A two-year comparison of reverse total shoulder arthroplasty mini-humeral tray and augmented mini-glenoid baseplate implants vs. standard implants.

BACKGROUND: Patients who undergo reverse total shoulder arthroplasty (RTSA) are getting younger with greater function expectations. This retrospective, longitudinal study of prospectively collected data compared perceived shoulder function and strength, active shoulder mobility, radiographic evidence of scapular notching, and implant survival over the initial 2-years post-RTSA among patient groups who received either standard central fixation point liner and glenoid baseplate implants, or lower size profile mini-humeral tray with offset trunnion options and mini-augmented glenoid baseplate implants. MATERIALS AND METHODS: Patients who underwent primary RTSA using standard central fixation point liner and glenoid baseplate implants (Group 1, n = 180) were compared with patients who underwent primary RTSA using lower size profile mini-humeral tray with offset trunnion options and mini-augmented glenoid baseplate implants (Group 2, n = 53) for active shoulder mobility, American Shoulder and Elbow Surgeons (ASES) score, perceived ability to lift 10 lbs (4.5 kg) overhead, radiographic evidence of scapular notching, and implant survival. Data was collected pre-surgery, 6-weeks, 6-months, 1-year, and 2-years post-RTSA (p ≤ 0.05). RESULTS: More Group 2 patients had more complex B or C Walch glenoid morphology, while Group 1 had more A1 or A2 types (p ≤ 0.001). Group 2 had greater active shoulder flexion at 6-months, 1-year, and 2-years (p ≤ 0.018) and external rotation (in adduction) at 6-months and 2-years (p ≤ 0.004) compared to Group 1, with higher ASES scores at 6-months and 2-years (p ≤ 0.026) (with small-to-medium effect sizes), and with more patients meeting or exceeding the minimal clinically important difference (MCID) at 2-years (p = 0.045) and patient acceptable symptomatic state (PASS) levels at 6-months, 1-year and 2-years (p ≤ 0.045). Scapular notching was identified in six of 53 (11.3%) Group 2 patients and in 32 of 180 (17.7%) Group 1 patients. Group 1 patients had more grade 2 or greater scapular notching grades compared to Group 2 (p = 0.04). Implant survival was comparable with Group 1 = eight of 180 (4.4%) and Group 2 = 1 of 53 (1.9%) of patients requiring removal for 95.6% and 98.1% implant survival, respectively. CONCLUSION: Limited scapular notching and excellent implant survival was observed in both groups. Despite including individuals with more complex glenoid deficiency, patients receiving the lower size profile implants generally displayed better active shoulder mobility and perceived shoulder function compared to those who received standard implants. These patients also more frequently met or exceeded the MCID by 2-years post-RTSA and PASS levels by 6-months, 1-year, and 2-years post-RTSA, with lower scapular notching grades. LEVEL OF EVIDENCE: Retrospective comparative study.

Mini-augmented glenoid baseplate and mini-humeral tray reverse total shoulder arthroplasty implant comparisons: two-year clinical outcomes.

