Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study.

BACKGROUND: Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics. PATIENTS AND METHODS: MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab [high tumor mutational burden (TMB)]. The primary endpoint is the objective response rate (ORR). RESULTS: As of January 15, 2018, 19 patients with SGC were enrolled and treated in MyPathway (15 with HER2 amplification and/or overexpression and one each with a HER2 mutation without amplification or overexpression, PTCH-1 mutation, BRAF mutation, and high TMB). In the 15 patients with HER2 amplification/overexpression (with or without mutations) who were treated with pertuzumab + trastuzumab, 9 had an objective response (1 complete response, 8 partial responses) for an ORR of 60% (9.2 months median response duration). The clinical benefit rate (defined by patients with objective responses or stable disease >4 months) was 67% (10/15), median progression-free survival (PFS) was 8.6 months, and median overall survival was 20.4 months. Stable disease was observed in the patient with a HER2 mutation (pertuzumab + trastuzumab, n = 1/1, PFS 11.0 months), and partial responses in patients with the PTCH-1 mutation (vismodegib, n = 1/1, PFS 14.3 months), BRAF mutation (vemurafenib, n = 1/1, PFS 18.5 months), and high TMB (atezolizumab, n = 1/1, PFS 5.5+ months). No unexpected toxicity occurred. CONCLUSIONS: Overall, 12 of 19 patients (63%) with advanced SGC, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an objective response. Data from MyPathway suggest that matched targeted therapy for SGC has promising efficacy, supporting molecular profiling in treatment determination.

Spatio-temporal patterns of orchids flowering in Cameroonian rainforests.

We characterized the flowering patterns of 45 epiphytic orchid species occurring in Cameroonian rainforests to explore the environmental and evolutionary forces driving their phenology. We used a dataset of 3470 flowering events recorded over a period of 11 years in the Yaoundé living collection (82% of the flowering events) and from in situ observations (18% of the flowering events) to (i) describe flowering frequency and timing and synchronization among taxa; (ii) test flowering patterns for phylogenetic relatedness at the generic level; and (iii) investigate the spatial patterns of phenology. An annual flowering pattern prevailed among the species selected for this study. The species-rich African genera Angraecum and Polystachya are characterized by subannual and annual frequency patterns, respectively. However, in terms of flowering time, no phylogenetic signal was detected for the four most diverse genera (Ancistrorhynchus, Angraecum, Bulbophyllum, and Polystachya). Results suggest also an important role of photoperiod and precipitation as climatic triggers of flowering patterns. Moreover, 16% of the taxa cultivated ex situ, mostly Polystachya, showed significant differences in flowering time between individuals originating from distinct climatic regions, pointing toward the existence of phenological ecotypes. Phenological plasticity, suggested by the lack of synchronized flowering in spatially disjunct populations of Polystachya, could explain the widespread radiation of this genus throughout tropical Africa. Our study highlights the need to take the spatial pattern of flowering time into account when interpreting phylogeographic patterns in central African rainforests.

Decreased Clinical Severity of Strangles in Weanlings Associated with Restricted Seroconversion to Optimized Streptococcus equi ssp equi Assays.

BACKGROUND: Streptococcus equi ssp. equi causes characteristic clinical signs that are most severe in young horses, including fever, purulent nasal discharge, and lymph node abscessation in the head region. HYPOTHESIS/OBJECTIVES: Clinical, serologic, and microbiologic factors related to unexpectedly mild disease severity in a natural outbreak of strangles in immunologically naïve weanlings were investigated. ANIMALS: One-hundred and twelve warmblood weanlings. METHODS: Prospective longitudinal observational study of a natural outbreak of strangles. The entire cohort was examined at the peak of the outbreak by deep nasal swabs for culture and quantitative PCR (qPCR) for the presence of S. equi and clinically and serologically in a sequential manner by an optimized ELISA from the index case throughout the outbreak until resolution. Descriptive statistics were calculated and comparisons made using a nondirectional Wilcoxon signed-rank test. RESULTS: Outbreak morbidity was 53%, with 9 of 14 horses culture positive and 26 of 53 horses qPCR positive for S. equi lacking clinical signs characteristic of strangles. By resolution, 91 of 112 had seroconverted to Antigen A by ELISA but seroconversion to antigen C (part of the SeM protein) was minimal. Sequencing of the isolates detected no alterations in the SeM protein, but identified a 61 bp deletion in the gene SEQ_0402. CONCLUSIONS AND CLINICAL IMPORTANCE: Absence of clinical signs alone in naïve horses may be an insufficient criterion to release horses from strangles quarantine measures. Restricted seroconversion to antigen C may have been associated with decreased clinical severity. The role of a minor gene deletion in SEQ_0402 in the virulence of S. equi warrants further investigation.

