Load bearing improves the limits of agreement for repeated in vivo measures of the speed of sound in human Achilles tendon

Axial acoustic wave propagation has been widely used in evaluating the mechanical properties of human bone in vivo. However, application of this technique to monitor soft tissues, such as tendon, has received comparatively little scientific attention. Laboratory-based research has established that axial acoustic wave transmission is not only related to the physical properties of equine tendon but is also proportional to tensile load to which it is exposed (Miles et al., 1996; Pourcelot et al., 2005). The reproducibility of the technique for in vivo measurements in human tendon, however, has not been established. The aim of this study was to evaluate the limits of agreement for repeated measures of the speed of sound (SoS) in human Achilles tendon in vivo. Methods: A custom built ultrasound device, consisting of an A-mode 1MHz emitter and two regularly spaced receivers, was used to measure the SoS in the mid-portion of the Achilles tendon in ten healthy males and ten females (mean age: 33.8 years, range 23-56 yrs; height: 1.73±0.08 m; weight: 68.4±15.3 kg). The emitter and receivers were held at fixed positions by a polyethylene frame and maintained in close contact with the skin overlying the tendon by means of elasticated straps. Repeated SoS measurements were taken with the subject prone (non-weightbearing and relaxed Achilles tendon) and during quiet bipedal and unipedal stance. In each instance, the device was detached and repositioned prior to measurement. Results: Limits of agreement for repeated SoS measures during non-weightbearing and bipedal and unipedal stance were ±53, ±28 and ±21 m/s, respectively. The average SoS in the non-weightbearing Achilles tendon was 1804±198 m/s. There was a significant increase in the average SoS during bilateral (2122±135 m/s) (P < 0.05) and unilateral (2221±79 m/s) stance (P < 0.05). Conclusions: Repeated SoS measures in human Achilles tendon were more reliable during stance than under non-weightbearing conditions. These findings are consistent with previous research in equine tendon in which lower variability in SoS was observed with increasing tensile load (Crevier-Denoix et al, 2009). Since the limits of agreement for Achilles tendon SoS are nearly 5% of the changes previously observed during walking and therapeutic heel raise exercises, acoustic wave transmission provides a promising new non-invasive method for determining tendon properties during sports and rehabilitation related activities.

Achilles tendinopathy modulates force frequency characteristics of eccentric exercise

Introduction Previous research has demonstrated that ground reaction force (GRF) recorded during eccentric ankle exercise is characterised by greater power in the 8-12Hz bandwidth when compared to that recorded during concentric ankle exercise. Subsequently, it was suggested that vibrations in this bandwidth may underpin the beneficial effect of eccentric loading in tendon repair. However, this observation has been made only in individuals without Achilles tendinopathy. This research compared the force frequency characteristics of eccentric and concentric exercises in individuals with and without Achilles tendinopathy., Methods Eleven male adults with unilateral mid-portion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Kinematics and GRF were recorded while the participants performed a common eccentric rehabilitation exercise protocol and a concentric equivalent. Ankle joint kinematics and the frequency power spectrum of the resultant GRF were calculated. Results Eccentric exercise was characterised by a significantly greater proportion of spectral power between 4.5 and 11.5Hz when compared to concentric exercise. There were no significant differences between limbs in the force frequency characteristics of concentric exercise. Eccentric exercise, in contrast, was defined by a shift in the power spectrum of the symptomatic limb, resulting in a second spectral peak at 9Hz, rather than 10Hz in the control limb. Conclusions Compared to healthy tendon, Achilles tendinopathy was characterised by lower frequency vibrations during eccentric rehabilitation exercises. This finding may be associated with changes in neuromuscular activation and tendon stiffness which have been shown to occur with tendinopathy and provides a possible rationale for the previous observation of a different biochemical response to eccentric exercise in healthy and injured Achilles tendons., (C)2012The American College of Sports Medicine

Bringing skills and general competences back into technological education

In this paper we show that industry-based student training is not limited to work experience; work integrated learning, internship or extended vacation work. It is also about bringing back the lost parts of technological education. We experience the unilateral focus on theoretical knowledge at the expense of skills and general competences as one important challenge in technological education. The lacking facilitation and training of practical skills and general competences in the curricula and programs are identified, but many institutions have failed to address the problem. Today’s curricula in many ways reduce technology to abstract concepts, calculations and models, and create a gap between the academic programs and the practical applications in the society. We explore two (Australia and Norway) initiatives on industry-based student training and discuss how these initiatives address and bridge the gap. We argue that these initiatives of industry-based student training contribute to bringing skills and general competences back into technological education, and that the effects are not limited to increased employability, but also include increased academic performance.

