Decoupling of stretch reflex and background muscle activity during anticipatory postural adjustments in humans

We studied the evolution of stretch reflexes in relation to background electromyographic (EMG) activity in the soleus muscle preceding the onset of voluntary arm raise movements. Our objective was to investigate if changes in reflex EMG and muscle activity occur simultaneously and are similarly scaled in amplitude. Ten human subjects stood with each foot on pedals able to exert short dorsiflexor pulses during stance. Subjects were asked to product consistent voluntary arm raise movements to a target upon a visual cue. In ¼ of trials, no pulse perturbations were given, but in the remaining ¾’s of all trials pulses were given randomly during a 600-ms period, from 400 ms before until 200 ms after the onset of the movements. Perturbation trials were sorted into 20-ms bins post hoc, and the amplitude of the reflex EMG component was calculated and compared to the EMG activity obtained when no pulses were given. Results showed that despite exhibiting similar profiles over time, the background EMG consistently inhibited before the reflex EMG did. However, times of reactivation (rebound) were variable across subjects, with background EMG activating before reflex for some subjects and vice versa for others. The minimum values of inhibition, time of inhibition and time of rebound for background and reflex EMG measures did not show significant linear correlations when all subjects’ data were considered. These results suggest that reflex and background EMG components of anticipatory postural adjustments evolve differently in time and amplitude. This has implications for the independent control of reflexes and voluntary muscle activity.     

Correlation of in vitro susceptibility with in vivo efficacy in mice for cefoxitin in comparison with cephalosporins.

Agar minimal inhibitory concentrations and mouse protection test effective doses were determined for each of four beta-lactam antibiotics against each of 12 Gram-negative and 3 Gram-positive bacterial cultures. The beta-lactamase activity of these cultures also was studied. The data were examined to determine whether relative in vivo efficacies could be predicted from relative in vitro activities. Although such predictions were quite accurate for cefoxitin and cefazolin, this was not true for cefamandole or for cephalothin. Such poor predictability was not necessarily associated with the susceptibility of these cephalosporins to hydrolysis by bacterial beta-lactamases. Although the clinical significance of these observations is not known, these data emphasize that relative in vitro activities should be used only with caution to estimate in vivo efficacies, since not all compounds show the excellent predictability observed here for cefazolin and cefoxitin.     

Investigation to find a suitable reference material for use as an inverse gas chromatography system suitability test

The purpose of this study was to find a suitable material for use as a system suitability test material for inverse gas chromatography (IGC). The purpose of a system check is to measure the variability of the instrument being used rather than the material being analysed. Having such a system check for IGC enables a basic GMP requirement to be met. IGC results can then be used in regulatory submissions to support other already established techniques for characterising pharmaceutical materials. Alpha-alumina was chosen because it is inorganic, stable at high temperatures, resistant to hydration and is already established as a system check material for surface area determination by nitrogen adsorption. Two columns (1 and 2) packed from the same reference sample jar of alpha-alumina and analysed under the same conditions yielded dispersive surface energies of 34.8+/-0.8 and 35.3+/-0.8 mJ/m(2), respectively, at 15% RH. Column 1 was analysed on a second IGC system, and gave a dispersive surface energy of 34.7+/-0.2 mJ/m(2). No significant change was evident after 7 months storage under laboratory ambient conditions. Analysis of material from a second reference sample jar of alpha-alumina produced results not noticeably different to those of the first, yielding a dispersive surface energy of 35.3+/-0.1 mJ/m(2). A change was seen to occur in the surface properties alpha-alumina when the humidity was varied, but the change appeared to be consistent across the two columns reported. Based upon the data in this experimental, alpha-alumina appears to be a suitable material for use as a system suitability test material for IGC.     

