Pd Case Research Articles

The treatment gap for deep brain stimulation in Parkinson's disease: a comparative analysis of cost and utilisation in high-income countries.

ObjectiveParkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, globally affecting approximately 120 per 100,000 people by age 70. Deep brain stimulation (DBS) is a US Federal Drug Administration (FDA)-approved and highly effective treatment for late-stage PD. However, country-specific reimbursement regulations and health policies may affect access to PD-DBS. We aimed to evaluate the uptake rate and 'treatment gap' for DBS across high-income countries.MethodsWe reviewed previous literature to investigate the cost and utilisation of PD-DBS in high-income countries across Asia, Europe, Oceania, and North America (Australia, Canada, France, Germany, Hong Kong, Japan, Korea, the Netherlands, New Zealand, Norway, Spain, Switzerland, UK, and USA). Using previous estimates of DBS candidate eligibility rates, we calculated theoretical DBS uptake rates and treatment gaps nationally.ResultsPD-DBS utilisation was highest in Australia and the USA and lowest in Korea and New Zealand. The total cost of PD-DBS in the first 12months was highest in the USA and France and lowest in the UK and Germany. The utilisation rate (i.e. uptake rate) of PD-DBS (% DBS surgeries per PD case) was highest in Australia and the USA, and lowest in New Zealand and the UK, where the treatment gap reflected these trends.ConclusionsOur results highlight differences in access to DBS for PD patients among high-income countries, which we discuss in the context of health systems. Better access to effective PD treatments such as DBS is critical given the increasing prevalence of PD in an ageing world and the associated, avoidable morbidity.

Inferring pathogen presence when sample misclassification and partial observation occur

Abstract Surveillance programmes are essential for detecting emerging pathogens and often rely on molecular methods to make inference about the presence of a target disease agent. However, molecular methods rarely detect target DNA perfectly. For example, molecular pathogen detection methods can result in misclassification (i.e. false positives and false negatives) or partial detection errors (i.e. detections with ‘ambiguous’, ‘uncertain’ or ‘equivocal’ results). Then, when data are to be analysed, these partial observations are either discarded or censored; this, however, disregards information that could be used to make inference about the true state of the system. There is a critical need for more direction and guidance related to how many samples are enough to declare a unit of interest ‘pathogen free’. Here, we develop a Bayesian hierarchal framework that accommodates false negative, false positive and uncertain detections to improve inference related to the occupancy of a pathogen. We apply our modelling framework to a case study of the fungal pathogen Pseudogymnoascus destructans (Pd) identified in Texas bats at the invasion front of white‐nose syndrome. To improve future surveillance programmes, we provide guidance on sample sizes required to be 95% certain a target organism is absent from a site. We found that the presence of uncertain detections increased the variability of resulting posterior probability distributions of pathogen occurrence, and that our estimates of required sample size were very sensitive to prior information about pathogen occupancy, pathogen prevalence and diagnostic test specificity. In the Pd case study, we found that the posterior probability of occupancy was very low in 2018, but occupancy probability approached 1 in 2020, reflecting increasing prior probabilities of occupancy and prevalence elicited from the site manager. Our modelling framework provides the user a posterior probability distribution of pathogen occurrence, which allows for subjective interpretation by the decision‐maker. To help readers apply and use the methods we developed, we provide an interactive RShiny app that generates target species occupancy estimation and sample size estimates to make these methods more accessible to the scientific community (https://rmummah.shinyapps.io/ambigDetect_sampleSize). This modelling framework and sample size guide may be useful for improving inferences from molecular surveillance data about emerging pathogens, non‐native invasive species and endangered species where misclassifications and ambiguous detections occur.

Emergent properties from CuPd alloy films under near-infrared excitation

Noble-transition metal alloys offer emergent optical and electronic properties for near-infrared (NIR) optoelectronic devices. We investigate the optical and electronic properties of CuxPd1-x alloy thin films and their ultrafast electron dynamics under NIR excitation. Ultraviolet photoelectron spectroscopy measurements supported by density functional theory calculations show strong d-band hybridization between the Cu 3d and Pd 4d bands. These hybridization effects result in emergent optical properties, most apparent in the dilute Pd case. Time-resolved terahertz spectroscopy with NIR (e.g., 1550nm) excitation displays composition-tunable electron dynamics. We posit that the negative peak in the normalized increment of transmissivity (ΔT/T) below 2ps from dilute Pd alloys is due to non-thermalized hot-carrier generation. On the other hand, Pd-rich alloys exhibit an increase in ΔT/T due to thermalization effects upon ultrafast NIR photoexcitation. CuxPd1-x alloys in the dilute Pd regime may be a promising material for future ultrafast NIR optoelectronic devices.

