A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson's disease and dementia with Lewy bodies.

INTRODUCTION: Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the 'total outlier count'). We aimed to quantify patterns of neurodegenerative dissimilarity in participants with PD and DLB and evaluate the potential clinical relevance of total outlier count by testing its association with key clinical measures in PD and DLB. MATERIALS AND METHODS: We included 108 participants with PD and 61 with DLB. PD participants were subclassified into high and low visual performers as this has previously been shown to stratify those at increased dementia risk. We generated z-scores from T1w-MRI scans for each participant relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n = 58,836). Outliers (z < -1.96) were aggregated across 169 brain regions per participant. To measure dissimilarity, individuals' Hamming distance scores were calculated. We also examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition. RESULTS: There was significantly greater inter-individual dissimilarity in brain-outlier patterns in PD poor compared to high visual performers (W = 522.5; p < 0.01) and in DLB compared to PD (W = 5649; p < 0.01). PD poor visual performers had significantly greater total outlier counts compared to high (ß = -4.73 (SE = 1.30); t = -3.64; p < 0.01) whereas a conventional group-level GLM failed to identify differences. Higher total outlier counts were associated with poorer MoCA (ß = -0.55 (SE = 0.27), t = -2.04, p = 0.05) and composite cognitive scores (ß = -2.01 (SE = 0.79); t = -2.54; p = 0.02) in DLB, and visuoperception (ß = -0.67 (SE = 0.19); t = -3.59; p < 0.01), in PD. CONCLUSIONS: Neuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB, where patterns of atrophy are variable.

Thalamic white matter macrostructure and subnuclei volumes in Parkinson's disease depression.

Depression is a common non-motor feature of Parkinson's disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14-20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

Measurement of the tilt of a moving domain wall shows precession-free dynamics in compensated ferrimagnets.

One fundamental obstacle to efficient ferromagnetic spintronics is magnetic precession, which intrinsically limits the dynamics of magnetic textures. We experimentally demonstrate that this precession vanishes when the net angular momentum is compensated in domain walls driven by spin-orbit torque in a ferrimagnetic GdFeCo/Pt track. We use transverse in-plane fields to provide a robust and parameter-free measurement of the domain wall internal magnetisation angle, demonstrating that, at the angular compensation, the DW tilt is zero, and thus the magnetic precession that caused it is suppressed. Our results highlight the mechanism of faster and more efficient dynamics in materials with multiple spin lattices and vanishing net angular momentum, promising for high-speed, low-power spintronic applications.

Physicochemical characterization of inorganic deposits associated with granulomas in cutaneous sarcoidosis.

BACKGROUND: Sarcoidosis, characterized by epithelioid granulomas, is considered to be caused by a complex interplay between genetics and environmental agents. It has been hypothesized that exogenous inorganic particles as crystalline silica could be a causal or adjuvant agent in sarcoidosis onset. OBJECTIVES: To investigate the location, frequency and physicochemical characteristics of foreign materials and mineral tissue deposits in the granulomatous area of cutaneous sarcoidosis. METHODS: Skin biopsies (n = 14) from patients diagnosed with cutaneous sarcoidosis (mean age 43 years; 11 patients with extracutaneous involvement) were investigated using polarized light examination (PLE), µFourier Transform Infra-Red (µFT-IR) spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (FE-SEM/EDX). RESULTS: Combined PLE, µFT-IR, FE-SEM/EDX analysis allowed to characterize mineral deposits in 7/14 biopsies (50%). It identified crystalline silica (SiO2 ) inside granulomas in three biopsies and calcite (CaCO3 ) at their periphery in 4. CONCLUSION: This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO2 particles contribute to the granuloma formation, whereas CaCO3 deposits are related to the granuloma biology. However, the significance of the association between SiO2 deposits and sarcoidosis is still disputed.

Current-induced skyrmion generation and dynamics in symmetric bilayers.