Analyzing text recognition from tactually evoked EEG.

Tactual exploration of objects produce specific patterns in the human brain and hence objects can be recognized by analyzing brain signals during tactile exploration. The present work aims at analyzing EEG signals online for recognition of embossed texts by tactual exploration. EEG signals are acquired from the parietal region over the somatosensory cortex of blindfolded healthy subjects while they tactually explored embossed texts, including symbols, numbers, and alphabets. Classifiers based on the principle of supervised learning are trained on the extracted EEG feature space, comprising three features, namely, adaptive autoregressive parameters, Hurst exponents, and power spectral density, to recognize the respective texts. The pre-trained classifiers are used to classify the EEG data to identify the texts online and the recognized text is displayed on the computer screen for communication. Online classifications of two, four, and six classes of embossed texts are achieved with overall average recognition rates of 76.62, 72.31, and 67.62% respectively and the computational time is less than 2 s in each case. The maximum information transfer rate and utility of the system performance over all experiments are 0.7187 and 2.0529 bits/s respectively. This work presents a study that shows the possibility to classify 3D letters using tactually evoked EEG. In future, it will help the BCI community to design stimuli for better tactile augmentation n also opens new directions of research to facilitate 3D letters for visually impaired persons. Further, 3D maps can be generated for aiding tactual BCI in teleoperation.

Effect of the Dianhydride/Branched Diamine Ratio on the Architecture and Room Temperature Healing Behavior of Polyetherimides.

Traditional polyetherimides (PEIs) are commonly synthesized from an aromatic diamine and an aromatic dianhydride (e.g., 3,4'-oxidianiline (ODA) and 4,4'-oxidiphtalic anhydride (ODPA)) leading to the imide linkage and outstanding chemical, thermal and mechanical properties yet lacking any self-healing functionality. In this work, we have replaced the traditional aromatic diamine by a branched aliphatic fatty dimer diamine (DD1). This led to a whole family of self-healing polymers not containing reversible chemical bonds, capable of healing at (near) room temperature yet maintaining very high elastomeric-like mechanical properties (up to 6 MPa stress and 570% strain at break). In this work, we present the effect of the DD1/ODPA ratio on the general performance and healing behavior of a room temperature healing polyetherimide. A dedicated analysis suggests that healing proceeds in three steps: (i) an initial adhesive step leading to the formation of a relatively weak interface; (ii) a second step at long healing times leading to the formation of an interphase with different properties than the bulk material and (iii) disappearance of the damaged zone leading to full healing. We argue that the fast interfacial adhesive step is due to van der Waals interactions of long dangling alkyl chains followed by an interphase formation due to polymer chain interdiffusion. An increase in DD1/ODPA ratio leads to an increase in the healing kinetics and displacement shift of the first healing step toward lower temperatures. An excess of DD1 leads to the cross-linking of the polymer thereby restricting the necessary mobility for the interphase formation and limiting the self-healing behavior. The results here presented offer a new route for the development of room temperature self-healing thermoplastic elastomers with improved mechanical properties using fatty dimer diamines.

Analysis of distribution of DNA methylation in kidney-renal-clear-cell-carcinoma specific genes using entropy.

DNA Methylation is an epigenetic phenomenon in which methyl groups are added to the cytosines, thereby altering the physio-chemical properties of the DNA region and influencing gene expression. Aberrant DNA methylation in a set of genes or across the genome results in many epigenetic diseases including cancer. In this paper, we use entropy to analyze the extent and distribution of DNA methylation in Tumor Suppressor Genes (TSG's) and Oncogenes related to a specific type of cancer (viz.) KIRC (Kidney-renal-clear-cell-carcinoma). We apply various mathematical transformations to enhance the different regions in DNA methylation distribution and compare the resultant entropies for healthy and tumor samples. We also obtain the sensitivity and specificity of classification for the different mathematical transformations. Our findings show that it is not just the measure of methylation, but the distribution of the methylation levels in the genes that are significant in cancer.