Piloting education days for patients with early rheumatoid arthritis and their partners: a multidisciplinary approach

Objectives: To develop, pilot, refine and reassess an education day presented by a rheumatology multidisciplinary team (MDT) for recently diagnosed (less than six months) rheumatoid arthritis (RA) patients and their partners/carers. Methods: A patient education day was developed drawing on an assessment of local patient educational needs and preferences and input from a rheumatology MDT. Feedback from the first education day (2004) (Day 1; 12 patients; age range 19–63 years (median 46); 10 of whom were accompanied by a partner) informed the development of a second education day (2005) (Day 2; 19 patients; age range 36–75 years (median 57.5); 13 of whom were accompanied by a partner). Participants completed evaluation forms on both days and at follow‐up between six and seven weeks later, rating each session on a 5‐point scale on dimensions of ‘informative’, ‘useful’, ‘interesting’ and ‘enjoyable’. A global rating of the day's ‘usefulness’ was completed at the end of each day on a 10‐point scale. Participants were asked to write comments on each session and on aspects of the entire day. RA knowledge, and general and RA‐specific self‐efficacy were also measured on day 2 (and at follow‐up) using the 12‐item Patient Knowledge Questionnaire, the 10‐item generalized self‐efficacy scale and a four‐item RA‐specific self‐efficacy scale. Both qualitative and quantitative methodologies were used in the analysis. Results: Ratings for individual sessions were all high, with no session being rated below 4 out of 5 (1 = ‘totally disagree’ to 5 = ‘totally agree’) on both days. The majority of patients (84%) and their partners (57%) responded to the follow‐up. Many had used the information package distributed on the day. Some patients and their partners reported positive changes in RA management. Although patient knowledge did not increase significantly (medians 11 at both time points, p = 0.054) (Day 2), RA self‐efficacy improved (baseline 11 and 14, respectively), suggesting that patients were more confident in managing their condition (p = 0.010). Conclusions: The development of this ‘local’ education and information intervention was carried out in line with Medical Research Council guidelines, and the lessons learned from Day 1 informed further development for Day 2. A one‐day format for education of early RA involving the rheumatology MDT was rated highly by participants and warrants further examination. Although this study was a small ‘local’ intervention, its strengths are that it informs the possibility of wider developments of this kind using a MDT. Copyright © 2008 John Wiley & Sons, Ltd.     

Continuous magnesium infusions in the management of systemic anti-cancer therapy-related hypomagnesaemia

Background Hypomagnesaemia is a relatively-common side effect of some systemic anti-cancer therapies (SACT). Oral and intravenous magnesium (given as injections or short infusions) have problems arising from their poor tolerability, and need for frequent administrations, respectively. Objective Assessing the effectiveness and safety of weekly continuous magnesium infusions (CMI) in the management of SACT-related hypomagnesaemia. Methods CMIs (initiated at 10 mmol/day and up-titrated subject to response) were prescribed to patients with ≥3 magnesium readings <0.5 mmol/L despite intravenous replacement with bolus-or-short-infusions (BSI). Efficacy (compared to BSI): (a) reduction in the number of moderate/severe hypomagnesaemia episodes, and (b) increase in mean magnesium serum levels. Safety: non-occurrence of grade ≥3 toxicities (according to the common terminology criteria for adverse events v4). Results Three patients were treated (mean age: 62-years), pre-SACT levels were 0.629 ± 0.121 mmol/L. Efficacy: (a) 1 versus 18 episodes; (b) 0.639 ± 0.093 mmol/L versus 0.533 ± 0.191 mmol/L. All comparisons were statistically significant in favour of CMI (p < 0.001). No magnesium-related grade ≥2 side effects were observed. Conclusion CMIs resulted in a marked reduction in the number of episodes of hypomagnesaemia and higher magnesium levels, with no significant side effects. CMIs represent a potential option for the management of SACT-related hypomagnesaemia, although further research in an expanded cohort is required.     

Do educational interventions improve nurses' clinical decision making and judgement? A systematic review

Objectives

Despite the growing popularity of decision making in nursing curricula, the effectiveness of educational interventions to improve nursing judgement and decision making is unknown. We sought to synthesise and summarise the comparative evidence for educational interventions to improve nursing judgements and clinical decisions.

Design

A systematic review.

Data sources

Electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL and PsycINFO, Social Sciences Citation Index, OpenSIGLE conference proceedings and hand searching nursing journals.

