Design and Characterization of 5 µm Pitch InGaAs Photodiodes Using In Situ Doping and Shallow Mesa Architecture for SWIR Sensing.

This paper presents the complete design, fabrication, and characterization of a shallow-mesa photodiode for short-wave infra-red (SWIR) sensing. We characterized and demonstrated photodiodes collecting 1.55 µm photons with a pixel pitch as small as 3 µm. For a 5 µm pixel pitch photodiode, we measured the external quantum efficiency reaching as high as 54%. With substrate removal and an ideal anti-reflective coating, we estimated the internal quantum efficiency as achieving 77% at 1.55 µm. The best measured dark current density reached 5 nA/cm2 at -0.1 V and at 23 °C. The main contributors responsible for this dark current were investigated through the study of its evolution with temperature. We also highlight the importance of passivation with a perimetric contribution analysis and the correlation between MIS capacitance characterization and dark current performance.

Characterizing the effect of low intensity transcranial magnetic stimulation on the soleus H-reflex at rest.

Modulation of a Hoffmann (H)-reflex following transcranial magnetic stimulation (TMS) has been used to assess the nature of signals transmitted from cortical centers to lower motor neurons. Further characterizing the recruitment and time-course of the TMS-induced effect onto the soleus H-reflex adds to the discussion of these pathways and may improve its utility in clinical studies. In 10 healthy controls, TMS was used to condition the soleus H-reflex using TMS intensities from 65 to 110% of the resting motor threshold (RMT). Early facilitation [- 5 to - 3 ms condition-test (C-T) interval] was evident when TMS was 110% of RMT (P < 0.05). By comparison, late facilitation (+ 10 to + 20 ms C-T interval) was several times larger and observed over a wider range of TMS intensities, including 65-110% of RMT. The early inhibition (- 3 to - 1 ms C-T interval) had a low TMS threshold and was elicited over a wide range of intensity from 65% to 95% of RMT (all P < 0.05). A second inhibitory phase was seen ~ 4 ms later (+ 1 to + 4 ms C-T intervals) and was only observed for a TMS intensity of 95% of RMT (P < 0.05). The present findings reaffirm that subthreshold TMS strongly modulates soleus motor neurons and demonstrates that distinct pathways can be selectively probed at discrete C-T intervals when using specific TMS intensities.

Fully Depleted, Trench-Pinned Photo Gate for CMOS Image Sensor Applications.

Tackling issues of implantation-caused defects and contamination, this paper presents a new complementary metal-oxide-semiconductor (CMOS) image sensor (CIS) pixel design concept based on a native epitaxial layer for photon detection, charge storage, and charge transfer to the sensing node. To prove this concept, a backside illumination (BSI), p-type, 2-µm-pitch pixel was designed. It integrates a vertical pinned photo gate (PPG), a buried vertical transfer gate (TG), sidewall capacitive deep trench isolation (CDTI), and backside oxide-nitride-oxide (ONO) stack. The designed pixel was fabricated with variations of key parameters for optimization. Testing results showed the following achievements: 13,000 h+ full-well capacity with no lag for charge transfer, 80% quantum efficiency (QE) at 550-nm wavelength, 5 h+/s dark current at 60 °C, 2 h+ temporal noise floor, and 75 dB dynamic range. In comparison with conventional pixel design, the proposed concept could improve CIS performance.

Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury.

The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153.

Reduced postactivation depression of soleus H reflex and root evoked potential after transcranial magnetic stimulation.

Postactivation depression of the Hoffmann (H) reflex is associated with a transient period of suppression following activation of the reflex pathway. In soleus, the depression lasts for 100-200 ms during voluntary contraction and up to 10 s at rest. A reflex root evoked potential (REP), elicited after a single pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to exhibit similar suppression. The present study systematically characterized the effect of transcranial magnetic stimulation (TMS) on postactivation depression using double-pulse H reflexes and REPs. A TMS pulse reduced the period of depression to 10-15 ms for both reflexes. TMS could even produce postactivation facilitation of the H reflex, as the second reflex response was increased to 243 ± 51% of control values at the 75-ms interval. The time course was qualitatively similar for the REP, yet the overall increase was less. While recovery of the H reflex was slower in the relaxed muscle, the profile exhibited a distinct bimodal shape characterized by an early peak at the 25-ms interval, reaching 72 ± 23% of control values, followed by a trough at 50 ms, and then a gradual recovery at intervals > 50 ms. The rapid recovery of two successively depressed H reflexes, ∼ 25 ms apart, was also possible with double-pulse TMS. The effect of the TMS-induced corticospinal excitation on postactivation depression may be explained by a combination of pre- and postsynaptic mechanisms, although further investigation is required to distinguish between them.

Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous group 1 afferents.