Alterations in circadian entrainment precede the onset of depression-like behavior that does not respond to fluoxetine.

Growing evidence links adverse prenatal conditions to mood disorders. We investigated the long-term behavioral alterations induced by prenatal exposure to excess glucocorticoids (dexamethasone--DEX). At 12 months, but not earlier, DEX-exposed mice displayed depression-like behavior and impaired hippocampal neurogenesis, not reversible by the antidepressant fluoxetine (FLX). Concomitantly, we observed arrhythmic glucocorticoid secretion and absent circadian oscillations in hippocampal clock gene expression. Analysis of spontaneous activity showed progressive alterations in circadian entrainment preceding depression. Circadian oscillations in clock gene expression (measured by means of quantitative PCR) were also attenuated in skin fibroblasts before the appearance of depression. Interestingly, circadian entrainment is not altered in a model of depression (induced by methylmercury prenatal exposure) that responds to FLX. Altogether, our results suggest that alterations in circadian entrainment of spontaneous activity, and possibly clock gene expression in fibroblasts, may predict the onset of depression and the response to FLX in patients.

Tet3 mediates stable glucocorticoid-induced alterations in DNA methylation and Dnmt3a/Dkk1 expression in neural progenitors.

Developmental exposure to excess glucocorticoids (GCs) has harmful neurodevelopmental effects, which include persistent alterations in the differentiation potential of embryonic neural stem cells (NSCs). The mechanisms, however, are largely unknown. Here, we investigated the effects of dexamethasone (Dex, a synthetic GC analog) by MeDIP-like genome-wide analysis of differentially methylated DNA regions (DMRs) in NSCs isolated from embryonic rat cortices. We found that Dex-induced genome-wide DNA hypomethylation in the NSCs in vitro. Similarly, in utero exposure to Dex resulted in global DNA hypomethylation in the cerebral cortex of 3-day-old mouse pups. Dex-exposed NSCs displayed stable changes in the expression of the DNA methyltransferase Dnmt3a, and Dkk1, an essential factor for neuronal differentiation. These alterations were dependent on Tet3 upregulation. In conclusion, we propose that GCs elicit strong and persistent effects on DNA methylation in NSCs with Tet3 playing an essential role in the regulation of Dnmt3a and Dkk1. Noteworthy is the occurrence of similar changes in Dnmt3a and Dkk1 gene expression after exposure to excess GC in vivo.

Two new species of the genus Igerna (Hemiptera: Cicadellidae: Megophthalminae) from India.

Two new megophthalmine species of leafhoppers, Igerna kolasibensis sp. nov. and I. shillongensis sp. nov., are described from India, Mizoram and Meghalaya, respectively. Detailed morphological descriptions, illustrations and photographs are provided. An updated key to the species and taxonomic notes on the genus are provided.

A novel cisplatin mediated apoptosis pathway is associated with acid sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer.

Platinum-based anticancer drugs, including cisplatin and carboplatin, have been cornerstones in the treatment of solid tumors. We report here that these DNA-damaging agents, particularly cisplatin, induce apoptosis through plasma membrane disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways. Our objectives were to: quantify the composition of membrane metabolites; and determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS-mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting analysis revealed enhanced apoptosis as measured by: increased phosphocholine, and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and nucleoside triphosphate concentrations. The plasma membrane alterations were accompanied by increased ASMase activity, leading to the upregulation of FAS, FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA, CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase activity and the intrinsic pathways in cisplatin-mediated membrane demise, and contribute to our understanding of the mechanisms by which ovarian tumors may become resistant to cisplatin.

Effect of thermal annealing on the phase evolution of silver tungstate in Ag/WO3 films.