Review methods

Studies published since 1960, reporting any educational intervention that aimed to improve nurses’ clinical judgements or decision making were included. Studies were assessed for relevance and quality. Data extracted included study design; educational setting; the nature of participants; whether the study was concerned with the clinical application of skills or the application of theory; the type of decision targeted by the intervention (e.g. diagnostic reasoning) and whether the evaluation of the intervention focused on efficacy or effectiveness. A narrative approach to study synthesis was used due to heterogeneity in interventions, study samples, outcomes and settings and incomplete reporting of effect sizes.

Results

From 5262 initial citations 24 studies were included in the review. A variety of educational approaches were reported. Study quality and content reporting was generally poor. Pedagogical theories were widely used but use of decision theory (with the exception of subjective expected utility theory implicit in decision analysis) was rare. The effectiveness and efficacy of interventions was mixed.

Conclusions

Educational interventions to improve nurses’ judgements and decisions are complex and the evidence from comparative studies does little to reduce the uncertainty about ‘what works’. Nurse educators need to pay attention to decision, as well as pedagogical, theory in the design of interventions. Study design and reporting requires improvement to maximise the information contained in reports of educational interventions.     

Age-related changes in conventional road versus off-road triathlon performance

The aims of this study were: (i) to analyze age-related declines in swimming, cycling, and running performances for road-based and off-road triathlons, and (ii) to compare age-related changes in these three disciplines between road-based and off-road triathlons. Swimming, cycling, running and total time performances of the top five males between 20 and 70 years of age (in 5-year intervals) were analyzed for short distance road-based (1.5 km swim, 40 km cycle, and 10 km run) and off-road (1.5 km swim, 30 km mountain bike, and 11 km trail run) triathlons at the 2009 World Championships. Independently of age, there was a lesser age-related decline in cycling performance (P < 0.01) compared to running and swimming for road-based triathlon. In contrast, age-related decline did not differ between the three locomotion modes for off-road triathlon. With advancing age, the performance decline was less pronounced (P < 0.01) for road-based than for off-road triathlon in swimming (≥65 years), cycling (≥50 years), running (≥60 years), and total event (≥55 years) times, respectively. These results suggest that the rate of the decline in performance for off-road triathlon is greater than for road-based triathlon, indicating that the type of discipline (road vs. mountain bike cycling and road vs. trail running) exerts an important influence on the magnitude of the age-associated changes in triathlon performance.     

Pronounced inter- and intrachromosomal variation in linkage disequilibrium across the zebra finch genome