Shedding Synchrotron Light on Catalyst Strain Dynamics in Electrochemical Environment

In the case of heterogeneous catalysis (where the reactions occur onto the catalyst surface), the most promising approach in material design follows the Sabatier principle: the ability of the surface to bind adsorbates and the strength of the bonds define the reaction thermodynamics and kinetics. In this respect, the catalyst surface chemistry and structure (crystallographic orientation of the facets and/or strain) are used as levers to optimize its performance. However, it is largely accepted that the structure of PEMWE anode and PEMFC cathode catalysts does not remain unaltered over the long term operation due to harsh (electro)chemical conditions and it is of a high interest to understand the structural changes during the electrocatalysis. In this contribution we use X-ray diffraction techniques to qualitatively and quantitatively describe those changes and shed light on the strain evolution in nanostructured catalysts during operation in the electrochemical environment.Using the newly upgraded 4th generation EBS source at European Synchrotron Radiation Facility, we study Pt and Pd catalysts in liquid half cells at various potentials. In the Pd case we focus on the phase and structural dynamics during H insertion, allowing to unveil the electrochemically-driven Pd hydrides phase transition, which was until now mostly investigated in the gas phase. The fine XRD patterns measured operando provided the first detection of theoretically predicted supersaturated and undersaturated metastable states, involved in a core-shell mechanism of the phase transition (Figure 1) [1].In the case of Pt nanocatalyst, monitoring the structural features of the catalyst during cyclic voltammetry permits studying adsorption and oxidation processes. Deconvoluting both effects (adsorption and oxidation) is possible by following different parameters of the analyzed XRD patterns with high temporal resolution. Such experiments reveal important dynamic trends linked to the surface oxidation and degradation, directly impacting the output of accelerated stress tests (AST) [2]. Carefully determining the charge passed through the circuit during the CV also allows to establish a near-linear correlation between the expansion of the bulk lattice parameter of Pt nanoparticles and their oxide surface coverage. Since the latter is known to be a descriptor of catalysts activity toward numerous reactions (oxygen reduction and fuel oxidation), the measurement of the lattice parameter according to this simple diffraction approach allows experimental access to this descriptor during operando measurements in device-relevant sample environments [2]. This constitutes a main advantage compared to spectroscopic techniques and is foreseen to find a wide range of applications, as demonstrated by measuring the structural behavior of the state-of-the-art PtNiIr octahedra catalyst in operating PEMFC. In this case, the results allow correlating the degradation of the catalysts cycled to different lower potentials with the oxidation and strain dynamics. Based on this data, the operating conditions for this catalyst can be determined, further defining the application of this material.[1] Chattot, R. et al., J. Am. Chem. Soc. 143(41), 17068–17078 (2021).[2] Martens, I. et al., ACS Appl. Energy Mater. 2 (11), 7772-7780 (2019). Figure 1

Global multi-center phase I trial of the intraperitoneal infusion of anti-EpCAM x anti-CD3 bispecific antibody catumaxomab for advanced gastric carcinoma with peritoneal metastasis.

