Linkage and heritability analysis of migraine symptom groupings: A comparison of three different clustering methods on twin data

Migraine is a painful disorder for which the etiology remains obscure. Diagnosis is largely based on International Headache Society criteria. However, no feature occurs in all patients who meet these criteria, and no single symptom is required for diagnosis. Consequently, this definition may not accurately reflect the phenotypic heterogeneity or genetic basis of the disorder. Such phenotypic uncertainty is typical for complex genetic disorders and has encouraged interest in multivariate statistical methods for classifying disease phenotypes. We applied three popular statistical phenotyping methods—latent class analysis, grade of membership and grade of membership “fuzzy” clustering (Fanny)—to migraine symptom data, and compared heritability and genome-wide linkage results obtained using each approach. Our results demonstrate that different methodologies produce different clustering structures and non-negligible differences in subsequent analyses. We therefore urge caution in the use of any single approach and suggest that multiple phenotyping methods be used.

Is there a difference between narrowing of the spinal canal and neurological deficits comparing Denis and Magerl classifications?

We have read with great interest the retrospective study by Caffaro and Avanzi1 evaluating the relation between narrowing of the spinal canal and neurological deficits in patients with burst-type fractures of the spine. The authors are to be commended for obtaining detailed neurological and radiological data in a large cohort of 227 patients. The authors conclude: “The percentage of narrowing of the spinal canal proved to be a pre-disposing factor for the severity of the neurological status in thoracolumbar and lumbar burst-type fractures according to the classifications of Denis and Magerl.” Although this conclusion is mainly in accordance with previous findings, we would like to comment on the methodological approach applied in the current study.

Chronological age and age-related cognitive deficits are associated with an increase in multiple types of driving errors in late life

Objective: Older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe. Little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly. We evaluated the association of cognitive function and age, with driving errors. Method: A sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging (visual attention, processing speed, inhibition, reaction time, task switching) and the UFOV® which is a validated screening instrument for older drivers. Participants completed an on-road driving test. Generalized linear models were used to estimate the associations of cognitive factor with specific driving errors and number of errors in self-directed and instructor navigated conditions. Results: All errors types increased with chronological age. Reaction time was not associated with driving errors in multivariate analyses. A cognitive factor measuring Speeded Selective Attention and Switching was uniquely associated with the most errors types. The UFOV predicted blindspot errors and errors on dual carriageways. After adjusting for age, education and gender the cognitive factors explained 7% of variance in the total number of errors in the instructor navigated condition and 4% of variance in the self-navigated condition. Conclusion: We conclude that among older drivers errors increase with age and are associated with speeded selective attention particularly when that requires attending to the stimuli in the periphery of the visual field, task switching, errors inhibiting responses and visual discrimination. These abilities should be the target of cognitive training.

Continuing the critical analysis of 'meaningful relationships' in the context of the 'twin pillars'

This article continues the critical analysis of ‘meaningful relationships’ in the context of the operation of the ‘twin pillars’ which underpin the parenting provisions. It will be argued that the attitude of judicial officers to three key questions influence how they interpret this concept and consequently apply the best interest considerations. Relevant to this discussion is an examination of the Full Court’s approach to the key parenting sections, particularly the interaction of the primary and additional considerations. Against this backdrop, a current proposal to amend the ‘twin pillars’ will be examined.

Are motivational deficits part of the behavioural phenotype of Down syndrome?

Motivational deficits are generally accepted to be part of the behavioural phenotype associated with Down syndrome (DS). A motivational profile comprising low or inconsistent levels of task persistence, avoidance of challenging activities and over-dependence on adult direction has been described. However, comparisons are usually made between children with DS and those who are developing typically, without the inclusion of samples with intellectual disability (ID) from aetiologies other than DS. Such comparisons are needed to determine the extent to which motivational deficits are specific to DS, as opposed to being a feature of ID generally. Methods: The current study collected data about the personality-motivation profiles of children in three groups matched for mental age. They consisted of 80 typically developing (TD)3–7 year old children, 62 children with DS aged 7–15 years, and 54 children with moderate ID aged 7–15 years. Parents completed the 37-item EZ-Personality Questionnaire (EZPQ; Zigler et al., 2002), a measure of personality-motivational functioning. Results: There were significant differences between TD children and those with ID on all EZPQ scales. In most respects children with DS did not differ significantly from others with moderate ID, although they were rated as having greater expectancy of success and fewer negative reactions. Conclusion: The finding that children with DS are less motivated than TD children of the same mental age is consistent with previous studies in which parents have rated motivation. It seems, however, that motivation difficulties are associated with ID more generally, rather than being specific to those with DS. The study raises questions about phenotypic versus experiential effects on motivation for children with ID.

