Comparison of double inversion recovery magnetic resonance imaging (DIR-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in detection of prostate cancer: A pilot study.

INTRODUCTION: DCE-MRI is established for detecting prostate cancer (PCa). However, it requires a gadolinium contrast agent, with potential risks for patients. The application of DIR-MRI is simple and may allow cancer detection without the use of an intravenous contrast agent by differentially nullifying signal from normal and abnormal prostate tissue, creating contrast between the cancer and background normal prostate. In this pilot study we gathered data from DIR-MRI and DCE-MRI of the prostate for an equivalence trial. We also looked at how the DIR-MRI appearance varies with the aggressiveness of PCa. METHOD: DIR-MRI and DCE-MRI were acquired. The images were assessed by an experienced Consultant Radiologist and a novice reporter (Radiographer). The potential PCa lesions were quantified using a lesion to normal ratio (LNR). Radiological pathological correlation was made to identify the MRI lesions that represented significant PCa. A Wilcoxon sign rank was used to compare DCE-LNR and DIR-LNR for PCa containing lesions. Pearson's correlation was used to look at the relationship between DIR-LNR and PCa grade group (aggressiveness). RESULTS: DCE-LNR and DIR-LNR were found to be significantly different (Z = -5.910, p < 0.001). However, a significant correlation was found between PCa grade group and DIR-LNR. CONCLUSION: DIR and DCE sequences are not equivalent and significant cancer is more conspicuous on the DCE sequence. However, DIR-LNR does correlate with PCa aggressiveness. IMPLICATIONS FOR PRACTICE: With the correlation of PCa grade group with DIR-LNR this may be a useful sequence in evaluation of the prostate; stratifying the risk of there being clinically significant PCa before biopsy is performed. Furthermore, given that DIR-LNR appears to predict PCa aggressiveness DIR might be used as part of a multiparametric MRI protocol designed to avoid biopsy.

Antidepressant treatment among social workers, human service professionals, and non-human service professionals: A multi-cohort study in Finland, Sweden and Denmark.

BACKGROUND: Social workers have an elevated risk for mental disorders, but little is known about their antidepressant treatment. AIMS: To examine any and long-term antidepressant treatment among social workers in Finland, Sweden and Denmark. METHODS: We linked records from drug prescription registers to three prospective cohorts: the Finnish Public Sector study, years 2006-2011, and nation-wide cohorts in Sweden and Denmark, years 2006-2014, including a total of 1.5 million employees in (1) social work, (2) other social and health care professions, (3) education and (4) office work. We used Cox proportional hazards models to estimate hazard ratios for any and long-term (>6 months) antidepressant treatment among social workers compared to the three reference occupational groups and carried out meta-analyses. RESULTS: During follow-up, 25% of social workers had any prescriptions for antidepressants (19-24% reference occupations) and 20% for long-term treatment (14-19% reference occupations). The pooled effects for any and long-term treatment showed that probabilities were 10% higher in social workers compared to other health and social care professionals and 30% higher compared to education and non-human service professionals. Probabilities for any treatment in the three countries were relatively similar, but for long-term treatment social workers in Finland had a greater risk compared with other human service professions. LIMITATIONS: There were differences between the cohorts in the availability of data. Specific diagnoses for the antidepressant treatment were not known neither adherence to treatment. CONCLUSION: Social workers have a higher risk for any and long-term antidepressant treatment than other human and non-human service professionals.

Pathophysiology of melanocortin receptors and their accessory proteins.

The melanocortin receptors (MCRs) and their accessory proteins (MRAPs) are involved in regulation of a diverse range of endocrine pathways. Genetic variants of these components result in phenotypic variation and disease. The MC1R is expressed in skin and variants in the MC1R gene are associated with ginger hair color. The MC2R mediates the action of ACTH in the adrenal gland to stimulate glucocorticoid production and MC2R mutations result in familial glucocorticoid deficiency (FGD). MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated. MRAPs have been shown to modulate the function of MCRs and genetic variants in MRAPs are associated with diseases including FGD type 2 and potentially early onset obesity. This review provides an insight into recent advances in MCRs and MRAPs physiology, focusing on the disorders associated with their dysfunction.

Informal caregiving as a risk factor for type 2 diabetes in individuals with favourable and unfavourable psychosocial work environments: A longitudinal multi-cohort study.

