood pressures comes from large randomised studies using office blood pressures as an end-point. There is an urgent need for further study to provide arbitration between self-measurement and office blood pressures although each measurement must contribute to the management of hypertension.

Methods In the current work, we examined NK cell (NKG2A+ CD3-) responses to SIV vaginal challenge in vaginal and cervical mucosa using IHC and ISH. Results NK cells are maintained at a low baseline level in the genital tissue of naive animals. In the first week post infection, a small number of NK cells (up to 1500 cells/cm sq) infiltrated into genital mucosa. The initial recruiting signal didn’t require viral replication as shown by equal NK influx in animals challenged with either WT or AT-2 inactivated viruses. The majority of infiltrating NK cells was Granzyme H+ and 40-60% was IFN-gamma+. However, viral inoculation also enhanced the expression of HLA-E in genital tissues, generating an inhibitory environment to NK functionality. In addition, mucosal NK cells appeared to be IL2Rbeta negative, indicating impaired IL-2 and IL15 signaling. Therefore, the initial influx of NK cells was not able to eliminate early viral infection at genital mucosa. Surprisingly, in the second week, the number of mucosal NK cells rapidly decreased, which is inversely associated with the number of infected cells in genital tissues and is consistent with an increase in the level of sera IP10 and IL18. Interestingly, at the end of the fourth week (the VL set point), the number of NK cells in genital mucosa was partially recovered, probably because of less viral replication due to CD4 depletion and a reduction of sera IP10 and IL18. Conclusion In this study, we found that densities of cervical NK cells are inversely correlated with those of infected cells in animals at Day 5-10 post infection (n=7, p=0.0187).

Background The long-term goal for an efficacious HIV vaccine is to provide sterilizing protection from HIV infection. Thus far, this scenario has only been achieved experimentally using live-attenuated SIV vaccines. As such, great interest lies in identifying correlates of protection from a successful host response to pathogenic SIV. To this end, we have used a global genomics approach, tissue analysis, and explant cultures to identify immune complex (IC) signaling as an important component of a protective host response in the female reproductive tract (FRT) of animals vaccinated with the live-attenuated virus known as SIV mac239 ΔNef.

Groundwater beneath the Ord River Irrigation Area (ORIA) in northern Australia has risen in elevation by 10–20 m during the past 40 years with attendant concerns about water logging and soil salinization. Persistent groundwater accession has been attributed to excessive irrigation and surface water leakage; however, analysis of daily water-table records from the past 10 years yielded a contrary result. On a seasonal basis, water-table elevation typically fell during irrigation (dry) seasons and rose during fallow (wet) seasons, conflicting with the conventional view that irrigation and not rainfall must be the dominant control on groundwater accession. Previous investigations of unexpectedly large infiltration losses through the cracking clay soils provide a plausible explanation for the apparent conundrum. Because rainfall is uncontrolled and occurs independently of the soil moisture condition, there is greater opportunity for incipient ponding and rapid infiltration through preferred flow pathways. In contrast, irrigation is scheduled when needed and applications are stopped after soil wetting is achieved. Contemporary groundwater management in the ORIA is focused on improving irrigation efficiency during dry seasons but additional opportunities may exist to improve groundwater conditions and salinity risk through giving equal attention to the wet-season water balance.

Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. In an acute study (N=7) 400 mg oral acebutolol produced similar peak plasma levels of Ac and Am but Am had a longer half life. Group mean pulse and blood pressure fell significantly, although the size of individual blood pressure fall varied five-fold. There was no significant change in plasma renin activity. Correlations were found between drug concentration and β-blockade, assessed as % reduction in exercise tachycardia, and between both of these and the fall in post exercise systolic blood pressure. Similar comparisons were made in a chronic optimum dose study (N=11) both pre-dose and three hours post-dose. Am concentration was consistently higher than Ac at both times. Blood pressure was lowered equally pre-and post-dose when compared to placebo and plasma renin activity (PRA) was reduced on active treatment. Correlations were again shown between drug concentrations and β-blockade but none were found with changes in blood pressure or PRA. Between subject differences in blood pressure response could not be fully explained in terms of the other measurements but it is unlikely that pharmacokinetic differences are the major source of this variability.

A checklist composed of 66 adjectives was used to measure sex-role stereotypes of college and senior high school students (15- to 21-year-olds) in the University of Kansas area. Three hypotheses were tested: (a) Traditional ways of describing men and women will be very much in evidence, and a strong agreement between the sexes concerning these attributes will exist. (b) Females will stereotype sex roles to a lesser degree than males. (c) Females will value feminine characteristics more positively than masculine characteristics, but males as usual will value masculine characteristics more positively than feminine characteristics. All the hypotheses were supported with a single exception: Male subjects did not differentially value masculine and feminine characteristics.