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The blood–brain barrier (BBB) protects the brain but is also an important obstacle for the effective delivery of therapeutics in Alzheimer’s disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer’s disease relevant pathology need to be better characterized. This study is an open-labelled single-arm trial (NCT03739905) to investigate the feasibility of modulating BBB permeability in the default mode network and the impact on cognition, amyloid and tau pathology as well as BBB integrity. Nine participants [mean age 70.2 ± 7.2 years, mean Mini-Mental State Examination (MMSE) 21.9] underwent three biweekly procedures with follow-up visits up to 6 months. The BBB permeability of the bilateral hippocampi, anterior cingulate cortex and precuneus was transiently increased without grade 3 or higher adverse events. Participants did not experience worsening trajectory of cognitive decline (ADAS-cog11, MMSE). Whole brain vertex-based analysis of the 18F-florbetaben PET imaging demonstrated clusters of modest SUVR reduction in the right parahippocampal and inferior temporal lobe. However, CSF and blood biomarkers did not demonstrate any amelioration of Alzheimer’s disease pathology (P-tau181, amyloid-β42/40 ratio), nor did it show persistent BBB dysfunction (plasma PDGFRbeta and CSF-to-plasma albumin ratio). This study provides neuroimaging and fluid biomarker data to characterize the safety profile of MRgFUS BBB modulation in neurodegeneration as a potential strategy for enhanced therapeutic delivery.

INTRODUCTIONIt remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology.METHODSIn 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy.RESULTSIncreased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status.DISCUSSIONOur study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.

Compact military-grade jet engines offer many potential applications, including use in remotely piloted vehicles, but can be expensive to use for research and development purposes. A study aimed at increasing the power and thrust output of an inexpensive commercial compact engine found a material limitation issue in the turbomachinery. To gain the additional power, hotter turbine inlet temperatures were required. This temperature increase exceeded the limit of current uncooled metal turbine rotors but could be achieved through turbine rotors made from ceramics, such as silicon nitride, which would allow an increase in the thrust and power output by a factor of 1.44. Current ceramic turbine manufacturing methods are costly and time-consuming for rapid prototyping, but recent breakthroughs in ceramic additive manufacturing have allowed for cheaper methods and faster production which are beneficial for use in research and development when designs are being rapidly changed and tested. This research demonstrated, through finite element analysis, that a silicon nitride turbine rotor could meet the increased turbine inlet temperature conditions to provide the desired thrust and power increase. Furthermore, as a proof of concept, an additively manufactured drop-in replacement alumina turbine rotor was produced for the JetCat P400 small-scale engine in a manner that was cost-effective, timely, and potentially scalable for production. This compact engine was used to demonstrate that a cost-effective ceramic turbine could be manufactured. At the time of publication, the desired ceramic material, silicon nitride, was not available for additive manufacturing.

Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe.To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19.Prospective observational.A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis).A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences.Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group.Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05.Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue.These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition.2.Stage 3.

Background: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to “long-haul” COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation. Methods: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20–75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power. Interpretation: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

