Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk. ...In a population-based case-control study designed to investigate the relation between these medications and prostate cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with prostate cancer between January 1, 2002, and December 31, 2005, and 942 age-matched controls from King County, Washington. A significant 21% reduction in the risk of prostate cancer was observed among current users of aspirin compared with nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (>5 years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk. There was no evidence that the association with aspirin use varied by disease aggressiveness, but there was effect modification (Pinteraction = 0.02) with a genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763). Prostate cancer risk was not related to use of either nonaspirin NSAIDs or acetaminophen. These results contribute further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research.
Abstract
The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010–2014. Participants were randomized to receive ...either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.
In this study, we characterized the impact of regulatory water releases relative to watershed inputs on the quality of receiving waters to identify if and how managed releases could be scheduled to ...mitigate nutrient export and downstream water quality impairment. We specifically investigated freshwater flow partitioning to the Caloosahatchee River and Estuary (CRE) from a large managed lake, Lake Okeechobee, and the CRE's upstream watershed, the C‐43 basin, in southwest Florida (USA). A water balance was developed to identify dominant freshwater inflow sources (i.e., Lake Okeechobee vs. watershed inputs) over time. From the water balance, analyses of historical trends were performed to detect changes in freshwater inflow contributions to the CRE. Further, seasonal and annual concentration variations and long‐term concentration‐discharge (C‐Q) relationships were analyzed to better understand biogeochemical and hydrological processes in the system in relation to freshwater source. Since 1966, we found the duration and magnitude of flows from the C‐43 basin were higher than those from Lake Okeechobee releases. However, recent increases in the annual water volume and proportion of inflow coming from Lake Okeechobee to the CRE were observed. The C‐Q analysis revealed that nitrate and ammonium concentrations in the CRE were responsive to changes in discharge, while total phosphorus and orthophosphate concentrations were chemostatic. While modifications to the Lake Okeechobee operation schedule could potentially mitigate downstream inorganic nitrogen loading, this potential is limited by complex, seasonal C‐Q relationships and confounding effects from surrounding watersheds.
Plain Language Summary
Water levels in large lakes at risk of flooding into surrounding areas are controlled using engineered structures like dams. To ensure water levels do not overtop a lake's banks, water is released from control structures and then flows into downstream waterways like rivers and estuaries. When a managed lake has water quality challenges, such as excess nutrient concentrations or harmful algal blooms, water releases may affect the quality of downstream waters, but determining the role of released waters on downstream water quality is challenging. In this study, we analyzed nitrogen and phosphorus concentrations in the Caloosahatchee River and Estuary (CRE), a waterway that receives released water from Lake Okeechobee, a large managed lake, to understand whether there were relationships between Lake Okeechobee water releases and nutrient concentrations in the CRE. We found that released water had an impact on downstream water quality, but that water runoff from the surrounding land area had a greater effect. Nitrogen concentrations varied based on the time of year and amount of flowing water, while phosphorus concentrations did not. Therefore, changes to the timing and volume of water releases may not affect downstream phosphorus concentrations, but could potentially improve downstream nitrogen concentrations.
Key Points
Downstream nitrate & ammonium concentrations were seasonally responsive to flow, while total phosphorus & orthophosphate were chemostatic
Nutrient concentrations were strongly related to watershed inputs, and less consistently to regulatory releases
Restoring downstream water quality will require reservoir and watershed management, and actions that go beyond modified release scheduling
We report results from the Cryogenic Dark Matter Search at the Soudan Underground Laboratory (CDMS II) featuring the full complement of 30 detectors. A blind analysis of data taken between October ...2006 and July 2007 sets an upper limit on the weakly interacting massive particle (WIMP) nucleon spin-independent cross section of 6.6x10;{-44} cm;{2} (4.6x10;{-44} cm;{2} when combined with previous CDMS II data) at the 90% confidence level for a WIMP mass of 60 GeV/c;{2}. This achieves the best sensitivity for dark matter WIMPs with masses above 44 GeV/c;{2}, and significantly restricts the parameter space for some favored supersymmetric models.
Up to 1% of adults will have a leg ulcer at some time. The majority of leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or weakness of the valves in the ...veins of the leg. Prevention and treatment of venous ulcers is aimed at reducing the pressure either by removing/repairing the veins, or by applying compression bandages/stockings to reduce the pressure in the veins.The majority of venous ulcers heal with compression bandages, however ulcers frequently recur. Clinical guidelines therefore recommend that people continue to wear compression, usually in the form of hosiery (tights, stockings, socks) after their ulcer heals, to prevent recurrence.
To assess the effects of compression (socks, stockings, tights, bandages) in preventing the recurrence of venous ulcers. If compression does prevent ulceration compared with no compression, then to identify whether there is evidence to recommend particular levels of compression (high, medium or low, for example), types of compression, or brands of compression to prevent ulcer recurrence after healing.
For this update we searched The Cochrane Wounds Group Specialised Register (searched 1 March 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2); Ovid MEDLINE (1950 to February Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, February 29, 2012); Ovid EMBASE (1980 to 2012 Week 08); and EBSCO CINAHL (1982 to 1 March 2012).