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5-0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65-115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.

Interaction of transcutaneous spinal stimulation and transcranial magnetic stimulation in human leg muscles.

Transcutaneous spinal stimulation is a noninvasive method that can activate dorsal and/or ventral roots depending on the location and intensity of stimulation. Reflex root-evoked potentials (REPs) were studied in muscles that traditionally evoke large (soleus) and small H-reflexes (tibialis anterior), as well as muscles where H-reflexes are difficult to study (hamstrings). This study characterizes the interaction of the REP and the motor-evoked potential (MEP). Transcranial magnetic stimulation (TMS) delivered 11-25 ms before spinal stimulation resulted in more than linear summation of the two responses. Because of overlap, the modulation was quantified after subtracting the contribution of the conditioning MEP or REP. At rest, the mean-rectified soleus response was facilitated by up to ~250 µV (21-times the MEP or 161% of the REP). The increases were more reliable during a voluntary contraction (up to ~300 µV, 517% of the MEP or 181% of the REP). At the 13-ms interval, the mean-rectified response in the pre-contracted hamstrings was increased by 227% of the MEP or 300% of the REP. In some subjects, TMS could also eliminate the post-activation depression produced using two spinal stimuli, confirming that the interaction can extend to presynaptic spinal neurons. The spatiotemporal facilitation in tibialis anterior was not significant. However, the large MEP was facilitated when the spinal stimulus preceded TMS by 100-150 ms, presumably because of rebound excitation. These strong interactions may be important for inducing motor plasticity and improved training procedures for recovery after neurological damage.

Effect of percutaneous stimulation at different spinal levels on the activation of sensory and motor roots.

Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

Effect of Motor State on Postactivation Depression of the Soleus H-Reflex in Parkinson's Disease During Deep Brain Stimulation and Dopaminergic Medication Treatment: A Pilot Study.

PURPOSE: Postactivation depression of the Hoffmann reflex is reduced in Parkinson's disease (PD), but how the recovery is influenced by the state of the muscle is unknown. The present pilot study examined postactivation depression in PD at rest and during a voluntary contraction while patients were off treatment and while receiving medications and/or deep brain stimulation. METHODS: The authors recruited nine patients with PD treated with implanted deep brain stimulation and examined postactivation depression under four treatment conditions. Paired pulses were delivered 25 to 300 ms apart, and soleus Hoffmann reflex recovery was tested at rest and during voluntary plantar flexion. Trials were matched for background muscle activity and compared with 10 age-matched controls. RESULTS: Patients with Parkinson disease who were OFF medications (OFF meds) and OFF stimulation (OFF stim) at rest showed less postactivation depression at the 300 ms interpulse interval (86.1% ± 21.0%) relative to control subjects (36.4% ± 6.1%; P < 0.05). Postactivation depression was restored when dopaminergic medication and/or deep brain stimulation was applied. Comparisons between resting and active motor states revealed that the recovery curves were similar OFF meds/OFF stim owing to faster recovery in PD seen at rest. In contrast, the effect of the motor state was different ON meds/OFF stim and ON meds/ON stim (both P < 0.05), with a nonsignificant trend OFF meds/ON stim ( P > 0.08). During a contraction, recovery curves were similar between all treatment conditions in PD and control. CONCLUSIONS: Disrupted Hoffmann reflex recovery is restored to control levels in PD patients at rest when receiving medications and/or deep brain stimulation or when engaged in voluntary contraction.

Effects of Deep Brain Stimulation and Dopaminergic Medication on Excitatory and Inhibitory Spinal Pathways in Parkinson Disease.

PURPOSE: Abnormal activity within the corticospinal system is believed to contribute to the motor dysfunction associated with Parkinson disease. However, the effect of treatment for parkinsonian motor symptoms on dysfunctional descending input to the motor neuron pool remains unclear. METHODS: We recruited nine patients with PD treated with deep brain stimulation and examined the time course of interaction between a conditioning pulse from transcranial magnetic stimulation and the soleus H-reflex. Patients with Parkinson disease were examined under four treatment conditions and compared with 10 age-matched control subjects. RESULTS: In healthy controls, transcranial magnetic stimulation conditioning led to early inhibition of the H-reflex (76.2% ± 6.3%) at a condition-test interval of -2 ms. This early inhibition was absent when patients were OFF medication/OFF stimulation (132.5% ± 20.4%; P > 0.05) but was maximally restored toward control levels ON medication/ON stimulation (80.3% ± 7.0%). Of note, early inhibition ON medication/ON stimulation tended to be stronger than when medication (85.4% ± 5.9%) or deep brain stimulation (95.7% ± 9.4%) were applied separately. Late facilitation was observed in controls at condition-test intervals ≥5 ms but was significantly reduced (by 50% to 80% of controls) in Parkinson disease OFF stimulation at condition-test intervals ≥15 ms. The late facilitation was akin to control subjects when patients were ON stimulation. CONCLUSIONS: The present pilot study demonstrates that the recruitment of early inhibition and late facilitation is disrupted in untreated Parkinson disease and that medication and deep brain stimulation may act together to normalize supraspinal drive to the motor neuron pool.

