We compared the gastrointestinal effects of milk-based diets in which the ?-casein component was either the A1 or A2 type in male Wistar rats fed the experimental diets for 36 or 84?h. Gastrointestinal transit time was significantly greater in the A1 group, as measured by titanium dioxide recovery in the last 24?h of feeding. Co-administration of naloxone decreased gastrointestinal transit time in the A1 diet group but not in the A2 diet group. Colonic myeloperoxidase and jejunal dipeptidyl peptidase (DPP)-4 activities were greater in the A1 group than in the A2 group. Naloxone attenuated the increase in myeloperoxidase activity but not that in DPP-4 activity in the A1 group. Naloxone did not affect myeloperoxidase activity or DPP-4 activity in the A2 group. These results confirm that A1 ?-casein consumption has direct effects on gastrointestinal function via opioid-dependent (gastrointestinal transit and myeloperoxidase activity) and opioid-independent (DPP-4 activity) pathways.
Thermal reaction norms are fundamental relationships for geographic comparisons of organism response to temperature. They are shaped by an organism's environmental history and provide insights into both the global patterns of thermal sensitivity and the physiological mechanisms underlying temperature response. In this study we conducted the first measure of the thermal reaction norm for feeding, comparing the radula rasping rate of two tropical and one polar limpet species. The consistency of thermal response was tested through comparisons with limpet duration tenacity. Feeding and duration tenacity of limpets are ecologically important muscular mechanisms that rely on very different aspects of muscle physiology, repeated concentric (shortening) and isometric (fixed length) contraction of muscles, respectively. In these limpets the thermal reaction norms of feeding limpets were best described by a single break point at a maximum temperature with linear declines at higher (Siphonaria atra) or lower temperatures (Nacella concinna and Cellana radiata) rather than a bell-shaped curve. The thermal reaction norms for duration tenacity were similar in the two tropical limpets. However, the rasping rate in Antarctic N. concinna increased linearly with temperature up to a maximum at 12.3 °C (maximal range 8.5-12.3 °C) when feeding stopped. In contrast, duration tenacity in N. concinna was maximal at 1.0 °C (-0.6 to 3.8 °C) and linearly decreased with increasing temperature. The thermal reaction norms of muscular activity were, therefore, inconsistent within and between species, indicating that different mechanisms likely underlie different aspects of species sensitivities to temperature.
The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies.
Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users.
Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors.
The vestibular system undergoes considerable modification during spaceflight . This is paralleled by microgravity-induced muscle atrophy . However, the possibility of vestibulo-autonomic regulatory mechanisms affecting skeletal muscle structure and function have not yet been addressed.
The metabolic status of dinosaurs has long been debated but remains unresolved as no consistent picture has emerged from a range of anatomical and isotopic evidence. Quantitative analysis of dinosaur energetics, based on general principles applicable to all vertebrates, shows that many features of dinosaur lifestyle are compatible with a physiology similar to that of extant lizards, scaled up to dinosaur body masses and temperatures. The analysis suggests that sufficient metabolic scope would have been available to support observed dinosaur growth rates and allow considerable locomotor activity, perhaps even migration. Since at least one dinosaur lineage evolved true endothermy, this study emphasizes there was no single dinosaur physiology. Many small theropods were insulated with feathers and appear to have been partial or full endotherms. Uninsulated small taxa, and all juveniles, presumably would have been ectothermic, with consequent diurnal and seasonal variations in body temperature. In larger taxa, inertial homeothermy would have resulted in warm and stable body temperatures but with a basal metabolism significantly below that of extant mammals or birds of the same size. It would appear that dinosaurs exhibited a range of metabolic levels to match the broad spectrum of ecological niches they occupied.
ALCAPA (anomalous left coronary artery from pulmonary artery) syndrome is a rare congenital abnormality that involves an anomalous insertion of the left coronary artery into the pulmonary artery. Ninety percent of patients present in the first year of life with signs and symptoms of heart failure or sudden cardiac death secondary to chronic myocardial ischemia. There have been an increasing number of reports of ALCAPA patients surviving to adulthood. There seems, however, to be a tendency to die suddenly in the third decade of life. Adult survivors are either asymptomatic or present with mitral regurgitation, cardiomyopathy, myocardial ischemia, or malignant arrhythmias. The management of the older patient presenting with symptoms resulting from ischemia and progressive left ventricular dysfunction remains a challenge. Treatment is largely based on guidelines for adult congenital heart disease management and an extrapolation of evidence from heart failure practice. Currently, surgical reimplantation of the anomalous coronary onto the aorta is the mainstay of treatment. The management of heart failure, sudden cardiac death, and ventricular arrhythmia present problems that are not addressed by reimplantation of the anomalous vessel alone. In this report, we present two cases with different modes of presentation and discuss treatment options.
