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Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette’s syndrome, the supplementary motor area in Parkinson’s disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

ABSTRACT This paper aims to assess the influence of flash calcined dredging sediments (CFC), having pozzolanic reactivity, on the early-age hydration and autogenous deformation behaviour of blended cements, where cement [...]

Space radiation is a notable hazard for long-duration human spaceflight1. Associated risks include cancer, cataracts, degenerative diseases2and tissue reactions from large, acute exposures3. Space radiation originates from diverse sources, including galactic cosmic rays4, trapped-particle (Van Allen) belts5and solar-particle events6. Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth’s magnetic field7,8and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter9,10. Limited data from the Apollo missions11–13and ground measurements with substantial caveats are also available14. Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations9. Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design.

Conventional deep brain stimulation (DBS) programming via trial-and-error warrants improvement to ensure swift achievement of optimal outcomes. The definition of a sweet spot for subthalamic DBS in Parkinson’s disease (PD-STN-DBS) may offer such advancement. This investigation examines the association of long-term motor outcomes with contact selection during monopolar review and different strategies for anatomically informed contact selection in a retrospective real-life cohort of PD-STN-DBS. We compared contact selection based on a monopolar review (MPR) to multiple anatomically informed contact selection strategies in a cohort of 28 PD patients with STN-DBS. We employed a commercial software package for contact selection based on visual assessment of individual anatomy following two predefined strategies and two algorithmic approaches with automatic targeting of either the sensorimotor STN or our previously published sweet spot. Similarity indices between chronic stimulation and contact selection strategies were correlated to motor outcomes at 12 months follow-up. Lateralized motor outcomes of chronic DBS were correlated to the similarity between chronic stimulation and visual contact selection targeting the dorsal part of the posterior STN (rho = 0.36, p = 0.007). Similar relationships could not be established for MPR or any of the other investigated strategies. Our data demonstrates that a visual contact selection following a predefined strategy can be linked to beneficial long-term motor outcomes in PD-STN-DBS. Since similar correlations could not be observed for the other approaches to anatomically informed contact selection, we conclude that clear definitions and prospective validation of any approach to imaging-based DBS-programming is warranted.

BackgroundSubthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) improves quality of life (QoL), motor and non-motor symptoms (NMS). However, in previous studies, 43%–49% of patients did not experience clinically relevant postoperative QoL improvement. To inform individualised prediction of postoperative QoL improvement, we developed a stratification analysis of QoL outcomes based on preoperative non-motor total burden, severity of motor progression and motor response in levodopa challenge tests.MethodsThis was a prospective, open-label, multicentre, international study with a 6-month follow-up. A distribution-based threshold identified ‘QoL responders’ in the PDQuestionnaire-8 Summary Index (PDQ-8 SI). After baseline stratification based on the NMS Scale, Hoehn and Yahr Scale and levodopa response assessed with the Unified PD Rating Scale-III, we compared postoperative QoL response between these strata. To assess the clinical usefulness and statistical feasibility of stratifications, we compared cumulative distribution function curves, respectively PDQ-8 within-stratum variation.ResultsAll main outcomes improved postoperatively. Based on the 8.1 points threshold for clinically meaningful PDQ-8 SI improvement, only 80/161 patients were classified as ‘QoL responders’. The absolute risk reductions for QoL non-response among respective non-motor, motor progression and levodopa response strata were 23%, 8% and 3%, respectively. Only non-motor stratification reduced PDQ-8 within-stratum variation compared with the overall cohort.ConclusionsNon-motor stratification, but not motor progression or levodopa response stratification, is clinically useful and statistically feasible for personalised preoperative prediction of postoperative QoL outcome of STN-DBS for PD. Our findings highlight that non-motor assessments are necessary components of a case-based, holistic approach of DBS indication evaluations geared towards optimising postoperative QoL outcomes.Trial registration numberGermanClinicalTrialsRegister: #6735.

ABSTRACT This paper reports on the short-term and creep pull-out behavior of different polypropylene fibers from a concrete matrix. 85 displacement controlled tests are carried out for two types of [...]

