496 research outputs found
Ministry of Defence impunity: the Overseas Operations (Service Personnel and Veterans) Act 2021
This article critically interrogates the policy objectives of the Overseas Operations (Service Personnel and Veterans) Act 2021 and its means to achieve them. While the Ministry of Defence claimed the legislation aimed to protect service personnel and veterans from the “problem of ‘lawfare’” following “repeated investigations … in connection with historical operations”, the Act, despite amendments, continues to strengthen impunity of the British Government for human rights violations, and international and domestic crimes committed in overseas military operations. It does so through three flawed modus operandi: introducing an unwarranted presumption against prosecutions, the superfluous curtailing of judicial discretion over time limitations to bring tort and human rights claims, and the securing of finality of claims despite less-than-adequate investigations. As such, the Act remains deeply problematic as it intentionally curtails the bringing of the types of claims that led to the International Criminal Court’s probe into British war crimes in Iraq. It is argued that the consequences of the Act’s policy aims are symptomatic of the British state’s refusal to confront the crimes, liability, and human rights violations of proximate military conflicts such as Iraq and Afghanistan and limit claims arising from abuse committed during future overseas operations. More generally, the Act is part of a wider attempt by this government to put the executive beyond legal or parliamentary reproach
The role of dopamine in learning, movement & motivation
The primary aim of the research I have undertaken is to better understand the influence of dopamine on behavior and to build on knowledge of the various roles of dopamine in the healthy brain but also to improve understanding of the deficits affecting patients with Parkinson’s disease (PD), the hallmark of which is dopamine depletion.
By testing PD patients on cognitive and motor tasks, we are able to probe the effects of dopamine depletion in humans. Testing PD patients in different medication states also provides a method with which to attempt to tease apart the various roles of dopamine from each other. My first two experiments use the PD model to this end whereas the third experiment utilises a pharmacological manipulation in healthy individuals.
The aim of my first experiment was to tease apart the relative contribution of dopamine to learning from its influence on action performance, and by doing this to better understand the deficits which have been observed in PD patients in reinforcement learning tasks.
The second experiment focuses on the motor deficits observed in PD. The aim of this study was to test whether these motor deficits can at least in part explained by the deficits in reward sensitivity.
The third and final experiment in this thesis uses a pharmacological manipulation in healthy individuals to isolate the role of dopamine in set shifting in the context of a response to cues with negative hedonic valence, with the hope of better understanding the neurobiology underlying pathological behaviours associated with the hyperdopaminergic state
Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson's disease.
Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson's Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson's disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.GRF gratefully acknowledges support by the German Research Council (Deutsche Forschungsgemeinschaft, KFO-219). Ray Dolan is supported by the Wellcome Trust (R.J.D., Senior Investigator Award 098362/Z/12/Z)
and the the Senate of Berlin (R.J.D., Einstein Fellowship). Ben Seymour is funded by the Wellcome Trust and the National Institute of Information and Communications Technology, Japan; Peter Dayan is funded by the Gatsby Charitable Foundation
The effect of motivation on movement: a study of bradykinesia in Parkinson's disease.
Bradykinesia is a cardinal feature of Parkinson's disease (PD). Despite its disabling impact, the precise cause of this symptom remains elusive. Recent thinking suggests that bradykinesia may be more than simply a manifestation of motor slowness, and may in part reflect a specific deficit in the operation of motivational vigour in the striatum. In this paper we test the hypothesis that movement time in PD can be modulated by the specific nature of the motivational salience of possible action-outcomes
Improved Kinematics and Motor Control in a Longitudinal Study of a Complex Therapy Movement in Chronic Stroke
Impaired motor control post-stroke is typically measured using clinical assessments employing categorical and subjective scoring. We investigated quantitative kinematic parameters of a complex movement with therapy in chronic stroke. Tri-axial accelerometry of the more-affected arm of 24 patients was recorded during early-(day 2-3) and late-(days 12-14) therapy, and for 13 patients at 6-month follow-up. Clinical assessments included the classification of motor-function as low, moderate, or high. Kinematic parameters were measured during Wii-baseball swings to assess the effect of time and the level of motor-function. Clinical tests improved over time (all p < 0.01). Increased acceleration magnitude over time was significant only at proximal sensors (p < 0.05), and there was an effect of motor-function at distal sensors (p < 0.05). Normalized velocity decreased (p < 0.05) at all sensors over time. Peak acceleration and peak deceleration increased over time, predominately at proximal sensors. Kinematic parameters provide an objective and quantitative measure of change in motor-function that is not possible with clinical assessments. The complex patterns of change were not consistent between and within levels of motor-function but reflected improved motor control that was sustained over time. These data emphasize the potential for ongoing improvements in motor capacity in chronic stroke with additional rehabilitation
Generation of broad XUV continuous high harmonic spectra and isolated attosecond pulses with intense mid-infrared lasers
We present experimental results showing the appearance of a near-continuum in
the high-order harmonic generation (HHG) spectra of atomic and molecular
species as the driving laser intensity of an infrared pulse increases. Detailed
macroscopic simulations reveal that these near-continuum spectra are capable of
producing IAPs in the far field if a proper spatial filter is applied. Further,
our simulations show that the near-continuum spectra and the IAPs are a product
of strong temporal and spatial reshaping (blue shift and defocusing) of the
driving field. This offers a possibility of producing IAPs with a broad range
of photon energy, including plateau harmonics, by mid-IR laser pulses even
without carrier-envelope phase stabilization.Comment: 7 pages, 5 figures, submitted to J.Phys. B (Oct 2011
Functional immune characterization of HIV-associated non-small-cell lung cancer.
