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The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18–80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87–4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. St Jude Medical Neuromodulation Division.

Introduces a variety of fish that live in the deepest zones of the ocean, including viperfish, jellyfish, jewel squid, and the blobfish.

Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius–ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior–ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS—either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3–4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov, number NCT00954421. Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), −29·6% reduction; t=–0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship.

The deep ocean comprises more than 90 percent of our planet's biosphere and is home to some of the world's most dazzling creatures, which thrive amid extreme pressures, scarce food supplies, and frigid temperatures. Living things down here behave in remarkable and surprising ways, and cutting-edge technologies are shedding new light on these critically important ecosystems. This beautifully illustrated book leads you down into the canyons, trenches, and cold seeps of the watery abyss, presenting the deep ocean and its inhabitants as you have never seen them before.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation and has become a standard of care in a range of movement disorders. This Review discusses the evolution and current status of DBS technology and anticipates future advances.

Introduces fifty strange animals from the sea.

Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment. In this randomised, sham-controlled trial, we recruited patients with cervical dystonia from centres in Germany, Norway, and Austria. Eligible patients (ie, those aged 18–75 years, disease duration ≥3 years, Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score ≥15 points) were randomly assigned (1:1) to receive active neurostimulation (frequency 180 Hz; pulse width 120 μs; amplitude 0·5 V below adverse event threshold) or sham stimulation (amplitude 0 V) by computer-generated randomisation lists with randomly permuted block lengths stratified by centre. All patients, masked to treatment assignment, were implanted with a deep brain stimulation device and received their assigned treatment for 3 months. Neurostimulation was activated in the sham group at 3 months and outcomes were reassessed in all patients after 6 months of active treatment. Treating physicians were not masked. The primary endpoint was the change in the TWSTRS severity score from baseline to 3 months, assessed by two masked dystonia experts using standardised videos, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148889. Between Jan 19, 2006, and May 29, 2008, we recruited 62 patients, of whom 32 were randomly assigned to neurostimulation and 30 to sham stimulation. Outcome data were recorded in 60 (97%) patients at 3 months and 56 (90%) patients at 6 months. At 3 months, the reduction in dystonia severity was significantly greater with neurostimulation (–5·1 points [SD 5·1], 95% CI −7·0 to −3·5) than with sham stimulation (−1·3 [2·4], −2·2 to −0·4, p=0·0024; mean between-group difference 3·8 points, 1·8 to 5·8) in the intention-to-treat population. Over the course of the study, 21 adverse events (five serious) were reported in 11 (34%) of 32 patients in the neurostimulation group compared with 20 (11 serious) in nine (30%) of 30 patients in the sham-stimulation group. Serious adverse events were typically related to the implant procedure or the implanted device, and 11 of 16 resolved without sequelae. Dysarthria (in four patients assigned to neurostimulation vs three patients assigned to sham stimulation), involuntary movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression (one vs two) were the most common non-serious adverse events reported during the course of the study. Pallidal neurostimulation for 3 months is more effective than sham stimulation at reducing symptoms of cervical dystonia. Extended follow-up is needed to ascertain the magnitude and stability of chronic neurostimulation effects before this treatment can be recommended as routine for patients who are not responding to conventional medical therapy. Medtronic.

\"Join scientists on a journey from coastlines to the deep seafloor and meet the weird, wonderful, and unforgettable creatures they discovered along the way\"--P. [4] of cover.

Introduction Improving positive airway pressure (PAP) adherence is crucial to sleep apnea therapy success. Although behavioral interventions may be deployed to increase PAP adherence, operationalization remains an ongoing clinical challenge. Treatment outcomes may be optimized by forecasting PAP use to identify patients at risk for non-adherence enabling early intervention. We build upon our previous work by leveraging a larger dataset, additional metadata, and new Deep Learning approaches to forecast future PAP adherence. Methods We collected a cohort of N=21,397 subjects with daily PAP usage recorded during 2015-2021. We defined the input to models as the number of minutes the PAP machine was used during each day for the first 30-days. The ground truth was defined as the PAP adherence of the patients at the 3-month, 6- month, and 1-year endpoints. Adherence was calculated based on a 30-day window as ≥4-hours of usage for ≥70% of nights. We evaluated a Deep Neural Network (DNN) model with 10-fold cross- validation to forecast future adherence by leveraging previous daily usage information. Results were compared to a naive method which assumes adherence at each time point equals adherence during the first 30-days. Results The DNN models predicted adherence with a sensitivity of 90%, 81%, 77% and a specificity of 90%, 81%, 77%, for 3-month, 6-month, and 1-year endpoints, with ROC-AUC values of 0.97, 0.89, and 0.84 respectively. The models converged to ROC-AUC performance >0.90 for the first 90-days within the first 7 to 14-days of PAP use. Conclusion DNN models demonstrated strong predictive performance for PAP adherence, as defined by the CMS adherence criteria, measured by sensitivity, specificity, and overall ROC-AUC results at clinically relevant 90-day, 6-month, and 1-year timepoints. AI approaches show promise as early predictors of the likelihood to meet key therapy utilization thresholds within the first 1-2 weeks of therapy, enabling early PAP intervention or transition to alternative therapies. Support (if any) AASM Foundation SRA205-SR-19