A novel device using the Nordic hamstring exercise to assess eccentric knee flexors strength : a reliability and retrospective injury study

STUDY DESIGN: Reliability and case-control injury study. OBJECTIVES: 1) To determine if a novel device, designed to measure eccentric knee flexors strength via the Nordic hamstring exercise (NHE), displays acceptable test-retest reliability; 2) to determine normative values for eccentric knee flexors strength derived from the device in individuals without a history of hamstring strain injury (HSI) and; 3) to determine if the device could detect weakness in elite athletes with a previous history of unilateral HSI. BACKGROUND: HSIs and reinjuries are the most common cause of lost playing time in a number of sports. Eccentric knee flexors weakness is a major modifiable risk factor for future HSIs, however there is a lack of easily accessible equipment to assess this strength quality. METHODS: Thirty recreationally active males without a history of HSI completed NHEs on the device on 2 separate occasions. Intraclass correlation coefficients (ICCs), typical error (TE), typical error as a co-efficient of variation (%TE), and minimum detectable change at a 95% confidence interval (MDC95) were calculated. Normative strength data were determined using the most reliable measurement. An additional 20 elite athletes with a unilateral history of HSI within the previous 12 months performed NHEs on the device to determine if residual eccentric muscle weakness existed in the previously injured limb. RESULTS: The device displayed high to moderate reliability (ICC = 0.83 to 0.90; TE = 21.7 N to 27.5 N; %TE = 5.8 to 8.5; MDC95 = 76.2 to 60.1 N). Mean±SD normative eccentric flexors strength, based on the uninjured group, was 344.7 ± 61.1 N for the left and 361.2 ± 65.1 N for the right side. The previously injured limbs were 15% weaker than the contralateral uninjured limbs (mean difference = 50.3 N; 95% CI = 25.7 to 74.9N; P < .01), 15% weaker than the normative left limb data (mean difference = 50.0 N; 95% CI = 1.4 to 98.5 N; P = .04) and 18% weaker than the normative right limb data (mean difference = 66.5 N; 95% CI = 18.0 to 115.1 N; P < .01). CONCLUSIONS: The experimental device offers a reliable method to determine eccentric knee flexors strength and strength asymmetry and revealed residual weakness in previously injured elite athletes.

Double tax agreements and the international allocation of business income in Australia

Increasingly, the effectiveness of the present system of taxation of international businesses is being questioned. The problem associated with the taxation of such businesses is twofold. A system of international taxation must be a fair and equitable system, distributing profits between the relevant jurisdictions and, in doing so, avoiding double taxation. At the same time, the prevention of fiscal evasion must be secured. In an attempt to achieve a fair and equitable system Australia adopts unilateral, bilateral and multilateral measures to avoid double taxation and restrict the avoidance of tax. The first step in ascertaining the international allocation of business income is to consider the taxation of business income according to domestic law, that is, the unilateral measures. The treatment of international business income under the Australian domestic law, that is, the Income Tax Assessment Act 1936 (Cth) and Income Tax Assessment Act 1997 (Cth), will depend on two concepts, first, whether the taxpayer is a resident of Australia and secondly, whether the income is sourced in Australia. After the taxation of business profits has been determined according to domestic law it is necessary to consider the applicability of the bilateral measures, that is, the Double Tax Agreements (DTAs) to which Australia is a party, as the DTAs will override the domestic law where there is any conflict. Australia is a party to 40 DTAs with another seven presently being negotiated. The preamble to Australia's DTAs provides that the purpose of such agreements is 'to conclude an Agreement for the avoidance of double taxation and the prevention of fiscal evasion with respect to taxes on income'. Both purposes, for different reasons, are equally important. It has been said that: The taxpayer hopes the treaty will prevent the double taxation of his income; the tax gatherer hopes the treaty will prevent fiscal evasion; and the politician just hopes. The first purpose, the avoidance of double taxation, is achieved through the provision of rules whereby the Contracting States agree to the classification of income and the allocation of that income to a particular State. In this sense DTAs do not allocate jurisdiction to tax but rather provide an arrangement whereby the States agree to restrict their substantive law. The restriction is either through the non-taxing of the income or via the provision of a tax credit.

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

Analysis of the MTHFR C677T variant with migraine phenotypes

Background The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender. Findings The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%). Conclusions MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.

A pharmacogenomic evaluation of migraine therapy

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.