Dear Editor,
In the combined anti-retroviral therapy (cART) era, non-small cell lung cancer (NSCLC) is a highly incident cause of morbidity and mortality in people living with HIV (PLHIV)[1]. The immune-pathogenesis of NSCLC and HIV infection both rely on programmed-death 1 (PD-1) receptor-ligand interaction as a mechanism to induce T-cell exhaustion. To date, PLHIV have been excluded from clinical trials of immune-checkpoint inhibitors (ICPI), on the presumption that anti-tumour immunity might be compromised by HIV infection. To verify this, we evaluated the clinico-pathologic significance of PD-ligands expression in a consecutive series of 221 archival NSCLC samples, 24 of which were HIV-associated (Table S1)
A Longitudinal Electromyography Study of Complex Movements in Poststroke Therapy. 1: Heterogeneous Changes Despite Consistent Improvements in Clinical Assessments
Poststroke weakness on the more-affected side may arise from reduced corticospinal drive, disuse muscle atrophy, spasticity, and abnormal coordination. This study investigated changes in muscle activation patterns to understand therapy-induced improvements in motor-function in chronic stroke compared to clinical assessments and to identify the effect of motor-function level on muscle activation changes. Electromyography (EMG) was recorded from five upper limb muscles on the more-affected side of 24 patients during early and late therapy sessions of an intensive 14-day program of Wii-based Movement Therapy (WMT) and for a subset of 13 patients at 6-month follow-up. Patients were classified according to residual voluntary motor capacity with low, moderate, or high motor-function levels. The area under the curve was calculated from EMG amplitude and movement duration. Clinical assessments of upper limb motor-function pre- and post-therapy included the Wolf Motor Function Test, Fugl-Meyer Assessment and Motor Activity Log Quality of Movement scale. Clinical assessments improved over time (p < 0.01) with an effect of motor-function level (p < 0.001). The pattern of EMG change by late therapy was complex and variable, with differences between patients with low compared to moderate or high motor-function levels. The area under the curve (p = 0.028) and peak amplitude (p = 0.043) during Wii-tennis backhand increased for patients with low motor-function, whereas EMG decreased for patients with moderate and high motor-function levels. The reductions included movement duration during Wii-golf (p = 0.048, moderate; p = 0.026, high) and Wii-tennis backhand (p = 0.046, moderate; p = 0.023, high) and forehand (p = 0.009, high) and the area under the curve during Wii-golf (p = 0.018, moderate) and Wii-baseball (p = 0.036, moderate). For the pooled data over time, there was an effect of motor-function (p = 0.016) and an interaction between time and motor-function (p = 0.009) for Wii-golf movement duration. Wii-baseball movement duration decreased as a function of time (p = 0.022). There was an effect on Wii-tennis forehand duration for time (p = 0.002), an interaction of time and motor-function (p = 0.005) and an effect of motor-function level on the area under the curve (p = 0.034) for Wii-golf. This study demonstrated different patterns of EMG changes according to residual voluntary motor-function levels, despite heterogeneity within each level that was not evident following clinical assessments alone. Thus, rehabilitation efficacy might be underestimated by analyses of pooled data
Dopamine, Salience, and Response Set Shifting in Prefrontal Cortex.
Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. l-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease
Remote constraint induced therapy of the upper extremity (ReCITE): A feasibility study protocol
Background: Difficulty using the upper extremity in everyday activities is common after stroke. Constraint-induced movement therapy (CIMT) has been shown to be effective in both sub-acute and chronic phases of stroke recovery and is recommended in clinical practice guidelines for stroke internationally. Despite reports of equivalence of outcome when stroke rehabilitation interventions are delivered using telehealth, there has been limited evaluation of CIMT when using this mode of delivery. ReCITE will (a) evaluate the feasibility and acceptability of CIMT when delivered via telehealth to stroke survivors (TeleCIMT) and (b) explore therapists' experiences and use of an online support package inclusive of training, mentoring and resources to support TeleCIMT delivery in clinical practice. /
Methods: A prospective single-group, single blinded, study design with embedded process evaluation will be conducted. The study will be conducted at three outpatient services in Sydney, Australia. A multi-faceted therapist support package, informed by the Capabilities, Opportunity, Motivation- Behaviour model (COM-B), will be used to support occupational therapists to implement TeleCIMT as part of routine care to stroke survivors. Each service will recruit 10 stroke survivor participants (n = 30) with mild to moderate upper extremity impairment. Upper extremity and quality of life outcomes of stroke survivor participants will be collected at baseline, post-intervention and at a 4 week follow-up appointment. Feasibility of TeleCIMT will be evaluated by assessing the number of stroke participants who complete 80% of intensive arm practice prescribed during their 3 week program (i.e., at least 24 h of intensive arm practice). Acceptability will be investigated through qualitative interviews and surveys with stroke survivors, supporter surveys and therapist focus groups. Qualitative interviews with therapists will provide additional data to explore their experiences and use of the online support package. /
Discussion: The COVID-19 pandemic resulted in a rapid transition to delivering telehealth. The proposed study will investigate the feasibility and acceptability of delivering a complex intervention via telehealth to stroke survivors at home, and the support that therapists and patients require for delivery. The findings of the study will be used to inform whether a larger, randomized controlled trial is feasible
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