e16102 Background: Advanced gastric cancer (GC) patients (pts) have high incidence of peritoneal metastasis (PM), resulting in ascites, cachexia and poor life quality. EpCAM is highly expressed on GC but no on peritoneum. Catumaxomab intraperitoneal infusion (i.p.) was previously demonstrated to eradicate EpCAM+ cancers and control the malignant ascites in Europe (Heiss. Int. J. Cancer.2010). We present initial safety, pharmacokinetics (PK), and efficacy from the multi-center phase I trial of Catumaxomab on GC pts with PM in Asian population (NCT04222114). Methods: GC pts who had progressed on at least two prior standard systemic therapies with peritoneal metastasis were enrolled. Pts received Catumaxomab i.p. of 10 μg, 20 μg, 50 μg and 150 μg on days 1, 4, 8 and 11, respectively in the 1st cycle. From the 2nd cycle, Pts received Catumaxomab i.p. of 20 μg, 50 μg, 150 μg on days 1, 4 and 8, respectively. The cycle was 42 days in Cohort A, and 28 days in Cohort B. Catumaxomab PK were evaluated, tumor measurements and quantification of ascites by five-point method (Oriuchi, JJCO,2005) were performed Q6W. The primary endpoint was overall survival (OS); secondary endpoints were response rate of ascites, progression-free interval of peritoneal metastatic lesions and puncture-free survival (PuFS); Data cut-off date was Jan 29,2022. Results: 17 pts from 14 sites (median age: 52.5 yr, ECOG PS: 0 [n=2], 1 [n=14], 2[n=1], Cohort A:9, Cohort B:8) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was pyrexia (76.5%) and abdominal pain (58.8%). Grade ≥3 treatment related adverse events (TRAE) of abdominal pain (23.5%), bilirubin conjugated increased (23.5%), lymphocyte count decreased (17.6%), ALT increased (11.8%), and AST increased (11.8%) were reported. No treatment related death or neurotoxicity occurred in the study. Median overall survival was 102 days (95%CI: 38-166), with 10 (58.8%) deaths observed. For ascites, CR+PR was observed in 4 cases (33%), no PD case was reported. No therapeutic ascites drainage was recorded after cycle 1. Median PuFS was 116 days (95%CI: 28-157). Median progression-free interval of peritoneal metastatic lesions was 102 days (95%CI: 38-166). PK: Catumaxomab concentrations in plasma increased in a dose-dependent manner and were similar to Caucasian population in Europe. Conclusions: This clinical study indicated that multiple cycles of Catumaxomab i.p. were safe and well tolerated in Asian population. PK profile was similar. Early efficacy signals were promising, especially in pts with ascites, which will be further investigated in phase 3 study. Clinical trial information: NCT04222114.

Clinical outcomes and prognostic analysis of conversion surgery for initially unresectable biliary tract cancer: Japan-Korea collaboration study

There are small scale retrospective studies showing efficacy of conversion surgery for initially unresectable biliary tract cancer (UR BTC) patients who responded long-term chemotherapy or radiation therapy. This study aimed to establish new evidence by evaluating effect of conversion surgery for UR-LA BTC from Japan and Korea. Patients with initially UR BTC including intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PHCC), distal bile duct cancer (DBC), and gallbladder cancer (GBC) and Amplla of vater cancer (AVC) who underwent conversion surgery between January 2013 to December 2017 following chemotherapy or radiotherapy were retrospectively collected from Japanese and Korean institutes. A total of 91 patients, including 27 ICC, 24 PHCC, 32 GBC, 7 DBC and 1 AVC cases, were enrolled. The reasons for unresectability were local progression without distant metastasis in 66 cases (73%) and distant metastasis in 25 cases (27%). As preoperative chemotherapy, gemcitabine-based multidrug therapy was performed for 70 patients (77%), and radiation therapy was performed for 19 patients (21%). The result of evaluation of the responses using RECIST showed 5 CR cases (5%), 52 PR cases (57%), 27 SD cases (30%) and 1 PD case (1%). The median interval from the induction of treatment to surgical resection was 6.4 months. The surgical procedures comprised hepatectomy with bile duct resection in 56 cases (62%), pancreaticoduodenectomy in 7 cases (8%) and hepatopancreatoduodenectomy in 8 cases (9%). Combined vascular resection was performed 25 patients (27%). Postoperative complication over Clavian-Dindo Grade III occurred in 48 cases (53%). There were 5 mortality cases (5%). R0 resection was performed for 74 cases (81%). Pathologically CR was achieved for 13 cases (14%). Five year survival rate of initially UR-BTC patients who underwent conversion surgery after preoperative therapy was 43.9% (median survival time: 39.2 months). Selected patients diagnosed with initially unresectable bile duct cancer are able to undergo conversion surgery and may have long-term survival after potentially curative resection.

Patients Characteristics and Psychosocial Treatment in Psychodynamic and Cognitive Behavior Therapy.

