Intriguing Low-Temperature Phase in the Antiferromagnetic Kagome Metal FeGe.

The properties of kagome metals are governed by the interdependence of band topology and electronic correlations resulting in remarkably rich phase diagrams. Here, we study the temperature evolution of the bulk electronic structure of the antiferromagnetic kagome metal FeGe using infrared spectroscopy. We uncover drastic changes in the low-energy interband absorption at the 100 K structural phase transition that has been linked to a charge-density-wave (CDW) instability. We explain this effect by the minuscule Fe displacement in the kagome plane, which results in parallel bands in the vicinity of the Fermi level. In contrast to conventional CDW materials, however, the spectral weight shifts to low energies, ruling out the opening of a CDW gap in FeGe.

Electrohydrodynamics of diffuse porous colloids.

The present article deals with the electrohydrodynamic motion of diffuse porous particles governed by an applied DC electric field. The spatial distribution of monomers as well as the charge distribution across the particle are considered to follow sigmoidal distribution involving decay length. Such a parameter measures the degree of inhomogeneity of the monomer distribution across the particle. The diffuse porous particles resemble several colloidal entities which are often seen in the environment as well as in biological and pharmaceutical industries. Considering the impact of bulk pH and ion steric effects, we modelled the electrohydrodynamics of such porous particulates based on the modified Boltzmann distribution for the spatial distribution of electrolyte ions and the Poisson equation for electric potential as well as the conservation of mass and momentum principles. We adopt regular perturbation analysis with weak field assumption and the perturbed equations are solved numerically to calculate the electrophoretic mobility and neutralization fraction of the particle charge during its motion as well as fluid collection efficiency. We further deduced the closed form relation between the drag force experienced by the charged porous particle and the fluid collection efficiency. In addition to the numerical results, we further derived the closed form analytical results for all the intrinsic parameters indicated above derived within the Debye-Hückel electrostatic framework and homogeneous distribution of monomers within the particle for which the decay length vanishes. The deduced mathematical results as indicated above will be useful to analyze several electrostatic and hydrodynamic features of a wide class of porous particulate and environmental entities.

A randomised controlled trial study on the effectiveness of high-fidelity simulation in enhancing skills among undergraduate medical students.

INTRODUCTION: High-fidelity simulation (HFS) provides a high level of interactivity and realistic experience for the learner by means of using full scale computerised patient simulators. It imitates clinical experience in a controlled and safe environment that closely resembles reality. The purpose of this study was to compare the efficacy of HFS versus video-assisted lecture (VAL) based education in enhancing and consolidating retention of skills among undergraduate medical students. MATERIALS AND METHODS: A randomised controlled trial (RCT) study involving 111 undergraduate medical students was conducted where the competency of skills was assessed by objective structured clinical examination (OSCE) in the first, fourth and seventh/eighth weeks. A cohort of 12-14 students was enrolled for each session. The randomisation of the participants into control (VAL-based teaching) and intervention (HFS-based teaching) groups was achieved by implementing the computer-based random sequence generation method. VAL-based teaching module was a fully interactive face-to-face teaching session where a prerecorded video clip was used. The video clip detailed the diagnosis of tension pneumothorax in an acute medical emergency and its management by performing needle decompression on a high-fidelity patient simulator (METIman). HFS-based teaching module was delivered as a fully interactive hands-on training session conducted on the same METIman to demonstrate the diagnosis of tension pneumothorax in an acute medical emergency and its management by performing needle decompression. OSCE scores were compared as the denominator of learning (enhancement and retention of skills) between two groups who underwent training with either VAL-based or HFS-based teachings. The OSCE assessments were used to evaluate the participants' performance as a group. These scores were used to compare the enhancement and medium-term retention of skills between the groups. The outcome was measured with the mean and standard deviation (SD) for the total OSCE scores for skills assessments. We used General Linear Model two-way mixed ANOVA to ascertain the difference of OSCE marks over assessment time points between the control and the intervention groups. ANCOVA and two-way mixed ANOVA were used to calculate the effect size and the partial Eta squared. p value less than 0.05 was taken to be statistically significant. RESULTS: The two-way mixed ANOVA showed no statistically significant difference in mean OSCE scores between intervention and control groups (p=0.890), although the mean score of the intervention group was better than the control group. CONCLUSION: Our study demonstrated that HFS was not significantly effective over VAL-based education in enhancing skills and consolidating retention among undergraduate medical students. Further research is needed to determine its suitability for inclusion in the course curriculum considering the cost-effectiveness of implementing HFS that may supplement traditional teaching methods.

Comparative occurrence of ESBL/AmpC beta-lactamase-producing Escherichia coli and Salmonella in contract farm and backyard broilers.

