Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit.

The steady-state myofilament Ca sensitivity was determined in skinned cardiac trabeculae from the rabbit right ventricle (diameter, 0.13-0.34 mm) at 36, 29, 22, 15, 8, and 1 degree C. Muscles were stimulated to 0.5 Hz and stretched to a length at which maximum twitch tension was generated. The preparation was then skinned with 1% vol/vol Triton X-100 in a relaxing medium (10 mM EGTA, pCa 9.0). Each preparation was exposed to a series of Ca-containing solutions (pCa 6.3-4.0) at two of the six temperatures studied (temperature was regulated to +/- 0.1 degree C). The pCa values (mean +/- SD, n = 6) corresponding to half maximal tension at 36, 29, 22, 15, 8, and 1 degree C were 5.47 +/- 0.07, 5.49 +/- 0.07, 5.34 +/- 0.05, 5.26 +/- 0.09, 4.93 +/- 0.06, and 4.73 +/- 0.04, respectively. Mean (+/- SD) maximum tension (Cmax) developed by the preparation as a percentage of that at 22 degrees C was 118 +/- 10, 108 +/- 5, 74 +/- 6, 57 +/- 7, and 29 +/- 5% at 36, 29, 15, 8, and 1 degree C, respectively. As cooling led to a shift of Ca sensitivity towards higher [Ca2+] and a reduction of Cmax, the Ca sensitivity curves over this range of temperatures do not cross over as has been described for canine Purkinje fibers (Fabiato 1985). Since tension is decreased by cooling at all levels of [Ca2+] it is unlikely that changes in myofilament Ca sensitivity play a role in the large hypothermic inotropy seen in rabbit ventricular muscle. The increase in sensitivity of the myofilaments to Ca on warming from 1 to 29 degrees C might be related to the increase in force seen on rewarming from a rapid cooling contracture in intact rabbit ventricular muscle

The influence of large predators on the feeding ecology of two African mesocarnivores: the black-backed jackal and the brown hyaena

Interactions between apex and mesopredators and their impacts on prey populations have been well documented, while the influence of apex predators such as lions on carrion availability and the subsequent impacts at lower trophic levels are not fully understood. Here we assess dietary overlap between two sympatric carnivores (brown hyaena, Parahyaena brunnea, and black-backed jackal, Canis mesomelas) in neighbouring reserves with and without apex predators (lions, Panthera leo,and wild dog, Lycaon pictus). We investigate whether apex predators facilitate niche partitioning between mesocarnivores by creating additional scavenging opportunities through predatory activity. We found that brown hyaena density was higher in the area with apex predators, while black-backed jackal density was higher in the area without apex predators. Black-backed jackal scats contained broadly similar dietary items at both sites, while large mammal remains occurred significantly more frequently in brown hyaena scats collected inthe presence of apex predators. In the absence of apex predators there was a markedly higher degree of overlap between brown hyaena and jackal diets, suggesting increased levels of inter-specific competition. Our results suggest that apex predators potentially reduce levels of inter-specific competition for food between mesocarnivores by providing additional scavenging opportunities for specialist scavengers such as brown hyaena

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Analysing detection gaps in acoustic telemetry data to infer differential movement patterns in fish

A wide array of technologies are available for gaining insight into the movement of wild aquatic animals. Although acoustic telemetry can lack the fine‐scale spatial resolution of some satellite tracking technologies, the substantially longer battery life can yield important long‐term data on individual behavior and movement for low per‐unit cost. Typically, however, receiver arrays are designed to maximize spatial coverage at the cost of positional accuracy leading to potentially longer detection gaps as individuals move out of range between monitored locations. This is particularly true when these technologies are deployed to monitor species in hard‐to‐access locations. Here, we develop a novel approach to analyzing acoustic telemetry data, using the timing and duration of gaps between animal detections to infer different behaviors. Using the durations between detections at the same and different receiver locations (i.e., detection gaps), we classify behaviors into “restricted” or potential wider “out‐of‐range” movements synonymous with longer distance dispersal. We apply this method to investigate spatial and temporal segregation of inferred movement patterns in two sympatric species of reef shark within a large, remote, marine protected area (MPA). Response variables were generated using network analysis, and drivers of these movements were identified using generalized linear mixed models and multimodel inference. Species, diel period, and season were significant predictors of “out‐of‐range” movements. Silvertip sharks were overall more likely to undertake “out‐of‐range” movements, compared with gray reef sharks, indicating spatial segregation, and corroborating previous stable isotope work between these two species. High individual variability in “out‐of‐range” movements in both species was also identified. We present a novel gap analysis of telemetry data to help infer differential movement and space use patterns where acoustic coverage is imperfect and other tracking methods are impractical at scale. In remote locations, inference may be the best available tool and this approach shows that acoustic telemetry gap analysis can be used for comparative studies in fish ecology, or combined with other research techniques to better understand functional mechanisms driving behavior