The study addresses the question as to what extent the otolith-mediated gravity vector maintains the stability of the coordinate frames of the vestibulo-ocular reflex and the oculomotor system, described by Listings Plane. Under normal 1 G conditions it has been demonstrated in the monkey that Listings Plane (LP) and the 3D vestibulo-ocular response (3D-VOR) are close to collinear . In the present study the coordinate frames of the oculomotor system and the three-dimensional vestibulo-ocular reflex (3D-VOR) system were measured under one-g gravity conditions and during a period of prolonged microgravity, on-board the International Space Station (ISS). To this end, the coordinate frame of the oculomotor system is described in Listings coordinates and that of the 3D-VOR system by the minimal gain vector. The findings demonstrate that under Earthbound, one-g conditions the two coordinate frames diverge by approximately 20° in the human. In the absence of the gravity vector the radical loss in the otolith-mediated contribution to the dynamic VOR leads to a reduction of the torsional VOR component and in turn to a forward tilt of the oculomotor coordinate frame, described by the minimal gain vector. In contrast, the torsional component of LP during horizontal and vertical saccades was found to increase, resulting in a backward tilt of LP. Together with the backward tilt of LP a small but consistent change in LP vergence was observed. The thickness of LP did not appear to change in the absence of gravity. The changes in coordinate frame orientation persisted over the six-month periods spent in zero gravity. The postflight measurements demonstrate that re-adaptation to preflight values proceeds over several days to weeks. The findings demonstrate that the gravity vector represents a common reference for vestibular and oculomotor responses. They also support the idea that the gravity vector provides a central reference for the entire sensorimotor complex.
Adequate vascular access for femoral trans-catheter aortic valve replacement is fundamental to the success of the procedure. Assessment of vascular calibre, tortuosity and calcification is performed by angiography and multi-slice computed tomography (MSCT). Can DynaCT provide the same information as MSCT? 15 Patients underwent MSCT, angiography and DynaCT. Vessel diameter measurements were taken in three positions of the left and right ilio-femoral arteries. Tortuosity was assessed using an index of the direct distance and the distance taken by the artery between two points. Calcification was assessed in MSCT and DynaCT using a simple scoring system. Concordance correlation coefficient of arterial calibre between angiography and MSCT was 0.96 (95 % CI 0.94-0.97). DynaCT and angiography was 0.94 (95 % CI 0.91-0.96) and Dyna CT and MSCT, 0.95 (95 % CI 0.92-0.97). Bland-Altman tests demonstrate a mean difference between the angiogram and the MSCT of 0.06 mm (+0.97, -1.42), angiogram and DynaCT, 0.13 mm, (+1.00, -0.87), DynaCT and MSCT, 0.2 mm, (+1.15, -0.76). Tortuosity comparisons gave a median tortuosity index for MSCT 1.29 and DynaCT 1.23 (p = 0.472). Calcification comparisons of MSCT and DynaCT using correlation coefficients demonstrate a correlation of 0.245 (p = 0.378). Effective radiation doses were: DynaCT; 3.63 ± 0.65 mSv and angiography; 0.57 ± 0.72 mSv, MSCT; 7.15 ± 2.58 mSv. DynaCT is equal to MSCT and angiography in assessing femoral artery calibre. Like MSCT, it can assess tortuosity and can produce 3D images but is inferior in the assessment of calcification.
Haplogroup H dominates present-day Western European mitochondrial DNA variability (>40%), yet was less common (~19%) among Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete haplogroup H mitochondrial genomes from ancient human remains. We then compare this real-time genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of haplogroup H were largely established by the Mid Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated haplogroup H genomes allow us to reconstruct the recent evolutionary history of haplogroup H and reveal a mutation rate 45% higher than current estimates for human mitochondria.
Photographs are commonly taken of children in medical and research contexts. With the increased availability of photographs through the internet, it is increasingly important to consider their potential for negative consequences and the nature of any consent obtained. In this research we explore the issues around photography in low-resource settings, in particular concentrating on the challenges in gaining informed consent.
Activity-induced nitric oxide (NO) imbalance and "nitrosative stress" are proposed mechanisms of disrupted Ca(2+) homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO) functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study) without and with exercise as countermeasure in order to assess (i) the negative effects of chronic muscle disuse by nitrosative stress, (ii) to test for possible attenuation by exercise countermeasure in bed rest and (iii) to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre) and at end (End) from a bed rest disuse control group (CTR, n=9) and two bed rest resistive exercise groups either without (RE, n=7) or with superimposed vibration stimuli (RVE, n=7). At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, -SERCA1 and -PMCA) and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.
There is no generally accepted value for the lower temperature limit for life on Earth. We present empirical evidence that free-living microbial cells cooling in the presence of external ice will undergo freeze-induced desiccation and a glass transition (vitrification) at a temperature between -10°C and -26°C. In contrast to intracellular freezing, vitrification does not result in death and cells may survive very low temperatures once vitrified. The high internal viscosity following vitrification means that diffusion of oxygen and metabolites is slowed to such an extent that cellular metabolism ceases. The temperature range for intracellular vitrification makes this a process of fundamental ecological significance for free-living microbes. It is only where extracellular ice is not present that cells can continue to metabolise below these temperatures, and water droplets in clouds provide an important example of such a habitat. In multicellular organisms the cells are isolated from ice in the environment, and the major factor dictating how they respond to low temperature is the physical state of the extracellular fluid. Where this fluid freezes, then the cells will dehydrate and vitrify in a manner analogous to free-living microbes. Where the extracellular fluid undercools then cells can continue to metabolise, albeit slowly, to temperatures below the vitrification temperature of free-living microbes. Evidence suggests that these cells do also eventually vitrify, but at lower temperatures that may be below -50°C. Since cells must return to a fluid state to resume metabolism and complete their life cycle, and ice is almost universally present in environments at sub-zero temperatures, we propose that the vitrification temperature represents a general lower thermal limit to life on Earth, though its precise value differs between unicellular (typically above -20°C) and multicellular organisms (typically below -20°C). Few multicellular organisms can, however, complete their life cycle at temperatures below ?-2°C.