The present study was conducted to detect the occurrence of beta-lactamase and biofilm-producing Escherchia coli and Salmonella in apparently healthy broiler birds reared in household and contract poultry farms. In total, 150 cloacal swabs were collected from apparently healthy broiler birds of various age groups reared in backyard (n = 100) and contract farms (n = 50) in West Bengal (India). The isolation rate of ESBL producers was significantly more (P < 0·05) reared in contract poultry farms than those reared in backyard. Majority of the E. coli isolates possessed blaCTX-M followed by blaSHV and blaTEM . Majority of the Salmonella strains possessed blaTEM followed by blaCTX-M , and no blaSHV was detected. The selected sequences of the PCR products were found cognate with blaCTX-M-1 , blaCTX-M-2 , blaCTX-M-9 , blaCTX-M-14 , blaCTX-M-15 , blaSHV-12 and blaTEM-52 . The study detected 46·8% of E. coli and 42·5% of Salmonella strains as biofilm producers. Beta-lactamase-producing Enterobacteriaceae strains showed resistance against tetracycline, chloramphenicol, doxycycline, co-trimoxazole and ampicillin and sensitivity to imipenem-EDTA, colistin and gentamicin. The study revealed the partial clonal relationship of ESBL sequences possessed by the poultry isolates of the present study and local clinical isolates available in the database. The study made consumer awareness about careful handling of live birds or poultry meat to avoid the zoonotic transmission of antimicrobial-resistant Enterobacteriaceae.

Mid-term follow-up of percutaneous access for standard and complex EVAR using the ProGlide device.

OBJECTIVES: Endovascular Aneurysm Repair is an established treatment for abdominal aortic aneurysm which requires arterial access via the groin. Most centres perform percutaneous ultrasound-guided access into the common femoral artery for delivery of the stent graft. The profile of endovascular devices necessitates large sheath sizes, therefore formal closure of the arterial puncture site is required. Various percutaneous devices are available, with data lacking on efficacy and mid-term safety profile. We present outcomes from a single centre with the Perclose ProGlide™ (Abbott Vascular Devices, CA, USA) suture-mediated system, using the well described "pre-close" technique. MATERIALS & METHODS: Data were collected from operative records and electronic medical records. Patients undergoing standard (EVAR) or complex (F/B-EVAR) aneurysm repair between March 2015 and September 2019 were included. Complications were recorded per-patient and per-groin procedure. RESULTS: 266 patients were included; 182 (68.4%) standard infrarenal EVAR, 84 (31.6%) F/B-EVAR. There were a total of 484 groin procedures performed. Intraoperative Perclose ProGlide™ success was 98.1% (per patient) or 99.0% (per groin procedure). 30-day groin complication rate was 6.1% (per patient) or 3.1% (per groin procedure). There were no pre- or peri-operative factors which predicted the occurrence of groin complications. The rate of groin complications was not related to sheath size. CONCLUSIONS: Our data support the use of percutaneous access with a pre-close technique for a variety of endovascular aneurysm repair procedures with both large- and small-bore access. The Perclose ProGlide™ system provides excellent mid-term complication-free and reintervention-free outcomes for groin procedures.

Morphology of enteric glia in colorectal carcinoma: A comparative study of tumor site and its proximal normal margin.

OBJECTIVE: Colorectal carcinoma (CRC) is the third most common cancer in the world and fifth most common cancer in India. To understand the extent of perineural invasion (PNI) in CRC it is essential to study the morphology of enteric glial cells (EGCs). The aim of the study was to analyze the numerical density of EGCs and area of myenteric ganglia (MG) in the colonic tissue samples collected from CRC patients. MATERIAL AND METHODS: Fifteen intraoperative tissue specimens were collected from the tumor site and 2cm proximal to the upper extent of tumor. The samples were divided into four groups: group 1 (n=15): proximal tumor free colonic tissue; group 2 (n=3): well-differentiated; group 3 (n=8): moderately differentiated; group 4 (n=4): poorly differentiated adenocarcinoma. After processing the tissues were subjected to hematoxylin and eosin staining. The anti-S100ß and anti-GFAP antibodies were used to observe the EGCs. RESULTS: In the H&E stained sections the number of myenteric ganglia appeared to be decreasing with increasing grade of adenocarcinoma. Immunostaining showed significant decreasing pattern in the numerical density of EGCs per myenteric ganglion and mean area of myenteric ganglia in relation to the thickness of circular muscle, corresponding to the increasing grades of adenocarcinoma. The morphology of the EGCs remained unaltered in the colonic tissue adjacent to the tumor site. CONCLUSION: Significant loss of EGCs and neurodegeneration corresponded with the grade of tumor emphasizing on its prognostic value. The PNI was not seen in the clear margin proximal to the tumor site.

