Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet.

Broad absorption signatures from alkali metals, such as the sodium (Na I) and potassium (K I) resonance doublets, have long been predicted in the optical atmospheric spectra of cloud-free irradiated gas giant exoplanets1-3. However, observations have revealed only the narrow cores of these features rather than the full pressure-broadened profiles4-6. Cloud and haze opacity at the day-night planetary terminator are considered to be responsible for obscuring the absorption-line wings, which hinders constraints on absolute atmospheric abundances7-9. Here we report an optical transmission spectrum for the 'hot Saturn' exoplanet WASP-96b obtained with the Very Large Telescope, which exhibits the complete pressure-broadened profile of the sodium absorption feature. The spectrum is in excellent agreement with cloud-free, solar-abundance models assuming chemical equilibrium. We are able to measure a precise, absolute sodium abundance of logεNa = [Formula: see text], and use it as a proxy for the planet's atmospheric metallicity relative to the solar value (Zp/Zʘ = [Formula: see text]). This result is consistent with the mass-metallicity trend observed for Solar System planets and exoplanets10-12.

Observation of an Electric Quadrupole Transition in a Negative Ion: Experiment and Theory.

The first direct experimental observation of an electric quadrupole (E2) absorption transition between bound states of an atomic negative ion has been made. The transition was observed in the negative ion of bismuth by resonant (1+1) photon detachment from Bi^{-} via ^{3}P_{2}→^{3}P_{0} excitation. The E2 transition properties were completely independently calculated using a hybrid theoretical approach to account for the strong multilevel electron interactions and relativistic effects. The experimental and ab initio theoretical results are in excellent agreement, providing valuable new insight into this complex system and forbidden transitions in negative ions more generally.

Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer.

BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50-0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33-0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37-0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29-1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28-0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31-0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat 'Good' versus 'Poor' [2.7 versus 1.5 months; HR 0.71 (0.49-0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682.

Expiratory flow limitation and breathing strategies in overweight adolescents during submaximal exercise.

OBJECTIVE: To investigate whether ventilatory factors limit exercise in overweight and obese children during a 6-min step test and to compare ventilatory responses during this test with those of healthy weight children. DESIGN: Cross-sectional, prospective comparative study. SUBJECTS: Twenty-six overweight/obese subjects and 25 healthy weight subjects with no known respiratory illness. MEASUREMENTS: Various fatness and fat distribution parameters (using air displacement plethysmography and anthropometry), pulmonary function tests, breath-by-breath gas analysis during exercise, perceived exertion. RESULTS: Young people who are overweight or obese are more likely to experience expiratory flow limitation (expFL) during submaximal exercise compared with their healthy weight peers [OR 7.2 (1.4, 37.3), P=0.019]. Subjects who had lower lung volumes at rest were even more likely to experience exercise-induced expFLs [OR 8.35 (1.4-49.3)]. Both groups displayed similar breathing strategies during submaximal exercise. CONCLUSION: Young people who are overweight/obese are more likely to display expFL during submaximal exercise compared with children of healthy weight . Use of compensatory breathing strategies appeared to enable overweight children to avoid the experience of breathlessness at this intensity of exercise.

Candidate for laser cooling of a negative ion: observations of bound-bound transitions in La(-).

Despite the tremendous advances in laser cooling of neutral atoms and positive ions, no negatively charged ion has been directly laser cooled. The negative ion of lanthanum, La(-), has been proposed as the best candidate for laser cooling of any atomic anion [ and , Phys. Rev. A 81, 032503 (2010)]. Tunable infrared laser photodetachment spectroscopy is used to measure the bound-state structure of La(-), revealing a spectrum of unprecedented richness with multiple bound-bound electric dipole transitions. The potential laser-cooling transition ((3)F(2)(e)→(3)D(1)(o)) is identified and its excitation energy is measured. The results confirm that La^{-} is a very promising negative ion for laser-cooling applications.

Phylogeographic evidence for two mesic refugia in a biodiversity hotspot.