Introduction: The most prevalent psychotherapy schools are psychodynamic (PDT) and cognitive behavior therapy (CBT). There are no scientific guidelines on which type of patient should be treated by which therapist, and how they can find the best one. Part of the answer can be derived from data on who is treated in which way.Objective: Objective of this study was to compare patients in routine PDT and CBT to describe similarities and differences in regard to patient status and treatment.Materials and Methods: A research psychotherapist visited 73 cognitive behavior therapists and 58 psychodynamic psychotherapists in their office and asked them to report about the last cases they had seen. There were 188 CBT and 134 PD case reports.Results: There were no significant differences in socio-demographics between PDT and CBT patients. The average number of treatment session so far was significantly higher in PDT than CBT. There were longer duration of illness, more parallel medical treatments and higher rates of sick leave in CBT patients. While assessment of capacities with the Mini-ICF-APP showed no differences, more participation restrictions were found in CBT patients. Correspondingly there were more sociomedical interventions, especially in regard to work.Conclusions: The differences between PDT and CBT may be explained by the fact that PDT requires analytical capabilities on the side of the patient, which may exclude patients with social problems, while CBT is coping oriented which allows the inclusion of all kinds of patients. Still, in both treatment modes, complex patients are treated with multidimensional interventions.

Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson\u2019s case

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer’s disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson’s disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.

Role of Heteronuclear Interactions in Selective H2 Formation from HCOOH Decomposition on Bimetallic Pd/M (M = Late Transition FCC Metal) Catalysts

In this study, by using spin-polarized density functional theory calculations, we have elucidated the role of heteronuclear interactions in determining the selective H2 formation from HCOOH decomposition on bimetallic Pdshell/Mcore (M = late transition FCC metal (Rh, Pt, Ir, Cu, Au, Ag)) catalysts. We found that the catalysis of HCOOH decomposition strongly depends on the variation of surface charge polarization (ligand effect) and lattice distance (strain effect), which are caused by the heteronuclear interactions between surface Pd and core M atoms. In particular, the contraction of surface Pd–Pd bond distance and the increase in electron density in surface Pd atoms in comparison to the pure Pd case are responsible for the enhancement of the selectivity to H2 formation via HCOOH decomposition. Our calculations also unraveled that the d band center location and the density of states for the d band (particularly dz2, dyz, and dxz) near the Fermi level are the important indicators that explain the impact o...

Effects of participation in physical training program for patient with parkinson's disease: a case report

The aim of this study was to investigate the effects of physical activity in people with Parkinson’s disease PD (case study). To this, a subject (54 years) participant of the PARKVIDA project performed physical exercise training 3 days/week. The intensity of physical activity was mild-moderate monitored by frequencimeter and consisted of aerobic exercises, strength and specific (motor coordination and balance) adapted from Gobbi’s protocol. Before and after the period of 8 months were applied the tests: quality of life (SF-36), balance (unipodal support test), body composition, cardio respiratory fitness (spirometry) and a part of AAHPERD battery: coordination, agility, strength and flexibility. The results showed changes in physical aspects such as agility, balance, flexibility and coordination, concomitant with improvement in cardiorespiratory fitness and quality of life (dimension pain). In conclusion, this study suggests that changes promoted by physical activity can contribute to improve cardio respiratory conditioning, reducing the perception of pain and physical and motor improvements in patient with PD.

Importance of Pd monomer pairs in enhancing the oxygen reduction reaction activity of the AuPd(1 0 0) surface: A first principles study

Based on density functional theory calculations, we present that pairs of 1st nearest Pd monomers play an important role in significantly enhancing the oxygen reduction reaction (ORR) on the AuPd(100) surface. While the catalytic ORR activity tends to be sensitive to the surface atomic ordering, we find that the Pd monomer pairs lead to a substantial reduction in the activation barrier for O/OH hydrogenation with no significant suppression of O–O bond scission, thereby considerably lowering the overall activation energy for the ORR as compared to the case of pure Pd(100). On the other hand, an isolated Pd monomer tends to greatly suppress the O–O bond cleavage reaction, which in turn slows down the ORR kinetics. Unlike the monodentate adsorption of O2 on an isolated Pd monomer, the pairing of Pd monomers allows O2 adsorption in a bidentate configuration and consequently facilitating O–O bond scission. However, the barrier for OH hydrogenation at each Pd site shows no significant change between the isolated and paired cases, while it is noticeably lower than the pure Pd case.

