How high (and far) can you go? On setting fines in cartel cases involving vertically-integrated undertakings and foreign sales

Refresh-free dynamic standard-cell based memories: Application to a QC-LDPC decoder

The area and power consumption of low-density parity check (LDPC) decoders are typically dominated by embedded memories. To alleviate such high memory costs, this paper exploits the fact that all internal memories of a LDPC decoder are frequently updated with new data. These unique memory access statistics are taken advantage of by replacing all static standard-cell based memories (SCMs) of a prior-art LDPC decoder implementation by dynamic SCMs (D-SCMs), which are designed to retain data just long enough to guarantee reliable operation. The use of D-SCMs leads to a 44% reduction in silicon area of the LDPC decoder compared to the use of static SCMs. The low-power LDPC decoder architecture with refresh-free D-SCMs was implemented in a 90nm CMOS process, and silicon measurements show full functionality and an information bit throughput of up to 600 Mbps (as required by the IEEE 802.11n standard).

Chronic PEGylated obestatin treatment prevents the onset of high fat diet-induced hypertension and endothelial dysfunction in the absence of metabolic actions

Background: Obestatin is a gastrointestinal peptide with established metabolic actions and emerging vascular effects which involve activation of NO signalling. The aim of this study was to investigate effects of a recently-characterised stable analogue, PEGylated obestatin (PEG-OB), in the setting of diet-induced obesity which is associated with both metabolic and vascular dysfunction. Methods: Male Sprague Dawley rats (6 weeks; n=8) were maintained on standard (SD) or high fat (HF) diet (60% fat) for 8 weeks with once-daily injection of either PEG-OB (50nmol/kg/day) or saline from 2 weeks. Results: HF feeding for 8 weeks resulted in marked body weight gain which was not affected by chronic PEG-OB treatment (HF saline, 175.0±12.2; HF PEG-OB, 190.4±6.4g; P=NS). Similarly, blood glucose, as indicated by HbA1c (HF saline, 6.30±0.15; HF PEG-OB, 6.13±0.36%; P=NS) and insulin tolerance (HF saline, 105.2±52.5; HF PEG-OB, 90.3±45.4mmol/L.min; P=NS), were unaltered by PEG-OB. Despite the apparent lack of metabolic effects, chronic PEG-OB treatment markedly attenuated development of HF-induced hypertension (HF saline, 146.5±4.9mmHg; HF PEG-OB, 123.0±9.7mmHg; P<0.01), assessed by tail-cuff plethysmography. Furthermore, organ bath pharmacology in isolated aortic rings, indicated that HF diet-induced endothelial dysfunction was completely prevented by PEG-OB (acetylcholine, EC50: SD saline, 335±113; HF saline, 758±164; HF PEG-OB, 277±85nmol/L; P<0.05). However, contraction to phenylephrine and relaxation to the NO donor, sodium nitroprusside, were unaltered between groups. Conclusions: PEG-OB exerts beneficial effects on hypertension and endothelial function in diabetes independently of metabolic actions suggesting that obestatin signalling may represent a novel therapeutic target to reduce the risk of associated cardiovascular complications.

Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial

Importance: The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.

Objective: To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.

Design, Setting, and Participants: Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.

Exposures: Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.

Main Outcomes and Measures: Failure-free survival (FFS) and overall survival.

Results: A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).

Conclusions and Relevance: Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.

Trial Registration: clinicaltrials.gov Identifier: NCT00268476; ISRCTN78818544.

Abundance and diversity of sedimentary bacterial communities in a coastal productive setting in the Western Irish Sea

The bacterial community composition and biomass abundance from a depositional mud belt in the western Irish Sea and regional sands were investigated by phospholipid ester-linked fatty acid profiling, denaturing gradient gel electrophoresis and barcoded pyrosequencing of 16S rRNA genes. The study area varied by water depth (12-111 m), organic carbon content (0.09-1.57% TOC), grain size, hydrographic regime (well-mixed vs. stratified), and water column phytodetrital input (represented by algal polyunsaturated PLFA). The relative abundance of bacterial-derived PLFA (sum of methyl-branched, cyclopropyl and odd-carbon number PLFA) was positively correlated with fine-grained sediment, and was highest in the depositional mud belt. A strong association between bacterial biomass and eukaryote primary production was suggested based on observed positive correlations with total nitrogen and algal polyunsaturated fatty acids. In addition, 16S rRNA genes affiliated to the classes Clostridia and Flavobacteria represented a major proportion of total 16S rRNA gene sequences. This suggests that benthic bacterial communities are also important degraders of phytodetrital organic matter and closely coupled to water column productivity in the western Irish Sea.

Effect of providing free glasses on children's educational outcomes in China: cluster randomized controlled trial

Objective: To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. Design: Cluster randomized, investigator masked, controlled trial.Setting 252 primary schools in two prefectures in western China, 2012-13. Participants: 3177 of 19 934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study.Interventions Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. Main outcome measures: Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. Results: Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, −0.04 to 0.09) or family wealth (0.01, −0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. Conclusions: The provision of free glasses to Chinese children with myopia improves children’s performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting. Trial Registration: Current Controlled Trials ISRCTN03252665.