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.

Neuronal clusterin expression is associated with cognitive protection in amyotrophic lateral sclerosis.

AIMS: Clusterin is a topologically dynamic chaperone protein with the ability to participate in both intra- and extacellular proteostasis. Clusterin has been shown to be upregulated in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) and has been shown to protect against TDP-43 protein misfolding in animal and cell models. Previous studies have demonstrated an association between the pathological burden of TDP-43 misfolding and cognitive deficits in ALS, demonstrating high specificity, but correspondingly low sensitivity owing to a subset of individuals with no evidence of cognitive deficits despite a high burden of TDP-43 pathology, called mismatch cases. METHODS: Hypothesizing that differences in the ability to cope with protein misfolding in these cases may be due to differences in expression of protective mechanisms such as clusterin expression, we assessed the spatial expression of clusterin and another chaperone protein, HspB8, in post mortem brain tissue of mismatch cases. We employed a modified in situ hybridization technique called BaseScope, with single cell, single transcript resolution. RESULTS: Mismatch cases demonstrated differential spatial expression of clusterin, with a predominantly neuronal pattern, compared to cases with cognitive manifestations of their TDP-43 pathology who demonstrated a predominantly glial distribution of expression. CONCLUSIONS: Our data suggest that, in individuals with TDP-43 pathology, predominantly neuronal expression of clusterin in extra-motor brain regions may indicate a cell protective mechanism delaying clinical manifestations such as cognitive dysfunction.

Singlet Pathway to the Ground State of Ultracold Polar Molecules.

Starting from weakly bound Feshbach molecules, we demonstrate a two-photon pathway to the dipolar ground state of bi-alkali molecules that involves only singlet-to-singlet optical transitions. This pathway eliminates the search for a suitable intermediate state with sufficient singlet-triplet mixing and the exploration of its hyperfine structure, as is typical for pathways starting from triplet dominated Feshbach molecules. By selecting a Feshbach state with a stretched singlet hyperfine component and controlling the laser polarizations, we assure coupling to only single hyperfine components of the A^{1}Σ^{+} excited potential and the X^{1}Σ^{+} rovibrational ground state. In this way an ideal three level system is established, even if the hyperfine structure is not resolved. We demonstrate this pathway with ^{6}Li^{40}K molecules, and discuss its application to other important molecular species.

Studying land use dynamics using decadal satellite images and Dyna-CLUE model in the Mahanadi River basin, India.

Population growth rate indicates the proportional rate of settlement expansion and landscape modification in any river basin. The Mahanadi River basin (MRB), which is a densely populated, cropland and forest-dominated landscape, is selected as a case study area for studying the nature of built-up expansion and the corresponding land cover modifications. Satellite data-derived land use/land cover (LU/LC) maps for the years 1995, 2005, and 2015 were used for identification of landscape changes during the past three decades. One of the major LU/LC changes are observed in terms of increase in the water, which may be attributed to construction of new dams at the cost of the croplands and forest areas. Conversion of forest to cropland and expansion and densification of built-up areas in and around the existing built-up areas are also identified as a major LU/LC change. The geostatistical analysis was performed to identify the relationship between LU/LC classes with drivers, which showed that built-up areas were more in topographically flat terrain with higher soil depth, and expanded more around the existing built-up areas; cropland areas were more at lower elevation and less sloppy terrain, and forest areas were more at higher elevation. The LU/LC scenario of 2025 was projected using a spatially explicit dynamic conversion of land use and its effects (Dyna-CLUE) modeling platform with the LU/LC change trends of past 10 years (2005-2015) and 20 years (1995-2015). The major LU/LC changes observed during 2005-2015 were built-up expansion by 36.53% and deciduous forest and cropland reduction by 0.35% and 0.45%, respectively. Thus, the corresponding predicted change during 2015-2025 estimated built-up expansion by 25.70% and deciduous forest and croplands loss by 0.43% and 0.35%, respectively. On the other hand, during 1995 to 2015, the total built-up expansion and deciduous forest and cropland reduction were observed 50.79%, 0.45%, and 0.73%, respectively. Thus, the predicted changes during 2015-2025 were estimated as 18.48% built-up expansion and 0.22% and 0.21% deciduous forest and cropland loss. However, with the conditions of restricted deforestation and less landscape modification, the LU/LC projections show less built-up area expansion, reducing the cropland, fallow land, plantation, and waste land. The reduced numbers of land cover conversions types during 2005-2015 compared with 1995-2005 indicate more stabilized landscape. The input LU/LC maps and statistical analysis demonstrated the landscape modifications and causes observed in the basin. The model projected LU/LC maps are giving insights to possible changes under multiple pathways, which will help the agriculture, forest, urban, and water resource planners and managers in improved policy-making processes.