AIM: To examine whether informal caregiving is associated with increased risk of type 2 diabetes (T2D), and whether job strain and social support at work modify the association. METHODS: Individual participant's data were pooled from three cohort studies-the French GAZEL study, the Swedish Longitudinal Occupational Survey of Health (SLOSH) and the British Whitehall II study-a total of 21,243 study subjects. Informal caregiving was defined as unpaid care for a closely related person. Job strain was assessed using the demand-control model, and questions on co-worker and supervisor support were combined in a measure of social support at work. Incident T2D was ascertained using registry-based, clinically assessed and self-reported data. RESULTS: A total of 1058 participants developed T2D during the up to 10 years of follow-up. Neither informal caregiving (OR: 1.09, 95% CI: 0.92-1.30) nor high job strain (OR: 1.04, 95% CI: 0.86-1.26) were associated with T2D risk, whereas low social support at work was a risk factor for T2D (OR: 1.18, 95% CI: 1.02-1.37). Also, informal caregivers who were also exposed to low social support at work were at higher risk of T2D (OR: 1.40, 95% CI: 1.08-1.82) compared with those who were not informal caregivers and had high social support at work (multiplicative test for interaction, P=0.04; additive test for interaction, synergy index=10). CONCLUSION: Informal caregiving was not independently associated with T2D risk. However, low social support at work was a risk factor, and informal caregivers with low social support at work had even higher risks of T2D.

No support for Heincke's law in hagfish (Myxinidae): lack of an association between body size and the depth of species occurrence.

This study tests for interspecific evidence of Heincke's law among hagfishes and advances the field of research on body size and depth of occurrence in fishes by including a phylogenetic correction and by examining depth in four ways: maximum depth, minimum depth, mean depth of recorded specimens and the average of maximum and minimum depths of occurrence. Results yield no evidence for Heincke's law in hagfishes, no phylogenetic signal for the depth at which species occur, but moderate to weak phylogenetic signal for body size, suggesting that phylogeny may play a role in determining body size in this group.

Pain expectations in neuropathic pain: Is it best to be optimistic?

BACKGROUND: Pain expectancy may be an important variable that has been found to influence the effectiveness of treatments for pain. Much of the literature supports a self-fulfilment perspective where expectations for pain relief predict the actual pain experienced. However, in conditions such as neuropathic pain (NeP) where pain relief is difficult to attain, expectations for pain relief could be unrealistic. The objective of this study was to investigate the relationship between realistic/unrealistic expectations and 6-month, post-treatment outcomes. METHODS: We performed a retrospective analysis of a large cohort of patients with NeP (n = 789) attending tertiary care centres to determine the association between unrealistic (both positive and negative) and realistic expectations with outcomes after multidisciplinary treatment. An expectation variable with three categories was calculated: realistic expectations were those whose expected reduction in pain was similar to the observed mean group reduction in pain, while optimistic and pessimistic expectations were those who over- or under-estimated the expected response to treatment, respectively. The association between baseline realistic/unrealistic expectations and 6-month pain-related disability, catastrophizing and psychological distress was assessed. RESULTS: Univariable analyses suggested that realistic expectations were associated with lower levels of disability, catastrophizing and psychological distress, compared to unrealistic expectations. However, after adjustment for baseline symptom severity, multivariable analysis revealed that patients with optimistic expectations had lower levels of disability, than those with realistic expectations. Those with pessimistic expectations had higher levels of catastrophizing and psychological distress at follow-up. CONCLUSIONS: These findings are largely congruent with the self-fulfilment perspective to expectations. SIGNIFICANCE: This study defined realistic pain expectations with patient data. Examining the relationship between expectations between pain and disability in a large cohort of patients with neuropathic pain.

Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol.

Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2(tm1a/tm1a)) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2(tm1a/tm1a) mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2(tm1a/tm1a) mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling.

Impact on health-related quality of life and costs of managing chronic neuropathic pain in academic pain centres: Results from a one-year prospective observational Canadian study.