Height, stunting, and refractive error among rural Chinese schoolchildren: the See Well to Learn Well project.

PURPOSE: To evaluate the hypothesis that changes in nutritional status could be partly responsible for observed increases in myopia prevalence among Chinese children. DESIGN: Cross-sectional cohort study. METHODS: Rural Chinese secondary school children participating in a study of interventions to promote spectacle use were randomly sampled (20% of children with uncorrected vision >6/12 bilaterally, and 100% of remaining children) and underwent cycloplegic refraction with subjective refinement and measurement of height and weight. Stunting was defined according to the World Health Organization standard population. RESULTS: Among 3226 children in the sample, 2905 (90.0%) took part. Among 1477 children undergoing refraction, 1371 (92.8%) had height and weight measurements. These children had a mean age of 14.5 +/- 1.4 years, 59.8% were girls, and mean spherical equivalent refraction was -1.93 +/- 1.82 diopters. Stunting was present in 87 children (6.4%). While height was inversely associated with refractive error (RE) (taller children were more myopic) among boys (r = -0.147, P = .001), this disappeared when adjusting for age, and no such association was observed among girls. Neither girls nor boys with stunting differed significantly in refraction from children without stunting, and neither stunting nor height was associated with RE when adjusting for age, height, and parental education. The power of this study to have detected a 0.75 diopters difference in RE between children with and without stunting was 0.96. CONCLUSION: Results from this cross-sectional study are not consistent with the hypothesis that nutritional status is a determinant of RE in this setting.

Music therapy for end-of-life care: an updated systematic review

Background: Music therapy during palliative and end-of-life care is well established and positive benefits for patients have been reported.
Aim: Assess the effectiveness of music therapy versus standard care alone or standard care in combination with other therapies for improving psychological, physiological and social outcomes among adult patients in any palliative care setting.
Data sources: In order to update an existing Cochrane systematic review, we searched MEDLINE, CINAHL, EMBASE, PsycINFO, CENTRAL, ClinicalTrials.gov register, and Current Controlled Trials register to identify randomised or quasi-randomised controlled trails published between 2009 and April 2015. Nine electronic music therapy journals were searched from 2009 until April 2015, along with reference lists and contact was made with key experts in music therapy. Only studies published in English were eligible for inclusion. Two reviewers independently screened titles, abstracts, assessed relevant studies for eligibility, extracted data and judged risk of bias for included studies. Disagreements were resolved through discussion with a third reviewer. Data were synthesised in Revman using the random effects model. Heterogeneity was assessed using l2.
Results: Three studies were included in the review. Findings suggest music therapy may be effective for helping to reduce pain in palliative care patients (standard mean deviation (SMD) = -0.42, 95% CI -0.68 to -0.17, P = 0.001).
Conclusions: Available evidence did not support the use of music therapy to improve overall quality-of-life in palliative care. While this review suggests music therapy may be effective for reducing pain, this is based on studies with a high risk of bias. Further high quality research is required.

Lattice-based Encryption Over Standard Lattices in Hardware

Lattice-based cryptography has gained credence recently as a replacement for current public-key cryptosystems, due to its quantum-resilience, versatility, and relatively low key sizes. To date, encryption based on the learning with errors (LWE) problem has only been investigated from an ideal lattice standpoint, due to its computation and size efficiencies. However, a thorough investigation of standard lattices in practice has yet to be considered. Standard lattices may be preferred to ideal lattices due to their stronger security assumptions and less restrictive parameter selection process. In this paper, an area-optimised hardware architecture of a standard lattice-based cryptographic scheme is proposed. The design is implemented on a FPGA and it is found that both encryption and decryption fit comfortably on a Spartan-6 FPGA. This is the first hardware architecture for standard lattice-based cryptography reported in the literature to date, and thus is a benchmark for future implementations.
Additionally, a revised discrete Gaussian sampler is proposed which is the fastest of its type to date, and also is the first to investigate the cost savings of implementing with lamda_2-bits of precision. Performance results are promising in comparison to the hardware designs of the equivalent ring-LWE scheme, which in addition to providing a stronger security proof; generate 1272 encryptions per second and 4395 decryptions per second.

Immune-derived PD-L1 gene expression defines a subgroup of stage II/III colorectal cancer patients with favorable prognosis that may be harmed by adjuvant chemotherapy

A recent phase 2 study of metastatic colorectal carcinoma (CRC) patients showed that mismatch repair gene status was predictive of clinical response to PD-1-targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV CRC, suggesting that the amount of PD-L1 protein expression could identify late stage patients who may benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic CRC are also present in stage II/III CRC, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a significant association of PD-L1 gene expression with MSI in early stage CRC (P < 0.001) and show that unlike in non-CRC tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low v PD-L1high HR = 9.09; CI, 2.11-39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI,1.10-22.35). Building on the promising results from the metastatic CRC PD-1-targeting trial, we provide compelling evidence that PD-L1high/MSI/immunehigh stage II/III CRC patients should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment.