Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats

1. It is currently unknown whether long-term voluntary exercise has enduring cardioprotective effects in animal models.

2. The present study was conducted in three groups of rats: (i) sedentary controls (n = 6); (ii) 24 h runners (n = 8; unlimited access to running wheels); and (iii) 2 h runners (n = 8; access to running wheels limited to 2 h daily). After termination of the 6 week exercise protocol, all rats were implanted with the telemetric electrocardiogram transmitters and were studied 1 week later.

3. Resting heart rate (HR) values in the control rats, 24 h runners and 2 h runners were 372 ± 7, 361 ± 9 and 298 ± 5 b.p.m., respectively (P < 0.05 for 2 h runners vs controls). The high-frequency spectral power in the control rats, 24 h runners and 2 h runners was 3.9 ± 0.2, 4.3 ± 0.3 and 5.3 ± 0.3 s2, respectively (P < 0.05 for 2 h runners vs controls), whereas intrinsic HR was 383 ± 3, 377 ± 2 and 346 ± 3 b.p.m., respectively (P < 0.001 for 2 h runners vs controls). Restraint stress provoked tachycardia of similar magnitude in all groups.

4. After completion of telemetric studies, haemodynamic indices and susceptibility to cardiac arrhythmias were assessed in anaesthetized animals, there were no major between-group differences in HR, arterial pressure, contractility indices or sensitivity to β-adrenoceptor stimulation (dobutamine) or blockade (atenolol). The effective refractory period in the control rats, 24 h runners and 2 h runners was 49 ± 2, 55 ± 2 and 60 ± 4 ms, respectively (P = 0.054 for 2 h runners vs controls). A significantly higher dose of aconitine was required to provoke ventricular arrhythmias in the 24 h and 2 h running groups compared with controls (489 ± 76, 505 ± 88 and 173 ± 33 μg, respectively; P < 0.05).

5. We conclude that, in rats, long-term voluntary exercise has enduring cardioprotective effects mediated at the level of both the central nervous system and the heart.

Identifying the core competencies of mental health telephone triage

Aims and objectives. The primary aim of this study was to identify the core competencies of mental health telephone triage, including key role tasks, skills, knowledge and responsibilities, in which clinicians are required to be competent to perform safe and effective triage.
Background. Recent global trends indicate an increased reliance on telephone-based health services to facilitate access to health care across large populations. The trend towards telephone-based health services has also extended to mental health settings, evidenced by the growing number of mental health telephone triage services providing 24-hour access to specialist mental health assessment and treatment. Mental health telephone triage services are critical to the early identification of mental health problems and the provision of timely, appropriate interventions. In spite of the rapid growth in mental health telephone triage and the important role these services play in the assessment and management of mental illness and related risks, there has been very little research investigating this area of practice.
Design. An observational design was employed to address the research aims.
Methods. Structured observations (using dual wireless headphones) were undertaken on 197 occasions of mental health telephone triage over a three-month period from January to March 2011.
Results. The research identified seven core areas of mental health telephone triage practice in which clinicians are required to be competent in to perform effective mental health telephone triage, including opening the call; performing mental status examination; risk assessment; planning and action; termination of call; referral and reporting; and documentation.
Conclusions. The findings of this research contribute to the evidence base for mental health telephone triage by articulating the core competencies for practice. Relevance to clinical practice. The mental health telephone triage competencies identified in this research may be used to define an evidence-based framework for mental health telephone triage practice that aims to improve the quality, consistency and accuracy of telephone-based mental health triage assessment.

8-modified-2'-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription

The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2′-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2′-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.

Utilising self-report data to measure racial discrimination in the labour market

Although economists have developed a series of approaches to modelling the existence of labour market discrimination, rarely is this topic examined by analysing self-report survey data. After reviewing theories and empirical models of labour market discrimination, we examine self-reported experience of discrimination at different stages in the labour market, among three racial groups utilising U.S. data from the 2001-2003 National Survey of American Life. Our findings indicate that African Americans and Caribbean blacks consistently report more experience of discrimination in the labour market than their non-Hispanic white counterparts. At different stages of the labour market, including hiring, termination and promotion, these groups are more likely to report discrimination than non-Hispanic whites. After controlling for social desirability bias and several human capital and socio-demographic covariates, the results remain robust for African Americans. However, the findings for Caribbean blacks were no longer significant after adjusting for social desirability bias. Although self-report data is rarely utilised to assess racial discrimination in labour economics, our study confirms the utility of this approach as demonstrated in similar research from other disciplines. Our results indicate that after adjusting for relevant confounders self-report survey data is a viable approach to estimating racial discrimination in the labour market. Implications of the study and directions for future research are provided.

The P-Loop domain of yeast Clp1 mediates interactions between CF IA and CPF factors in Pre-mRNA 3′ end formation

 Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3' end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5' RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3' end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3' end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3' endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3' end formation.