BACKGROUND: The management of chronic pain, including neuropathic pain (NeP), is a major public health issue. However, there is a paucity of data evaluating pain management strategies in real-life settings. OBJECTIVE: To inform policy makers about the economic value of managing chronic NeP in academic centres by conducting a subeconomic assessment of a Canadian multicentre cohort study aimed at determining the long-term outcomes of the management of chronic NeP in academic pain centres. Specific questions regarding the economic value of this type of program were answered by a subset of patients to provide further information to policy makers. METHODS: Baseline demographic information and several pain-related measurements were collected at baseline, three, six and 12 months in the main study. A resource use questionnaire aimed at determining NeP-related costs and the EuroQoL-5 Dimension were collected in the subset study from consenting patients. Statistical analyses were conducted to compare outcomes over time and according to responder status. RESULTS: A total of 298 patients were evaluated in the present economic evaluation. The mean (± SD) age of the participants was 53.7±14.0 years, and 56% were female. At intake, the mean duration of NeP was >5 years. Statistically significant improvements in all pain and health-related quality of life outcomes were observed between the baseline and one-year visits. Use decreased over time for many health care resources (eg, visits to the emergency room decreased by one-half), which resulted in overall cost savings. CONCLUSION: The results suggest that increased access to academic pain centres should be facilitated in Canada.

Muscle Articulations: Flexible Jaw Joints Made of Soft Tissues.

This study surveys animals that use soft tissues rather than rigid links to build jaw joints. Hard biting elements are useful; they are used in piercing or shearing during feeding and interactive behaviors and can directly impact survival and reproduction. The best understood biting systems include biting elements that are mounted on rigid jaw links that form a joint capable of transmitting the bite reaction forces. As such, jaws must incorporate joints that resist compression. Many jaw joints are "sliding joints", in which jaw links come into direct contact and the shape of the sliding contact surfaces dictates possible motions. There are, however, organisms that have biting elements on jaws that are made of flexible muscle and connective tissues. If arranged as a muscular hydrostat, in which multiple orientations of the muscle fibers may co-contract to provide turgid skeletal support, the multifunctional joint not only (a) provides the force to move the biting elements, but also (b) creates repositionable pivots and (c) transmits bite reaction forces. Such flexible joints, termed "muscle articulations", may be important to a number of soft-bodied animals. In this survey, we review the function of previously described muscle articulations: the joints found between inarticulate brachiopods' valves, cephalopods' beaks, the hooks of kalyptorhynch flatworms, and errant polychaetes' jaws. We also review the morphology, physiology, and feeding behaviors of the hagfish as a putative muscle articulation in an effort to understand how this jawless craniate is capable of biting with surprising force, seemingly without the benefit of any obvious method of opposing the force of the dental plate that is used to remove portions of food. Initial analysis suggests that a muscle articulation may be a key feature in coordinating head and body movements to provide the leverage needed for strong "bites".

Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society.

BACKGROUND: Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians. OBJECTIVE: To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management. METHODS: RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use. RESULTS: Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacosamide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions. CONCLUSIONS: These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.

An analytical coarse-graining method which preserves the free energy, structural correlations, and thermodynamic state of polymer melts from the atomistic to the mesoscale.

Structural and thermodynamic consistency of coarse-graining models across multiple length scales is essential for the predictive role of multi-scale modeling and molecular dynamic simulations that use mesoscale descriptions. Our approach is a coarse-grained model based on integral equation theory, which can represent polymer chains at variable levels of chemical details. The model is analytical and depends on molecular and thermodynamic parameters of the system under study, as well as on the direct correlation function in the k → 0 limit, c0. A numerical solution to the PRISM integral equations is used to determine c0, by adjusting the value of the effective hard sphere diameter, dHS, to agree with the predicted equation of state. This single quantity parameterizes the coarse-grained potential, which is used to perform mesoscale simulations that are directly compared with atomistic-level simulations of the same system. We test our coarse-graining formalism by comparing structural correlations, isothermal compressibility, equation of state, Helmholtz and Gibbs free energies, and potential energy and entropy using both united atom and coarse-grained descriptions. We find quantitative agreement between the analytical formalism for the thermodynamic properties, and the results of Molecular Dynamics simulations, independent of the chosen level of representation. In the mesoscale description, the potential energy of the soft-particle interaction becomes a free energy in the coarse-grained coordinates which preserves the excess free energy from an ideal gas across all levels of description. The structural consistency between the united-atom and mesoscale descriptions means the relative entropy between descriptions has been minimized without any variational optimization parameters. The approach is general and applicable to any polymeric system in different thermodynamic conditions.