Catalytic Activity of Ru for Metal-Assisted Etching of Si

Metal-assisted chemical etching of Silicon (Si) in hydrofluoric acid (HF) solution is an electroless method to produce porous Si (1, 2). Such etching generally uses not only metal-modified Si but also an oxidizing agent as hydrogen peroxide, metal ions and oxygen. We reported that etching rate of platinum (Pt), rhodium (Rh), gold (Au) and silver (Ag)-particle-modified Si depended on catalytic activity of metal for oxygen reduction (3), and palladium (Pd) exhibits high catalytic activity for the etching of Si without an oxidizing agent even under dissolved oxygen-free and dark conditions (4). This etching reaction using Pd is explained by electron injection into the conduction band of Si due to Pd assisted anodic oxidization of Si (Fig. 1). In this study, we have investigated the catalytic activity of ruthenium (Ru), which is in the same platinum group as Pd, for etching of Si in a HF solution. Single-crystalline n-Si wafers (CZ, (100), ca. 10 Ω cm) were used as substrates. Si wafers were immersed in 1 mM (M = mol dm-3) ruthenium chloride (RuCl3) solution including 0.15 M HF at 313 K for electroless displacement metal deposition. Metal deposited Si wafers were immersed in a 7.3 M HF solution at 298 K under dark conditions for 24 h. Argon or oxygen gas bubbling was applied to the HF solution before and during etching to remove or saturate the dissolved oxygen in the solution, respectively. The etching rate of Si was measured by a gravimetric procedure. No metal deposition occurred on mirror-polished Si wafers even by immersing in the deposition solution for even long time of 24 h. On the other hand, on Si wafers roughed with sand paper (#1200), Ru particles were deposited by immersing in the solution for 5 min. The etching rates of such Ru-particle-deposited Si wafers in 7.3 M HF solution were 1.1×10-5 and 2.0×10-4 g cm-2 h-1 under oxygen-free and -saturated conditions, respectively. The etch rate in the oxygen-free case is much higher than 1.2×10-6 g cm-2 h-1 of Pt-particle-modified case and one order lower than 3.4×10-4 g cm-2 h-1 the of Pd case. Figure 2 shows the SEM images of Ru-particle-deposited Si wafers before and after etching with the oxygen free HF solution. Ru particles were localized on scratches before etching (fig. 2a). After etching, a porous layer covered whole surface of Si (Fig. 2b and c). Pores, which have Ru particle at the bottom, were formed. The depth of pores, ca. 0.2 mm, is much shorter than 1 mm of depth calculated using the gravimetric procedure. These results indicate that Ru has much lower activity for electroless displacement deposition than that of other noble metals and high catalytic activity for metal assisted etching of Si similar to Pd. ACKNOWLEDGEMENTS The present work was partly supported by JSPS KAKENHI (26289276). REFERENCES Z. Huang, N. Geyer, P. Werner, J. Boor, U Gösele, Adv. Mater., 23,285 (2011).S. Yae, Y. Kawamoto, H. Tanaka, N. Fukumuro, and H. Matsuda, Electrochem.Commun., 5, 632 (2003).S. Yae, Y. Morii, N. Fukumuro, H. Matsuda, Nanoscale Res. Lett., 7, 352 (2012).S. Yae, M. Tashiro, M. Abe, N. Fukumuro, and H. Matsuda, J. Electrochem. Soc., 157, D90 (2010). Figure 1

Applying Fuzzy and Probabilistic Uncertainty Concepts to the Material Flow Analysis of Palladium in Austria