Fermi Volume Evolution and Crystal-Field Excitations in Heavy-Fermion Compounds Probed by Time-Domain Terahertz Spectroscopy.

We measure the quasiparticle weight in the heavy-fermion compound CeCu_{6-x}Au_{x} (x=0, 0.1) by time-resolved terahertz spectroscopy for temperatures from 2 up to 300 K. This method distinguishes contributions from the heavy Kondo band and from the crystal-electric-field satellite bands by different terahertz response delay times. We find that the formation of heavy bands is controlled by an exponentially enhanced, high-energy Kondo scale once the crystal-electric-field states become thermally occupied. We corroborate these observations by temperature-dependent dynamical mean-field calculations for the multiorbital Anderson lattice model and discuss consequences for quantum-critical scenarios.

Depolarizing-Field Effects in Epitaxial Capacitor Heterostructures.

We identify a transient enhancement of the depolarizing field, leading to an unexpected quench of net polarization, during the growth of a prototypical metal-ferroelectric-metal epitaxial system made of BaTiO_{3} and SrRuO_{3}. Reduced conductivity and, hence, charge screening efficiency in the early growth stage of the SrRuO_{3} top electrode promotes a breakdown of ferroelectric BaTiO_{3} into domains. We demonstrate how a thermal annealing procedure can recover the single-domain state. By tracking the polarization state in situ, using optical second harmonic generation, we bring new understanding to interface-related electrostatic effects in ferroelectric capacitors.

Effect of Wetting and Dewetting Dynamics on Atomic Force Microscopy Measurements.

Water bridge dynamics between an atomic force microscopy (AFM) tip and a flat substrate is studied by using a multibody dissipative particle dynamics (MDPD) model. First, the numerical model is validated by comparing the present results of droplet contact angles and liquid bridges with those reported in the literature. Then, the ability of MDPD to capture the meniscus shape and behavior for different operating conditions and geometric parameters is examined for both static and dynamic cases. Hence, several parametric studies and analyses of the AFM tip configuration and its operating conditions are reported. It is found that a critical capillary number of about 0.001 is calculated based on 5% change on the force measurements between the static and dynamic results. It is also demonstrated that the hysteresis behavior in the capillary force exerted on the AFM tip can be successfully predicted by using the MDPD model when the tip approaches or retracts from the substrate. Moreover, there is an excellent agreement in the results of breakup distance for different water bridge volumes between the predictions of the MDPD model and the theory. Also, the hysteresis of capillary force exerted on an AFM tip composed of multibody design is studied. The prediction on the transition of the capillary force vs distance between the AFM tip and the substrate is in good agreement with the experimental results. Therefore, we demonstrate a validated MDPD model which can successfully capture liquid bridge dynamics. This model can be used as a powerful design tool for meniscus manipulation technology, such as dip-pen nanolithography, as well as for studying dynamic, e.g., tapping mode AFM tip, interactions with a liquid bridge.

Ultra-high selectivity pulsed plasmachemical deposition reaction pathways.

Glycidyl methacrylate pulsed plasmas have been investigated using time-resolved in situ mass spectrometry. At low pulsed plasma duty cycles, monomer fragmentation leading to the formation of polymerisation initiator species occurs within each short electrical discharge pulse (ton = microseconds timescale). This is followed by conventional step-wise monomer addition polymerisation occurring during the subsequent extended off-period (toff = milliseconds timescale), culminating in the growth of well-defined poly(glycidyl methacrylate) chains. Key attributes associated with this high selectivity pulsed plasmachemical functional thin film synthesis approach are the absence of the requirement for any additional chemicals (catalyst, solvent, etc.) in combination with very low power consumption (mW) and ambient temperature.

Impact of contemporary patterns of chemotherapy utilization on survival in patients with advanced cancer of the urinary tract: a Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC).

Background: Cisplatin-based combination chemotherapy is the standard treatment of advanced urinary tract cancer (aUTC), but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival. Patients and methods: This was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by Eastern Cooperative Oncology Group performance status ≤ 1, creatinine clearance ≥ 60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. Results: 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67-2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or comorbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. About 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used. Conclusions: The importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.

Pre-exposure prophylaxis: awareness, acceptability and risk compensation behaviour among men who have sex with men and the transgender population.

OBJECTIVES: This exploratory study examined the facilitators of and barriers to acceptance of pre-exposure prophylaxis (PrEP) and potential risk compensation behaviour emerging from its use among men who have sex with men (MSM) and transgender individuals (TGs) in India. METHODS: A questionnaire was administered to 400 individuals registered with a targeted intervention programme. Logistic regression models were used to identify facilitators of and barriers to PrEP acceptance. RESULTS: The respondents consisted of 68% MSM and 32% TGs. Risk behaviour categorization identified 40% as low risk, 41% as medium risk and, 19% as high risk for HIV infection. About 93% of the respondents were unaware of PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being married or in a live-in relationship (OR 2.08; P = 0.46), having a high calculated risk (OR 3.12; P = 0.33), and having a high self-perceived risk (OR 1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs had higher odds of acceptance of PrEP under conditions of additional cost (OR 2.12; P = 0.02) and once-daily pill (OR 2.85; P = 0.04). Individuals identified as low risk for HIV infection showed lower odds of potential risk compensation, defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P = 0.84), as compared with medium-risk individuals. The associations, although not statistically significant, are nevertheless important for public health action given the limited scientific evidence on PrEP use among MSM and TGs in India. CONCLUSIONS: With high acceptability and a low likelihood of risk compensation behaviour, PrEP can be considered as an effective prevention strategy for HIV infection among MSM and TGs in India.

Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study.

Look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses. Data from the UK Transfusion Medicine Epidemiology Review have been analysed to determine the accuracy of the blood donation history provided by the relatives of cases. Our results show that only a small percentage of cases were found to be registered as donors on UK Blood Service (UKBS) databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate.

First comprehensive tool for screening pain in Parkinson's disease: the King's Parkinson's Disease Pain Questionnaire.

BACKGROUND AND PURPOSE: Pain is highly prevalent in Parkinson's disease (PD), impacting patients' ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. METHODS: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test-retest) and diagnostic performance of the questionnaire were analysed. RESULTS: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS  = 0.80) but weak or moderate with other pain assessments. Test-retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS  = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%-98.3%. CONCLUSIONS: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes.

Analysis of a Prey-Predator Model with Non-local Interaction in the Prey Population.

Non-local reaction-diffusion equation is an important area to study the dynamics of the individuals which compete for resources. In this paper, we describe a prey-dependent predator-prey model with Holling type II functional response with a generalist predator. In particular, we want to see the behavior of the system in the presence of non-local interaction. Introduction of non-local intraspecific competition in prey population leads to some new characteristics in comparison with the local model. Comparisons have been made between the local and non-local interactions of the system. The range of non-local interaction enlarges the parametric domain on which stationary patterns exist. The periodic oscillation for the local model in the Hopf domain can be stabilized by suitable limit of strong non-local interaction. An increase in the range of non-local interaction increases the Turing domain up to a certain level, and then, it decreases. Also, increasing the range of non-local interaction results in the overlap of nearby foraging areas and hence alters the size of the localized patches and formation of multiple stationary patches. Numerical simulations have been carried out to validate the analytical findings and to establish the existence of multiple stationary patterns, oscillatory solution, two-periodic solution and other spatiotemporal dynamics.

Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer.

BACKGROUND: Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%-15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients. PATIENTS AND METHODS: This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N = 62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N = 61). In the experimental arm, treatment included loading doses of apatorsen followed by up to six cycles of apatorsen plus GC. Patients receiving at least four cycles could continue apatorsen monotherapy as maintenance until progression or unacceptable toxicity. The primary end point was OS. RESULTS: OS was not significantly improved in the single or combined 600- or 1000-mg apatorsen arms versus placebo [hazard ratio (HR), 0.86 and 0.90, respectively]. Exploratory study of specific statistical modeling showed a trend for improved survival in patients with baseline poor prognostic features treated with 600 mg apatorsen compared with placebo (HR = 0.72). Landmark analysis of serum Hsp27 (sHsp27) levels showed a trend toward survival benefit for poor-prognosis patients in 600- and 1000-mg apatorsen arms who achieved lower area under the curve sHsp27 levels, compared with the placebo arm (HR = 0.45 and 0.62, respectively). Higher baseline circulating tumor cells (≥5 cells/7.5 ml) was observed in patients with poor prognosis in correlation with poor survival. Treatment-emergent adverse events were manageable and more common in both apatorsen-treatment arms. CONCLUSIONS: Even though apatorsen combined with standard chemotherapy did not demonstrate a survival benefit in the overall study population, patients with poor prognostic features might benefit from this combination. Serum Hsp27 levels may act as a biomarker to predict treatment outcome. Further exploration of apatorsen in poor-risk patients is warranted.