Background Chance fracture (CFx) with concomitant intra-abdominal injury has variable occurrence rates ranging from 33 to 89%. No single study has compared the incidence of simultaneous abdominal injury between pediatric and adult populations. This study compares the rate of simultaneous intra-abdominal injury and chance fracture in these populations.Methods A retrospective review of pediatric and adult patients with chance fracture in comparable pediatric and adult trauma centers was performed. Patient demographics, mechanism of injury (MOI), and injury patterns were collected from 2002 to 2019 for pediatric patients and 2015 to 2018 for adults. Student t-test analyses were performed to determine statistical significance between the cohorts.Results The pediatric group had a similar incidence of abdominal solid organ injuries compared to adults (16 [20.5%] vs. 40 [19.7%], p<0.879), but the pediatric group had a greater number of total intra-abdominal (49 [62.8%] vs. 47 [23.1%], p < 0.001) and hollow organ injuries (40 [51.3%] vs. 17 [8.4%], p < 0.001). Motor vehicle collision was the most common mechanism of injury for both groups (72 pediatric [92.3%] vs. 85 adult [41.7%]) but adults suffered from more falls (3 pediatric vs. 81 adult, p < 0.001). Pediatric patients with CFx caused by MVCs had more intra-abdominal injuries (48 [66.7%] vs. 25[29.8%], p < 0.001) and hollow organ injuries compared to adults (39 [54.2%] vs. 8[9.5%], p < 0.001).Conclusion In the setting of Chance fracture after trauma, pediatric patients are more likely to have a concomitant intra-abdominal organ injury (63% vs. 23%), especially hollow viscus injury (51.3% vs. 8.4%) compared with adults regardless of mechanism.

New functional materials, such as mixed matrix membranes and metal–organic framework (MOF) monoliths, outperform traditional materials in gas separation and storage applications, among other pressing challenges. However, while most engineered materials nowadays exhibit spatial heterogeneities on different length scales, available simulation techniques to date cannot capture this spatial complexity fully. Herein, we present the MicMecimplementation of the micromechanical model we introduced earlier as a systematic coarse-graining approach to routinely access these larger length scales and characterize the mechanical properties of these materials. We thoroughly discuss the key components of our open-source code and validate it both on an analytical system and a case study on correlated reodefects in the UiO-66 MOF. We reveal that the time step that can be reached in micromechanical simulations is 2 to 3 orders of magnitude larger than for atomistic simulations, while still capturing well the macroscopic mechanical properties of the spatially disordered UiO-66 material. It is our hope that the MicMecimplementation discussed here may provide a complementary tool to existing atomistic and coarse-grained software and aid the computational design of new materials for pressing applications.

Deep brain stimulation of the anterior limb of the internal capsule (ALIC)/nucleus accumbens is an effective treatment in patients with obsessive-compulsive disorder but may increase impulsive behavior. We aimed to investigate how active stimulation alters subdomains of impulsive decision making and whether respective effects depend on the location of stimulation sites.

Objectives: Ocrelizumab demonstrated significant clinical benefit for the treatment of relapsing (RMS) and primary progressive (PPMS) multiple sclerosis (MS), an incurable disease characterized by disability progression. This study evaluated the clinical and economic impact of ocrelizumab relative to current clinical practice, including other disease-modifying therapies (DMT), available in Portugal. Methods: Markov models for MS were adapted to estimate the impact of ocrelizumab across three patient populations: treatment-naïve RMS, previously treated RMS, and PPMS. Health states were defined according to the Expanded Disability Status Scale. For RMS, the model further captured the occurrence of relapses and progression to secondary progressive multiple sclerosis (SPMS). A lifetime time-horizon and Portuguese societal perspective were adopted. Results: For RMS patients, ocrelizumab was estimated to maximize the expected time (years) without progression to SPMS (10.50) relative to natalizumab (10.10), dimethyl fumarate (8.64), teriflunomide (8.39), fingolimod (8.38), interferon β-1a (8.33) and glatiramer acetate (8.18). As the most effective option, with quality-adjusted life year (QALY) gains between 0.3 and 1.2, ocrelizumab was found to be cost-saving relative to natalizumab and fingolimod, and presented incremental cost-effectiveness ratios (ICER) below €16,720/QALY relative to the remaining DMT. For PPMS patients, the ICER of ocrelizumab versus best supportive care was estimated at €78,858/QALY. Conclusions: Ocrelizumab provides important health benefits for RMS and PPMS patients, comparing favourably with other widely used therapies. In RMS, ocrelizumab was revealed to be either cost-saving or have costs-per-QALY likely below commonly accepted cost-effectiveness thresholds. In PPMS, ocrelizumab fills a clear clinical gap in the current clinical practice. Overall, ocrelizumab is expected to provide good value for money in addressing the need of MS patients.