Understanding the relationship between life-history variation and population structure in marine invertebrates is not straightforward. This is particularly true of polar species due to the difficulty of obtaining samples and a paucity of genomic resources from which to develop nuclear genetic markers. Such knowledge, however, is essential for understanding how different taxa may respond to climate change in the most rapidly warming regions of the planet. We therefore used over two hundred polymorphic Amplified Fragment Length Polymorphisms (AFLPs) to explore population connectivity at three hierachical spatial scales in the direct developing Antarctic topshell Margarella antarctica. To previously published data from five populations spanning a 1500 km transect along the length of the Western Antarctic Peninsula, we added new AFLP data for four populations separated by up to 6 km within Ryder Bay, Adelaide Island. Overall, we found a nonlinear isolation-by-distance pattern, suggestive of weaker population structure within Ryder Bay than is present over larger spatial scales. Nevertheless, significantly positive F st values were obtained in all but two of ten pairwise population comparisons within the bay following Bonferroni correction for multiple tests. This is in contrast to a previous study of the broadcast spawner Nacella concinna that found no significant genetic differences among several of the same sites. By implication, the topshells direct-developing lifestyle may constrain its ability to disperse even over relatively small geographic scales.
Return to work after a leave on disability is a common phenomenon, but little is known about the attitudes of employees or their supervisors towards the disability management process. We report on employee and supervisor feedback from one disability management experience.
The present study demonstrates that various response patterns of subjective visual vertical (SVV) can be identified during unilateral centrifugation (UC). It is proposed that these response types correspond to different degrees of compensation after disease. This is advantageous for monitoring the effect of rehabilitative measures and is useful in medico-legal issues. It also emerges that diagnosis of unilateral utricle function requires the determination not only of asymmetry ratio but also offset of SVV estimates.
Monitoring of therapeutic response in mucopolysaccharidosis (MPS) patients is problematic as most biomarkers are specific for either disease complications or specific organ system involvement. Recent studies have indicated that serum heparin-cofactor II-thrombin complex (HCII-T) may serve as an important biomarker in the group of MPSs where dermatan sulphate is stored. This complex forms when blood coagulates in the presence of glycosaminoglycans (GAGs) where the ultimate amount of HCII-T that forms reflects the concentration of circulating GAGs. We have studied serum HCII-T levels in 9 MPS I and 11 MPS II treated patients and have compared values to studies of urinary GAGs. In severe MPS I patients treated with either transplantation or enzyme replacement therapy (ERT), serum HCII-T levels never reach the range of normal despite normalization of uGAGs in some patients. Some attenuated MPS I patients have normalization of HCII-T but require a protracted exposure time relative to the drop in urinary GAGs. Treated MPS II patients show a clear correlation of serum HCII-T levels with the presence of antibodies to Idursulfase, with antibody positive patients showing an early drop in HCII-T levels with eventual increases in levels often to levels above those seen at baseline. This is contrasted by a robust and persistent drop in uGAGs. Antibody negative MPS II patients show a drop in HCII-T levels on treatment but levels never normalize despite normalization of uGAGs. This study highlights the utility and biologic relevance of serum HCII-T levels in monitoring therapy in these disorders.
To investigate the reliability, validity and feasibility of a computer-assisted manual segmentation method for determining the synovial membrane volume as a surrogate measure for synovitis in patients with rheumatoid arthritis (RA).
The most potent foreign antigens for natural killer T cells (NKT cells) are ?-linked glycolipids, whereas NKT cell self-reactivity involves weaker recognition of structurally distinct ?-linked glycolipid antigens. Here we provide the mechanism for the autoreactivity of T cell antigen receptors (TCRs) on NKT cells to the mono- and tri-glycosylated ?-linked agonists ?-galactosylceramide (?-GalCer) and isoglobotrihexosylceramide (iGb3), respectively. In binding these disparate antigens, the NKT cell TCRs docked onto CD1d similarly, achieving this by flattening the conformation of the ?-linked ligands regardless of the size of the glycosyl head group. Unexpectedly, the antigenicity of iGb3 was attributable to its terminal sugar group making compensatory interactions with CD1d. Thus, the NKT cell TCR molds the ?-linked self ligands to resemble the conformation of foreign ?-linked ligands, which shows that induced-fit molecular mimicry can underpin the self-reactivity of NKT cell TCRs to ?-linked antigens.