Bicep femoris voluntary activation deficits contribute to eccentric knee flexor weakness following intermittent running

INTRODUCTION: Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Eccentric hamstring muscle weakness following intermittent running has been implicated within the aetiology of HSI. This weakness following intermittent running is often greater eccentrically than concentrically, however the cause of this unique, contraction mode specific phenomenon is unknown. AIM: To determine if this preferential eccentric decline in strength is caused by declines in voluntary hamstring muscle activation. METHODS: Fifteen recreationally active males completed 18 × 20m overground sprints. Maximal strength (concentric and eccentric knee flexor and concentric knee extensor) was determined isokinetically at the velocities of ±1800.s-1 and ±600.s- while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. RESULTS: Overground intermittent running caused greater eccentric (27.2 Nm; 95% CI = 11.2 to 43.3; p=0.0001) than concentric knee flexor weakness (9.3 Nm; 95% CI = -6.7 to 25.3; P=0.6361). Following the overground running, voluntary activation levels of the lateral hamstrings showed a significant decline (0.08%; 95% CI = 0.045 to 0.120; P<0.0001). In comparison, medial hamstring activation showed no change following intermittent running. CONCLUSION: Eccentric hamstring strength is decreased significantly following intermittent overground running. Voluntary activation deficits in the biceps femoris muscle are responsible for some portion of this weakness. The implications of this finding are significant because the biceps femoris muscle is the most frequently strained of all the hamstring muscles and because fatigue appears to play an important part in injury occurrence.

Do voluntary activation deficits contribute to eccentric weakness following intermittent running?

Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Eccentric hamstring muscle weakness following intermittent running has been implicated within the aetiology of HSI. This weakness following intermittent running is often greater eccentrically than concentrically, however the cause of this unique, contraction mode specific phenomenon is unknown. PURPOSE: To determine if this preferential eccentric decline in strength is caused by declines in voluntary hamstring muscle activation. METHODS: Fifteen recreationally active males completed 18 × 20m overground sprints. Maximal strength (concentric and eccentric knee flexor and concentric knee extensor) was determined isokinetically at the velocities of ±1800.s-1 and ±600.s- while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. RESULTS: Overground intermittent running caused greater eccentric (27.2 Nm; 95% CI = 11.2 to 43.3; p=0.0001) than concentric knee flexor weakness (9.3 Nm; 95% CI = -6.7 to 25.3; P=0.6361). Following the overground running, voluntary activation levels of the lateral hamstrings showed a significant decline (0.08%; 95% CI = 0.045 to 0.120; P<0.0001). In comparison, medial hamstring activation showed an increased level of activation following intermittent running (0.12%; 95% CI = 0.049 to 0.030; P = 0.0102). CONCLUSION: Eccentric hamstring strength is decreased significantly following intermittent overground running. Voluntary activation deficits in the biceps femoris muscle are responsible for some portion of this weakness. The implications of this finding are significant because the biceps femoris muscle is the most frequently strained of all the hamstring muscles and because fatigue appears to play an important part in injury occurrence.

Knee flexor strength and biceps femoris activation deficits following hamstring strain injury

Background: Hamstring strain injuries (HSI) are prevalent in sport and re-injury rates have been high for many years. Maladaptation following HSI are implicated in injury recurrence however nervous system function following HSI has received little attention. Aim: To determine if recreational athletes with a history of unilateral HSI, who have returned to training and competition, will exhibit lower levels of voluntary activation (VA) and median power frequency (MPF) in the previously injured limb compared to the uninjured limb at long muscle lengths. Methods: Twenty-eight recreational athletes were recruited. Of these, 13 athletes had a history of unilateral HSI and 15 had no history of HSI. Following familiarisation, all athletes undertook isokinetic dynamometry testing and surface electromyography assessment of the biceps femoris long head and medial hamstrings during concentric and eccentric contractions at ± 180 and ± 60deg/s. Results: The previously injured limb was weaker at all contraction speeds compared to the uninjured limb (+180deg/s mean difference(MD) = 9.3Nm, p = 0.0036; +60deg/s MD = 14.0Nm, p = 0.0013; -60deg/s MD = 18.3Nm, p = 0.0007; -180deg/s MD = 20.5Nm, p = 0.0007) whilst VA was only lower in the biceps femoris long head during eccentric contractions (-60deg/s MD = 0.13, p = 0.0025; -180deg/s MD = 0.13, p = 0.0003). There were no between limb differences in medial hamstring VA or MPF from either biceps femoris long head or medial hamstrings in the injured group. The uninjured group showed no between limb differences with any of the tested variables. Conclusion: Previously injured hamstrings were weaker than the contralateral uninjured hamstring at all tested speeds and contraction modes. During eccentric contractions biceps femoris long head VA was lower in the previously injured limb suggesting neural control of biceps femoris long head may be altered following HSI. Current rehabilitation practices have been unsuccessful in restoring strength and VA following HSI. Restoration of these markers should be considered when determining the success of rehabilitation from HSI. Further investigations are required to elucidate the full impact of lower levels of biceps femoris long head VA following HSI on rehabilitation outcomes and re-injury risk.

Assessment of neuroretinal function in a group of functional amblyopes with documented LGN deficits

Purpose In this study we examine neuroretinal function in five amblyopes, who had been shown in previous functional MRI (fMRI) studies to have compromised function of the lateral geniculate nucleus (LGN), to determine if the fMRI deficit in amblyopia may have its origin at the retinal level. Methods We used slow flash multifocal ERG (mfERG) and compared averaged five ring responses of the amblyopic and fellow eyes across a 35 deg field. Central responses were also assessed over a field which was about 6.3 deg in diameter. We measured central retinal thickness using optical coherence tomography. Central fields were measured using the MP1-Microperimeter which also assesses ocular fixation during perimetry. MfERG data were compared with fMRI results from a previous study. Results Amblyopic eyes had reduced response density amplitudes (first major negative to first positive (N1-P1) responses) for the central and paracentral retina (up to 18 deg diameter) but not for the mid-periphery (from 18 to 35 deg). Retinal thickness was within normal limits for all eyes, and not different between amblyopic and fellow eyes. Fixation was maintained within the central 4° more than 80% of the time by four of the five participants; fixation assessed using bivariate contour ellipse areas (BCEA) gave rankings similar to those of the MP-1 system. There was no significant relationship between BCEA and mfERG response for either amblyopic or fellow eye. There was no significant relationship between the central mfERG eye response difference and the selective blood oxygen level dependent (BOLD) LGN eye response difference previously seen in these participants. Conclusions Retinal responses in amblyopes can be reduced within the central field without an obvious anatomical basis. Additionally, this retinal deficit may not be the reason why the LGN BOLD (blood oxygen level dependent) responses are reduced for amblyopic eye stimulation.

Marker gene elimination from transgenic barley, using co-transformation with adjacent 'twin T-DNAs' on a standard Agrobacterium transformation vector

We have tested a methodology for the elimination of the selectable marker gene after Agrobacterium-mediated transformation of barley. This involves segregation of the selectable marker gene away from the gene of interest following co-transformation using a plasmid carrying two T-DNAs, which were located adjacent to each other with no intervening region. A standard binary transformation vector was modified by insertion of a small section composed of an additional left and right T-DNA border, so that the selectable marker gene and the site for insertion of the gene of interest (GOI) were each flanked by a left and right border. Using this vector three different GOIs were transformed into barley. Analysis of transgene inheritance was facilitated by a novel and rapid assay utilizing PCR amplification from macerated leaf tissue. Co-insertion was observed in two thirds of transformants, and among these approximately one quarter had transgene inserts which segregated in the next generation to yield selectable marker-free transgenic plants. Insertion of non-T-DNA plasmid sequences was observed in only one of fourteen SMF lines tested. This technique thus provides a workable system for generating transgenic barley free from selectable marker genes, thereby obviating public concerns regarding proliferation of these genes.