Afferent regulation of leg motor cortex excitability after incomplete spinal cord injury.

An incomplete spinal cord injury (SCI) impairs neural conduction along spared ascending sensory pathways to disrupt the control of residual motor movements. To characterize how SCI affects the activation of the motor cortex by spared ascending sensory pathways, we examined how stimulation of leg afferents facilitates the excitability of the motor cortex in subjects with incomplete SCI. Homo- and heteronymous afferents to the tibialis anterior (TA) representation in the motor cortex were electrically stimulated, and the responses were compared with uninjured controls. In addition, we examined if cortical excitability could be transiently increased by repetitively pairing stimulation of spared ascending sensory pathways with transcranial magnetic stimulation (TMS), an intervention termed paired associative stimulation (PAS). In uninjured subjects, activating the tibial nerve at the ankle 45-50 ms before a TMS pulse in a conditioning-test paradigm facilitated the motor-evoked potential (MEP) in the heteronymous TA muscle by twofold on average. In contrast, prior tibial nerve stimulation did not facilitate the TA MEP in individuals with incomplete SCI (n = 8 SCI subjects), even in subjects with less severe injuries. However, we provide evidence that ascending sensory inputs from the homonymous common peroneal nerve (CPN) can, unlike the heteronymous pathways, facilitate the motor cortex to modulate the TA MEP (n = 16 SCI subjects) but only in subjects with less severe injuries. Finally, by repetitively coupling CPN stimulation with coincident TA motor cortex activation during PAS, we show that 7 of 13 SCI subjects produced appreciable (>20%) facilitation of the MEP following the intervention. The increase in corticospinal tract excitability by PAS was transient (<20 min) and tended to be more prevalent in SCI subjects with stronger functional ascending sensory pathways.

Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson's disease: A potential biomarker for optimal electrode placement.

BACKGROUND: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. OBJECTIVE: We explored whether recovery of the H-reflex-an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD-could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. METHODS: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. RESULTS: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. CONCLUSION: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

A nuclear export signal and phosphorylation regulate Dok1 subcellular localization and functions.

Dok1 is believed to be a mainly cytoplasmic adaptor protein which down-regulates mitogen-activated protein kinase activation, inhibits cell proliferation and transformation, and promotes cell spreading and cell migration. Here we show that Dok1 shuttles between the nucleus and cytoplasm. Treatment of cells with leptomycin B (LMB), a specific inhibitor of the nuclear export signal (NES)-dependent receptor CRM1, causes nuclear accumulation of Dok1. We have identified a functional NES (348LLKAKLTDPKED359) that plays a major role in the cytoplasmic localization of Dok1. Src-induced tyrosine phosphorylation prevented the LMB-mediated nuclear accumulation of Dok1. Dok1 cytoplasmic localization is also dependent on IKKbeta. Serum starvation or maintaining cells in suspension favor Dok1 nuclear localization, while serum stimulation, exposure to growth factor, or cell adhesion to a substrate induce cytoplasmic localization. Functionally, nuclear NES-mutant Dok1 had impaired ability to inhibit cell proliferation and to promote cell spreading and cell motility. Taken together, our results provide the first evidence that Dok1 transits through the nucleus and is actively exported into the cytoplasm by the CRM1 nuclear export system. Nuclear export modulated by external stimuli and phosphorylation may be a mechanism by which Dok1 is maintained in the cytoplasm and membrane, thus regulating its signaling functions.

Suppression of EMG activity by subthreshold paired-pulse transcranial magnetic stimulation to the leg motor cortex.

Cortical activity driving a voluntary muscle contraction is inhibited by very low-intensity transcranial magnetic stimulation (TMS) and is reflected in the suppression of the average rectified EMG. This approach offers a method to test the contribution of cortical neurons actively involved in a motor task, but requires a large number of stimuli (approximately 100) to suitably depress the average EMG. Here, we investigated whether two pulses of subthreshold TMS at interstimulus intervals (ISIs) ranging between 1 and 12 ms could enhance the amount of EMG suppression in the tibialis anterior muscle compared to a single pulse. Pairs of subthreshold TMS at an ISI of 7 ms produced the maximum EMG suppression that was 42% more than the inhibition elicited using a single pulse. In addition, the signal-to-noise ratio of the TMS-induced suppression was further increased by a second pulse, delivered 7 ms later. The reduction in the EMG at the 7 ms paired-pulse interval occurred without any short-latency excitation suggesting that the two stimuli increased the activation of cortical inhibitory neurons. Subthreshold paired-pulse TMS at ISIs of 1-3 ms was prone to EMG excitation in the period that immediately preceded the inhibition and is consistent with the recruitment of short-interval intracortical facilitation (SICF). We propose that pairs of subthreshold TMS outside the range of SICF with an inter-pulse interval of 7 ms is optimal to inhibit ongoing cortical activity during human motor movement.