Association analysis of ten candidate genes in a large multinational cohort of small for gestational age children and children with idiopathic short stature (NESTEGG study).

BACKGROUND: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. PATIENTS AND METHODS: We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. RESULTS: We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. CONCLUSION: IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.

Effective potentials for representing polymers in melts as chains of interacting soft particles.

This paper outlines the derivation of an analytical pair potential in a coarse grained description of polymer melts where each chain is represented as a collection of soft spheres. Each particle is located at the center of mass of a polymer subchain, while the polymer is divided into an arbitrary number of identical chain subsections, each comprised of a large number of monomers. It is demonstrated that the soft effective pair potentials acting between these center-of-mass sites is described by a soft repulsive region at separation distances less than the average size of each coarse grained unit and a long repulsive tail, with a small attractive component. The attractive component is located at a length scale beyond the size of the coarse grained unit and its form varies with the level of interpenetration between the coarse-grained units. Consistent with numerically derived potentials, it is found that the short range features of the potential dominate the liquid structure, while the long-tail features dominate the virial-route thermodynamics of the system. It follows that the accurate determination of the effective potential in both short and large separation distances is relevant for ensuring structural and thermodynamic consistency in the coarse-grained description of the macromolecular liquid. It is further shown that due to the sensitivity of thermodynamic properties to the large-scale features of the potential, which are irrelevant to the reproducibility of structural correlations, the determination of thermodynamically accurate potentials by numerical optimization of structure alone is not a reliable strategy in the high-density regime for high levels of coarse-graining.

Deficiency of ALADIN impairs redox homeostasis in human adrenal cells and inhibits steroidogenesis.

UNLABELLED: Triple A syndrome is a rare, autosomal recessive cause of adrenal failure. Additional features include alacrima, achalasia of the esophageal cardia, and progressive neurodegenerative disease. The AAAS gene product is the nuclear pore complex protein alacrima-achalasia-adrenal insufficiency neurological disorder (ALADIN), of unknown function. Triple A syndrome patient dermal fibroblasts appear to be more sensitive to oxidative stress than wild-type fibroblasts. To provide an adrenal and neuronal-specific disease model, we established AAAS-gene knockdown in H295R human adrenocortical tumor cells and SH-SY5Y human neuroblastoma cells by lentiviral short hairpin RNA transduction. AAAS-knockdown significantly reduced cell viability in H295R cells. This effect was exacerbated by hydrogen peroxide treatment and improved by application of the antioxidant N-acetylcysteine. An imbalance in redox homeostasis after AAAS knockdown was further suggested in the H295R cells by a decrease in the ratio of reduced to oxidized glutathione. AAAS-knockdown SH-SY5Y cells were also hypersensitive to oxidative stress and responded to antioxidant treatment. A further impact on function was observed in the AAAS-knockdown H295R cells with reduced expression of key components of the steroidogenic pathway, including steroidogenic acute regulatory and P450c11ß protein expression. Importantly a significant reduction in cortisol production was demonstrated with AAAS knockdown, which was partially reversed with N-acetylcysteine treatment. CONCLUSION: Our in vitro data in AAAS-knockdown adrenal and neuronal cells not only corroborates previous studies implicating oxidative stress in this disorder but also provides further insights into the pathogenic mechanisms in triple A syndrome.

ACTH resistance: genes and mechanisms.

ACTH resistance is a rare disorder typified by familial glucocorticoid deficiency (FGD), a genetically heterogeneous disease. Previously, genetic defects in FGD have been identified in the ACTH receptor gene (MC2R), its accessory protein (MRAP) and the steroidogenic acute regulatory protein gene (STAR). The defective mechanisms here are failures in ACTH ligand binding and/or receptor trafficking for MC2R and MRAP and, in the case of STAR mutations, inefficient cholesterol transport to allow steroidogenesis to proceed. Novel gene defects in FGD have recently been recognised in mini-chromosome maintenance-deficient 4 homologue (MCM4) and nicotinamide nucleotide transhydrogenase (NNT). MCM4 is one part of a DNA repair complex essential for DNA replication and genome stability, whilst NNT is involved in the glutathione redox system that protects cells against reactive oxygen species. The finding of mutations in these two genes implicates new pathogenetic mechanisms at play in FGD, and implies that the adrenal cortex is exquisitely sensitive to replicative and oxidative stresses.