AbstractMaterial flow analysis (MFA) is a widely applied tool to investigate resource and recycling systems of metals and minerals. Owing to data limitations and restricted system understanding, MFA results are inherently uncertain. To demonstrate the systematic implementation of uncertainty analysis in MFA, two mathematical concepts for the quantification of uncertainties were applied to Austrian palladium (Pd) resource flows and evaluated: (1) uncertainty ranges expressed by fuzzy sets and (2) uncertainty ranges defined by normal distributions given as mean values and standard deviations. Whereas normal distributions represent the traditional approach for quantifying uncertainties in MFA, fuzzy sets may offer additional benefits in relation to uncertainty quantification in cases of scarce information. With respect to the Pd case study, the fuzzy representation of uncertain quantities is more consistent with the actual data availability in cases of incomplete databases, and fuzzy sets serve to highlight the effect of uncertainty on resource efficiency indicators derived from the MFA results. For both approaches, data reconciliation procedures offer the potential to reduce uncertainty and evaluate the plausibility of the model results. With respect to Pd resource management, improved formal collection of end‐of‐life (EOL) consumer products is identified as a key factor in increasing the recycling efficiency. In particular, the partial export of EOL vehicles represents a substantial loss of Pd from the Austrian resource system, whereas approximately 70% of the Pd in the EOL consumer products is recovered in waste management. In conclusion, systematic uncertainty analysis is an integral part of MFA required to provide robust decision support in resource management.

Quantum valley Hall states and topological transitions in Pt(Ni, Pd)-decorated silicene: a first-principles study.

The electronic states and topological behaviors of Pt(Ni, Pd)-decorated silicene are investigated by using an ab-initio method. All the three kinds of the adatoms prefer hollow sites of the silicene, guaranteeing the Dirac cones unbroken. The Pt(Ni, Pd)-decorated silicene systems all present quantum valley Hall (QVH) states with the gap opened exactly at the Fermi level. The gaps of the QVH states can be increased substantially by applying a positive electric field. Very fascinating phase transitions from QVH to quantum spin Hall (QSH) and then to QVH again are achieved in the Pt/Ni-decorated silicene when a negative electric field is applied. The QSH state in the Pd case with a negative electric field is, however, quenched because of relatively larger Rashba spin-orbit coupling (SOC) than the intrinsic SOC in the system. Our findings may be useful for the applications of silicene-based devices in valleytronics and spintronics.

Phase I study of biweekly docetaxel, cisplatin, and S-1 combination neoadjuvant chemotherapy for stage III gastric cancer.

153 Background: It is unclear neoadjuvant chemotherapy for stage III gastric cancer can provide satisfactory outcomes. Therefore, we conducted a phase I study to clarify recommend dose (RD) of biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Methods: A dose escalation method was employed. S1 (80mg/m2/day; day1-7, 15-21) and docetaxel (20mg/m2/day; day1, 15) were fixed and cisplatin (day1, 15) was increased by 5mg/m2 from level I (20mg/m2/day). Each course was lasted for one month. Toxicity was examined by the CTCAE version 4.0 during two courses. Results: A total of 21 patients (male/female=14/7, mean age=63 years) was enrolled in this study. Of these, nine stage IIIA, nine stage IIIB, and three stage IIIC were included. In level I, There was no DLT case. In level II, we encountered perforation of gastric cancer in one case without any other DLT in the remaining five cases. In level III, IV, V, and VI, we did not encounter any cases with DLT. So, we decided that the RD of cisplatin was 50mg/m2/day (Level VI), which is regarded as maximum safety dose in the outpatient clinic. Response status was as follows: one PR case, 19 non CR/non-PD cases and one PD case. Total gastrectomy was performed in 14 cases, and distal gastrectomy in seven cases. Histologically, grade 1a was found in 13 cases, grade 1b in three cases, grade 2 in four cases, and grade 3 was one case. Five cases (23.8%) suffered from postoperative complications (two anastomotic leakage; one pneumonia; one pancreatic fistula; one chyloascites) although all cases recovered conservatively. Conclusions: RD of cisplatin was 50mg/m2/day in biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Phase II study is now going on to confirm the usefulness of this treatment.

Glia maturation factor levels are elevated in the striatum and substantia nigra in Parkinson's disease

Glia maturation factor (GMF) is an inflammatory protein, discovered in our laboratory, plays a major role in the pathogenesis of CNS inflammatory diseases. Although GMF has been implicated as a major contributing factor in the pathogenesis of EAE, an animal model of Multiple Sclerosis, there has not been a direct demonstration of GMF expression in human PD brains. In the present study we demonstrate a significant up regulation of GMF expression in human PD brain. Human brain tissues were obtained from autopsy, with PMI less than 6 h, at UI Deeded Body Program. For the comparison, we examined brain tissue from cases with clinically diagnosed and neuropathologically confirmed Parkinson's disease and age‐matched non‐PD controls. Our results show degenerating TH‐ immunostained neurons/ fibers associated with activated microglia and astrocytes in the autopsied brain from PD case. In PD brain, GMF appears to be localized to activated astrocytes and dopaminergic neurons. Additionally, we quantitatively estimated GMF protein by ELISA in different regions of PD brains. We demonstrated a significant increase (over 10 fold) in GMF levels in the substantia nigra and striatum of human PD brains compare to non‐PD. Thus, our results provide strong evidence that under conditions of neurodegeneration in PD the expression of GMF is significantly upregulated. (Supported by VA Merit Review award and NINDS grant NS073670).

