Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

Sequencing of the Sea Lamprey (Petromyzon marinus) Genome Provides Insights into Vertebrate Evolution

Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms

Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial

Summary: Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more eff ective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more eff ective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and effi cacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m², l-folinic acid 175 mg, fl uorouracil 400 mg/m² bolus, then 2400 mg/m² by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the fi rst 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratifi cation variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no signifi cant diff erences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had complications prolonging hospital stay (p=0·81). 98% (50 of 51) of postoperative chemotherapy patients had T3 or more advanced tumours confi rmed at post-resection pathology compared with 91% (90 of 99) of patients following preoperative chemotherapy (p=0·10). Preoperative therapy resulted in signifi cant downstaging of TNM5 compared with the postoperative group (p=0·04), including two pathological complete responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p<0·0001), resection margin involvement (4% [ four of 99] vs 20% [ten of 50], p=0·002), and blinded centrally scored tumour regression grading: 31% (29 of 94) vs 2% (one of 46) moderate or greater regression (p=0·0001). Interpretation Preoperative chemotherapy for radiologically staged, locally advanced operable primary colon cancer is feasible with acceptable toxicity and perioperative morbidity. Proceeding to the phase 3 trial, to establish whether the encouraging pathological responses seen with preoperative therapy translates into improved long-term oncological outcome, is appropriate

Increased Glenoid Retroversion Is Associated With Increased Rotator Cuff Strength in the Shoulder.

BACKGROUND: The rotator cuff muscles are critical secondary stabilizers in the shoulder. Increased glenoid retroversion and rotator cuff strength have been associated with the risk of posterior shoulder instability; however, the effect of increased glenoid retroversion on rotator cuff strength remains unclear. PURPOSE/HYPOTHESIS: The purpose was to examine the association between glenoid version and rotator cuff strength in the shoulder in a young and healthy population with no history of shoulder instability. The hypothesis was that increased glenoid retroversion would be associated with increases in rotator cuff muscle strength. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A prospective cohort study was conducted over a 4-year period within a high-risk population to identify the risk factors for shoulder instability. Analyzed participants included 574 freshmen entering a United States service academy. Baseline data collected upon entry into the study included magnetic resonance imaging measurements of glenoid version. Rotator cuff strength was also assessed at baseline using a handheld dynamometer. Internal and external rotation strength were assessed with the glenohumeral joint positioned in neutral and in 45° of abduction. The current study represents an analysis of the baseline data from this cohort. RESULTS: The mean age, height, and weight of participants was 18.77 ± 0.97 years, 176.81 ± 8.48 cm, and 73.80 ± 12.45 kg, respectively. The mean glenoid version at baseline was 7.79°± 4.85° of retroversion. Univariate linear regression analyses demonstrated that increased glenoid retroversion was associated with increased internal and external rotation strength of the rotator cuff in neutral and 45° of abduction ( CONCLUSION: The results of this study demonstrate that as glenoid retroversion increases, internal and external rotation strength of the rotator cuff also increase in a young and healthy athletic population. These compensatory changes may contribute to increased glenohumeral dynamic stability in the presence of worse static stability with increasing retroversion

A Scalable and Regioselective Synthesis of 2‑Difluoromethyl Pyridines from Commodity Chemicals

A scalable <i>de novo</i> synthesis of difluoromethyl pyridines from inexpensive materials is reported. The pyridyl subunit is built around the difluoromethyl group rather than a late stage introduction of this moiety. This user-friendly approach allows access to a diverse range of substitution patterns on all positions on the ring system and on the difluoromethyl group