Psychosocial risk factors, pre-motor symptoms and first-time hospitalization with Parkinson's disease: a prospective cohort study.

BACKGROUND AND PURPOSE: Experimental studies support a link between stress and development of parkinsonian symptoms, but prospective population studies are lacking. The aim of the current study is to determine the effects of several psychosocial factors on the risk of Parkinson's disease (PD), as well as to identify potential pre-motor symptoms for PD in a large prospective cohort study. METHODS: In 1991-1993, a total of 9955 women and men free of PD from the Copenhagen City Heart Study were asked about major life events, economic hardship, social network, impaired sleep and vital exhaustion. The participants were followed for first-time hospitalization with PD in nationwide registers until 2011. RESULTS: Vital exhaustion was associated with a higher risk of PD hospitalization in an exposure-dependent manner (P(trend) = 0.001), with high vs. low vital exhaustion being associated with a hazard ratio of 2.50 [95% confidence interval (CI): 1.28-4.89]. A slightly higher risk of PD hospitalization (hazard ratio = 1.49; 95% CI: 0.87-2.56) was suggested in participants with impaired sleep at baseline. No more than weak associations were observed for economic hardship, major life events or inadequate social network in the current study. CONCLUSIONS: Overall, the hypothesis that psychosocial risk factors affect the risk of PD is not supported. The results, however, suggest that vital exhaustion may be a pre-motor marker of the neurodegenerative process eventually leading to motor symptoms and clinical PD. Vital exhaustion may be useful for screening aimed at early detection and when considering disease-modifying therapies in people at high risk of clinical PD.

Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.

The melanocortin receptor (MCR) family consists of five G-protein-coupled receptors (MC1R-MC5R) with diverse physiological roles. MC1R controls pigmentation, MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, MC3R and MC4R have a vital role in energy homeostasis and MC5R is involved in exocrine function. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins that have been shown to regulate MCR expression and function. In the adrenal gland, MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency, where inactivating MRAP mutations account for ∼20% of cases. MRAP is highly expressed in both the zona fasciculata and the undifferentiated zone. Expression in the undifferentiated zone suggests that MRAP could also be important in adrenal cell differentiation and/or maintenance. In contrast, the role of adrenal MRAP2, which is highly expressed in the foetal gland, is unclear. The expression of MRAPs outside the adrenal gland is suggestive of a wider physiological purpose, beyond MC2R-mediated adrenal steroidogenesis. In vitro, MRAPs have been shown to reduce surface expression and signalling of all the other MCRs (MC1,3,4,5R). MRAP2 is predominantly expressed in the hypothalamus, a site that also expresses a high level of MC3R and MC4R. This raises the intriguing possibility of a CNS role for the MRAPs.

Prolonged swing phase rectus femoris activity is not associated with stiff-knee gait in children with cerebral palsy: a retrospective study of 407 limbs.

Prolonged swing phase rectus femoris (RF) activity has been implicated as a cause of stiff-knee gait (SKG) in children with cerebral palsy (CP) and continues to be cited as an indicator for RF intervention. The purpose of this study was to determine what, if any, association exists between abnormal RF activity during preswing, initial swing and/or midswing and SKG in children with CP. This retrospective analysis involved three examiners independently reviewing sagittal plane knee kinematic and RF surface electromyographic (EMG) data from 407 affected limbs of 234 pediatric patients with CP. Five kinematic parameters were rated by each examiner as normal or pathologic: peak knee flexion, knee range of motion during initial swing, total knee range of motion, peak knee flexion timing, and rate of knee flexion. These ratings were used to classify each limb into one of three groups: SKG, Borderline SKG, or Non-SKG. From a representative EMG tracing, RF activity was examined during: the first half of preswing, the latter 2/3 of initial swing, and midswing. Chi-squared tests were used to determine if significant associations existed between SKG and RF activation during these three subphases. There was no association between SKG and prolonged RF activity during the latter 2/3 of initial swing or during midswing. However, a significant relationship between SKG and RF activity during the first half of preswing was found (p<0.001). Neither prolonged RF activity during initial swing, nor the presence of RF activity during midswing, were associated with SKG, thus refuting these commonly held associations.