ABSTRACT The binding properties of continuous casting stainless steel slag were studied when activated by a combination of Na silicate and 5 M NaOH as well as K silicate and [...]

The cross-talk between thymocytes and thymic stromal cells is fundamental for T cell development. In humans, intrathymic development of dendritic cells (DCs) is evident but its physiological significance is unknown. Here we showed that DC-biased precursors depended on the expression of the transcription factor IRF8 to express the membrane-bound precursor form of the cytokine TNF (tmTNF) to promote differentiation of thymus seeding hematopoietic progenitors into T-lineage specified precursors through activation of the TNF receptor (TNFR)-2 instead of TNFR1. In vitro recapitulation of TNFR2 signaling by providing low-density tmTNF or a selective TNFR2 agonist enhanced the generation of human T cell precursors. Our study shows that, in addition to mediating thymocyte selection and maturation, DCs function as hematopoietic stromal support for the early stages of human T cell development and provide proof of concept that selective targeting of TNFR2 can enhance the in vitro generation of T cell precursors for clinical application.

Deep brain stimulation is an effective treatment for obsessive–compulsive disorder but is rarely used. Action is needed by psychologists, psychiatrists and insurers so that patients with otherwise intractable cases can receive this therapy to improve their mental health.

Open questions remain regarding the optimal target, or sweetspot, for deep brain stimulation (DBS) in, for example, Parkinson's disease. Previous studies introduced different methods of mapping DBS effects to determine sweetspots. While having a direct impact on surgical targeting and postoperative programming in DBS, these methods so far have not been compared.

The North Dakota court system is the only state court in the nation that has not made cuts due to budget woes, according to the November/December 2012 issue of the [...]

The September 11 killing of the U.S. ambassador to Libya, Christopher Stevens, and three other Americans during an attack by an angry mob on the U.S. consulate in Benghazi has [...]

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OBJECTIVE--To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS--A total of 14 consecutive [...]

OBJECTIVE--In type 2 diabetes, chronic hyperglycemia is detrimental to β-cells, causing apoptosis and impaired insulin secretion. The transcription factor cAMP-responsive element-binding protein (CREB) is crucial for β-cell survival and function. We investigated whether prolonged exposure of β-cells to high glucose affects the functional integrity of CREB. RESEARCH DESIGN AND METHODS--INS-1E cells and rat and human islets were used. Gene expression was analyzed by RT-PCR and Western blotting. Apoptosis was detected by cleaved caspase-3 emergence, DNA fragmentation, and electron microscopy. RESULTS--Chronic exposure of INS-1E cells and rat and human islets to high glucose resulted in decreased CREB protein expression, phosphorylation, and transcriptional activity associated with apoptosis and impaired β-cell function. High-glucose treatment increased CREB polyubiquitination, while treatment of INS-1E cells with the proteasome inhibitor MG-132 prevented the decrease in CREB content. The emergence of apoptosis in INS-1E cells with decreased CREB protein expression knocked down by small interfering RNA suggested that loss of CREB protein content induced by high glucose contributes to β-cell apoptosis. Loading INS-1E cells or human islets with a cell-permeable peptide mimicking the proteasomal targeting sequence of CREB blocked CREB degradation and protected INS-1E cells and human islets from apoptosis induced by high glucose. The insulin secretion in response to glucose and the insulin content were preserved in human islets exposed to high glucose and loaded with the peptide. CONCLUSIONS--These studies demonstrate that the CREB degradation by the ubiquitin-proteasome pathway contributes to β-cell dysfunction and death upon glucotoxicity and provide new insight into the cellular mechanisms of glucotoxicity., The deterioration of β-cell function and survival caused by chronic exposure to supraphysiological concentrations of glucose is termed glucotoxicity (1-6). Evidence (1-8) supports the notion that increased β-cell death by [...]

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control with a decrease in energy consumption. However, only little is known about the effect of short pulse width stimulation beyond the setting of an acute challenge.Objective: To compare 4 weeks of STN-DBS with conventional pulse width stimulation (60 µs) to 4 weeks of STN-DBS with short pulse width stimulation (30 µs) regarding motor symptom control.Methods: This study was a monocentric, double-blinded, randomized crossover non-inferiority trial investigating whether short pulse width stimulation with 30 µs maintains equal motor control as conventional 60 µs stimulation over a period of 4 weeks (German Clinical Trials Register No. DRKS00017528). Primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life.Results: Due to a high dropout rate, the calculated sample size of 27 patients was not met and 24 patients with Parkinson’s disease and STN-DBS were included in the final analysis. However, there were no differences in any investigated outcome parameter between the two treatment conditions.Conclusion: This study demonstrates that short pulse width settings (30 µs) provide non-inferior motor symptom control as conventional (60 µs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

The Couffo basin is not well known, and neither are its aquatic living resources, such as fish fauna, which are subjected to high exploitation rates. The objectives of this study were to establish length-weight ratios (LWRs) and length-length ratios (LLRs) for the most important species in the catches and those of certain economic value. A total of 12,191 specimens belonging to 40 commercial species of actinopterygian fishes were caught with several fishing gears and methods between February 2018 and March 2021. Allometric coefficient bof the LWRs (BW = a ×TLb) ranged from 2.194 for Enteromius callipterusto 3.673 for Protopterus annectenswith a mean of 2.902 ± 0.315. The growth of thirteen species was isometric, that of fourteen species was negatively allometric, and that of the remaining thirteen species was positively allometric. Coefficient of determination r2for the LLRs of 39 of the 40 selected species mentioned above was significant and ranged from 0.781 in Gobionellus occidentalisto 0.997 in Elops senegalensiswith a mean value of 0.951 ± 0.049. The results will be useful for further studies on assessments of population dynamics and the sustainable conservation of the already limited fish stocks in the Couffo River basin.

Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson’s disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future.

Peroxisome proliferator-activated receptor (PPAR) a is a transcription factor controlling lipid and glucose homeostasis. PPARα-deficient (-/-) mice are protected from high-fat diet-induced insulin resistance. However, the impact of PPARα in the pathophysiological setting of obesity-related insulin resistance is unknown. Therefore, PPAR[α.sup.-/-] mice in an obese (ob/ob) background were generated. PPARα deficiency did not influence the growth curves of the obese mice but surprisingly resulted in a severe, age-dependent hyperglycemia. PPARα deficiency did not aggravate peripheral insulin resistance. By contrast, PPAR[α.sup.-/-] ob/ob mice developed pancreatic β-cell dysfunction characterized by reduced mean islet area and decreased insulin secretion in response to glucose in vitro and in vivo. In primary human pancreatic islets, PPARα agonist treatment prevented fatty acid-induced impairment of glucose-stimulated insulin secretion, apoptosis, and triglyceride accumulation. These results indicate that PPARα improves the adaptative response of the pancreatic β-cell to pathological conditions. PPARα could thus represent a promising target in the prevention of type 2 diabetes. Diabetes 55:1605-1613, 2006, Type 2 diabetes is triggered by several factors such as obesity, environmental cues, and genetic predisposition. Type 2 diabetes usually develops when peripheral insulin resistance, due to ectopic fat overload [...]

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Objective: The aim of this study was to estimate the cost of illness (COI) of Duchenne muscular dystrophy (DMD) and its relation to disease progression, using age as a proxy, and according to the ambulatory status of patients. Methods: We conducted a cross-sectional study of patients diagnosed with DMD identified through the Portuguese Neuromuscular Patients Association (APN). Data regarding patient and caregiver demographics, patient health status, resource utilization and cost, and informal care were collected using a custom semistructured questionnaire. Labor productivity and absenteeism losses were captured using the Work Productivity and Activity Impairment questionnaire. Costs were valued using a societal perspective. Results: A total of 46 patient–caregiver pairs were included, of which eight of the patients were ambulant and 38 were nonambulant. Age had a decreasing effect on COI, independent of the patient’s disease stage. Annualized lifetime costs were at their highest in nonambulant patients around the mean age of loss of ambulation (10 years of age). The mean per patient stage-specific costs (year 2019 values) of DMD were estimated at €48,991 in the nonambulant stage and €19,993 in the ambulant stage. Direct nonmedical costs were the main cost drivers, followed by indirect costs. Conclusions: Our results indicate a close relation between overall disease costs and disease progression. DMD is associated with a substantial economic burden, which appears to be larger around the time ambulation is lost (10 years of age). The availability of new therapeutic options that delay disease progression, especially loss of ambulation, may prove to be highly beneficial for not only patients with DMD but also their families and society.

Importance: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml).Background: Different prostaglandin analogues have been commercially approved, with differences in tolerability.Design: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial.Participants: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen.Methods: Participants were randomised to tafluprost (Group 1; n= 33) or bimatoprost (Group 2; n= 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints.Main outcome measures: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy.Results: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p< 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected.Conclusions and relevance: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy.ClinicalTrials.gov Identifier NCT02471105.

Obsessive–compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers.

Goal orientation can assist in the further development of self-management techniques. Goal orientation can also be beneficial to organizational learning procedures and corporate culture development.

This article describes the development and validation process for an instrument to assess goal orientation (an individual disposition toward developing or validating one's ability in achievement settings). In contrast to previous goal orientation instruments, three goal orientation dimensions are identified (learning, avoid, and prove), and the instrument is domain specific to work settings. The results of exploratory factor analysis, reliability analysis (internal consistency and test-retest), confirmatory factor analysis, and nomological network analysis all support the conclusion that the instrument operationalizes the theorized three-dimensional construct.

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Assessment of affective-behavioral states in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS) is essential. To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach’s alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach’s alpha = 0.72–0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84–0.95). Sensitivities and specificities exceeded 0.7. The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted.

The human leukocyte antigen (HIA) class 11 genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 has been identified as a marker strongly predisposing to insulin-dependent diabetes mellitas (EDDM) in Caucasian populations. Its frequency in control populations [...]

We aimed to investigate the efficacy of new subperception stimulation paradigms including 1.2 kHz‐high‐frequency stimulation (HFS) and advanced‐HFS field‐shaping algorithm (dorsal horn HFS [DHHFS]) in refractory cases which initially benefited from conventional spinal cord stimulation (SCS) and lost the effect throughout time. In the context of a rescue‐therapy, patients underwent externalization of the implanted SCS‐leads and were tested with multiple combinations of new SCS paradigms. Pain intensity was analyzed using the numeric rating scale (NRS), and data were collected preoperatively and at multiple postoperative follow‐ups. Thirty‐seven patients underwent externalization of the leads. Mean preoperative NRS‐score was 8.1/10 points (SD ± 0.9) for the ON‐stimulation period. Patients received a combination of either tonic, burst and 1.2 kHz‐HFS, or burst and 1.2 kHz‐HFS, DHHFS, or 1.2 kHz‐HFS and DHHFS, or 1.2 kHz‐HFS alone. The mean postoperative NRS‐score after the testing‐phase was 3.8/10 points (SD ± 2.5), showing a 48.0% mean reduction (p< 0.001). In total, 29 patients reported a significant reduction above 50% in NRS‐scores and therefore were reimplanted with new generators that could deliver the new paradigms. Eight patients underwent full SCS‐system explantation. The patients who continued with the new paradigms (n= 29) reported mean NRS‐scores of 3.5/10 points (SD ± 1.7) 12 months postoperatively, still showing a significant reduction of 43.3% when compared to preoperative scores (p< 0.001). Rescue‐therapy with combination of multiple waveforms, including tonic, burst, 1.2 kHz‐HFS, and DHHFS, was associated with a significant pain relief in patients with failed conventional SCS. This approach is a safe and efficient and should be considered before explantation of the SCS‐system.