BACKGROUND: Augmented glenoid baseplate and offset humeral tray reverse total shoulder arthroplasty (RTSA) implants may decrease the mechanical impingement that creates scapular notching and improve shoulder function. This study evaluated the clinical efficacy of three different RTSA glenoid baseplate and offset humeral tray combinations for patient-reported shoulder function, pain and instability, radiographic imaging evidence of glenoid baseplate or humeral stem subsidence and migration, bony changes associated with implant loosening, and scapular notching over the initial 2 years post-RTSA. Primary outcomes included active shoulder mobility, perceived function, pain, instability, scapular notching, and implant survival. METHODS: Sixty-seven patients from 6 research sites received one of three different glenoid baseplate and humeral tray combinations. Group 1 (n = 21) received a mini-augmented glenoid baseplate with a standard humeral tray; Group 2 (n = 23) received a standard glenoid baseplate and a mini-humeral tray with 3 trunnion offset options; Group 3 (n = 23) received both a mini-augmented glenoid baseplate and a mini-humeral tray with 3 trunnion offset options. Subjects underwent radiologic evaluation, completed the ASES scale, the EQ-5D-5L quality of life scale, VAS shoulder pain and instability questions, and active shoulder mobility measurements pre-operatively, and 6-weeks, 6-months, 1-2 years post-RTSA. RESULTS: Improved active shoulder mobility, quality of life, perceived function, decreased shoulder pain and instability, excellent implant survival and minimal scapular notching were observed for all groups. Group 3 had better overall active shoulder mobility than the other groups and better perceived function than Group 1. CONCLUSION: The group that received the mini-augmented glenoid baseplate and mini-humeral tray combination had better overall active shoulder flexion, external rotation at 90° abduction, and internal rotation. This group also had better perceived shoulder function compared to the group that received a mini-augmented glenoid baseplate with a standard humeral tray.

Top-down threat bias in pain perception is predicted by intrinsic structural and functional connections of the brain.

Top-down processes such as expectations play a key role in pain perception. In specific contexts, inferred threat of impending pain can affect perceived pain more than the noxious intensity. This biasing effect of top-down threats can affect some individuals more strongly than others due to differences in fear of pain. The specific characteristics of intrinsic brain characteristics that mediate the effects of top-down threat bias are mainly unknown. In this study, we examined whether threat bias is associated with structural and functional brain connectivity. The variability in the top-down bias was mapped to the microstructure of white matter in diffusion weighted images (DWI) using MRTrix3. Mean functional connectivity of five canonical resting state networks was tested for association with bias scores and with the identified DWI metrics. We found that the fiber density of the splenium of the corpus callosum was significantly low in individuals with high top-down threat bias (FWE corrected with 5000 permutations, p < 0.05). The mean functional connectivity within the language/memory and between language/memory and default mode networks predicted the bias scores. Functional connectivity within language memory networks predicted the splenium fiber density, higher pain catastrophizing and lower mindful awareness. Probabilistic tractography showed that the identified region in the splenium connected several sensory regions and high-order parietal regions between the two hemispheres, indicating the splenium's role in sensory integration. These findings demonstrate that individuals who show more change in pain with changes in the threat of receiving a stronger noxious stimulus have lower structural connectivity in the pathway necessary for integrating top-down cue information with bottom-up sensory information. Conversely, systems involved in memory recall, semantic and self-referential processing are more strongly connected in people with top-down threat bias.

Threat Prediction from Schemas as a Source of Bias in Pain Perception.

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.

Divergence between functional magnetic resonance imaging and clinical indicators of language dominance in preoperative language mapping.

Accurate determination of hemispheric language dominance prior to epilepsy surgery is critically important to minimize cognitive morbidity. Functional MRI (fMRI) is a noninvasive method that is highly concordant with other clinical indicators of language laterality, and is now commonly used to confirm language dominance. However, there is also a high frequency of divergence between fMRI findings and other clinical indices that complicate determination of dominance and surgical decision-making in individual patients. Despite this, divergent cases are rarely published or discussed. This article provides three illustrative examples to demonstrate common scenarios where fMRI may produce conflicting or otherwise difficult-to-interpret findings. We will also discuss potential reasons for divergence and propose a flow-chart to aid clinical decision making in such situations.

Midterm Performance of a Guided-Motion Bicruciate-Stabilized Total Knee System: Results From the International Study of Over 2000 Consecutive Primary Total Knee Arthroplasties.

BACKGROUND: The JOURNEY II Bi-Cruciate Stabilizing Total Knee System (BLINDED) is a second-generation guided-motion knee implant that has been used in over 100,000 primary total knee arthroplasties (TKAs) worldwide. However, performance information is limited. METHODS: Data for 2059 primary TKAs were abstracted at 7 US and 3 European sites. Estimates of cumulative incidence of revision were compared with registry data for cemented posterior-stabilized implants. RESULTS: Average age was 64.3 years (range, 18-91); 58.5% were females; and 12.3% TKAs were in subjects younger than 55 years. Patellae were resurfaced in 95.9%. Median time since primary TKA was 4.2 years; longest was 6.1 years; and 78.9% were 3 years or more since primary TKA. Of 67 revisions (3.2%), 20 (30%) involved femoral or tibial component removal compared to 42% in the Australian Joint Registry (Australian Orthopedic Association National Joint Replacement Registry). All-component revisions accounted for 15 of 67, femoral component only for 2 of 67, tibial component only for 3 of 67, patellar component with/without tibial insert exchange for 17 of 67, and isolated tibial insert exchange for 30 of 67. In addition, there were 18 reoperations without component exchange. Component revision indications were infection (33%), mechanical loosening (21%), fracture of bone around the joint (16%), and instability (15%). Kaplan-Meier revision estimate was 3.1 and 3.6 per 100 TKAs at 3 and 5 years, respectively, compared to Australian Orthopedic Association National Joint Replacement Registry estimates of 3.1 and 4.1 per 100 TKAs. CONCLUSION: The revision rate for the second-generation implant was similar to cemented posterior-stabilized registry controls.

Language lateralization of a bilingual person with epilepsy using a combination of fMRI and neuropsychological assessment findings.

This report describes the findings of language functional magnetic resonance imaging (fMRI) in a left-handed Urdu and English speaker with right hemisphere-originating epilepsy and unclear language dominance. fMRI is a reliable method for determining hemispheric language dominance in presurgical planning. However, the effects of bilingualism on language activation depend on many factors including age of acquisition and proficiency in the tested language, and morphological properties of the language itself. This case demonstrates that completing fMRI in both spoken languages and interpreting the results within the context of a neuropsychological assessment are essential in arriving at accurate conclusions about language distribution in bilingual patients.

Cognitive dysfunction at epilepsy onset as a marker for seizure recurrence.

BACKGROUND: Cognitive dysfunction has been correlated with seizure control in chronic epilepsy and in newly diagnosed epilepsy, which potentially makes it a good marker for predicting disease course and seizure control. However, there is a lack of prospective studies examining the role of cognitive dysfunction in predicting seizure recurrence at the earliest stages of the disease, such as following the first unprovoked seizure (UFS) or new onset epilepsy (NOE). METHODS: Thirty three adult participants (FS=18, NOE=15) from the Halifax First Seizure Clinic (HFSC) completed a cognitive screening assessment at baseline (typically 3 months following diagnosis); seizure-recurrence was evaluated one year after the initial HFSC visit. RESULTS: Cognitive impairment, defined as at least one z-score in the impaired range (≤-1.5) relative to published test norms, was documented in 76% of the patients with seizure recurrence at follow-up and in 55% without seizure recurrence. Speed/executive functions and Memory were the most frequently affected domains, with impaired performance noted in 35% and 29% of the entire sample, respectively. Although the seizure recurrence vs. non-recurrence groups did not differ significantly on likelihood of impairment in any specific cognitive domains, a regression model of seizure recurrence that included years of education, baseline mood and anxiety scores, normal vs. abnormal baseline MRI, and impaired (vs. unimpaired) function in six cognitive domains was significant overall (Χ2 (10) = 24.04, p =.007*, R2N =.77). The regression model was no longer significant with the cognitive variables removed. CONCLUSIONS: Subtle cognitive dysfunction, especially in the domains of executive functions and memory are prevalent in individuals at the earliest stages of epilepsy. In addition to abnormal MRI and EEG findings at baseline, which are far less prevalent in FS and NOE, cognitive factors show promise in helping predict seizure recurrence in these populations.

The use of actigraphy to objectively define motion and function before and after shoulder arthroplasty.

Introduction: Actigraphy is a quantitative means of measuring activity data that has proven viable in post-surgery recovery analysis for arthroplasties in lower extremities, but scant literature has been published on the utilization actigraphy to evaluate shoulder motion and function before and after shoulder arthroplasty. The purpose of this prospective cohort study is to identify if actigraphy can serve as a valid means for objective evaluation of shoulder function and motion before and after shoulder arthroplasty. Secondarily, the data collected by the actigraphy can be analyzed with standard patient-reported outcomes to report correlations between the subjective and objective methods used in this study. Materials and methods: Sixty-four subjects wore an actigraphy device for one day at pre-op, six, twelve and twenty-four weeks. In addition, subjects completed three patient-reported outcome surveys at each time-point. Student t-tests were used to compare percent activity preoperatively with 24-weeks and to compare PROs preoperatively with 24-week results; categorical variables were compared with one-way ANOVAs. Results: All Patient reported outcome scores significantly improved following arthroplasty (p-value<0.001). The percent of physical activity was highly correlated with vector magnitude (p-value<0.001), but neither percent activity or the vector magnitude were correlated with any of the PROs: UCLA Pain p-value = 0.656, SANE p-value = 0.328, UCLA Function p-value = 0.532. Conclusions: Actigraphy results from this study mirror findings in previous literature utilizing the technology in similar manners and demonstrate its potential for motion and function analysis before and after total shoulder arthroplasties. Despite both being suitable methods independently for the evaluation of shoulder function, there was no significant correlation between standard actigraphy measurements and PROs at 24-weeks. Future research to determine clinical utility and an overall broader scope for actigraphy monitoring could benefit from improved technology, such as increased battery life for prolonged durations of data collection during observation periods.

Modeling CO2 reduction on Pt(111).

Density functional theory was used to model the electrochemical reduction of CO2 on Pt(111) with an explicit solvation layer and the presence of extra hydrogen atoms to represent a negatively charged electrode. We focused on the electronic energy barriers for the first four lowest energy proton-electron transfer steps for reducing CO2 on Pt(111) beginning with adsorbed *CO2 and continuing with *COOH, *CO + H2O, *COH, and ending with *C + H2O. We find that simple elementary steps in which a proton is transferred to an adsorbate (such as the protonation of *CO to *COH) have small barriers on the order of 0.1 eV. Elementary steps in which a proton is transferred and a C-O bond is simultaneously cleaved show barriers on the order of 0.5 eV. All barriers calculated for these steps show no sign of being insurmountable at room temperature. To explain why these barriers are so small, we analyze the charge density and the density of states plots to see that first, the electron transfer is decoupled from the proton transfer so that in the initial state, the surface and adsorbate are already charged up and can easily accept the proton from solution. Also, we see that in the cases where barriers are on the order of 0.1 eV, electron density in the initial state localizes on the oxygen end of the adsorbate, while electron density is more spread out on the surface for initial states of the C-O bond cleaving elementary steps.

Balance of nanostructure and bimetallic interactions in Pt model fuel cell catalysts: in situ XAS and DFT study.

We have studied the effect of nanostructuring in Pt monolayer model electrocatalysts on a Rh(111) single-crystal substrate on the adsorption strength of chemisorbed species. In situ high energy resolution fluorescence detection X-ray absorption spectroscopy at the Pt L(3) edge reveals characteristic changes of the shape and intensity of the "white-line" due to chemisorption of atomic hydrogen (H(ad)) at low potentials and oxygen-containing species (O/OH(ad)) at high potentials. On a uniform, two-dimensional Pt monolayer grown by Pt evaporation in ultrahigh vacuum, we observe a significant destabilization of both H(ad) and O/OH(ad) due to strain and ligand effects induced by the underlying Rh(111) substrate. When Pt is deposited via a wet-chemical route, by contrast, three-dimensional Pt islands are formed. In this case, strain and Rh ligand effects are balanced with higher local thickness of the Pt islands as well as higher defect density, shifting H and OH adsorption energies back toward pure Pt. Using density functional theory, we calculate O adsorption energies and corresponding local ORR activities for fcc 3-fold hollow sites with various local geometries that are present in the three-dimensional Pt islands.

One-step amino acid selective isotope labeling of proteins in prototrophic Escherichia coli strains.

Amino acid selective isotope labeling is a useful approach to simplification of nuclear magnetic resonance (NMR) spectra of large proteins. Cell-free protein synthesis offers essentially unlimited flexibility of labeling patterns but is labor-intensive and expensive. In vivo labeling is simple in principle but generally requires auxotrophic strains, inhibitors of amino acid synthesis, or complex media formulations. We describe a simple procedure for amino acid selective labeling of proteins expressed in prototrophic Escherichia coli strains. Excellent labeling selectivity was achieved for histidine, lysine, methionine, and alanine. Simplicity and robustness of this protocol make it a useful tool for protein NMR.

Refining the evolutionary time machine: An assessment of whole genome amplification using single historical Daphnia eggs.

Whole genome sequencing is instrumental for the study of genome variation in natural populations, delivering important knowledge on genomic modifications and potential targets of natural selection at the population level. Large dormant eggbanks of aquatic invertebrates such as the keystone herbivore Daphnia, a microcrustacean widespread in freshwater ecosystems, provide detailed sedimentary archives to study genomic processes over centuries. To overcome the problem of limited DNA amounts in single Daphnia dormant eggs, we developed an optimized workflow for whole genome amplification (WGA), yielding sufficient amounts of DNA for downstream whole genome sequencing of individual historical eggs, including polyploid lineages. We compare two WGA kits, applied to recently produced Daphnia magna dormant eggs from laboratory cultures, and to historical dormant eggs of Daphnia pulicaria collected from Arctic lake sediment between 10 and 300 years old. Resulting genome coverage breadth in most samples was ~70%, including those from >100-year-old isolates. Sequence read distribution was highly correlated among samples amplified with the same kit, but less correlated between kits. Despite this, a high percentage of genomic positions with single nucleotide polymorphisms in one or more samples (maximum of 74% between kits, and 97% within kits) were recovered at a depth required for genotyping. As a by-product of sequencing we obtained 100% coverage of the mitochondrial genomes even from the oldest isolates (~300 years). The mitochondrial DNA provides an additional source for evolutionary studies of these populations. We provide an optimized workflow for WGA followed by whole genome sequencing including steps to minimize exogenous DNA.

The comorbidity and cognition in multiple sclerosis (CCOMS) neuroimaging protocol: Study rationale, MRI acquisition, and minimal image processing pipelines.

The Comorbidity and Cognition in Multiple Sclerosis (CCOMS) study represents a coordinated effort by a team of clinicians, neuropsychologists, and neuroimaging experts to investigate the neural basis of cognitive changes and their association with comorbidities among persons with multiple sclerosis (MS). The objectives are to determine the relationships among psychiatric (e.g., depression or anxiety) and vascular (e.g., diabetes, hypertension, etc.) comorbidities, cognitive performance, and MRI measures of brain structure and function, including changes over time. Because neuroimaging forms the basis for several investigations of specific neural correlates that will be reported in future publications, the goal of the current manuscript is to briefly review the CCOMS study design and baseline characteristics for participants enrolled in the three study cohorts (MS, psychiatric control, and healthy control), and provide a detailed description of the MRI hardware, neuroimaging acquisition parameters, and image processing pipelines for the volumetric, microstructural, functional, and perfusion MRI data.

In situ X-ray probing reveals fingerprints of surface platinum oxide.

In situ X-ray absorption spectroscopy (XAS) at the Pt L(3) edge is a useful probe for Pt-O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard X-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF code and complementary extended X-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at high electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.

Higher Framingham Risk Scores are associated with greater loss of brain volume over time in multiple sclerosis.

BACKGROUND: Few studies have evaluated the association between comorbidities associated with increased vascular risk and brain volume changes in multiple sclerosis (MS). To date, findings have not been consistent with respect to which comorbidities are associated with lower brain volumes or whether comorbidities associated with increased vascular risk are associated with greater brain volume loss over time. OBJECTIVES: We aimed to evaluate the association between the Framingham Risk Score (FRS) which evaluates vascular risk and normalized whole brain volume in MS. METHODS: We included 98 participants with MS who underwent two brain MRIs two years apart, from which whole brain volumes were calculated. Each participant reported their comorbidities and medications taken. Blood pressure, height and weight were recorded and we calculated the FRS. We tested the association between the FRS at baseline and brain volume at the second time point using quantile regression adjusting for baseline normalized brain volume, age, gender and use of disease-modifying therapy. RESULTS: As the FRS increased, brain volume was lower, both at enrollment (ß= -0.24; 95%CI: -0.42, -0.04) and at follow-up (-0.27; 95%CI: -0.45, -0.08). After further adjustment for age, gender, and use of disease modifying therapy, higher FRS remained associated with lower brain volume at follow-up at the 90th percentile of brain volume (ß= -2.22; 95%CI: -3.40, -1.04) but not at the 10th or 50th percentiles. CONCLUSION: Higher FRS were associated with lower brain volumes in persons with MS at baseline, and with brain volume loss over time. This effect was most pronounced for persons with higher brain volumes at baseline, which suggests that prevention, detection and effective management of comorbidities associated with vascular risk in people with MS is particularly important early in the disease course.

Blumensaat Line as a Prediction of Native Anterior Cruciate Ligament Length.

BACKGROUND: Graft-tunnel mismatch (GTM) is a condition in which the anterior cruciate ligament (ACL) graft is either too long or too short. GTM is particularly problematic when bone-patellar tendon-bone grafts are used because of a potential compromise in fixation of the bone plug on the tibia. HYPOTHESIS: The Blumensaat line (BL), a radiographic landmark representing the roof of the intercondylar fossa, will accurately approximate the native ACL (nACL) length and may aid in the prevention of GTM. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A total of 130 patients (66 males, 64 females) underwent direct measurement of the nACL during knee arthroscopy. The lengths of the nACL and patellar ligament (PL) were measured intraoperatively, and BL length was measured on lateral knee radiographs. The nACL length was compared with PL and BL lengths to calculate the absolute difference (AD). Mean AD was calculated and used to determine mean percentage difference (MPD). Pearson correlation coefficients (CC) between BL, PL, and nACL length were calculated, along with inter- and intraobserver reliability coefficients for the measurement of BL. RESULTS: For male patients, the mean length of the nACL was 32.5 mm, BL was 30.4 mm, and PL was 49.2 mm. The AD between the BL and nACL was 2.4 ± 1.3 mm, MPD was 2.6% ± 1.9%, and CC was 0.88. The CC between the PL and nACL was 0.08. For female patients, the mean length of the nACL was 30.2 mm, BL was 27.5 mm, and PL was 44.4 mm. The AD between the BL and nACL was 2.7 ± 1.7 mm, MPD was 4.5% ± 2.4%, and CC was 0.93. The CC between the PL and nACL was 0.1. The inter- and intraobserver reliability coefficients for the measurement of BL were 0.86 and 0.83, respectively. CONCLUSION: A strong correlation was found between BL and nACL with a high inter- and intraobserver reliability. This correlation provides a simple and reliable method to closely approximate nACL length before reconstruction and may aid in the prevention of graft-tunnel mismatch.

Brain network topology predicts participant adherence to mental training programs.

Adherence determines the success and benefits of mental training (e.g., meditation) programs. It is unclear why some participants engage more actively in programs for mental training than others. Understanding neurobiological factors that predict adherence is necessary for understanding elements of learning and to inform better designs for new learning regimens. Clustering patterns in brain networks have been suggested to predict learning performance, but it is unclear whether these patterns contribute to motivational aspects of learning such as adherence. This study tests whether configurations of brain connections in resting-state fMRI scans can be used to predict adherence to two programs: meditation and creative writing. Results indicate that greater system segregation and clustering predict the number of practice sessions and class participation in both programs at a wide range of network thresholds (corrected p value < 0.05). At a local level, regions in subcortical circuitry such as striatum and accumbens predicted adherence in all subjects. Furthermore, there were also some important distinctions between groups: Adherence to meditation was predicted by connectivity within local network of the anterior insula and default mode network; and in the writing program, adherence was predicted by network neighborhood of frontal and temporal regions. Four machine learning methods were applied to test the robustness of the brain metric for classifying individual capacity for adherence and yielded reasonable accuracy. Overall, these findings underscore the fact that adherence and the ability to perform prescribed exercises is associated with organizational patterns of brain connectivity.

Spatial normalization of multiple sclerosis brain MRI data depends on analysis method and software package.

BACKGROUND: Spatially normalizing brain MRI data to a template is commonly performed to facilitate comparisons between individuals or groups. However, the presence of multiple sclerosis (MS) lesions and other MS-related brain pathologies may compromise the performance of automated spatial normalization procedures. We therefore aimed to systematically compare five commonly used spatial normalization methods for brain MRI - including linear (affine), and nonlinear MRIStudio (LDDMM), FSL (FNIRT), ANTs (SyN), and SPM (CAT12) algorithms - to evaluate their performance in the presence of MS-related pathologies. METHODS: 3 Tesla MRI images (T1-weighted and T2-FLAIR) were obtained for 20 participants with MS from an ongoing cohort study (used to assess a real dataset) and 1 healthy control participant (used to create a simulated lesion dataset). Both raw and lesion-filled versions of each participant's T1-weighted brain images were warped to the Montreal Neurological Institute (MNI) template using all five normalization approaches for the real dataset, and the same procedure was then repeated using the simulated lesion dataset (i.e., total of 400 spatial normalizations). As an additional quality-assurance check, the resulting deformations were also applied to the corresponding lesion masks to evaluate how each processing pipeline handled focal white matter lesions. For each normalization approach, inter-subject variability (across normalized T1-weighted images) was quantified using both mutual information (MI) and coefficient of variation (COV), and the corresponding normalized lesion volumes were evaluated using paired-sample t-tests. RESULTS: All four nonlinear warping methods outperformed conventional linear normalization, with SPM (CAT12) yielding the highest MI values, lowest COV values, and proportionately-scaled lesion volumes. Although lesion-filling improved spatial normalization accuracy for each of the methods tested, these effects were small compared to differences between normalization algorithms. CONCLUSIONS: SPM (CAT12) warping, ideally combined with lesion-filling, is recommended for use in future MS brain imaging studies requiring spatial normalization.

Crystallization and preliminary X-ray studies of the N-domain of the Wilson disease associated protein.

Wilson disease associated protein (ATP7B) is essential for copper transport in human cells. Mutations that affect ATP7B function result in Wilson's disease, a chronic copper toxicosis. Disease-causing mutations within the N-domain of ATP7B (WND) are known to disrupt ATP binding, but a high-resolution X-ray structure of the ATP-binding site has not been reported. The N-domain was modified to delete the disordered loop comprising residues His1115-Asp1138 (WNDDelta(1115-1138)). Unlike the wild-type N-domain, WNDDelta(1115-1138) formed good-quality crystals. Synchrotron diffraction data have been collected from WNDDelta(1115-1138) at the Canadian Light Source. A native WNDDelta(1115-1138) crystal diffracted to 1.7 A resolution and belonged to space group P4(2)2(1)2, with unit-cell parameters a = 39.2, b = 39.2, c = 168.9 A. MAD data were collected to 2.7 A resolution from a SeMet-derivative crystal with unit-cell parameters a = 38.4, b = 38.4, c = 166.7 A. The WNDDelta(1115-1138) structure is likely to be solved by phasing from multiwavelength anomalous diffraction (MAD) experiments.