We aimed to identify common mistakes made when radiographing yearling sale horses. Radiographic examinations from repositories at eight yearling sales held in Australia in 2003 were assessed by one of four veterinary radiology specialists. Each radiographic examination consisted of a maximum of 34 radiographs. Each radiograph was assessed for errors associated with movement, exposure, positioning, labeling or marker placement, and processing, and categorized as either ideal, less than ideal or nondiagnostic. In addition, from the first 800 sets catalogued, 167 were selected randomly and read twice by the four radiologists for agreement analysis. A total of 81,297 radiographs were examined for errors affecting quality. Positioning errors were the most common reason for radiographs to be considered nondiagnostic (2432/81,297; 3%), with the flexed lateromedial (LM) metacarpophalangeal joint, LM metatarsophalangeal joint, and the dorsomedial palmarolateral (DMPaLO) carpal views being the most frequently involved. Overexposure (14,357/81,297; 17.7%) was the most common reason for radiographs being categorized as less than ideal with the LM stifle view the most represented. Agreement within and between radiologists for reporting errors in positioning of the flexed LM metacarpophalangeal joint, LM metatarsophalangeal joint, and DMPaLO carpal views varied from slight to almost perfect. The low repeatability within radiologists on some views suggests that before declaring a radiograph nondiagnostic it is worth considering rereading it at another time. Care should be taken in positioning of the flexed LM metacarpophalangeal, LM metatarsophalangeal, and DMPaLO carpus views to maximize radiograph quality.
To investigate the reliability, feasibility, and validity of a computer-assisted manual segmentation (outlining) technique for measuring magnetic resonance imaging (MRI) bone erosion and edema at the wrist in rheumatoid arthritis (RA).
The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3? loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.
With the introduction of next generation high throughput sequencing in 2005 and the resulting revolution in genetics, ancient DNA research has rapidly developed from an interesting but marginal field within evolutionary biology into one that can contribute significantly to our understanding of evolution in general and the development of our own species in particular. While the amount of sequence data available from ancient human, other animal and plant remains has increased dramatically over the past five years, some key limitations of ancient DNA research remain. Most notably, reduction of contamination and the authentication of results are of utmost importance. A number of studies have addressed different aspects of sampling, DNA extraction and DNA manipulation in order to establish protocols that most efficiently generate reproducible and authentic results. As increasing numbers of researchers from different backgrounds become interested in using ancient DNA technology to address key questions, the need for practical guidelines on how to construct and use an ancient DNA facility arises. The aim of this article is therefore to provide practical tips for building a state-of-the-art ancient DNA facility. It is intended to help researchers new to the field of ancient DNA research generally, and those considering the application of next generation sequencing, in their planning process.
The amplified fragment length polymorphism (AFLP) technique is a widely used multi-purpose DNA fingerprinting tool. The ability to size-separate fluorescently labelled AFLP fragments on a capillary electrophoresis instrument has provided a means for high-throughput genome screening, an approach particularly useful in studying the molecular ecology of nonmodel organisms. While the per-marker-generated costs for AFLP are low, fluorescently labelled oligonucleotides remain costly. We present a cost-effective method for fluorescently end-labelling AFLPs that should make this tool more readily accessible for laboratories with limited budgets. Both standard fluorescent AFLPs and the end-labelled alternatives presented here are repeatable and produce similar numbers of fragments when scored using both manual and automated scoring methods. While it is not recommended to combine data using the two approaches, the results of the methods are qualitatively comparable, indicating that AFLP end-labelling is a robust alternative to standard methods of AFLP genotyping. For researchers commencing a new AFLP project, the AFLP end-labelling method outlined here is easily implemented, as it does not require major changes to PCR protocols and can significantly reduce the costs of AFLP studies.
Effective utilisation of blood products is fundamental. The introduction of maximum surgical blood ordering schedules (MSBOS) for operations has been shown to improve transfusion services. A retrospective analysis was undertaken to establish an evidence-based MSBOS for revision total hip replacement (THR) and total knee revision (TKR). The impact of this schedule on blood conservation was analysed.
Ecologists have long been fascinated by the flora and fauna of extreme environments. Physiological studies have revealed the extent to which lifestyle is constrained by low temperature but there is as yet no consensus on why the diversity of polar assemblages is so much lower than many tropical assemblages. The evolution of marine faunas at high latitudes has been influenced strongly by oceanic cooling during the Cenozoic and the associated onset of continental glaciations. Glaciation eradicated many shallow-water habitats, especially in the Southern Hemisphere, and the cooling has led to widespread extinction in some groups. While environmental conditions at glacial maxima would have been very different from those existing today, fossil evidence indicates that some lineages extend back well into the Cenozoic. Oscillations of the ice-sheet on Milankovitch frequencies will have periodically eradicated and exposed continental shelf habitat, and a full understanding of evolutionary dynamics at high latitude requires better knowledge of the links between the faunas of the shelf, slope and deep-sea. Molecular techniques to produce phylogenies, coupled with further palaeontological work to root these phylogenies in time, will be essential to further progress.
Midfoot osteoarthritis (OA) is a degenerative condition of the foot that can be treated non-operatively by the use of orthotics. This prospective study was conducted to determine the effects of custom-made semi-rigid foot orthoses (FOs) and rigid carbon fibre (CF) footplates for the treatment of midfoot OA evaluated using specifically designed questionnaires. Fifty-seven subjects diagnosed with midfoot OA were recruited through a private clinic for inclusion in the study. Subjects were required to complete pre-treatment questionnaires prior to receiving orthotic treatment. All subjects received a pair of custom-made full-length semi-rigid FOs and 36 subjects also received CF footplates that were incorporated into the soles of the shoes worn on the symptomatic feet. Subjects completed post-treatment questionnaires at six weeks, three months and six months after receiving the orthotic treatment. The results demonstrated that there were no significant differences between the results of the subjects who received CF footplates and those who did not. The results of the questionnaires demonstrated that subjects experienced significant improvements in pain, activity levels, walking ability and footwear comfort at all intervals following the orthotic treatment (p?0.01). Subjects satisfaction with the appearance of their footwear did not decrease with the orthotic treatment despite needing shoes to fit the FOs and CF footplates. The questionnaires also demonstrated that subjects were generally satisfied with the orthotic treatment for the management of their midfoot OA.