Molecular mechanisms of migraine

Migraine is a common complex disorder that affects a large portion of the population and thus incurs a substantial economic burden on society. The disorder is characterized by recurrent headaches that are unilateral and usually accompanied by nausea, vomiting, photophobia, and phonophobia. The range of clinical characteristics is broad and there is evidence of comorbidity with other neurological diseases, complicating both the diagnosis and management of the disorder. Although the class of drugs known as the triptans (serotonin 5-HT1B/1D agonists) has been shown to be effective in treating a significant number of patients with migraine, treatment may in the future be further enhanced by identifying drugs that selectively target molecular mechanisms causing susceptibility to the disease. Genetically, migraine is a complex familial disorder in which the severity and susceptibility of individuals is most likely governed by several genes that may be different among families. Identification of the genomic variants involved in genetic predisposition to migraine should facilitate the development of more effective diagnostic and therapeutic applications. Genetic profiling, combined with our knowledge of therapeutic response to drugs, should enable the development of specific, individually-tailored treatment.

Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

Endophenotype profiles of MTHFR and ACE gene polymorphisms in migraine susceptibility

Background Migraine is a debilitating neurological disorder affecting approximately 12% of the Caucasian population. There are two main sub-types of migraine, migraine without aura (MO) and migraine with aura (MA). Migraine exhibits varied phenotypic expression with sufferers experiencing a range of neurological and other symptoms. It is likely that multiple susceptibility genes play a role in this varied phenotypic expression, thus investigation of genotype-phenotype relationships may provide valuable insights into the role of susceptibility genes in this disorder. Methods This study investigated the links between migraine susceptibility genes, methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE), and clinical manifestation through statistical analyses. Results The result showed that for the MTHFR genotypes, there was a statistically significant correlation with the TT homozygous genotype and visual disturbances, unilateral head pain and physical activity discomforts. It was also found that bilateral head pain was associated with the male gender. Conclusion From these study results, it is plausible to state that MTHFR genotypes affect the phenotypic expression of migraine disease manifestation.

Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (VO2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of L-[ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ?4-fold in LOW (P < 0.01) and ?11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.

Progressive adult antimetropia

Antimetropia, a sub-classification of anisometropia, is a rare refractive condition in which one eye is myopic and the fellow eye is hyperopic. This case report describes the ocular characteristics and atypical refractive progression in an adult male with a moderate degree of non-amblyopic antimetropia over a 20-year period. The potential mechanisms underlying unilateral axial elongation, anisometropia and myopia progression in adulthood are discussed.

Olfactory glia enhance neonatal axon regeneration

Olfactory ensheathing cells (OECs) migrate with olfactory axons that extend from the nasal epithelium into the olfactory bulb. Unlike other glia, OECs are thought to migrate ahead of growing axons instead of following defined axonal paths. However it remains unknown how the presence of axons and OECs influences the growth and migration of each other during regeneration. We have developed a regeneration model in neonatal mice to examine whether (i) the presence of OECs ahead of olfactory axons affects axonal growth and (ii) the presence of olfactory axons alters the distribution of OECs. We performed unilateral bulbectomy to ablate olfactory axons followed by methimazole administration to further delay neuronal growth. In this model OECs filled the cavity left by the bulbectomy before new axons extended into the cavity. We found that delaying axon growth increased the rate at which OECs filled the cavity. The axons subsequently grew over a significantly larger region and formed more distinct fascicles and glomeruli in comparison with growth in animals that had undergone only bulbectomy. In vitro, we confirmed (i) that olfactory axon growth was more rapid when OECs were more widely distributed than the axons and (ii) that OECs migrated faster in the absence of axons. These results demonstrate that the distribution of OECs can be increased by repressing by growth of olfactory axons and that olfactory axon growth is significantly enhanced if a permissive OEC environment is present prior to axon growth.

A nation's role in addressing base erosion and profit shifting : sovereignty in relation to transfer pricing

The notion of sovereignty is central to any international tax issue. While a nation is free to design its tax laws as it sees fit and raise revenue in accordance with the needs of its citizens, it is not possible to undertake such a task in isolation. Tax interactions between sovereign states cannot be avoided. Ultimately, the interactions mean that a nation must decide whether or engage in both collaboration and co ordination with other nations and supranational bodies alike or maintain a unilateral stance in relation to its tax policy. This article considers a modern conceptualisation of sovereignty to argue that a move towards a more unified approach to addressing international base erosion and profit sharing may be the ultimate exercise of national fiscal sovereignty.