Coupled RNA polymerase II transcription and 3′ end formation with yeast whole-cell extracts

 RNA polymerase II (RNAP II) transcription and pre-mRNA 3' end formation are linked through physical and functional interactions. We describe here a highly efficient yeast in vitro system that reproduces both transcription and 3' end formation in a single reaction. The system is based on simple whole-cell extracts that were supplemented with a hybrid Gal4-VP16 transcriptional activator and supercoiled plasmid DNA templates encoding G-less cassette reporters. We found that the coupling of transcription and processing in vitro enhanced pre-mRNA 3' end formation and reproduced requirements for poly(A) signals and polyadenylation factors. Unexpectedly, however, we show that in vitro transcripts lacked m⁷G-caps. Reconstitution experiments with CF IA factor assembled entirely from heterologous components suggested that the CTD interaction domain of the Pcf11 subunit was required for proper RNAP II termination but not 3' end formation. Moreover, we observed reduced termination activity associated with extracts prepared from cells carrying a mutation in the 5'-3' exonuclease Rat1 or following chemical inhibition of exonuclease activity. Thus, in vitro transcription coupled to pre-mRNA processing recapitulates hallmarks of poly(A)-dependent RNAP II termination. The in vitro transcription/processing system presented here should provide a useful tool to further define the role of factors involved in coupling.

Leg muscle pH following sprint running

In an effort to compare the disturbances in leg muscle pH during sprint running, muscle biopsies were obtained from the gastrocnemius and vastus lateralis muscles of six healthy men (three endurance-trained and three nonendurance-trained) before and after a treadmill sprint run (TSR) to fatigue (54-105 s) at roughly 125% of their aerobic capacities. Following the TSR, repeated blood samples were taken from a hand vein and later analyzed for pH, PCO2, and lactic acid (HLa). The muscle specimens were analyzed in duplicate for pH and HLa. Resting-muscle pH was 7.03 +/- 0.02 (means +/- SE) and 7.04 +/- 0.01 for the gastrocnemius and vastus lateralis muscles, respectively. At the termination of the TSR, the pH in these muscles was 6.88 +/- 0.05 and 6.86 +/- 0.03, respectively. After a 400-m timed run on the track, the pH in the gastrocnemius of four of the subjects averaged 6.63 +/- 0.03, while blood pH and HLa were 7.10 +/- 0.03 and 12.3 mM, respectively. Although no differences in pH and HLa were observed between the vastus lateralis and gastrocnemius muscles at the end of the treadmill trial, it is speculated that the lesser disturbance in acid-base balance seen in endurance performers may have been due to a lesser production of metabolites in their running musculature when compared to nonendurance performers.

Response rates in Australian market research

RICA commissioned Deakin University to “establish whether response rates are in decline in the Australian market research industry and to identify, as far as possible, the reasons for these declines if they exist. This is likely to involve a review of previous research, a literature review and collection of data on response rates provided on a confidential basis and with the assistance of AMSRO to facilitate data provision.”

Attempts were made to contact all listed market research companies in Australia, including all major internet panel companies. While industry co-operation was not high with the study, sufficient data was provided to depict current response rates and to show how they had declined over time. Because of the low contactability issues, this Report proposes the use of better methods to compute the reliability of survey estimates by taking account of past survey results.

The literature review revealed a wealth of recent studies, with the main emphasis being on studies of telephone and internet surveys. This review of the research produced 34 evidence-based guidelines for social researchers. While some of these reflect current practice, the emergence of the internet as the main survey method raises a number of disclosure and sampling issues. Esomar (2012) has produced 28 issues to be raised with providers, which sets the basis for good industry practice. This suggests an opportunity for the industry to adopt these standards as its own and to conduct training courses for major clients and suppliers. There are many panel providers, some of whom are not AMSRO members. AMSRO may need to examine what role it can play in mandating or encouraging adherence to these standards as a way of promoting the industry.

Talks with key industry people, as well as the literature, have revealed the importance of blended surveys, where multiple contact and response mechanisms are used. Particularly where an internet panel is used as one source, this poses representativeness and weighting issues which are difficult to resolve. The Report recommends that where blended survey methods are used, measures be taken to measure contactability in the other contact media, along with more sophisticated weighting schemes. The industry should examine its training courses to ensure that industry expertise keeps pace with these developments.
Summary of Results

The results focus on two main collection methods – the telephone and the internet. As far as the telephone is concerned response rates have been in a gradual decline the last decade. This outcome is hard to detect because the data show considerable fluctuations from one survey wave to the next. Among cold-calling surveys, telephone response rates are typically below 10%, for a range of topics and survey types. Co-operation rates, (the ratio of obtained interviews to refusals) are typically below 0.2 (that is below one interview to five refusals). Telephone interviews with clients have a higher response rate – typically above 20% with co-operation rates above 1.0. It would appear that some topics, such as financial services, may induce a lower level of co-operation. Government sponsored surveys have higher response rates, at times over 50%, but even here a sharp decline in response rates over time for one long running monitor was observed. Co-operation rates were also higher in government sponsored surveys.

