Evidence of bacteriophage-mediated horizontal transfer of bacterial 16S rRNA genes in the viral metagenome of the marine sponge Hymeniacidon perlevis

Marine sponges have never been directly examined with respect to the presence of viruses or their potential involvement in horizontal gene transfer. Here we demonstrate for the first time, the presence of viruses in the marine sponge Hymeniacidon perlevis. Moreover, bacterial 16s rDNA was detected in DNA isolated from these viruses, indicating that phage-derived transduction appears to occur in H. perlevis. Phylogenetic analysis revealed that bacterial 16s rDNA isolated from sponge-derived viral and total DNA differed significantly, indicating that not all species are equally involved in transduction.

A Common KIF6 Polymorphism Increases Vulnerability to Low-Density Lipoprotein Cholesterol: Two Meta-Analyses and a Meta-Regression Analysis

Background: We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.

Dexamethasone reduces pain, vomiting and overall complications following tonsillectomy in adults: a systematic review and meta-analysis of randomised controlled trials

Background: Tonsillectomy is one of the most common surgical procedures, but there is debate whether systemic steroids should be used to reduce pain and post-operative complications.

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials

Background Moderate di?erences in e?cacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could a? ect treatment choices. We sought any such di?erences.

Methods We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plusanthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44 000); one anthracyclinebased regimen versus another (n=7000) or versus cyclo phosphamide, methotrexate, and ?uorouracil (CMF; n=18 000); and polychemotherapy versus no chemotherapy (n=32 000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to de? ne standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported.

Findings In trials adding four separate cycles of a taxane to a ?xed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided signi?cance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no signi?cant di?erence (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or
standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little a? ected by age, nodal status, tumour diameter or di?erentiation (moderate or poor; few were well di?erentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality di?erences paralleled breast cancer mortality di?erences, despite taxane, anthracycline, and other toxicities.

Interpretation 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute bene?t, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both.

Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials

Background: As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen.
Methods: We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment.
Findings: In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0.53 [SE 0.03] during years 0-4 and RR 0.68 [0.06] during years 5-9 [both 2p<0.00001]; but RR 0.97 [0.10] during years 10-14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10-19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0.67 [0.08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0.71 [0.05] during years 0-4, 0.66 [0.05] during years 5-9, and 0.68 [0.08] during years 10-14; p<0.0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality.
Interpretation: 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen.
Funding: Cancer Research UK, British Heart Foundation, and Medical Research Council.