Magnetic skyrmions are quasiparticle-like textures which are topologically different from other states. Their discovery in systems with broken inversion symmetry sparked the search for materials containing such magnetic phase at room temperature. Their topological properties combined with the chirality-related spin-orbit torques make them interesting objects to control the magnetization at nanoscale. Here we show that a pair of coupled skyrmions of opposite chiralities can be stabilized in a symmetric magnetic bilayer system by combining Dzyaloshinskii-Moriya interaction (DMI) and dipolar coupling effects. This opens a path for skyrmion stabilization with lower DMI. We demonstrate in a device with asymmetric electrodes that such skyrmions can be independently written and shifted by electric current at large velocities. The skyrmionic nature of the observed quasiparticles is confirmed by the gyrotropic force. These results set the ground for emerging spintronic technologies where issues concerning skyrmion stability, nucleation and propagation are paramount.

Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in a murine model.

OBJECTIVE: To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model. MATERIALS AND METHODS: Immunologically naïve nude mice (athymic nude-Foxn1nu ) were injected subcutaneously bilaterally in both flanks (n = 36) with 2.5 × 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumours developed into 1-cm palpable nodules. AuNRs encapsulated in human serum albumin protein (HSA) nanoparticles were synthesised with or without a TKI and injected directly into the tumour nodule. Irradiation was administered with an 808-nm light-emitting diode laser for 6 min. Mice were humanely killed 14 days after irradiation; tumours were excised, formalin fixed, paraffin embedded, and evaluated for size and the percentage of necrosis by a genitourinary pathologist. The untreated contralateral flank tumours were used as controls. RESULTS: In mice that did not receive irradiation, TKI alone yielded 4.2% tumour necrosis on the injected side and administration of HSA-AuNR-TKI alone yielded 11.1% necrosis. In the laser-ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA-AuNR there was 63.4% necrosis. The combination of laser irradiation and HSA-AuNR-TKI had cell kill rate of 100%. CONCLUSIONS: In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticles produced moderate necrosis. Irradiation with and without gold particles alone also improves tumour necrosis. However, when irradiation is paired with gold particles and drug-loaded nanoparticles, the combined therapy showed the most significant and synergistic complete tumour necrosis of 100% (P < 0.05). This study illustrates the potential of combination nanotechnology as a new approach in the treatment of urological cancers.

Technology Based Treatment for UreteroPelvic Junction Obstruction.

Surgical management of ureteropelvic junction obstruction (UPJO) has historically been performed with open pyeloplasty. With the advent of endourology, laparoscopy, and robotics, minimally-invasive techniques have been described and accepted as alternatives to open surgery. Each of these approaches has its own advantages and disadvantages, equipment needs, degree of invasiveness, and experience of the treating urologist. Advocates and critics have their own say as to their preferred technique. In this article, we review the chronological evolution of these techniques and discuss their current role in the management of UPJO.

Racial Disparities in Histology and Short-Term Renal Functional Outcomes Following Robotic Nephron-Sparing Surgery.

PURPOSE: To identify variations in renal function and histology between Caucasian Americans (CA) and African Americans (AA) undergoing robotic nephron-sparing surgery (NSS). METHODS: A retrospective chart review was performed on patients who underwent NSS. Multivariate analysis identified factors affecting postoperative estimated glomerular filtration rate (eGFR). Histology was re-reviewed by pathology to confirm papillary type. RESULTS: A total of 331 patients underwent NSS: CA (n = 212), AA (n = 105), Hispanic (n = 10), and other (n = 4). AA average age (60.1 years) was lower than CA (62.3 years) (P < .001), with a higher proportion of AA women (46%) than CA (37%) (P = .021). AA had a higher incidence of diabetes (58.2%) and hypertension (93.9%). Preoperative average eGFR was similar: 70.35 mL/min for AA versus 69.06 mL/min for CA. Average postoperative eGFR was 50.59 mL/min for AA and 57.85 mL/min for CA. Postoperative creatinine increased more in AA (0.44 mg/dL) versus CA (0.33 mg/dL) (P < .001) even when stratified by pathological stage. Clear cell renal cell carcinoma (RCC) was the most common histology with AA (45%) and CA (60%). A greater than 2-fold higher incidence of papillary RCC was observed in AA (31%) versus CA (13%). AA exhibited a greater proportion of high-grade or type 2 papillary RCC (40% and 30%) versus CA (25% and 13%). CONCLUSIONS: AA patients were treated at a younger age, with a larger proportion of women. Postoperatively, AA experienced a greater increase in serum creatinine. Final histology demonstrated greater papillary RCC incidence in AA and increased likelihood for type 2 papillary RCC, a more aggressive histology.

Safety and early effectiveness of robot-assisted partial nephrectomy for large angiomyolipomas.

OBJECTIVE: To evaluate a multicentre series of robot-assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs). PATIENTS AND METHODS: Between 2005 and 2016, 40 patients with large or symptomatic AMLs underwent RAPN at five academic centres in the USA. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analysed. Surgical outcomes were compared between patients who underwent selective arterial embolisation (SAE) before RAPN and patients who did not undergo pre-RAPN SAE. RESULTS: The median (interquartile range [IQR]) tumour diameter was 7.2 (5-8.5) cm, and the median (IQR) nephrometry score was 9 (7-10). Six patients (15%) had a history of tuberous sclerosis and 11 (28%) had previously undergone SAE. The median (IQR) operative time and warm ischaemia time was 207 (180-231) and 22.5 (16-28) min, respectively. A non-clamping technique was used in eight (20%) patients. The median (IQR) estimated blood loss was 200 (100-245) mL, and four patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and seven postoperative complications occurred in six patients (15%). During a median (IQR) follow-up of 8 (1-15) months, none of the patients developed AML-related symptoms. The median estimated glomerular filtration rate preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before RAPN and those who did not. CONCLUSIONS: Robot-assisted partial nephrectomy appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with a favourable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy.

Accelerometer Measurement of Head Movement During Laparoscopic Surgery as a Tool to Evaluate Skill Development of Surgeons.

OBJECTIVE: To detect and measure surgeons' head movement during laparoscopic simulator performance to determine whether expert surgeons have economy of motion in their head movement, including change of direction, compared with intermediate and novice surgeons. We investigated head movement as an objective tool for assessment of laparoscopic surgical skill and its potential use for assessing novice surgeons' progress on the learning curve. DESIGN: After obtaining institutional review board approval, medical students, urology residents, and attending staff surgeons from an academic institution were recruited. Participants were grouped by level of experience and performed tasks on the Electronic Data Generation for Evaluation laparoscopic simulator. Surgeons wore a commercially available wireless electroencephalogram monitor as a flexible, adjustable, and lightweight headband with 7 sensors-2 forehead sensors, 2 ear sensors, and 3 reference sensors. The headband incorporates a 3-axis accelerometer enabling head movement quantification. A variance analysis was used to compare the average head movement acceleration data between each group. SETTING: Tulane University Medical Center, New Orleans, LA, an academic medical center and the principal teaching hospital for Tulane University School of Medicine. PARTICIPANTS: A total of following 19 participants were recruited for the study and stratified by surgical experience into novice (n = 6), intermediate (n = 9), and expert (n = 4) laparoscopy groups: 6 medical students, 9 urology residents (postgraduate years 1 to5), and 4 attending urologists, respectively. RESULTS: Analysis of the average acceleration rate of head movement showed statistically significant differences among groups on both the vertical axis (p = 0.006) and horizontal axis (p = 0.018) in the laparoscopic suturing task. This demonstrated the ability to distinguish between experts and novice laparoscopic surgeons. The average acceleration among groups did not demonstrate statistical significance on the vertical axis (p = 0.078) and horizontal axis (p = 0.077) in the peg transfer task. This may be in response to the ease of the task. The analysis of the forward-backward axis or depth perception also showed no significant differences between groups. CONCLUSION: Accelerometer-based motion analysis of head movement appears to be a useful tool to evaluate laparoscopic skill development of surgeons in terms of their economy of motion, and it could potentially be used for ergonomic assessment of training in the future, and progression on the learning curve.

NF-κB pathway controls mitochondrial dynamics.