Phylogeographic studies of flora in species-rich south-western Australia point to complex evolutionary histories, reflecting patterns of persistence and resilience to climatic changes during the Pleistocene. We asked whether coastal areas of the mid-west and south, as well as granite outcrops and inland ranges, have acted as major refugia within this region during Pleistocene climatic fluctuations by analysing phylogeographic patterns in the shrub Calothamnus quadrifidus R.Br. (Myrtaceae). We determined variation in chloroplast DNA data for 41 populations across the geographic range. Relationships and major clades were resolved using parsimony and Bayesian analyses. We tested for demographic and spatial expansion of the major clades and estimated clade divergence dates using an uncorrelated, lognormal relaxed clock based on two conservative chloroplast mutation rates. Two distinct phylogeographic clades were identified showing divergence during the Pleistocene, consistent with other phylogeographic studies of south-west Australian flora, emphasising the impact of climatic oscillations in driving divergence in this landscape. The southern clade was more diverse, having higher haplotype diversity and greater genetic structure, while the northern clade showed evidence of fluctuation in population size. Regions of high haplotype diversity with adjacent areas of low diversity observed in each clade indicated the locations of two coastal refugia: one on the south coast and another along the mid-west coast. This is the first evidence for major Pleistocene refugia using chloroplast genetic data in a common, widespread species from this region.

Contemporary pollen-mediated gene immigration reflects the historical isolation of a rare, animal-pollinated shrub in a fragmented landscape.

Fragmentation is generally considered to have negative impacts on widespread outbreeders but impacts on gene flow and diversity in patchy, naturally rare, self-compatible plant species remain unclear. We investigated diversity, gene flow and contemporary pollen-mediated gene immigration in the rare, narrowly distributed endemic shrub Calothamnus quadrifidus ssp. teretifolius. This taxon occurs in an internationally recognized biodiversity hotspot subjected to recent human-induced fragmentation and the condition of the remnants ranges from intact to highly degraded. Using microsatellites, we found that inbreeding, historically low gene flow and significant population differentiation have characterized the genetic system of C. quadrifidus ssp. teretifolius. Inbreeding arises from self-pollination, a small amount of biparental inbreeding and significant correlation of outcross paternity but fecundity was high suggesting populations might have purged their lethals. Paternity analyses show that pollinators can move pollen over degraded and intact habitat but populations in both intact and degraded remnants had few pollen parents per seed parent and low pollen immigration. Genetic diversity did not differ significantly between intact and degraded remnants but there were signs of genetic bottlenecks and reduced diversity in some degraded remnants. Overall, our study suggests human-induced fragmentation has not significantly changed the mating system, or pollen immigration to, remnant populations and therefore genetic connectivity need not be the highest conservation priority. Rather, for rare species adapted to higher levels of inbreeding, conservation efforts may be best directed to managing intact habitats and ecosystem processes.

Single-photon multiple detachment in fullerene negative ions: absolute ionization cross sections and the role of the extra electron.

We have obtained experimental photo-double- and photo-triple-detachment cross sections for the fullerene negative ion using Advanced Light Source photons of 17-90 eV. The cross sections are 2 and 2.5 times larger than those for C60 and appear to be compressed and shifted in photon energy as compared to C60. Our analysis reveals that the additional electron in C60- primarily produces screening which is responsible for the modification of the spectrum. Both screening effects, the shift and the compression, can be quantitatively accounted for by a linear transformation of the energy axis. Applying the transformation allows us to map the neutral and negative ion cross sections onto each other, pointing out the close relationship of correlated few-electron dynamics in neutral and negatively charged extended systems. In contrast, dynamics of neutral and negatively charged atoms or small molecules are typically not closely related.

Relationship between measures of aerobic fitness, speed and repeated sprint ability in full and part time youth soccer players.

AIM: The aim of the study was to investigate the relationship between repeated sprint ability (RSA) involving changes in direction, short linear sprinting and aerobic capacity in young elite soccer players. A secondary aim was to assess any differences in performance of these assessments between players of different age groups. METHODS: Thirty-two male adolescent soccer players belonging to the same elite club academy were assessed for RSA comprising 6 x 40m efforts interspersed by 25s recovery, linear sprinting speed over 15m, and aerobic capacity via the YYIE2 assessment. RESULTS: There was a significant correlation between performance in the YYIE2 and RSA total time, RSA fastest sprint and RSA percentage decrement (r = -0.71, -0.53, and -0.52 respectively. P<0.05). Significant differences were observed between age groups for distance covered in the YYIE2, RSA total time and RSA fastest sprint (P<0.01). No significant differences were observed for short linear sprinting. CONCLUSION: Assessments of RSA over 40m and incorporating changes of direction appear to be significantly correlated with YYIE2 performance in young elite level soccer players. In addition older players performed significantly better in the YYIE2 assessment and RSA protocol but not in short linear sprinting. These results have implications for the design of assessment protocols for young elite soccer players of different ages.

