We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near
,
,
,
,
, and 13q21.31, and ...identify and replicate novel findings near
,
, and
. We also validate previous findings near 5q33.3/
and
, whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Background/Aims: Patients with pancreatic ductal adenocarcinoma (PDA) have a median survival of less than six months from diagnosis. Palliative chemotherapy with the current standard gemcitabine does ...only marginally improve median survival. There may be subgroups of patients receiving palliative therapy that have a better prognosis. Factors predicting response to palliative therapy are ill-defined, though. Heparanase, an endoglycosidase degrading components of the extracellular matrix, promotes cell invasion, is involved in angiogenesis and plays a role in tumor metastases. It is expressed in PDA and its expression is associated with shorter postoperative survival after pancreatic resections. Methods: 58 patients with inoperable PDA were treated with gemcitabine therapy. Tissue sections from primary or metastatic tumor were used for immunohistochemical analysis. Heparanase expression was determined and correlated to tumor response, time to progression and survival. Results: Heparanase expression was detectable by immunohistochemistry in 36 out of 58 (62%) patients analyzed. Overall survival was 7.4 vs. 13.3 months (p = 0.006) in heparanase-positive and -negative tumors, respectively. Progression-free survival was 1.3 vs. 3.4 months, respectively (p = 0.47). Conclusion: Heparanase expression may be a useful marker to predict response to palliative therapy with gemcitabine in PDA.
A meta-analysis of studies comparing high doses of bupivacaine with ropivacaine for labor pain found a higher incidence of forceps deliveries, motor block, and poorer neonatal outcome with ...bupivacaine. The purpose of this study was to determine if there is a difference in these outcomes when a low concentration of patient-controlled epidural bupivacaine combined with fentanyl is compared with ropivacaine combined with fentanyl.
This was a multicenter, randomized, controlled trial, including term, nulliparous women undergoing induction of labor. For the initiation of analgesia, patients were randomized to receive either 15 ml bupivacaine, 0.1%, or 15 ml ropivacaine, 0.1%, each with 5 microg/ml fentanyl. Analgesia was maintained with patient-controlled analgesia with either local anesthetic, 0.08%, with 2 microg/ml fentanyl. The primary outcome was the incidence of operative delivery. We also examined other obstetric, neonatal, and analgesic outcomes.
There was no difference in the incidence of operative delivery between the two groups (148 of 276 bupivacaine recipients vs. 135 of 279 ropivacaine recipients; P = 0.25) or any obstetric or neonatal outcome. The incidence of motor block was significantly increased in the bupivacaine group compared with the ropivacaine group at 6 h (47 of 93 vs. 29 of 93, respectively; P = 0.006) and 10 h (29 of 47 vs. 16 of 41, respectively; P = 0.03) after injection. Satisfaction with mobility was higher with ropivacaine than with bupivacaine (mean +/- SD: 76 +/- 23 vs. 72 +/- 23, respectively; P = 0.013). Satisfaction for analgesia at delivery was higher for bupivacaine than for ropivacaine (mean +/- SD: 71 +/- 25 vs. 66 +/- 26, respectively; P = 0.037).
There was no difference in the incidence of operative delivery or neonatal outcome among nulliparous patients who received low concentrations of bupivacaine or ropivacaine for labor analgesia.
RIB INJURY - TENNIS Small, E W.; Kronberg, J D.
Medicine and science in sports and exercise,
05/2003, Letnik:
35, Številka:
Supplement 1
Journal Article
PDF