Tremor is a debilitating symptom that can lead to functional impairment. Pharmacotherapy is often successful, but up to 50% of patients are resistant to medications or cannot tolerate side effects. Thalamotomy to the ventral intermediate nucleus of the thalamus is a surgical intervention for refractory tremor. Thalamotomy surgeries include radiofrequency and incisionless procedures, such as Gamma Knife radiosurgery and magnetic resonance-guided focused ultrasound. Cognitive changes following thalamotomy have been inconsistently reported across studies. We performed a meta-analysis to summarize the impact of unilateral thalamotomy to the ventral intermediate nucleus of the thalamus across multiple cognitive domains. We searched MEDLINE, Embase Classic, Embase and EBM Reviews for relevant studies. Neuropsychological tests were categorized into seven cognitive domains: global cognition, verbal memory, non-verbal memory, executive function, phonemic fluency, semantic fluency and visuospatial processing. We calculated standardized mean differences as Hedges’ g and 95% confidence intervals of the change between pre- and postoperative cognitive scores. Pooling of standardized mean differences across studies was performed using random-effects models. Risk of bias across studies and quality of evidence for each cognitive domain were assessed with the National Institute of Health quality assessment tool and the GRADEpro Guideline Development Tool, respectively. Of the 1251 records reviewed, eight studies met inclusion criteria. We included 193 patients with essential tremor, Parkinson’s disease, or multiple sclerosis in the meta-analysis. There was a small significant decline in phonemic fluency [standardized mean difference = −0.29, 95% confidence interval: (−0.52, −0.05), P = 0.017] and a trend towards a decline in semantic fluency [standardized mean difference = −0.19, 95% confidence interval: (−0.40, 0.01), P = 0.056]. No postoperative changes were observed in the other cognitive domains (P values >0.14). In secondary analyses, we restricted the analyses to studies using magnetic resonance-guided focused ultrasound given its growing popularity and more precise targeting. In those analyses, there was no evidence of cognitive decline across any domain (P values >0.37). In terms of risk of bias, five studies were rated as ‘good’ and three studies were rated as ‘fair’. According to GRADEpro guidelines, the certainty of the effect for all cognitive domains was low. This study provides evidence that unilateral thalamotomy to the ventral intermediate nucleus of the thalamus is relatively safe from a cognitive standpoint, however, there may be a small decline in verbal fluency. Magnetic resonance-guided focused ultrasound might have a more favourable postoperative cognitive profile compared with other thalamotomy techniques.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion MRI methods for detecting such effects. In this work, the sensitivities of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at baseline and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in water diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a sensitive single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Rationale We evaluated K-means clustering to classify amyloid brain PETs as positive or negative. Patients and methods Sixty-six participants (31 men, 35 women; age range, 52-81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 dementia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 Parkinson-Lewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID software (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpretation based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data. Results Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal participants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with Parkinson-Lewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%. Conclusions K-means clustering may be a powerful algorithm for classifying amyloid brain PET.

Obesity is now recognised as a chronic disease which needs chronic treatment to treat or prevent obesity related complications. This article discusses the biology of weight regulation as a basis to understanding obesity as a disease, and to appreciate the complex and multifactorial nature of the obesity problem. Finally, the article highlights the dietary approaches as part of the multi-pronged approach to treating obesity and gives a brief update on intermittent fasting.

Obstructive sleep apnea (OSA) increases the risk of developing dementia. Home sleep apnea testing (HSAT) is a convenient and validated method to screen for OSA among cognitively well individuals; however, it is unknown if it is a clinically feasible and practical approach in clinic patients with cognitive impairment. We evaluated if HSAT was a feasible and practical approach to screen for OSA in clinic patients with cognitive impairment.Patients with cognitive impairment due to neurodegenerative and/or vascular etiologies completed OSA screening using HSAT. HSAT was considered a feasible technique if ≥ 80% of those who attempted HSAT obtained analyzable data (ie, ≥ 4 hours of flow, effort, and oxygen evaluation), and a practical technique if ≥ 50% of all patients approached for study inclusion obtained analyzable data.Of the 119 patients who were approached for participation, 83 were enrolled and offered HSAT; 5 did not complete HSAT screening, and the remaining 78 patients attempted HSAT; mean age (± standard deviation) of 72.86 (± 9.89) years and 46% were male. In those that attempted HSAT, 85.9% (67/78) obtained analyzable data and 56.3% (67/119) of eligible patients approached for study inclusion obtained analyzable data.HSAT is a feasible and practical technique in a clinic population with cognitive impairment. As OSA is a modifiable risk factor for patients with dementia, HSAT has the potential to lead to expedited treatment for OSA, which may potentially improve health-related outcomes such as cognition.

