DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.

RESULTS: Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.

CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).

Advanced energy efficient coordinated multi-point transmission for OFDMA

The ever-growing energy consumption in mobile networks stimulated by the expected growth in data tra ffic has provided the impetus for mobile operators to refocus network design, planning and deployment towards reducing the cost per bit, whilst at the same time providing a signifi cant step towards reducing their operational expenditure. As a step towards incorporating cost-eff ective mobile system, 3GPP LTE-Advanced has adopted the coordinated multi-point (CoMP) transmission technique due to its ability to mitigate and manage inter-cell interference (ICI). Using CoMP the cell average and cell edge throughput are boosted. However, there is room for reducing energy consumption further by exploiting the inherent exibility of dynamic resource allocation protocols. To this end packet scheduler plays the central role in determining the overall performance of the 3GPP longterm evolution (LTE) based on packet-switching operation and provide a potential research playground for optimizing energy consumption in future networks. In this thesis we investigate the baseline performance for down link CoMP using traditional scheduling approaches, and subsequently go beyond and propose novel energy e fficient scheduling (EES) strategies that can achieve power-e fficient transmission to the UEs whilst enabling both system energy effi ciency gain and fairness improvement. However, ICI can still be prominent when multiple nodes use common resources with di fferent power levels inside the cell, as in the so called heterogeneous networks (Het- Net) environment. HetNets are comprised of two or more tiers of cells. The rst, or higher tier, is a traditional deployment of cell sites, often referred to in this context as macrocells. The lower tiers are termed small cells, and can appear as microcell, picocells or femtocells. The HetNet has attracted signiffi cant interest by key manufacturers as one of the enablers for high speed data at low cost. Research until now has revealed several key hurdles that must be overcome before HetNets can achieve their full potential: bottlenecks in the backhaul must be alleviated, as well as their seamless interworking with CoMP. In this thesis we explore exactly the latter hurdle, and present innovative ideas on advancing CoMP to work in synergy with HetNet deployment, complemented by a novel resource allocation policy for HetNet tighter interference management. As system level simulator has been used to analyze the proposed algorithm/protocols, and results have concluded that up to 20% energy gain can be observed.

Les meilleures pratiques en prévention de la toxicomanie point de vue des adolcescents(es)

Au cours des dix dernières années, la proportion d'adolescents consommateurs de psychotropes a diminué (Institut National de Santé Publique du Québec (INSPQ), 2009). Bien que cette proportion ait diminué, il demeure évident que le nombre de jeunes consommateurs demeure préoccupant (INSPQ, 2009), et ce, malgré tous les efforts des gouvernements pour prévenir l'usage et l'abus de psychotropes. Or, tous les programmes de prévention ne se valent pas. Ce projet de recherche de type exploratoire permettra d'identifier les critères des activités de prévention en toxicomanie qui (1) ont influencé leur perception de la toxicomanie et (2) ont influencé leur propre consommation de psychotropes (soit à la hausse ou à la baisse), et ce, par la consultation d'adolescents. Les données résultent d'entrevues semi-structurées réalisées à partir d'un échantillon composé de 12 adolescents(es). Plusieurs critères ont été abordés lors des discussions soient les approches utilisées, les médiums utilisés, la nature du message, le niveau d'exposition, la nature de l'intervention, la nature des animateurs, les stratégies pédagogiques, les jeunes ciblés et enfin, le niveau d'implication des jeunes. Ce présent projet de mémoire présente donc la prise de position que les jeunes ont émise quant à ces critères.

Last End Point / Pinckney Island PSG - R036/R037

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Last End Point / Pinckney Island PSG - R036/R0378 Recreational Shellfish Ground in Beaufort County.

Chechessee Point PSG - R061

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Chechessee Point PSG - R061 Recreational Shellfish Ground in Beaufort County.

Haig Point S005

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Haig Point S005 Recreational Shellfish Ground in Beaufort County.

Coffin Point S127

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Coffin Point S127 Recreational Shellfish Ground in Beaufort County.

Santee Point S340

The South Carolina Department of Natural Resources provides maps to recreational and state shellfish grounds, available to the public for recreational harvesting or to commercial harvest. This map shows the location of Santee Point S340 Recreational Shellfish Ground in Georgetown County.

The Point teen health centers

This is a poster in both Spanish and English advertising The Point, a teen health center in Spartanburg S.C.

An integrated 256-point complex FFT processor for real-time spectrum analysis and measurement

This paper describes in detail the design of a custom CMOS Fast Fourier Transform (FFT) processor for computing 256-point complex FFT. The FFT is well suited for real-time spectrum analysis in instrumentation and measurement applications. The FFT butterfly processor consists of one parallel-parallel multiplier and two adders. It is capable of computing one butterfly computation every 100 ns thus it can compute 256-complex point FFT in 25.6 μs excluding data input and output processes.

Parallel decoding of turbo codes using multi-point trellis termination and collision-free interleavers

The UMTS turbo encoder is composed of parallel concatenation of two Recursive Systematic Convolutional (RSC) encoders which start and end at a known state. This trellis termination directly affects the performance of turbo codes. This paper presents performance analysis of multi-point trellis termination of turbo codes which is to terminate RSC encoders at more than one point of the current frame while keeping the interleaver length the same. For long interleaver lengths, this approach provides dividing a data frame into sub-frames which can be treated as independent blocks. A novel decoding architecture using multi-point trellis termination and collision-free interleavers is presented. Collision-free interleavers are used to solve memory collision problems encountered by parallel decoding of turbo codes. The proposed parallel decoding architecture reduces the decoding delay caused by the iterative nature and forward-backward metric computations of turbo decoding algorithms. Our simulations verified that this turbo encoding and decoding scheme shows Bit Error Rate (BER) performance very close to that of the UMTS turbo coding while providing almost %50 time saving for the 2-point termination and %80 time saving for the 5-point termination.