Randomised controlled trials evaluating compression bandages or hosiery for preventing the recurrence of venous ulcers.
Two review authors undertook data extraction and risk of bias assessment independently.
Four trials (979 participants) were eligible for inclusion in this review. One trial in patients with recently healed venous ulcers (n = 153) compared recurrence rates with and without compression and found that compression significantly reduced ulcer recurrence at six months (Risk ratio (RR) 0.46, 95% CI 0.27 to 0.76).Two trials compared high-compression hosiery (equivalent to UK class 3) with moderate-compression hosiery (equivalent to UK class 2). The first study (n=300) found no significant reduction in recurrence at five years follow up with high-compression hosiery compared with moderate-compression (RR 0.82, 95% CI 0.61 to 1.12). The second study (n = 338) assessed ulcer recurrence at three years follow up and found that high-compression hosiery reduced recurrence compared with moderate-compression (RR 0.57, 95% CI 0.39 to 0.81). Statistically significant heterogeneity precluded meta-analysis of the results from these studies. Patient-reported compliance rates were reported in both trials;,there was significantly higher compliance with medium-compression than with high-compression hosiery in one and no significant difference in the second.A fourth trial (166 patients) found no statistically significant difference in recurrence between two types of medium (UK class 2) compression hosiery (Medi versus Scholl: RR 0.74, 95% CI 0.45 to 1.2).No trials of compression bandages for preventing ulcer recurrence were identified.
There is evidence from one trial that compression hosiery reduces rates of reulceration of venous ulcers compared with no compression. Results from one trial suggest that recurrence is lower in high-compression hosiery than in medium-compression hosiery at three years whilst another trial found no difference at 5 years. Rates of patient intolerance of compression hosiery were high. There is insufficient evidence to aid selection of different types, brands, or lengths of compression hosiery.
The cytochrome CYP3A gene products, expressed in mammalian liver, are essential
for the metabolism of lipophilic substrates, including endogenous steroid
hormones and prescription drugs. CYP3A ...enzymes are extremely
versatile and are inducible by many of their natural and xenobiotic substrates.
Consequently, they form the molecular basis for many clinical drug-drug
interactions. The induction of CYP3A enzymes is species-specific, and we have postulated that it involves one or more cellular
factors, or receptor-like xeno-sensors. Here we identify one
such factor unequivocally as the nuclear receptor pregnenolone X receptor
(PXR) and its human homologue, steroid and xenobiotic receptor
(SXR). We show that targeted disruption of the mouse
PXR gene abolishes induction of CYP3A by prototypic inducers such as dexamethasone
or pregnenolone-16α-carbonitrile. In transgenic mice, an activated form
of SXR causes constitutive upregulation of CYP3A gene expression and
enhanced protection against toxic xenobiotic compounds. Furthermore, we show
that the species origin of the receptor, rather than the promoter structure
of CYP3A genes, dictates the species-specific pattern of CYP3A inducibility.
Thus, we can generate 'humanized' transgenic mice that are responsive
to human-specific inducers such as the antibiotic rifampicin. We conclude
that SXR/PXR genes encode the primary species-specific xeno-sensors that mediate
the adaptive hepatic response, and may represent the critical biochemical
mechanism of human xenoprotection.
Tropical tree height-diameter (H:D) relationships may vary by forest type and region making large-scale estimates of above-ground biomass subject to bias if they ignore these differences in stem ...allometry. We have therefore developed a new global tropical forest database consisting of 39 955 concurrent H and D measurements encompassing 283 sites in 22 tropical countries. Utilising this database, our objectives were: 1. to determine if H:D relationships differ by geographic region and forest type (wet to dry forests, including zones of tension where forest and savanna overlap). 2. to ascertain if the H:D relationship is modulated by climate and/or forest structural characteristics (e.g. stand-level basal area, A). 3. to develop H:D allometric equations and evaluate biases to reduce error in future local-to-global estimates of tropical forest biomass. Annual precipitation coefficient of variation (PV), dry season length (SD), and mean annual air temperature (TA) emerged as key drivers of variation in H:D relationships at the pantropical and region scales. Vegetation structure also played a role with trees in forests of a high A being, on average, taller at any given D. After the effects of environment and forest structure are taken into account, two main regional groups can be identified. Forests in Asia, Africa and the Guyana Shield all have, on average, similar H:D relationships, but with trees in the forests of much of the Amazon Basin and tropical Australia typically being shorter at any given D than their counterparts elsewhere. The region-environment-structure model with the lowest Akaike's information criterion and lowest deviation estimated stand-level H across all plots to within amedian −2.7 to 0.9% of the true value. Some of the plot-to-plot variability in H:D relationships not accounted for by this model could be attributed to variations in soil physical conditions. Other things being equal, trees tend to be more slender in the absence of soil physical constraints, especially at smaller D. Pantropical and continental-level models provided less robust estimates of H, especially when the roles of climate and stand structure in modulating H:D allometry were not simultaneously taken into account.
Background Malignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always ...appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment. Aims To develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials). Methods A systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set. Results 130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences. Conclusion Use of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice.
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune ...system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.
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