To characterize the impact of CPAP use on cognition in a clinical cohort with obstructive sleep apnea (OSA) and cognitive impairment due to neurodegenerative or vascular etiologies after controlling for baseline sleepiness.We retrospectively analyzed data from 171 patients with cognitive impairment and an OSA diagnosis confirmed with in-laboratory polysomnography or home sleep apnea testing (mean age 69.8 ± 10.6; 66% male) who were eligible to use CPAP. Baseline and follow-up Epworth Sleepiness Score (ESS), Montreal Cognitive Assessment (MoCA), and Mini-Mental Status Examination (MMSE) were obtained from clinical and research visits conducted before and after CPAP initiation. Good CPAP adherence was defined as CPAP use ≥4 h/night, for 7 days/week at follow-up. Associations between CPAP adherence and follow-up cognitive scores were analyzed using multivariable linear mixed-effects models.After adjusting for age, sex, body mass index, baseline ESS, duration of CPAP therapy, relevant comorbidities and the random effect of research study cohort, good CPAP adherence (compared to poor CPAP adherence or no use of CPAP) for a duration of 2-12 months was associated with a 2.3-point (1.2-3.3 95% CI) higher follow-up MoCA score (p 0.001) and a 1.2-point (0.3-2.3 95% CI) higher follow-up MMSE score (p = 0.01).In patients with OSA and cognitive impairment due to a neurodegenerative or vascular etiology, use of CPAP is associated with improved cognitive outcomes. The findings of this study may aid in motivating patients to use CPAP and support future randomized controlled trials in this area.

The long-term consequences of coronavirus disease 2019 (COVID-19) on brain physiology and function are not yet well understood. From the recently described NeuroCOVID-19 study, we examined cerebral blood flow (CBF) in 50 participants recruited to one of two groups: 1) adults who previously self-isolated at home due to COVID-19 (n = 39; 116.5 ± 62.2 days since positive diagnosis), or 2) controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (n = 11). Participants underwent arterial spin labeling magnetic resonance imaging at 3 T to yield measures of CBF. Voxel-wise analyses of CBF were performed to assess for between-group differences, after controlling for age and sex. Relative to controls, the COVID-19 group exhibited decreased CBF in the thalamus, orbitofrontal cortex, and regions of the basal ganglia. Within the COVID-19 group, CBF differences in occipital and parietal regions were observed between those with (n = 11) and without (n = 28) self-reported on-going fatigue. These results suggest long-term changes in brain physiology in adults across the post-COVID-19 timeframe. Moreover, CBF may aid in understanding the heterogeneous symptoms of the post-COVID-19 condition. Future longitudinal studies are needed to further characterize the consequences of COVID-19 on the brain.

BackgroundThere are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease.MethodWe measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore.ResultsThe Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sdz-score: FEV1−0.94±1.05, FVC −0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p10.03±0.99, FVC 0.04±0.97, FEV1/FVC −0.03±0.99) and external validation (z-scores: FEV10.31±0.99, FVC 0.24±0.97, FEV1/FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia.ConclusionWe present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population.

To evaluate the effects of Roux-en-Y gastric bypass (RYGB) versus best medical treatment in Asians with type 2 diabetes mellitus (T2DM) and class I obesity.In this 5-year single-centre, open-label randomized controlled trial, participants were randomized to RYGB or medical treatment including newer classes of diabetes medications (ClinicalTrials.gov:NCT02041234). The primary endpoint was diabetes remission defined as HbA1c ≤ 6% (≤42 mmol/mol) and discontinuation of glucose-lowering medication at 12 months post-intervention and beyond. Glycaemia and weight changes were assessed. Continuous glucose monitoring was performed.Of 28 subjects randomized, 26 were analyzed in the final cohort (14 medical, 12 RYGB; age:44 ± 10 years, 34.6% males, BMI:29.4 ± 1.6 kg/mOver 5 years, RYGB outperforms best medical treatment in glycemia and weight improvements for Asians with T2DM and class I obesity.