1T Pixel Using Floating-Body MOSFET for CMOS Image Sensors.

We present a single-transistor pixel for CMOS image sensors (CIS). It is a floating-body MOSFET structure, which is used as photo-sensing device and source-follower transistor, and can be controlled to store and evacuate charges. Our investigation into this 1T pixel structure includes modeling to obtain analytical description of conversion gain. Model validation has been done by comparing theoretical predictions and experimental results. On the other hand, the 1T pixel structure has been implemented in different configurations, including rectangular-gate and ring-gate designs, and variations of oxidation parameters for the fabrication process. The pixel characteristics are presented and discussed.

Peripheral sensory activation of cortical circuits in the leg motor cortex of man.

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45-50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5-37.5 ms. Similar time-dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent-evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H-reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short-latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short-interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long-interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I-wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons.

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10-25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50-60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.

Preferences and Inhalation Techniques for Inhaler Devices Used by Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Inhaler technique and patient preferences are often overlooked when selecting maintenance treatments for patients with chronic obstructive pulmonary disease (COPD), but are important issues in ensuring drug efficacy and patient adherence. Few data on these issues are available for new inhalation devices. OBJECTIVES: To evaluate the inhalation techniques for the HandiHaler®, Breezhaler®, Genuair®, and Respimat® inhalation devices, and patient preferences for the three latter inhalers that were recently developed. METHODS: A prospective two-center cross-sectional study of COPD patients was conducted. The patients were required to be current HandiHaler users who had not previously used the new inhalers (Breezhaler, Genuair, Respimat). The patients were given the new devices and asked to identify the one they preferred before and after using the inhaler. Each patient tried the HandiHaler and two devices out of the three new inhalers: one preferred by the patient and one imposed by the investigator. Their inhalation technique was evaluated using an assessment checklist. A logistic regression model was used to determine which device was used with the fewest errors. RESULTS: Of the 98 patients who completed the study, 57.1% (95% CI: 47.4-66.9) had an adequate HandiHaler technique. There was no difference between the proportions of patients with an adequate Breezhaler and Genuair inhalation technique (aOR 1.08, 95% CI: 0.51-2.30), but 62% fewer patients using Respimat had an adequate technique than those using Genuair (aOR for adequate technique 0.38, 95% CI: 0.18-0.82). There were no significant differences in the initial patient preferences for the three new inhalers, and no association between the patient's preference and an adequate inhaler technique. CONCLUSION: Inhalation techniques were suboptimal and varied between inhalers. The arrival of new inhalers is an opportunity to reassess patient techniques and preferences. Further studies should also explore the association between the inhaler preferences and treatment adherence of patients.

MAP kinase module: the Ksr connection.

Ksr has been genetically defined as a component of the Ras/MAP kinase pathway, but its role has been unclear. New studies now provide evidence that Ksr is important for signal transmission within the MAP kinase module, where it apparently acts as a location-regulated scaffold connecting MEK to Raf.

Intraoperative spinal cord monitoring using low intensity transcranial stimulation to remove post-activation depression of the H-reflex.

OBJECTIVE: To investigate whether low intensity transcranial electrical stimulation (TES) can be used to condition post-activation depression of the H-reflex and simultaneously monitor the integrity of spinal motor pathways during spinal deformity correction surgery. METHODS: In 20 pediatric patients undergoing corrective surgery for spinal deformity, post-activation depression of the medial gastrocnemius H-reflex was initiated by delivering two pulses 50-125ms apart, and the second H-reflex was conditioned by TES. RESULTS: Low intensity TES caused no visible shoulder or trunk movements during 19/20 procedures and the stimulation reduced post-activation depression of the H-reflex. The interaction was present in 20/20 patients and did not diminish throughout the surgical period. In one case, the conditioning effect was lost within minutes of the disappearance of the lower extremity motor evoked potentials. CONCLUSION: Post-activation depression was used to detect the arrival of a subthreshold motor evoked potential at the lower motor neuron. The interaction produced minimal movement within the surgical field and remained stable throughout the surgical period. SIGNIFICANCE: This is the first use of post-activation depression during intraoperative neurophysiological monitoring to directly assess the integrity of descending spinal motor pathways.