A comparison of the kinematics and kinetics of barefoot and shod running in children with cerebral palsy.

BACKGROUND: The biomechanics of barefoot and shod running are different for typically developing children but unknown for children with cerebral palsy (CP). Such differences may have implications for injury and performance. AIMS: The primary aims of this study were to compare the lower limb biomechanics of barefoot and shod running in children with CP, and to determine whether any differences were the same in GMFCS levels I and II. METHODS: This cross-sectional study examined 38 children with CP (n = 24 (GMFCS) level I; n = 14 GMFCS II), running overground at 3 speeds (jog, run, sprint) in barefoot and shod conditions. Marker trajectories and force plate data were recorded, and lower limb kinematics, kinetics and spatiotemporal variables were derived. Differences between barefoot and shod running were analysed using linear mixed models. RESULTS: For both GMFCS levels, barefoot running resulted in higher loading rates, but smaller impact peaks at all speeds. Barefoot running was associated with greater hip and knee power; less ankle dorsiflexion and hip flexion at initial contact, and less ankle and knee range of motion during stance, compared to shod running, at all speeds. Barefoot stride length was shortened, and cadence increased compared to shod during jogging and running but not sprinting. For GMFCS level I only, barefoot running involved a higher incidence of forefoot strike, greater ankle power generation and less hip range of motion during stance. SIGNIFICANCE: Running barefoot may facilitate running performance by increasing power generation at the ankle in children with CP, GMFCS level I. Higher barefoot loading rates may have implications for performance and injury.

Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators.

We present in this article an outline of some cyclotron-based irradiation techniques that can be used to directly radiolabel industrially manufactured nanoparticles, as well as two techniques for synthesis of labelled nanoparticles using cyclotron-generated radioactive precursor materials. These radiolabelled nanoparticles are suitable for a range of different in vitro and in vivo tracing studies of relevance to the field of nanotoxicology. A basic overview is given of the relevant physics of nuclear reactions regarding both ion-beam and neutron production of radioisotopes. The various issues that determine the practicality and usefulness of the different methods are discussed, including radioisotope yield, nuclear reaction kinetics, radiation and thermal damage, and radiolabel stability. Experimental details are presented regarding several techniques applied in our laboratories, including direct light-ion activation of dry nanoparticle samples, neutron activation of nanoparticles and suspensions using an ion-beam driven activator, spark-ignition generation of nanoparticle aerosols using activated electrode materials, and radiochemical synthesis of nanoparticles using cyclotron-produced isotopes. The application of these techniques is illustrated through short descriptions of some selected results thus far achieved. It is shown that these cyclotron-based methods offer a very useful range of options for nanoparticle radiolabelling despite some experimental difficulties associated with their application. For direct nanoparticle radiolabelling, if care is taken in choosing the experimental conditions applied, useful activity levels can be achieved in a wide range of nanoparticle types, without causing substantial thermal or radiation damage to the nanoparticle structure. Nanoparticle synthesis using radioactive precursors presents a different set of issues and offers a complementary and equally valid approach when laboratory generation of the nanoparticles is acceptable for the proposed studies, and where an appropriate radiolabel can be incorporated into the nanoparticles during synthesis.

The effect of a low-load plyometric running intervention on leg stiffness in youth with cerebral palsy: A randomised controlled trial.

AIM: To determine whether a running intervention utilising plyometric activities improved leg stiffness in youth with cerebral palsy (CP), GMFCS levels I and II. METHOD: This stratified randomised controlled trial examined the lower limb kinetics and kinematics of a sample of youths with CP during sub-maximal hopping and running, prior to and immediately following a 12-week running intervention that incorporated low load plyometric training. Included participants were 13 in the control group (mean age 13 years 2 months [SD 2 years 7 months]; six males; nine GMFCS level I; six unilateral) and 18 in the intervention group (mean age 12 years 9 months [SD 2 years 10 months]; 13 males; 11 GMFCS level I; nine unilateral). Derived variables included three-dimensional leg stiffness as well as resultant ground reaction force and change in leg length. Generalised linear mixed models were developed for statistical analysis. RESULTS: At follow-up the intervention group had greater leg stiffness than the control group during submaximal hopping (Intervention median = 3278Nm-1; Control median = 1556Nm-1; p < 0.01). At follow-up, participants in the intervention group in GMFCS Level I had greater leg stiffness than the control group during jogging (Intervention mean=38.84 (SD=25.55); Control mean=29.38 (SD=11.11); t = 2.61 p = 0.01). INTERPRETATION: A running training intervention which includes plyometric activities can improve leg stiffness in young people with CP, especially those in GMFCS level I.

The COVID-19 lockdown in Australia: a case study of exercise programming in male academy football players to prepare for return to play.

PURPOSE: In 2020, the COVID-19 pandemic forced global lockdowns. Herein, we examine the effect of a lockdown exercise programme in a case-study of youth Australian A-league academy football players. METHODS: Fifty-five u13-u15 age-grade players were provided with a 110 minute exercise programme including technical, tactical, cardiovascular and muscle strengthening exercises to perform 4 per week at home during the 10-week COVID-19 lockdown. RESULTS: Pre/Post lockdown, maximum aerobic speed was determined via the 30-15 intermittent fitness test (IFT). Exercise compliance was high (78.5% CI72.2-83.8) with an average of 3.15 sessions completed each week. All time-loss (TL) and medical attention (MA) injuries were recorded. Pre/Post lockdown, no difference in the mean incidence or burden of total time-loss (TL), match TL, training TL or medical attention (MA) injuries or injury rate ratio (1.21 CI:0.85-2.74) was observed. Similarly, no difference was observed in any injury incidence or burden data or the injury rate ratio (1.53 CI:0.85-2.74) when comparing the 9-week period prior to lockdown with the first 9 weeks post lockdown (9v9 only). A 9.6% (p = <0.01) increase was also observed in Pre/Post 30-15 IFT composite scores (18.7 CI: 18.3-19.1 to 20.5 CI:20-21). CONCLUSION: In this case study, compliance to the home-based exercise programme was high and no increase in injury was apparent. These findings must however be considered alongside the limitations associated within this case-study.

A comparison of leg stiffness in running between typically developing children and children with cerebral palsy.

BACKGROUND: Leg stiffness is important during running to increase velocity and maximise efficiency by facilitating use of the stretch-shortening cycle. Children with cerebral palsy who have neuromuscular impairments may have altered leg stiffness. The aim of this study was to describe leg stiffness during running in typically developing children and those with cerebral palsy in Gross Motor Function Classification Scale levels I and II at a range of speeds. METHODS: This cross-sectional study examined kinematic data collected from typically developing children (n = 21) and children with cerebral palsy (Gross Motor Function Classification Scale level I n = 25, Gross Motor Function Classification Scale level II n = 13) during jogging, running and sprinting. Derived variables were resultant ground reaction force, change in leg length and three-dimensional leg stiffness. Linear mixed models were developed for statistical analysis. FINDINGS: Children with cerebral palsy had reduced stiffness when jogging (Gross Motor Function Classification Scale level I affected t = 3.81 p < 0.01; non-affected t = 2.19 p = 0.03; Gross Motor Function Classification Scale level II affected t = 2.04 p = 0.04) and running (Gross Motor Function Classification Scale level I affected t = 3.23 p < 0.01) compared to typically developing children. Affected legs were less stiff than non-affected legs only in Gross Motor Function Classification Scale level I during running (t = 2.26 p = 0.03) and sprinting (t = 2.95 p < 0.01). INTERPRETATION: Children with cerebral palsy have atypical leg stiffness profiles which differ according to functional classification.

The effect of a running training intervention on ankle power generation in children and adolescents with cerebral palsy: A randomized controlled trial.

BACKGROUND: Children and adolescents with cerebral palsy who are classified as Gross Motor Function Classification Scale level I or II are usually able to run but lack ankle power generation for push-off. The aim of this study was to analyze the efficacy of a running training program in improving ankle power generation in children and adolescents with cerebral palsy. METHODS: This randomized controlled trial compared kinematic and spatiotemporal data collected during running from 38 children and adolescents with unilateral or bilateral cerebral palsy before and after a 12-week running program. Normalized speed, stride length, cadence, foot strike pattern, peak ankle power generation, peak hip flexor power generation in swing and propulsion strategy were calculated. Linear mixed models were developed to analyze differences between groups. FINDINGS: At follow-up the intervention group had increased normalized speed of running (t = -3.68 p < .01) while the control group got slower (t = 3.17 p < .01). In running, children in Gross Motor Function Classification Scale level II in the intervention group increased ankle power (t = 2.49 p = .01) while the control group did not change (t = 0.38 p = .71). In sprinting, children in Gross Motor Function Classification Scale levels I and II in the intervention group maintained ankle power (level I t = 0.32 p = .75; level II t = 1.56 p = .12) while those in the control group decreased ankle power (level I t = 4.69 p < .01; level II t = 2.52 p = .01). Most within-group differences did not result in significant between-group differences at follow-up. INTERPRETATION: Power generation for running may be responsive to targeted intervention in children with cerebral palsy.