Background Between 2013 and 2015, the UK Biobank collected accelerometer traces from 103,712 volunteers aged between 40 and 69 years using wrist-worn triaxial accelerometers for 1 week. This data set has been used in the past to verify that individuals with chronic diseases exhibit reduced activity levels compared with healthy populations. However, the data set is likely to be noisy, as the devices were allocated to participants without a set of inclusion criteria, and the traces reflect free-living conditions. Objective This study aims to determine the extent to which accelerometer traces can be used to distinguish individuals with type 2 diabetes (T2D) from normoglycemic controls and to quantify their limitations. Methods Machine learning classifiers were trained using different feature sets to segregate individuals with T2D from normoglycemic individuals. Multiple criteria, based on a combination of self-assessment UK Biobank variables and primary care health records linked to UK Biobank participants, were used to identify 3103 individuals with T2D in this population. The remaining nondiabetic 19,852 participants were further scored on their physical activity impairment severity based on other conditions found in their primary care data, and those deemed likely physically impaired at the time were excluded. Physical activity features were first extracted from the raw accelerometer traces data set for each participant using an algorithm that extends the previously developed Biobank Accelerometry Analysis toolkit from Oxford University. These features were complemented by a selected collection of sociodemographic and lifestyle features available from UK Biobank. Results We tested 3 types of classifiers, with an area under the receiver operating characteristic curve (AUC) close to 0.86 (95% CI 0.85-0.87) for all 3 classifiers and F1 scores in the range of 0.80-0.82 for T2D-positive individuals and 0.73-0.74 for T2D-negative controls. Results obtained using nonphysically impaired controls were compared with highly physically impaired controls to test the hypothesis that nondiabetic conditions reduce classifier performance. Models built using a training set that included highly impaired controls with other conditions had worse performance (AUC 0.75-0.77; 95% CI 0.74-0.78; F1 scores in the range of 0.76-0.77 for T2D positives and 0.63-0.65 for controls). Conclusions Granular measures of free-living physical activity can be used to successfully train machine learning models that are able to discriminate between individuals with T2D and normoglycemic controls, although with limitations because of the intrinsic noise in the data sets. From a broader clinical perspective, these findings motivate further research into the use of physical activity traces as a means of screening individuals at risk of diabetes and for early detection, in conjunction with routinely used risk scores, provided that appropriate quality control is enforced on the data collection protocol.

Simple Summary: Black Lives Matter has highlighted the increased social discrepancies that exist not only in the context of social justice but also in public health. Oral cancer screening is not exempt from disparity, with Black Americans less likely to seek screening leading to higher incidence and worse outcomes of oropharyngeal cancers. We investigate interaction analysis and Blinder–Oaxaca decomposition as tools to guide policy to address this disparity. Using National Health and Nutrition Examination Survey (NHANES) data from 2011–2018 we find that being both in poverty and Black results in sub-additive interaction, which is further deconstructed into differences in higher education levels and poverty status. (1) Background: The Black Lives Matter movement has highlighted the discrepancies in public health in regard to race. This study aims to investigate tools that can be used to analyze and investigate this discrepancy, which can be applied to policymaking. (2) Methods: National Health and Nutrition Examination Survey (NHANES) data from 2011–2018 was combined (N = 22,617) to investigate discrepancies of oral cancer screening in Black Americans. We give examples of counterfactual techniques that can be used to guide policy. Inverse probability treatment weighting (IPTW) was used to remove all measured confounding in an interaction analysis to assess the combined effect of socioeconomic status and race. Blinder–Oaxaca decomposition was then used to investigate the intervenable factors associated with differences in race. (3) Results: Sub-additive interaction was found on additive and multiplicative scales when all measured confounding was removed via IPTW (relative excess risk due to interaction (RERI)(OR) = −0.55 (−0.67–−0.42)). Decomposition analysis found that 32% of the discrepancy could be explained by characteristics of higher education and poverty status. (4) Conclusions: Black Americans in poverty are less likely to seek oral cancer screening than the additive likelihood would suggest. Blinder–Oaxaca decomposition is a strong tool to use for guiding policy as it quantifies clear breakdowns of what intervenable factors there are that would improve the discrepancy the most. Refereed/Peer-reviewed

BACKGROUND Between 2013 and 2015, the UK Biobank collected accelerometer traces from 103,712 volunteers aged between 40 and 69 years using wrist-worn triaxial accelerometers for 1 week. This data set has been used in the past to verify that individuals with chronic diseases exhibit reduced activity levels compared with healthy populations. However, the data set is likely to be noisy, as the devices were allocated to participants without a set of inclusion criteria, and the traces reflect free-living conditions. OBJECTIVE This study aims to determine the extent to which accelerometer traces can be used to distinguish individuals with type 2 diabetes (T2D) from normoglycemic controls and to quantify their limitations. METHODS Machine learning classifiers were trained using different feature sets to segregate individuals with T2D from normoglycemic individuals. Multiple criteria, based on a combination of self-assessment UK Biobank variables and primary care health records linked to UK Biobank participants, were used to identify 3103 individuals with T2D in this population. The remaining nondiabetic 19,852 participants were further scored on their physical activity impairment severity based on other conditions found in their primary care data, and those deemed likely physically impaired at the time were excluded. Physical activity features were first extracted from the raw accelerometer traces data set for each participant using an algorithm that extends the previously developed Biobank Accelerometry Analysis toolkit from Oxford University. These features were complemented by a selected collection of sociodemographic and lifestyle features available from UK Biobank. RESULTS We tested 3 types of classifiers, with an area under the receiver operating characteristic curve (AUC) close to 0.86 (95% CI 0.85-0.87) for all 3 classifiers and F1 scores in the range of 0.80-0.82 for T2D-positive individuals and 0.73-0.74 for T2D-negative controls. Results obtained using nonphysically impaired controls were compared with highly physically impaired controls to test the hypothesis that nondiabetic conditions reduce classifier performance. Models built using a training set that included highly impaired controls with other conditions had worse performance (AUC 0.75-0.77; 95% CI 0.74-0.78; F1 scores in the range of 0.76-0.77 for T2D positives and 0.63-0.65 for controls). CONCLUSIONS Granular measures of free-living physical activity can be used to successfully train machine learning models that are able to discriminate between individuals with T2D and normoglycemic controls, although with limitations because of the intrinsic noise in the data sets. From a broader clinical perspective, these findings motivate further research into the use of physical activity traces as a means of screening individuals at risk of diabetes and for early detection, in conjunction with routinely used risk scores, provided that appropriate quality control is enforced on the data collection protocol.

Surgically accessing pathological lesions located within the central nervous system (CNS) frequently requires creating an incision in cosmetic regions of the head and neck. The biggest factors of surgical success typically tend to focus on the middle portion of the surgery, but a vast majority of surgical complications tend to happen towards the end of a case, during closure of the surgical site incisions. One of the most difficult complications for a surgeon to deal with is having to take a patient back to the operating room for wound breakdowns and, even worse, wound or CNS infections, which can negate all the positive outcomes from the surgery itself. In this paper, we discuss the underlying anatomy, pharmacological considerations, surgical techniques and nutritional needs necessary to help facilitate appropriate wound healing. A successful surgery begins with preoperative planning regarding the placement of the surgical incision, being cognizant of cosmetics, and the effects of possible adjuvant radiation therapy on healing incisions. We need to assess patient's medications and past medical history to make sure we can optimise conditions for proper wound reepithelialisation, such as minimizing the amount of steroids and certain antibiotics. Contrary to harmful medications, it is imperative to optimise nutritional intake with adequate supplementation and vitamin intake. The goals of this paper are to reinforce the mechanisms by which surgical wounds can fail, leading to postoperative complications, and to provide surgeons with the reminder and techniques that can help foster a more successful surgical outcome.

Cellulose triacetate (CTA) is a workhorse polymeric membrane material for industrial CO2/CH4 separation. This study investigates the doping of CTA with ionic liquids (ILs) to reduce the crystallinity of the CTA and enhance its affinity with CO2, thus increasing CO2 permeability and CO2/light gas selectivity. CTA films doped with 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF4]) and 1-ethyl-3-methylimidazolium dicyanamide ([emim][dca]) were prepared; and the effect of IL loading on properties of the CTA, such as crystallinity, density, degradation temperature, glass transition temperature, and gas transport properties, were determined. The IL doping reduces the glass transition temperature and degree of crystallinity of CTA, increasing gas diffusivity and permeability. The IL doping also increases CO2/CH4 solubility selectivity and CO2/N2 permeability selectivity, due to the affinity of these ILs with CO2, compared to light gases such as CH4 and N2. This study demonstrates a promising route in manipulating the morphology and gas transport properties of semi-crystalline polymers by doping with ILs.

There are currently 13 indications approved by the U.S. Food and Drug Administration for use of hyperbaric oxygen therapy. The European Consensus Conference on Hyperbaric Medicine has 28 indications approved for its use. However, neither includes the use of hyperbaric oxygen therapy for neurological conditions such as migraines with aura. Recent research has made the attempt to fully understand the use of hyperbaric therapy in treatment of neurological conditions, but results have so far been inconclusive. We report a 23-year-old female with an 11-year history of migraines with aura who has received inadequate pharmacological treatment for her migraines since she began having them. Migraines have led her to significant loss of function. The patient underwent treatment at 1.5 absolute atmospheres in a hyperbaric chamber Monday through Friday for 1 hour each day for a total of 40 sessions but reported missing a few sessions over the 8-week period. No more than 1 session during a given week was missed and the patient received no other treatments for her migraines throughout this time period. By her 24th treatment, the patient had only experienced a single migraine with aura but without debilitating pain. The patient stated she had never had a migraine with such little intensity prior to initiation of hyperbaric treatment and did not have to take any days off from work or school. Follow-up at the end of her 40-day treatment period revealed a highly-satisfied patient who had only experienced the single episode of a mild migraine during the entire course of treatment. Thus, we believe that further research needs to be done to realize the full potential of hyperbaric oxygen therapy in the treatment of neurological conditions as this case highlights the potential for using hyperbaric oxygen therapy as prophylaxis against attacks in patients with treatment resistant migraines with aura.

Background and Purpose— Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. Methods— One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute–subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. Results— Multiple linear regression analyses were completed. Although larger infarcts ( β =0.37, P β =0.39, P β =0.17, P =0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. Conclusions— In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Introduction Corticobasal syndrome (CBS) resulting from genetic Alzheimer's disease (AD) has been described only once. Whether familial CBS-AD is a distinct clinical entity with its own imaging signature remains unknown. Methods Four individuals with CBS from two families underwent detailed assessment. For two individuals, regional atrophy and hypoperfusion were compared to autopsy-confirmed typical late-onset AD and corticobasal degeneration, as well as genetically proven PSEN1 cases with an amnestic presentation. Results One family harbored a novel mutation in PSEN1 :p.Phe283Leu. MRI demonstrated severe parietal, perirolandic, and temporal atrophy, with relative sparing of frontal and ipsilateral hippocampal regions. Autopsy confirmed pure AD pathology. The other family harbored a known PSEN1 mutation:p.Gly378Val. Discussion This report confirms familial CBS-AD as a distinct clinical entity, with a parietal-perirolandic-temporal atrophy signature. It illustrates the clinical heterogeneity that can occur despite a shared genetic cause and underscores the need for biomarkers such as amyloid imaging during life.

Background: The objective of this study was to demonstrate the use of the authors’ technique to improve long-term maintenance of nipple projection by using AlloDerm (LifeCell Corp., Branchburg, N.J.) as a central core in nipple reconstruction. Methods: The nipple reconstruction technique involved the use of a modified star dermal flap pattern measuring 5 cm in length and 1.0 to 1.5 cm in width, depending on the amount of desired projection to match the opposite nipple. Then, a 1.5 4.5-cm piece of AlloDerm was placed into the core of the newly reconstructed nipple and sutured closed. After the incisions were closed, an ocular eye bubble protector was used to prevent compressive forces on the newly reconstructed nipple, and strict postoperative use of this protector was maintained for 6 weeks. Results: A total of 30 nipple reconstructions were performed [14 transverse rectus abdominis musculocutaneous (TRAM) flaps and 16 tissue-expanded breast mounds]. Caliper measurements of nipple projection were recorded at the time of surgery and at 3, 6, and 12 months postoperatively. Twelve-month average maintenance of nipple projection was 56 percent for the TRAM flap group and 47 percent for the tissue-expanded group. There were no infections or associated complications. Conclusions: The authors’ results demonstrate that the use of a modified star dermal flap pattern with the placement of an AlloDerm graft core is a safe, easily performed, and reproducible technique for improving the long-term maintenance of projection in reconstructed nipples. (Plast. Reconstr. Surg. 119: 1663, 2007.)

from 50 to 90 years old. This research was performed as part of a nationwide multicenter cohort called the CREDOS study. Twentynine subjects with SMI progressed to MCI or Alzheimer’s disease (AD) and the others (n1⁄4100) did not progress. We compared baseline demographics, blood chemistry and neuropsychological tests results between the two groups and assessed predictors and the hazard ratio (HR) for the progression. Results: Follow up durations were ranged from 0.5 to 4.7 years. Median time to event was 3.64 years. Age, apolipoprotein E4 (APOE4) incidence, baseline Mini-Mental State Examination (MMSE) score, memory scores, geriatric depression scale (GDS) scores, Boston naming test, Rey complex figure copy/ recall and stroop test scores were different between groups. Old age, abnormal recall scores in MMSE, existence of APOE4 allele and lower verbal memory delayed recall scores were the most potent predictors related with the progression and the sum of the 4 predictors explained better for the progression. Conclusions: Subjects with SMI who progressed to MCI/ AD showed different baseline characteristics and neuropsychological tests results. Old age, worse baseline memory scores and APOE4 allele existence were related with the progression of SMI and combining them might be better to predict the progression. How to better coordinate the relative contributions of each predictor deserves further investigation.

Natural orifice translumenal endoscopic surgery (NOTES) is a minimally invasive procedure which utilizes the body's natural orifices to gain access to the peritoneal cavity. The VTEST is a virtual reality NOTES cholecystectomy simulator being built at the CeMSIM at RPI. We have developed a 2 DOF decoupled haptic device, which can provide translational and rotational haptic feedback to the user handling the flexible endoscope. Preliminary results indicate the device is capable of providing realistic feedback to the user while operating the device.

BACKGROUND Functional contributions of cognitive impairment may vary by domain and severity. OBJECTIVE (1) To characterize frequency of cognitive impairment by domain after stroke by severity (mild: -1.5 ≤ z-score < -2; severe: Z ≤ -2) and time (sub-acute: < 90d; chronic: 90d-2yrs); and (2) To assess the association of cognitive impairment with function in chronic stroke. METHODS Cognitive function was characterized among 215 people with sub-acute or chronic stroke (66.8 years, 43.3% female). Z-scores by cognitive domain were determined from normative data. Function was defined as the number of IADLs minimally independent. RESULTS 76.3% of sub-acute and 67.3% of chronic stroke participants had cognitive impairment in ≥ 1 domain (p-for-difference = 0.09). Severe impairment was most common in psychomotor speed (sub-acute: 53.5%; chronic: 33.7%). Impairment in executive function was common (sub-acute: 39.5%; chronic: 30.7%) but was usually mild. Severe impairment in psychomotor speed, visuospatial function, and language and any impairment in executive function and memory was associated with IADL impairment (p < 0.03). CONCLUSIONS Mild cognitive impairment is common after stroke but is not associated with functional disability. Impairment in psychomotor speed, executive function, and visuospatial function is common and associated with functional impairment so should be a focus of screening and rehabilitation post-stroke.

Objectives: To compare the validity of the Montreal Cognitive Assessment (MoCA) with the criterion standard of standardized neuropsychological testing and to compare the convergent validity of the MoCA with that of existing screening tools and global measures of cognition. Design: Cross-sectional observational study. Setting: Tertiary care hospital-based cognitive neurology subspecialty clinic. Participants: A convenience sample of 107 individuals with mild Alzheimer's disease (AD, n = 75) or mild cognitive impairment (MCI, n = 32) from the Sunnybrook Dementia Study. Measurements: In addition to the MoCA, all participants completed the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale (DRS), and detailed neuropsychological testing. Results: Convergent validity was supported, with MoCA scores correlating well with the MMSE (correlation coefficient (r) = 0.66, P < .001) and the DRS (r = 0.77, P < .001) and the MoCA better associated with the DRS than did the MMSE. Criterion validity was supported, with MoCA subscores according to cognitive domain correlating well with analogous neuropsychological tests and, in the case of memory (area under the receiver operating characteristic curve (AUC) = 0.86), executive (AUC = 0.79), and visuospatial function (AUC = 0.79), being reasonably sensitive to impairment in those domains. Conclusion: The MoCA is a valid assessment of cognition that shows good agreement with existing screening tools and global measures (convergent validity) and was superior to the MMSE in this regard. The MoCA domain-specific subscores align with performance on more-detailed neuropsychological tests, suggesting not only good criterion validity for the MoCA, but also that it may be useful in guiding further neuropsychological testing.

With increasing knowledge of clinical in vivo biomarkers and the pathological intricacies of Alzheimer's disease (AD), nosology is evolving. Harmonized consensus criteria that emphasize prototypic illness continue to develop to achieve diagnostic clarity for treatment decisions and clinical trials. However, it is clear that AD is clinically heterogeneous in presentation and progression, demonstrating variable topographic distributions of atrophy and hypometabolism/hypoperfusion. AD furthermore often keeps company with other conditions that may further nuance clinical expression, such as synucleinopathy exacerbating executive and visuospatial dysfunction and vascular pathologies (particularly small vessel disease that is increasingly ubiquitous with human aging) accentuating frontal-dysexecutive symptomatology. That some of these atypical clinical patterns recur may imply the existence of distinct AD variants. For example, focal temporal lobe dysfunction is associated with a pure amnestic syndrome, very slow decline, with atrophy and neurofibrillary tangles limited largely to the medial temporal region including the entorhinal cortex. Left parietal atrophy and/or hypometabolism/hypoperfusion are associated with language symptoms, younger age of onset, and faster rate of decline - a potential 'language variant' of AD. Conversely, the same pattern but predominantly affecting the right parietal lobe is associated with a similar syndrome but with visuospatial symptoms replacing impaired language function. Finally, the extremely rare frontal variant is associated with executive dysfunction out of keeping with degree of memory decline and may have prominent behavioural symptoms. Genotypic differences may underlie some of these subtypes; for example, absence of apolipoprotein E e4 is often associated with atypicality in younger onset AD. Understanding the mechanisms behind this variability merits further investigation, informed by recent advances in imaging techniques, biomarker assays, and quantitative pathological methods, in conjunction with standardized clinical, functional, neuropsychological and neurobehavioral evaluations. Such an understanding is needed to facilitate 'personalized AD medicine', and eventually allow for clinical trials targeting specific AD subtypes. Although the focus legitimately remains on prototypic illness, continuing efforts to develop disease-modifying therapies should not exclude the rarer AD subtypes and common comorbid presentations, as is currently often the case. Only by treating them as well can we address the full burden of this devastating dementia syndrome.

Pseudo-nitzschia is a toxin producing species of diatom that blooms commonly along the west coast of the United States. Previously the Outer Banks of North Carolina was not documented as an area able to support routine bloom formation of Pseudo-nitzschia (Hasle 2002). However, monitoring by the NOAA Phytoplankton Monitoring Network (PMN) in this region identified four blooms having occurred since 2005. Three of these blooms occurred in consecutive years (Shuler et al. 2012).

This chapter talks about a 45-year-old right-handed woman who was admitted to a Neurology clinic with several years of cognitive difficulty. She has a long-standing history of depression, which has been fairly well-controlled on sertraline 100mg daily. There are no other chronic medical problems or regular medications. CT of the head demonstrated very mild generalized atrophy with more pronounced atrophy of the head of the caudate nucleus. The initial diagnostic impression was Huntington disease, despite the lack of a clear family history. Genetic testing was performed, which demonstrated an expansion of the CAG repeat region in the huntingtin gene on chromosome 4. Additionally, a more thorough family history revealed that her father and several of his relatives had involuntary movements. Huntington disease (HD) is a neurodegenerative disease characterized clinically by the triad of a movement disorder, dementia, and behavioral disturbances.