Silver/tungsten oxide multi-layer films are deposited over quartz substrates by RF magnetron sputtering technique and the films are annealed at temperatures 200, 400 and 600°C. The effect of thermal annealing on the phase evolution of silver tungstate phase in Ag/WO3 films is studied extensively using techniques like X-ray diffraction, micro-Raman analysis, atomic force microscopy and photoluminescence studies. The XRD pattern of the as-deposited film shows only the peaks of cubic phase of silver. The film annealed at 200°C shows the presence of XRD peaks corresponding to orthorhombic phase of Ag2WO4 and peaks corresponding to cubic phase of silver with reduced intensity. It is found that, as annealing temperature increases, the volume fraction of Ag decreases and that of Ag2WO4 phase increases and becomes highest at a temperature of 400°C. When the temperature increases beyond 400°C, the volume fraction of Ag2WO4 decreases, due to its decomposition into silver and oxygen deficient phase Ag2W4O13. The micro-Raman spectra of the annealed films show the characteristic bands of tungstate phase which is in agreement with XRD analysis. The surface morphology of the films studied by atomic force microscopy reveals that the particle size and r.m.s roughness are highest for the sample annealed at 400°C. In the photoluminescence study, the films with silver tungstate phase show an emission peak in blue region centered around the wavelength 441 nm (excitation wavelength 256 nm).

Dealing with concept drifts in process mining.

Although most business processes change over time, contemporary process mining techniques tend to analyze these processes as if they are in a steady state. Processes may change suddenly or gradually. The drift may be periodic (e.g., because of seasonal influences) or one-of-a-kind (e.g., the effects of new legislation). For the process management, it is crucial to discover and understand such concept drifts in processes. This paper presents a generic framework and specific techniques to detect when a process changes and to localize the parts of the process that have changed. Different features are proposed to characterize relationships among activities. These features are used to discover differences between successive populations. The approach has been implemented as a plug-in of the ProM process mining framework and has been evaluated using both simulated event data exhibiting controlled concept drifts and real-life event data from a Dutch municipality.

Phylogenetic analysis of Staphylococcus aureus CC398 reveals a sub-lineage epidemiologically associated with infections in horses.

In the early 2000s, a particular MRSA clonal complex (CC398) was found mainly in pigs and pig farmers in Europe. Since then, CC398 has been detected among a wide variety of animal species worldwide. We investigated the population structure of CC398 through mutation discovery at 97 genetic housekeeping loci, which are distributed along the CC398 chromosome within 195 CC398 isolates, collected from various countries and host species, including humans. Most of the isolates in this collection were received from collaborating microbiologists, who had preserved them over years. We discovered 96 bi-allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses in veterinary-care settings (p = 2 × 10(-7)), it remained extremely rare among S. aureus isolates from human infections.

Effect of a checklist on advanced trauma life support workflow deviations during trauma resuscitations without pre-arrival notification.

BACKGROUND: Trauma resuscitations without pre-arrival notification are often initially chaotic, which can potentially compromise patient care. We hypothesized that trauma resuscitations without pre-arrival notification are performed with more variable adherence to ATLS protocol and that implementation of a checklist would improve performance. STUDY DESIGN: We analyzed event logs of trauma resuscitations from two 4-month periods before (n = 222) and after (n = 215) checklist implementation. Using process mining techniques, individual resuscitations were compared with an ideal workflow model of 6 ATLS primary survey tasks performed by the bedside evaluator and given model fitness scores (range 0 to 1). Mean fitness scores and frequency of conformance (fitness = 1) were compared (using Student's t-test or chi-square test, as appropriate) for activations with and without notification both before and after checklist implementation. Multivariable linear regression, controlling for patient and resuscitation characteristics, was also performed to assess the association between pre-arrival notification and model fitness before and after checklist implementation. RESULTS: Fifty-five (12.6%) resuscitations lacked pre-arrival notification (23 pre-implementation and 32 post-implementation; p = 0.15). Before checklist implementation, resuscitations without notification had lower fitness (0.80 vs 0.90; p < 0.001) and conformance (26.1% vs 50.8%; p = 0.03) than those with notification. After checklist implementation, the fitness (0.80 vs 0.91; p = 0.007) and conformance (26.1% vs 59.4%; p = 0.01) improved for resuscitations without notification, but still remained lower than activations with notification. In multivariable analysis, activations without notification had lower fitness both before (b = -0.11, p < 0.001) and after checklist implementation (b = -0.04, p = 0.02). CONCLUSIONS: Trauma resuscitations without pre-arrival notification are associated with a decreased adherence to key components of the ATLS primary survey protocol. The addition of a checklist improves protocol adherence and reduces the effect of notification on task performance.

Long-lasting neurotoxic effects of exposure to methylmercury during development.

Amongst environmental chemical contaminants, methylmercury (MeHg) remains a major concern because of its detrimental effects on developing organisms, which appear to be particularly susceptible to its toxicity. Here, we investigated the effects of low MeHg levels on the development of the nervous system using both in vitro and in vivo experimental models. In neural stem cells (NSCs), MeHg decreased proliferation and neuronal differentiation and induced cellular senescence associated with impairment in mitochondrial function and a concomitant decrease in global DNA methylation. Interestingly, the effects were heritable and could be observed in daughter NSCs never directly exposed to MeHg. By chronically exposing pregnant/lactating mice to MeHg, we found persistent behavioural changes in the male offspring, which exhibited depression-like behaviour that could be reversed by chronic treatment with the antidepressant fluoxetine. The behavioural alterations were associated with a decreased number of proliferating cells and lower expression of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampal dentate gyrus. MeHg exposure also induced long-lasting DNA hypermethylation, increased histone H3-K27 tri-methylation and decreased H3 acetylation at the Bdnf promoter IV, indicating that epigenetic mechanisms play a critical role in mediating the long-lasting effects of perinatal exposure to MeHg. Fluoxetine treatment restored the Bdnf mRNA expression levels, as well as the number of proliferating cells in the granule cell layer of the dentate gyrus, which further supports the hypothesis that links depression to impaired neurogenesis. Altogether, our findings have shown that low concentrations of MeHg induce long-lasting effects in NSCs that can potentially predispose individuals to depression, which we have reported earlier to occur in experimental animals exposed to MeHg during prenatal and early postnatal development.

A single centre study of coil embolization of intracranial aneurysms comparing bare platinum and PGLA-coated coils.

There is no robust consensus on the efficacy of polyglycolic/polylactic acid (PGLA)-coated coils used in the endovascular embolization of intracranial aneurysms. We present a comparative study of bare platinum coils and PGLA-coated Gugliemi Detachable Coils (GDC) in the treatment of intracranial aneurysms at a single centre, using target aneurysm recurrence and angiographic recanalization as the primary endpoints. We included all patients treated between 1998 and 2009 who had undergone at least one angiographic post-procedural follow-up. Patient demographics, clinical presentation, operative notes, and all relevant imaging were collected. Of the 441 aneurysms with follow-up, 290 were treated with at least one PGLA coil and 151 aneurysms were treated exclusively with bare platinum coils. At follow-up, 26.5% of platinum controls demonstrated angiographic recanalization, compared to 31.4% of PGLA-treated aneurysms (p=0.002). PGLA-treated aneurysms were more likely to have an angiographic remnant at follow-up (odds ratio [OR]=1.96, 95% confidence interval [CI]=1.26-3.04, p=0.003). The post-operative Raymond score was the only predictor of retreatment (OR=1.6, 95% CI=1.08-2.24, p=0.020), and was the second strongest predictor of a complete angiographic result at follow-up (OR=1.67, 95% CI=1.22-2.27, p=0.001). We concluded that PGLA-coated coils demonstrated poorer post-operative and long-term angiographic occlusion in the treatment of intracranial aneurysms, compared to bare platinum coils.

Observation of strong coupling through transmission modification of a cavity-coupled photonic crystal waveguide.

We investigate strong coupling between a single quantum dot (QD) and photonic crystal cavity through transmission modification of an evanescently coupled waveguide. Strong coupling is observed through modification of both the cavity scattering spectrum and waveguide transmission. We achieve an overall Q of 5800 and an exciton-photon coupling strength of 21 GHz for this integrated cavity-waveguide structure. The transmission contrast for the bare cavity mode is measured to be 24%. These results represent important progress towards integrated cavity quantum electrodynamics using a planar photonic architecture.

Effect of swarming on biodiversity in non-symmetric rock-paper-scissor game.

Cyclic dominance of species is a potential mechanism for maintaining biodiversity. The author investigates the generalised scenario when the cyclic dominance of three or more interacting species is described by a non-symmetric matrix game that has multiple Nash equilibria. Modified Lotka-Volterra equations are proposed to incorporate the effects of swarming, and the condition for biodiversity is derived. The species are modelled using replicator equations, where each member of the species is assigned a fitness value. The authors show, for the first time, that the 'swarming effect' has an important role to play in the maintenance of biodiversity. The authors have also discovered the existence of a critical value of the swarming parameter for a given mobility, above which there is a high probability of existence of biodiversity.