Recent reports on vestibular testing, relevant to clinical diagnosis, are reviewed.Besides the case history and bedside examination, objective measurement of the vestibuloocular reflex in all of its facets remains the cornerstone in the diagnostic process.
Although studies of population genetic structure are commonplace, a strong bias exists toward species from low latitudes and with relatively poor dispersal capabilities. Consequently, we used 280 amplified fragment length polymorphism bands to explore patterns of genetic differentiation among 8 populations of a high latitude broadcast-spawning marine mollusc, the Antarctic limpet Nacella concinna. Over 300 individuals were sampled along a latitudinal gradient spanning the Antarctic Peninsula from Adelaide Island to King George Island (67°-62°S), then to Signy Island (60°S) and South Georgia (54°S). Populations from the Antarctic Peninsula exhibited little genetic structure but were themselves strongly differentiated from both Signy and South Georgia. This finding was analytically highly robust and implies the presence of significant oceanographic barriers to gene flow in a species long regarded as a classic example of a widely dispersing broadcast spawner.
Ankylosing spondylitis is a seronegative spondyloarthropathy which predominantly affects the sacroiliac joints and the spine. The spine can become very kyphotic with time. Minor trauma is sufficient to produce a fracture, because of the underlying osteoporosis and because the ankylosed segments constitute large leverage arms. These fractures are unstable because the soft tissues are ossified and also involved in the fracture. Cervical spine fractures need an immobilisation which respects the pre-injury flexion deformity. Inadvertent application of a rigid collar which forces the previously flexed cervical spine into extension may lead to neurological deterioration and even death. We report such a case in a 59-year-old male patient.
This article reports the experience of the Victorian Department of Health in seeking clinician engagement in the testing of 11 quality-of-care indicators in 20 health services in Victoria. The Department previously developed a suite of 18 core indicators and seven subindicators known as the AusPSI set. We used routinely collected administrative data from the Victorian Admitted Episodes Dataset to produce variable life-adjusted display (VLAD) control charts for 11 selected indicators. The Department recognises that clinicians are responsible for the safety and quality of the care they provide, and therefore the necessity of engaging clinicians in the process of investigating apparent variation in patient care. Although using readily available and inexpensive routinely collected administrative data to measure clinical performance has a certain appeal, the use of administrative data and VLADs to identify apparent variations has posed significant challenges due to concerns about the quality of the data and resource requirements. When clinicians at a major Melbourne hospital were engaged, it resulted in an improvement in clinical practice. Investigating apparent variation in patient care provides an ideal opportunity for emerging clinical leaders to take local ownership and develop expertise in investigating apparent variation in processes of care and implementing change as required.
1. We present a statistical analysis of the scaling of resting (basal) metabolic rate, BMR, with body mass, B(m) and body temperature, T(b), in mammals. 2. Whilst the majority of the variance in ln BMR is explained by ln B(m), the T(b) term is statistically significant. The best fit model was quadratic, indicating that the scaling of ln BMR with ln B(m) varies with body size; the value of any scaling exponent estimated for a sample of mammals will therefore depend on the size distribution of species in the study. This effect can account for much of the variation in scaling exponents reported in the literature for mammals. 3. In all models, inclusion of T(b) reduced the strength of scaling with ln B(m). The model including T(b) suggests that birds and mammals have a similar underlying thermal dependence of BMR, equivalent to a Q(10) of 2.9 across the range of T(b) values 32-42 degrees C. 4. There was significant heterogeneity in both the mass scaling exponent and mean BMR across mammalian orders, with a tendency for orders dominated by larger taxa to have steeper scaling exponents. This heterogeneity was particularly marked across orders with smaller mean B(m) and the taxonomic composition of the sample will thus also affect the observed scaling exponent. After correcting for the effects of ln B(m) and T(b), Soricomorpha, Didelphimorphia and Artiodactyla had the highest BMR of those orders represented by more than 10 species in the data set. 5. Inclusion of T(b) in the model removed the effect of diet category evident from a model in ln B(m) alone and widely reported in the literature; this was caused by a strong interaction between diet category and T(b) in mammals. 6. Inclusion of mean ambient temperature, T(a), in the model indicated a significant inverse relationship between ln BMR and T(a), complicated by an interaction between T(a) and T(b). All other things being equal, a polar mammal living at -10 degrees C has a body temperature approximately 2.7 degrees C warmer and a BMR higher by approximately 40% than a tropical mammal of similar size living at 25 degrees C.
Atypical fibroxanthoma is an unusual tumour of skin seen mainly in the head and neck region of elderly patients. Clinically it appears as red, ulcerated nodules, which can be difficult to differentiate from other tumours without histopathological examination. Immunohistochemical analysis also aids diagnosis. The mainstay of treatment is operation. We present a case series of 16 patients with 17 atypical fibroxanthomas over a 5-year period in a district general hospital.