Whereas detailed kinetic models have already been implemented widely in computational fluid dynamics (CFD) simulations of gas-phase processes, CFD modeling of reactive gas–solid processes with detailed kinetics, especially in fluidized bed reactors, is a largely unexplored territory. To fill this gap, for the first time, an Euler–Euler based code, CATalytic CHemistrY FOAM (catchyFOAM) is developed to simulate gas–solid fluidized bed reactors while using microkinetic models for both the gas phase and the heterogeneous catalyst. First, the code is validated and tested by comparing with pseudohomogeneous ideal plug flow simulations, i.e., not explicitly accounting for separate gas and solid phases. Next, the capabilities of the model are illustrated by simulations of a gas–solid vortex reactor (GSVR) for the oxidative coupling of methane (OCM), with and without including pellet-scale mass transfer resistances and at both isothermal and adiabatic conditions. These simulations show that catchyFOAM is a powerful tool with numerous possibilities to design novel fluidized bed reactors and to optimize the conditions for processes involving catalytic surface chemistry, whether or not simultaneous with reactions in the gas phase (e.g., OCM, fluid catalytic cracking, catalytic partial oxidation).

The precipitation kinetics of calcium oxalate was investigated using a novel acidic reaction rate control and pH-monitoring method and a sequence of acid–base, coordination, nucleation, and growth differential equations. The results indicate that the complex formation is remarkably favorable and is diffusion rate-limited. The nucleation reaction is shown to initiate via the molecular assembly of near-zwitterionically polarized complexes. From experimental results, growth and formation of the crystal phase leads to an enthalpically less stabilized state.

Sleep disturbances and neuropsychiatric symptoms are some of the most common nonmotor symptoms in Parkinson’s disease (PD). The effect of subthalamic stimulation (STN-DBS) on these symptoms beyond a short-term follow-up is unclear. To examine 36-month effects of bilateral STN-DBS on quality of sleep, depression, anxiety, and quality of life (QoL) compared to standard-of-care medical therapy (MED) in PD. In this prospective, controlled, observational, propensity score matched, international multicenter study, we assessed sleep disturbances using the PDSleep Scale-1 (PDSS), QoL employing the PDQuestionnaire-8 (PDQ-8), motor disorder with the Scales for Outcomes in PD (SCOPA), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and dopaminergic medication requirements (LEDD). Within-group longitudinal outcome changes were tested using Wilcoxon signed-rank and between-group longitudinal differences of change scores with Mann-Whitney Utests. Spearman correlations analyzed the relationships of outcome parameter changes at follow-up. Propensity score matching applied on 159 patients (STN-DBS n = 75, MED n = 84) resulted in 40 patients in each treatment group. At 36-month follow-up, STN-DBS led to significantly better PDSS and PDQ-8 change scores, which were significantly correlated. We observed no significant effects for HADS and no significant correlations between change scores in PDSS, HADS, and LEDD. We report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes.

X-ray computed tomography (XCT) is the only non-destructive technique able to perform a complete quality control of additive manufactured products in a single inspection. Yet, high-quality scans are associated with large acquisition times and limited to high-end AM parts. In this paper we investigate a deep learning U-net segmentation algorithm to improve the segmentation of low-quality XCT scans. A high-quality XCT scan is acquired and aligned with low-quality XCT scans to create the ground truth data. The accuracy of the segmentation is quantified with the Jaccard index and physical properties of the parts.

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.

The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p < 0.01), indicating a moderate convergent validity. The SLTS-7 significantly increased with higher non-motor symptoms burden levels (p = 0.002). Life satisfaction in PD covers three specific aspects, namely physical, psycho-social, and treatment satisfaction. The new SLTS-7 is a valid, reliable, and easy-to-use tool to assess satisfaction with life and treatment in patients with PD screened for advanced therapies. Longitudinal studies analyzing the effect of advanced PD treatment on life and treatment satisfaction are warranted.

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication.” The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N?=?70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N?=?30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.