Structural and electronic properties of TM23 - pAgp (TM = Ni, Pd, and Pt) clusters in the dilute limit (p = 0–4): A density functional theory investigation

We studied the structural, energetic, and electronic properties of free-standing binary clusters in the dilute limit, TM23 − p Ag p with TM = Ni, Pd, and Pt, and p = 0–4, employing density functional theory within the generalized gradient approximation to the exchange-correlation energy functional, as implemented in the SIESTA code. For all studied systems, we found that the addition of Ag impurities decreases the binding energy of the clusters. The Ag impurities always prefer the surface sites, although not always the lowest coordination sites are occupied as it is observed in Pt, where large coordination surface sites are in general preferred. Clear Ag segregation is observed in Ni with the poly-icosahedral structure and Pt in the cubic-pyramidal structure. For Pd case a weak segregation and mixing patterns coexist depending upon which structure is shown, in the other cases in general a tendency to mixing is presented.

Sn–Ag–Cu solder reaction with Au/Pd/Ni(P) and Au/Pd(P)/Ni(P) platings

A comparative study between pure Pd and Pd(P) films on the solderability was performed. In the Sn–3Ag–0.5Cu/Au/Pd/Ni(P) system (pure Pd case), (Cu,Ni)6Sn5 and Ni3P were the predominant intermetallic species at the interface after the removal of the Au/Pd dual layer in soldering. We found that a significant growth of (Ni,Cu)3Sn4 occurred between (Cu,Ni)6Sn5 and Ni3P after aging at 180°C for 500h. This phenomenon was not observed in the reference case, in which a Pd(P) film had replaced the pure Pd layer before the reaction. The (Cu,Ni)6Sn5/(Ni,Cu)3Sn4 interface provided a crack initiation site, seriously deteriorating the high-speed ball shear resistance of the solder joints. The retarded growth of (Ni,Cu)3Sn4 in the Pd(P) case was attributed to the presence of an additional Ni2SnP nanolayer between (Cu,Ni)6Sn5 and Ni3P that prevented the outward diffusion of Ni, thereby inhibiting the formation of the undesired (Cu,Ni)6Sn5/(Ni,Cu)3Sn4 structure. The results of this study indicate Pd(P) film is more beneficial to the solderability than pure Pd.

Aberrant expression of Glia Maturation Factor in Human PD brain

Glia maturation factor (GMF) is an inflammatory protein, discovered in our laboratory, plays a major role in the pathogenesis of CNS inflammatory diseases. In the present study we demonstrate a significant up regulation of GMF in human PD brain. Human brain tissues were obtained from autopsy at University of Iowa Deeded Body Program. For the comparison, we examined brain tissue from five cases with clinically diagnosed and neuropathologically confirmed Parkinson's disease and six age‐matched non‐PD controls. Representative images showing degenerating TH+ neurons/fibers associated with activated microglia and astrocytes in the autopsied brain from PD case compared with age‐matched non‐PD controls. In the substantia nigra of patients with PD, GMF appears to be localized to astrocytes and dopaminergic neurons. We also estimated GMF protein levels in PD brains. We demonstrated a significant increase (over 10 fold) in GMF concentration in the SN and STR of PD patients compare to non‐PD controls. Thus, our results provide strong evidence that under conditions of neurodegeneration in PD the expression of GMF is significantly upregulated. (Supported by VA Merit Review award and NIH/NINSD grant NS‐47145)

Incidence of hip fracture in Parkinson disease: a population-based study in British Columbia, Canada

AimsParkinson's disease (PD) constitutes a significant risk for falls and subsequent hip fracture, yet the rate of hip fracture in this patient population has not been clearly delineated. We looked...