Endothermy has evolved at least twice, in the precursors to modern mammals and birds. The most widely accepted explanation for the evolution of endothermy has been selection for enhanced aerobic capacity. We review this hypothesis in the light of advances in our understanding of ATP generation by mitochondria and muscle performance. Together with the development of isotope-based techniques for the measurement of metabolic rate in free-ranging vertebrates these have confirmed the importance of aerobic scope in the evolution of endothermy: absolute aerobic scope, ATP generation by mitochondria and muscle power output are all strongly temperature-dependent, indicating that there would have been significant improvement in whole-organism locomotor ability with a warmer body. New data on mitochondrial ATP generation and proton leak suggest that the thermal physiology of mitochondria may differ between organisms of contrasting ecology and thermal flexibility. Together with recent biophysical modelling, this strengthens the long-held view that endothermy originated in smaller, active eurythermal ectotherms living in a cool but variable thermal environment. We propose that rather than being a secondary consequence of the evolution of an enhanced aerobic scope, a warmer body was the means by which that enhanced aerobic scope was achieved. This modified hypothesis requires that the rise in metabolic rate and the insulation necessary to retain metabolic heat arose early in the lineages leading to birds and mammals. Large dinosaurs were warm, but were not endotherms, and the metabolic status of pterosaurs remains unresolved.
The findings demonstrate that an enduring unilateral utricular dysfunction, possibly together with canal hypofunction, can occur after labyrinthine disease or injury. They also suggest that unilateral, isolated utricular dysfunction - or utricle paresis - can occur, representing a novel entity in the differential diagnosis of peripheral vestibular function. The occurrence of subjective visual vertical (SVV) asymmetry in the presence of symmetric vestibular evoked myogenic potentials (VEMPs) also confirms that the information from the utricles, rather than the saccules, dominates SVV estimation.
One of the most well-characterised plant pathogenic interactions involves Arabidopsis thaliana and the bacteria Pseudomonas syringae pathovar tomato (Pst). The standard Pst inoculation procedure involves infiltration of large populations of bacteria into plant leaves which means that metabolite changes cannot be readily assigned to the host or pathogen. A plant cell-pathogen co-culture based approach has been developed where the plant and pathogen cells are separated after 12h of co-culture via differential filtering and centrifugation. Fourier transform infrared (FT-IR) spectroscopy was employed to assess the intracellular metabolomes (metabolic fingerprints) of both host and pathogen and their extruded (extracellular) metabolites (metabolic footprints) under conditions relevant to disease and resistance. We propose that this system will enable the metabolomic profiling of the separated host and pathogen (i.e. dual metabolomics) and will facilitate the modelling of reciprocal responses.
Widespread recognition of the importance of biological studies at large spatial and temporal scales, particularly in the face of many of the most pressing issues facing humanity, has fueled the argument that there is a need to reinvigorate such studies in physiological ecology through the establishment of a macrophysiology. Following a period when the fields of ecology and physiological ecology had been regarded as largely synonymous, studies of this kind were relatively commonplace in the first half of the twentieth century. However, such large-scale work subsequently became rather scarce as physiological studies concentrated on the biochemical and molecular mechanisms underlying the capacities and tolerances of species. In some sense, macrophysiology is thus an attempt at a conceptual reunification. In this article, we provide a conceptual framework for the continued development of macrophysiology. We subdivide this framework into three major components: the establishment of macrophysiological patterns, determining the form of those patterns (the very general ways in which they are shaped), and understanding the mechanisms that give rise to them. We suggest ways in which each of these components could be developed usefully.
Based on the knowledge that traumatic brainstem damage often leads to alteration in brainstem functions, including the vestibulo-ocular reflex, the present study is designed to determine whether prediction of outcome in the early phase after severe traumatic brain injury is possible by means of vestibulo-ocular monitoring.
A pseudomeningocoele is an extradural collection of cerebrospinal fluid which results from a dural or arachnoid tear. The fluid is not contained within a protrusion of the meninges, which is typical for a real meningocoele. Although most pseudomeningocoeles probably go unrecognised, due to lack of symptoms, surgeons should maintain an index of suspicion when reviewing postoperative patients. Symptomatic pseudomeningocoeles warrant intervention, as the patients do not tolerate the symptoms. However, the literature neither suggests a trial of watching and waiting nor a suitable time frame for such a trial. The authors report the spontaneous resolution of a massive symptomatic pseudomeningocoele after 11 months. There is only one previous report of a similar case, where the pseudomeningocoele disappeared in three months.
We report a case of spontaneous coronary artery rupture (SCAR) in a 43-year-old male who presented with symptoms of sudden onset of chest pain and hemodynamic collapse. There were no abnormal electrocardiogram changes and serum troponin was not detected. Acute aortic dissection was suspected but urgent contrast computed tomography (CT) showed a large pericardial effusion with cardiac tamponade. This was later confirmed on trans-oesophageal echocardiogram. The SCAR was seen intra-operatively as an isolated perforation of the posterior descending artery. The patient was successfully managed with direct repair under cardiopulmonary bypass. Postoperative multi-detector dual-source 64-slice CT coronary angiography revealed normal coronary arteries with absence of atherosclerotic plaque in all coronary arterial segments. It is concluded that, though rare, a differential diagnosis of SCAR should be considered in cases of acute chest pain with cardiac tamponade in adult patients of all ages.
Surgical repair of post-myocardial infarction ventricular septal rupture is challenging with reported early mortality being substantial. In addition, congestive cardiac failure and ventricular tachyarrhythmia frequently occur long term after the operation, although frequency and predictive factors of these events have been poorly identified.
The BTBR T+tf/J (BTBR) strain is an inbred strain of mice that displays prominent social deficits and repetitive behaviors analogous to the defining symptoms of autism, along with complete congenital agenesis of the corpus callosum (CC). The BTBR strain is genetically distant from the widely used C57BL/6J (B6) strain, which exhibits high levels of sociability, a low level of repetitive behaviors, and an intact CC. Emerging evidence implicates compromised interhemispherical connectivity in some cases of autism. We investigated the hypothesis that the disconnection of CC fiber tracts contributes to behavioral traits in mice that are relevant to the behavioral symptoms of autism. Surgical lesion of the CC in B6 mice at postnatal day 7 had no effect on juvenile play and adult social approaches, and did not elevate repetitive self-grooming. In addition, LP/J, the strain that is genetically closest to the BTBR strain but has an intact CC, displayed juvenile play deficits and repetitive self-grooming similar to those seen in BTBR mice. These corroborative results offer evidence against the hypothesis that the CC disconnection is a primary cause of low sociability and a high level of repetitive behaviors in inbred mice. Our findings indicate that genes mediating other aspects of neurodevelopment, including those whose mutations underlie more subtle disruptions in white matter pathways and connectivity, are more likely to contribute to the aberrant behavioral phenotypes in the BTBR mouse model of autism.
Chronic groin pain is a common entity in the sporting population and causes considerable morbidity. The differential diagnosis is wide, and this article presents a review of the common causes with particular reference to anatomy, ultrasound and magnetic resonance imaging (MRI) findings.
Cardiac perforation and device erosion are infrequent but potentially lethal complications of percutaneous occluder device insertion. Transthoracic and transesophageal echocardiography (TEE) and gated cardiac computed tomography are useful in detecting this complication. In particular, TEE can detect characteristic features to confirm the diagnosis before rapid surgical correction. Deficient superior-anterior rim and encroachment of the occluder device on the posterior atrial wall are risk factors for device erosion. TEE performed before device insertion with awareness of manufacturers guidelines for atrial geometry and device sizing may reduce the occurrence of this serious complication.
The growth in smartphone market share has seen the increasing emergence of individuals collecting quantitative wellness data. Beyond the potential health benefits for the individual in regards to managing their own health, the data is highly related to preventative and risk factors for a number of lifestyle related diseases. This data has often been a component of public health data collection and epidemiological studies due to its large impact on the health system with chronic and lifestyle diseases increasingly being a major burden for the health service. However, collection of this kind of information from large segments of the community in a usable fashion has not been specifically explored in previous work. In this paper we discuss some of the technologies that increase the ease and capability of gathering quantitative wellness data via smartphones, how specific and detailed this data needs to be for public health use and the challenges of such anonymized data collection for public health. Additionally, we propose a conceptual architecture that includes the necessary components to support this approach to data collection.
Trans-catheter aortic valve implantation (TAVI) is now a well recognised procedure for the high risk surgical patient with native or bioprosthetic aortic valve stenosis. Transfemoral and transapical implantation techniques are well described. With increasing referral of more marginal transapical patients, we describe our experience of a transaortic TAVI approach which we believe reduces the postoperative wound pain, respiratory complications, operative risk and hospital stay.
Computed tomography (CT) and magnetic resonance imaging (MRI) are sensitive modalities for the assessment of the spine, but certain injuries remain poorly assessed with supine radiographs. We describe four cases in which cervical spine injuries were proven as unstable with erect radiographs after being previously evaluated with supine radiographs and CT scans.
Sonographic abnormalities of the achilles and patellar tendons are common findings in athletes, and tendinopathy is a common cause of pain and disability in athletes. However, it is unclear whether the sonographic changes are pathological or adaptive, or if they predict future injury. We undertook a cohort study to determine what sonographic features of the achilles and patellar tendons are consistent with changes as a result of ballet training, and which may be predictive of future development of disabling tendon symptoms.
The clinical value of optimising implant angles during transcatheter aortic valve replacements (TAVR) remains undefined. The Aortic Valve Guide (AVG) is a proprietary software that provides structured analysis of three-dimensional images from rotational angiography (DynaCT). This study compares AVG with preprocedural multislice computed tomography (MSCT) and DynaCT in optimal implant angle prediction for TAVR, and evaluates if an optimised implant angle is associated with reduced paravalvular regurgitation (PVR).
The metabolic theory of ecology (MTE) predicts the effects of body size and temperature on metabolism through considerations of vascular distribution networks and biochemical kinetics. MTE has also been extended to characterise processes from cellular to global levels. MTE has generated both enthusiasm and controversy across a broad range of research areas. However, most efforts that claim to validate or invalidate MTE have focused on testing predictions. We argue that critical evaluation of MTE also requires strong tests of both its theoretical foundations and simplifying assumptions. To this end, we synthesise available information and find that MTEs original derivations require additional assumptions to obtain the full scope of attendant predictions. Moreover, although some of MTEs simplifying assumptions are well supported by data, others are inconsistent with empirical tests and even more remain untested. Further, although many predictions are empirically supported on average, work remains to explain the often large variability in data. We suggest that greater effort be focused on evaluating MTEs underlying theory and simplifying assumptions to help delineate the scope of MTE, generate new theory and shed light on fundamental aspects of biological form and function.
Natural killer T cells (NKT cells) are divided into type I and type II subsets on the basis of differences in their T cell antigen receptor (TCR) repertoire and CD1d-antigen specificity. Although the mode by which type I NKT cell TCRs recognize CD1d-antigen has been established, how type II NKT cell TCRs engage CD1d-antigen is unknown. Here we provide a basis for how a type II NKT cell TCR, XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F pocket of CD1d. At the XV19 TCR-CD1d-sulfatide interface, the TCR? and TCR? chains sat centrally on CD1d, where the malleable CDR3 loops dominated interactions with CD1d-sulfatide. Accordingly, we highlight the diverse mechanisms by which NKT cell TCRs can bind CD1d and account for the distinct antigen specificity of type II NKT cells.
Transcatheter aortic valve replacements lower mortality in patients not suitable for surgical valve replacement compared to conservative treatment. Transcatheter valve-in-valve implants have been shown to be feasible in failed bioprostheses in aortic, mitral, pulmonary and tricuspid positions. We report the first Australasian experience of a transapical mitral valve-in-valve placement with an Edwards Sapien(®) transcatheter valve for a failed mitral bioprosthesis, focussing on the technical aspects of this novel procedure. Whilst the evidence for this niche indication is limited currently to case reports and case series, further evaluation of its long term outcomes may justify its use in this particularly high risk group of re-do sternotomy patients.
Inbred mouse strains differ greatly in social behaviors, making them a valuable resource to study genetic and non-genetic mechanisms underlying social deficits relevant to autism spectrum disorders. A hallmark symptom of autism is a lack of ability to understand other peoples thoughts and intentions, which leads to impairments in adjusting behaviors in response to ever-changing social situations in daily life. We compared the ability of BTBR T+tf/J (BTBR), a strain with low sociability, and C57BL/6J (B6), a strain with high sociability, for their abilities to modulate responses to social cues from different partners in the reciprocal social interaction test. Results indicate that BTBR exhibited low sociability toward different partners and displayed minimal ability to modify behaviors toward different partners. In contrast, B6 showed high sociability toward different partners and was able to modify social behaviors toward different partners. Consistent results were found in two independent cohorts of different ages, and in both sexes. In the three-chambered test, high sociability in B6 and low sociability in BTBR were independent of strain of the novel mouse. Since social deficits in BTBR could potentially be caused by physical disabilities in detecting social olfactory cues, or in cognitive abilities, we tested BTBR and B6 mice on measures of olfaction and cognition. BTBR mice displayed more sniffing of social odors emitted by soiled bedding than of an odorless novel object, but failed to show a preference for a live novel mouse over a novel object. On olfactory habituation/dishabituation to a sequence of odors, BTBR displayed discrimination abilities across three non-social and two social odors. However, as compared to B6, BTBR displayed less sniff time for both non-social and social odors, and no significant dishabituation between cage odors from two different novel mouse strains, findings that will be important to investigate further. BTBR was generally normal in spatial acquisition on the Morris water maze test, but showed deficits in reversal learning. Time spent freezing on contextual and cued fear conditioning was lower in BTBR than in B6. Our findings suggest that BTBR has poor abilities to modulate its responses to different social partners, which may be analogous to social cognition deficits in autism, adding to the value of this strain as a mouse model of autism.
Chronic Achilles tendinosis is a common musculoskeletal disorder often refractory to conservative management. Our study aimed to assess the safety and efficacy of the use of autologous skin-derived collagen-producing cells in the treatment of refractory Achilles tendinosis.
Since the first discovery of deep-sea hydrothermal vents along the Galápagos Rift in 1977, numerous vent sites and endemic faunal assemblages have been found along mid-ocean ridges and back-arc basins at low to mid latitudes. These discoveries have suggested the existence of separate biogeographic provinces in the Atlantic and the North West Pacific, the existence of a province including the South West Pacific and Indian Ocean, and a separation of the North East Pacific, North East Pacific Rise, and South East Pacific Rise. The Southern Ocean is known to be a region of high deep-sea species diversity and centre of origin for the global deep-sea fauna. It has also been proposed as a gateway connecting hydrothermal vents in different oceans but is little explored because of extreme conditions. Since 2009 we have explored two segments of the East Scotia Ridge (ESR) in the Southern Ocean using a remotely operated vehicle. In each segment we located deep-sea hydrothermal vents hosting high-temperature black smokers up to 382.8°C and diffuse venting. The chemosynthetic ecosystems hosted by these vents are dominated by a new yeti crab (Kiwa n. sp.), stalked barnacles, limpets, peltospiroid gastropods, anemones, and a predatory sea star. Taxa abundant in vent ecosystems in other oceans, including polychaete worms (Siboglinidae), bathymodiolid mussels, and alvinocaridid shrimps, are absent from the ESR vents. These groups, except the Siboglinidae, possess planktotrophic larvae, rare in Antarctic marine invertebrates, suggesting that the environmental conditions of the Southern Ocean may act as a dispersal filter for vent taxa. Evidence from the distinctive fauna, the unique community structure, and multivariate analyses suggest that the Antarctic vent ecosystems represent a new vent biogeographic province. However, multivariate analyses of species present at the ESR and at other deep-sea hydrothermal vents globally indicate that vent biogeography is more complex than previously recognised.
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