The extent of nonrandom association of alleles at two or more loci, termed linkage disequilibrium (LD), can reveal much about population demography, selection, and recombination rate, and is a key consideration when designing association mapping studies. Here, we describe a genome-wide analysis of LD in the zebra finch (Taeniopygia guttata) using 838 single nucleotide polymorphisms and present LD maps for all assembled chromosomes. We found that LD declined with physical distance approximately five times faster on the microchromosomes compared to macrochromosomes. The distribution of LD across individual macrochromosomes also varied in a distinct pattern. In the center of the macrochromosomes there were large blocks of markers, sometimes spanning tens of mega bases, in strong LD whereas on the ends of macrochromosomes LD declined more rapidly. Regions of high LD were not simply the result of suppressed recombination around the centromere and this pattern has not been observed previously in other taxa. We also found evidence that this pattern of LD has remained stable across many generations. The variability in LD between and within chromosomes has important implications for genome wide association studies in birds and for our understanding of the distribution of recombination events and the processes that govern them.Linkage disequilibrium (LD), which refers to the nonrandom association of alleles at two or more loci, plays an important role in evolutionary biology and gene mapping (Coop et al. 2008; Slatkin 2008). LD can reveal much about population demography and, because the extent of LD is approximately inversely proportional to the recombination rate, LD can also uncover variability in recombination rates across genomes and chromosomes (Hedrick 1988; Miyashita and Langley 1988; Daly et al. 2001; Jeffreys et al. 2001; Gabriel et al. 2002; Arnheim et al. 2007). Importantly, LD determines the power and precision of association mapping studies, directly influencing our ability to localize genes and/or loci responsible for traits and diseases (Kruglyak 1999; Weiss and Clark 2002).Studies of LD are dependent on the availability of genomic resources, and across vertebrates comprehensive genome-wide studies have been restricted to model species, in particular mammals. Studies in other organisms, however, are likely to reveal extensive variation in patterns of LD not seen in humans (Slatkin 2008), and organisms with different genomic architecture to mammals may provide novel insight into patterns of LD and genome evolution. Birds are interesting in this respect as most bird genomes are composed of many small (micro) chromosomes and relatively few large (macro) chromosomes. Linkage mapping studies have shown that microchromosomes have a higher recombination rate than their larger counterparts (International Chicken Genome Sequencing Consortium 2004; Stapley et al. 2008). Increased recombination rate is expected to reduce the amount of background LD; however, to date there has been no comprehensive analysis of how LD varies with chromosome length and across macrochromosomes and microchromosomes. With respect to LD in birds, the chicken Gallus gallus has received the most attention; studies have quantified LD in several breeds of domestic chicken but have only focused on relatively few chromosomes (Heifetz et al. 2005; Aerts et al. 2007; Andreescu et al. 2007; Wahlberg et al. 2007; Rao et al. 2008; Abasht et al. 2009). In chickens, LD extends very short distances, which reflects the high recombination rate and relatively large effective population size of domestic fowl relative to other livestock species. Passerines, which make up around half of all birds species, and diverged from chickens at least 80 million yr ago, are beginning to receive attention; however, all studies to date have either investigated single chromosomes (Backström et al. 2006), a few genomic regions (Balakrishnan and Edwards 2008), or have low marker coverage (Li and Merilä 2009).The zebra finch, the second bird to have its genome sequenced, can provide a useful target for a comprehensive LD study. In addition to having the two types of chromosomes (macro- and microchromosomes) characteristic of most birds, the zebra finch genome exhibits an unusual pattern of crossing over. Cytogenetic studies have revealed that the location of meiotic crossover events on the macrochromosomes is highly nonrandom, mostly occurring at the ends of the macrochromosomes (Pigozzi and Solari 2005; Calderón and Pigozzi 2006). This suggests there is a large recombination desert on all macrochromosomes, corresponding with the center of the metacentric chromosomes and the center of the long arm of the acrocentric chromosomes (Calderón and Pigozzi 2006). The suppressed recombination in the middle of the chromosomes is not necessarily related to the position of the centromere, nor to the presence of heterochromatin (Calderón and Pigozzi 2006), which is thought to suppress recombination. It is unknown how stable this pattern of recombination is or if this is characteristic of other zebra finch populations. If it is a persistent phenomenon of zebra finch chromosomes, it is likely to affect the extent of LD across macrochromosomes and generate extensive heterogeneity across and between chromosomes. Interestingly, this pattern has not been reported in chickens (Calderón and Pigozzi 2006; Groenen et al. 2009).Patterns of LD may also co-vary with other sequence features that are correlated with recombination rate, such as heterozygosity, GC content, and the number of genes. Recombination rate is expected to increase heterozygosity (Begun and Aquadro 1992; Nachman 2001), although this pattern may be obscured by the action of other forces such as selection and biased gene conversion (Maynard Smith and Haigh 1974; Ohta 1999). Recombination rate is also positively related to GC content and other sequence features known to co-vary with GC content, e.g., gene density, intron length, CpG motifs (Kong et al. 2002; Meunier and Duret 2004; Groenen et al. 2009). It is unknown how LD and these sequence features will co-vary in the presence of highly nonrandom recombination.The aim of this study was to construct genome-wide LD maps of the zebra finch in order to examine (1) whether LD extended further on macro- than microchromosomes, as predicted by previously described differences in recombination rate; (2) whether LD varied across macrochromosomes, corresponding to the biased location of crossing-over events on chromosome spreads; and (3) whether patterns of LD co-vary with heterozygosity, GC content, and the number of genes; and (4) to assess the stability of patterns in LD, by examining whether contemporary genome-wide variation in recombination rates, as detected by linkage mapping, is consistent with historical recombination rate variation, as inferred from LD maps.