One long data series from a telephone omnibus suggested that the “Do Not Call Register” which began in May, 2007 had some positive effects for the industry. Initially there was a spike in both response rates and co-operation. Although this was relatively short-lived, response rates thereafter declined more slowly and co-operation rates were somewhat higher and remained stable. These conclusions should be regarded as tentative as more data series would really be necessary to see if similar trends occurred elsewhere.

As far as the internet is concerned, panel response rates are around the 20% mark and appear to be relatively stable over the last few years. In this case, the gross response rate is the number of interviews divided by the number of invitations sent. As the number of invitations may be a function of the need to fill a survey quickly, it should be considered a gross indicator of response. In order to capture this phenomenon, a further measure has been devised, termed the “attempt rate” which measures the percentage of people who attempt to participate once sent the invitation. The available data suggests that it is relatively stable. However, it is also somewhat susceptible to the time the survey was left open. Finally, a co-operation rate was also calculated. It measures the ratio of completed to terminated interviews, typically at least five interviews to each termination, but often much higher. This measure is not directly comparable with the co-operation rate in telephone surveys because it cannot take account of the number of eligible people on the panel who open the invitation, see the company doing the survey or its length and decide not to take the survey. For internet client studies, response rates were typically somewhat higher than shown for the panels, but there was marked variability.

There was only one study provided of intercept interviews. It showed response rates of over 60% and co-operation rates of nearly 2 interviews per refusal. A strength and a weakness of intercept interviewing is the ability to be selective in who is asked to participate. As for mail, one government sponsored mail survey from 2010 is reported, with a response rate over 50%. The previous review contains more data, as mail appears to be infrequently used within the industry for commercial surveys.

While surveys remain a major and highly effective tool for the industry and its clients, issues with contactability and co-operation mean that even closer attention is needed to survey design, sampling, weighting and analysis than was previously the case.

Novel mechanism of Col10a1 nonsense-mediated mRNA decay

Nonsense-mediated mRNA decay (NMD) is a conserved surveillance mechanism that selectively targets mRNA transcripts carrying premature termination codons (PTCs) for rapid degradation in all studied eukaryotes. Mutations that introduce PTCs account for approximately one-third of all inherited genetic disorders, highlighting the importance of NMD in the molecular pathology of many diseases.
The experimental findings presented in this thesis demonstrate that the mechanism of Col10a1 NMD is different to previously described NMD pathways and could represent a failsafe NMD mechanism used by genes that have similar gene structures to COL10A1, which would escape the canonical NMD pathway.

Expropriation of "old order" mineral rights in South Africa: the Constitutional Court has its say (twice)

The Mineral and Petroleum Resources Development Act 28 of 2002 (ZA) (MPRDA) makes provision for the conversion of so-called “old order” rights to prospecting and mining rights. The consequences of the failure of holders of old order rights to apply for (a) Conversion or (b) new rights under different circumstances were decided by the South African Constitutional Court in two decisions during 2013. These cases are discussed against the background of the nature, content and termination of old order rights. It is also discussed whether such rights were expropriated by the MPRDA and, if so, whether compensation is payable by the state.

Interventions designed to promote exclusive breastfeeding in high-income countries: a systematic review

Worldwide, women fail to reach the recommended exclusive breastfeeding target of 6 months postpartum. The objective of this study was to present a conceptual and methodological synthesis of interventions designed to promote exclusive breastfeeding to 6 months in high-income countries.

Use of pregnancy counselling services in Australia 2007-2012

To assess the uptake of Medicare Benefit payments for non-directive pregnancy support counselling which commenced in November 2006.

Placing sensors for area coverage in a complex environment by a team of robots

Existing solutions to carrier-based sensor placement by a single robot in a bounded unknown Region of Interest (ROI) do not guarantee full area coverage or termination. We propose a novel localized algorithm, named Back-Tracking Deployment (BTD). To construct a full coverage solution over the ROI, mobile robots (carriers) carry static sensors as payloads and drop them at the visited empty vertices of a virtual square, triangular, or hexagonal grid. A single robot will move in a predefined order of directional preference until a dead end is reached. Then it back-tracks to the nearest sensor adjacent to an empty vertex (an "entrance" to an unexplored/uncovered area) and resumes regular forward movement and sensor dropping from there. To save movement steps, the back-tracking is carried out along a locally identified shortcut. We extend the algorithm to support multiple robots that move independently and asynchronously. Once a robot reaches a dead end, it will back-track, giving preference to its own path. Otherwise, it will take over the back-track path of another robot by consulting with neighboring sensors. We prove that BTD terminates within finite time and produces full coverage when no (sensor or robot) failures occur. We also describe an approach to tolerate failures and an approach to balance workload among robots. We then evaluate BTD in comparison with the only competing algorithms SLD [Chang et al. 2009a] and LRV [Batalin and Sukhatme 2004] through simulation. In a specific failure-free scenario, SLD covers only 40-50% of the ROI, whereas BTD covers it in full. BTD involves significantly (80%) less robot moves and messages than LRV.