Propulsion strategy in running in children and adolescents with cerebral palsy.

BACKGROUND: Running is a fundamental movement skill important for participation in physical activity. Children with cerebral palsy (CP) who are classified at Gross Motor Function Classification Scale (GMFCS) level I and II are able to run but may be limited by neuromuscular impairments. RESEARCH QUESTION: To describe the propulsion strategy (PS) during running of children and adolescents with CP. METHODS: This cross-sectional study used kinematic and kinetic data collected during running from 40 children and adolescents with unilateral or bilateral CP and 21 typically developing (TD) children. Maximum speed, peak ankle power generation (A2), peak hip flexor power generation in swing (H3) and PS (PS = A2/(A2 + H3)) were calculated. Linear mixed models were developed to analyze differences between groups. RESULTS: Maximum speed, A2 and PS were significantly less in children with CP GMFCS level I than in TD children and significantly less in children in GMFCS level II than level I. For children with CP, A2 and PS were significantly smaller in affected legs than non-affected legs. In affected legs, H3 was significantly larger in children in GMFCS level II than GMFCS level I but not different between TD children and children in GFMCS level II. SIGNIFICANCE: The contribution of ankle plantarflexor power to forward propulsion in running is reduced in young people with CP and is related to GMFCS level. This deficit appears to be compensated in part by increased hip flexor power generation but limits maximum sprinting speed.

The effect of joint translation constraint on within-participant variability of kinematics and kinetics during running in cerebral palsy.

BACKGROUND: Biomechanical data in cerebral palsy are inherently variable but no optimal model of translational joint constraint has been identified. The primary aim of this study was to determine which model of translational joint constraint resulted in the lowest within-participant variability of lower limb joint angles and moments. The secondary aim was to determine which model best distinguished known functional groups in Cerebral Palsy. METHODS: Three models (three degrees of freedom, six degrees of freedom and six degrees of freedom with specified joint translation constraint) were applied to data from running trials of 40 children with cerebral palsy. FINDINGS: Joint angle standard deviations were largest using the six degrees of freedom model and smallest using the constrained six degrees of freedom model (p < 0.050). For all joints in all planes of motion, joint moment standard deviations were largest using the six degrees of freedom model and smallest using the constrained six degrees of freedom model; standard deviations using the constrained model were smaller than the three degrees of freedom model by 10-30% of moment magnitude (0.01-0.03 Nm/kg; p < 0.001). The six degrees of freedom models distinguished functional subgroups with larger effect size than the three degrees of freedom model only for hip power generation in swing. INTERPRETATION: A model with specified joint constraint minimized within-participant variability during running and was useful for detecting differences in functional capacity in cerebral palsy.

Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis.

One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case-control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1(*)07 and DQA1(*)02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.

Upper limb corticomotor projections and physiological changes that occur with botulinum toxin-A therapy in children with hemiplegic cerebral palsy.

AIM: To investigate the corticomotor projection to the upper limb in children with hemiplegic cerebral palsy (CP) and the changes that occur with botulinum toxin (BTX)-A. METHODS: The study design is a pilot prospective randomized trial. Twenty-two children with hemiplegic CP aged 7 years to 13 years 11 months were recruited. Treatment group (12) received one series of BTX-A injections into the upper limb. Control group (10) did not receive upper limb BTX-A. All participants except one treatment group participant also received lower limb BTX-A. Transcranial magnetic stimulation (TMS) was performed at baseline, and 1, 3 and 6 months post-injection. Outcome measures were: change in position of affected and unaffected side first dorsal interosseous optimal site of stimulation (OPTx). RESULTS: A shift in affected and unaffected side OPTx was observed for both treatment and control groups, and there was no statistically significant difference between groups at 1, 3 or 6 months. Poor tolerance of TMS cortical stimuli >80% was observed. CONCLUSION: Corticomotor projections associated with the upper limb in children with hemiplegic CP show significant variability over a 6-month period. This variability may reflect central motor reorganization because of systemic BTX-A effect or developmental changes. Upper limb BTX-A therapy is associated with reorganization of both affected and unaffected projections. Poor tolerance of the TMS procedure, in conjunction with higher cortical thresholds, may limit the usefulness of TMS as an investigatory tool in young children with movement disorders.