The Optic atrophy 1 protein (OPA1) is a key element in the dynamics and morphology of mitochondria. We demonstrated that the absence of IκB kinase-α, which is a key element of the nonclassical NF-κB pathway, has an impact on the mitochondrial network morphology and OPA1 expression. In contrast, the absence of NF-κB essential modulator (NEMO) or IκB kinase-ß, both of which are essential for the canonical NF-κB pathway, has no impact on mitochondrial dynamics. Whereas Parkin has been reported to positively regulate the expression of OPA1 through NEMO, herein we found that PARK2 overexpression did not modify the expression of OPA1. PARK2 expression reduced the levels of Bax, and it prevented stress-induced cell death only in Bak-deficient mouse embryonic fibroblast cells. Collectively, our results point out a role of the nonclassical NF-κB pathway in the regulation of mitochondrial dynamics and OPA1 expression.

The use of personal flotation devices in the Northeast lobster fishing industry: An examination of the decision-making process.

BACKGROUND: This study explored perspectives of Northeast commercial lobstermen regarding the use of personal flotation devices (PFDs). Researchers sought to identify factors contributing to low PFD use, and motivators that could lead to increased use of PFDs. METHODS: This qualitative research (n = 72) included 25 commercial fishermen who participated in in-depth, semi-structured interviews, and 47 attendees of Lobstermen's meetings who engaged in focus groups. RESULTS: The results showed substantial barriers to PFD use. Fishermen described themselves as being proactive about safety whenever possible, but described a longstanding tradition of not wearing PFDs. Key factors integrally linked with the lack of PFD use were workability, identity/social stigma, and risk diffusion. CONCLUSION: Future safety interventions will need to address significant barriers to PFD use that include issues of comfort and ease of use, as well as social acceptability of PFDs and reorientation of risk perceptions related to falls overboard.

Techniques to resect the distal ureter in robotic/laparoscopic nephroureterectomy.

Treatment of clinically-organ confined high grade urothelial carcinoma of the upper tract has historically comprised open nephroureterectomy, with the distal ureter and bladder cuff mobilized through a separate open pelvic incision. To decrease morbidity, urologists have increasingly adopted laparoscopy and robotics in performing nephroureterectomy. In many published series of laparoscopic nephroureterectomy, the distal ureter and bladder cuff are detached from the bladder endoscopically by a variation of the "pluck" technique, with the resulting bladder defect left to heal by prolonged indwelling urethral catheter drainage. While the distal ureter and bladder cuff can be excised laparoscopically, it does require advanced laparoscopic skills. With the wrist articulation and stereoscopic vision in robotic surgery, robotic nephroureterectomy (RNU) and bladder cuff excision can be performed in antegrade fashion to mimic the open technique together with the ability to intracorporeally close the bladder defect in a watertight, mucosa to mucosa fashion after excising the bladder cuff. In this review, we discuss the published minimally invasive techniques in resecting the distal ureter and bladder cuff during laparoscopic and RNU.

Role of adhesion between asperities in the formation of elastic solid/solid contacts.

We investigated the formation of a contact between a smooth sphere of elastomer and a micro-patterned elastomer substrate. We focussed our attention on the transition between a contact only established at the top of the pillars, and a mixed contact with a central zone of full contact surrounded by a top contact corona, which was observed when the normal load was increased. The full contact zone always nucleated with a finite radius, and the transition appears to be a first-order transition, with a hysteresis due to the creation of an adhesive zone between the pillars. We propose to include the effect of the new inter-pillar adhesion to produce a realistic treatment of the mechanics of these complex contacts. This new approach quantitatively accounts for the evolution of the observed jump in the radius of the full contact with the geometrical parameters of the pattern.

Diagnoses associated with the greatest years of potential life lost for in-hospital deaths in the United States, 1988-2010.

OBJECTIVE: Premature mortality is a public health concern that can be quantified as years of potential life lost (YPLL). Studying premature mortality from in-hospital mortality can help guide hospital initiatives and resource allocation. This paper identified the diagnosis categories associated with in-hospital deaths that account for the highest YPLL and their trends over time. STUDY DESIGN: Retrospective review of the Nationwide Inpatient Sample (NIS), 1988-2010. METHODS: Using the NIS, YPLL on patients hospitalized in the United States from 1988 to 2010 was calculated. Hospitalizations were categorized by related principal diagnoses using the Healthcare Cost and Utilization Project (HCUP) single-level Clinical Classification Software (CCS) definitions. RESULTS: Between 1988 and 2010, total in-hospital estimated mortality of 20,154,186 people accounted for 198,417,257 YPLL (9.84 YPLL per in-hospital mortality; 8,626,837 estimated annual mean YPLL). The ten highest YPLL diagnosis categories accounted for 51% of the overall YPLL. The liveborn disease category (i.e., in-hospital live births) was the most common principal diagnosis and accounted for the highest YPLL at 1,070,053. The septicemia category accounted for the second highest YPLL at 548,922. The highest in-hospital mortality rate (20.8%) was associated with adult respiratory failure/insufficiency/arrest. The highest estimated in-hospital annual mean deaths occurred in patients with pneumonia at 69,134. For all in-hospital mortality, the inflation adjusted total in-hospital charges per YPLL was highest for acute myocardial infarction at $9292 per YPLL. CONCLUSIONS: Using YPLL, a framework has been provided to compare the impact of premature in-hospital mortality from dissimilar diseases. The methodology and results may be used to help guide further investigation of hospital quality initiatives and resource allocation.

Concept identification for a power take-off shielding campaign.

ABSTRACT Machinery entanglements, specifically power take-off (PTO) entanglements, are a leading cause of injuries and fatalities on farms. In order to address this life-threatening issue, a social marketing campaign is being developed to reduce barriers and emphasize motivators to shielding. This article discusses the process of designing, testing, and selecting concepts to be used in the campaign. Small-group discussions (triads) were held to test 13 message concepts. Participants were asked to provide feedback and select the two messages that they believed to be most powerful. Upon completion, three message concepts were selected to be finalized.

Memristive and neuromorphic behavior in a Li(x)CoO2 nanobattery.

The phenomenon of resistive switching (RS), which was initially linked to non-volatile resistive memory applications, has recently also been associated with the concept of memristors, whose adjustable multilevel resistance characteristics open up unforeseen perspectives in cognitive computing. Herein, we demonstrate that the resistance states of Li(x)CoO2 thin film-based metal-insulator-metal (MIM) solid-state cells can be tuned by sequential programming voltage pulses, and that these resistance states are dramatically dependent on the pulses input rate, hence emulating biological synapse plasticity. In addition, we identify the underlying electrochemical processes of RS in our MIM cells, which also reveal a nanobattery-like behavior, leading to the generation of electrical signals that bring an unprecedented new dimension to the connection between memristors and neuromorphic systems. Therefore, these LixCoO2-based MIM devices allow for a combination of possibilities, offering new perspectives of usage in nanoelectronics and bio-inspired neuromorphic circuits.

A qualitative analysis of power take-off driveline shields: barriers and motivators to shield use for New York State farmers.

Machinery entanglements are one of the top three causes of death in farming. Education on the risks of unshielded power take-off (PTO) equipment does not appear to significantly alter farmers' willingness to replace missing or broken shielding. Different assessments conducted in various regions of the U.S. indicate that as many as one-third to one-half of PTOs are inadequately shielded. Qualitative research was conducted with New York farmers to identify the factors that influence the decision to replace damaged or missing PTO driveline shields. Interview topics included: knowledge of entanglement risks, decisions regarding safety in general, decisions relating to PTO driveline shielding specifically, and the barriers and motivators to replacing missing or broken PTO driveline shields. Interviews with 38 farmers revealed the following themes: (1) farmers are fully aware of PTO entanglement risk, (2) insufficient time and money are primary barriers to purchasing or replacing damaged or missing PTO driveline shields, (3) PTO driveline shield designs are problematic and have led to negative experiences with shielding, and (4) risk acceptance and alternate work strategies are preferred alternatives to replacing shields. Our findings indicate that more innovative approaches will be required to make PTO driveline shield use a viable and attractive choice for farmers. New shield designs that address the practical barriers farmers face, as well as the provision of logistical and financial assistance for shield replacement, may alter the decision environment sufficiently to make replacing PTO driveline shielding a more attractive option for farmers.