Iron, silicate, and light co-limitation of three Southern Ocean diatom species

The effect of combined iron, silicate, and light co-limitation was investigated in the three diatom species Actinocyclus sp. Ehrenberg, Chaetoceros dichaeta Ehrenberg, and Chaetoceros debilis Cleve, isolated from the Southern Ocean (SO). Growth of all species was co-limited by iron and silicate, reflected in a significant increase in the number of cell divisions compared to the control. Lowest relative Si uptake and drastic frustule malformation was found under iron and silicate co-limitation in C. dichaeta, while Si limitation in general caused cell elongation in both Chaetoceros species. Higher light intensities similar to SO surface conditions showed a negative impact on growth of C. dichaeta and Actinocyclus sp. and no effect on C. debilis. This is in contrast to the assumed light limitation of SO diatoms due to deep wind driven mixing. Our results suggest that growth and species composition of Southern Ocean diatoms is influenced by a sensitive interaction of the abiotic factors, iron, silicate, and light

Applications of real number theorem proving in PVS

This work is supported by funding from the EPSRC under grants EP/H500162, EP/F02309X and GR/S31242Real number theorem proving has many uses, particularly for verification of safety critical systems and systems for which design errors may be costly. We discuss a chain of developments building on real number theorem proving in PVS. This leads from the verification of aspects of an air traffic control system, through work on the integration of computer algebra and automated theorem proving to a new tool, NRV, first presented here that builds on the capabilities of Maple and PVS to provide a verified and automatic analysis of Nichols plots. This automates a standard technique used by control engineers and greatly improves assurance compared with the traditional method of visual inspection of the Nichols plots.Publisher PDFPeer reviewe

The reliability and validity of three non-radiological measures of thoracic kyphosis and their relations to the standing radiological Cobb angle

UnlabelledHyperkyphosis is implicated in a mounting list of negative outcomes, including higher mortality. Hyperkyphosis research is hindered due to difficulties inherent in its measurement. By showing that three clinical measures of kyphosis are suitable for use in large scale, longitudinal, hyperkyphosis studies, we will facilitate much needed research in this field.IntroductionThe objective of this study is to describe the reliability of three non-radiological kyphosis measures (Debrunner kyphosis angle, flexicurve kyphosis index, and flexicurve kyphosis angle) and their validity compared to the Cobb angle and to approximate a Cobb angle from non-radiological kyphosis measures.MethodsWe analyzed data from 113 participants aged ≥ 60 years with kyphosis angle ≥ 40°. Cobb angle was measured on a standing lateral thoracolumbar radiograph using bounds at T4 and T12. Non-radiological measures of kyphosis were made three times by a single rater and a 4th time by a blinded second rater.ResultsIntra- and inter-rater reliabilities for non-radiological assessments were high (intra-class correlations of 0.96 to 0.98) and did not differ from each other. Pearson correlations, estimating validity, ranged from 0.62 to 0.69 and did not differ. The Debrunner angle was close to the Cobb angle, with scaling factor of 1.067 and an offset of 5°. The Flexicurve kyphosis angle had to be scaled by 1.53 to obtain the equivalent Cobb angle. The scaling factor for the Flexicurve kyphosis index to Cobb angle was 315, with an offset of 5°. Compared to the measured Cobb angle, Cobb angles predicted using the non-radiological measures had similar magnitude errors (standard deviations of the differences ranging between 10.24 and 11.26).ConclusionsEach non-radiological measurement had similar reliability and validity. Low cost, ease of use, and robustness to variations in spine contour argue for the Flexicurve in longitudinal kyphosis assessments. The approximate conversion factors provided will permit translation of non-radiological measures to Cobb angles

Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established