Showing papers by "University of Miami published in 2006"
TL;DR: In this paper, the authors examined some aspects of the hydrological cycle that are robust across the models, including the decrease in convective mass fluxes, the increase in horizontal moisture transport, the associated enhancement of the pattern of evaporation minus precipitation and its temporal variance, and decrease in the horizontal sensible heat transport in the extratropics.
Abstract: Using the climate change experiments generated for the Fourth Assessment of the Intergovernmental Panel on Climate Change, this study examines some aspects of the changes in the hydrological cycle that are robust across the models. These responses include the decrease in convective mass fluxes, the increase in horizontal moisture transport, the associated enhancement of the pattern of evaporation minus precipitation and its temporal variance, and the decrease in the horizontal sensible heat transport in the extratropics. A surprising finding is that a robust decrease in extratropical sensible heat transport is found only in the equilibrium climate response, as estimated in slab ocean responses to the doubling of CO2, and not in transient climate change scenarios. All of these robust responses are consequences of the increase in lower-tropospheric water vapor.
3,811 citations
TL;DR: A proposed standard protocol for describing IBMs and ABMs, developed and tested by 28 modellers who cover a wide range of fields within ecology, and considered as a first step for establishing a more detailed common format of the description of IBm and ABM.
2,633 citations
TL;DR: An introduction to e-learning and its role in medical education is provided by outlining key terms, the components of e-Learning, the evidence for its effectiveness, faculty development needs for implementation, evaluation strategies for e- learning and its technology, and how e- Learning might be considered evidence of academic scholarship.
Abstract: The authors provide an introduction to e-learning and its role in medical education by outlining key terms, the components of e-learning, the evidence for its effectiveness, faculty development needs for implementation, evaluation strategies for e-learning and its technology, and how e-learning might be considered evidence of academic scholarship. E-learning is the use of Internet technologies to enhance knowledge and performance. E-learning technologies offer learners control over content, learning sequence, pace of learning, time, and often media, allowing them to tailor their experiences to meet their personal learning objectives. In diverse medical education contexts, e-learning appears to be at least as effective as traditional instructor-led methods such as lectures. Students do not see e-learning as replacing traditional instructor-led training but as a complement to it, forming part of a blended-learning strategy. A developing infrastructure to support e-learning within medical education includes repositories, or digital libraries, to manage access to e-learning materials, consensus on technical standardization, and methods for peer review of these resources. E-learning presents numerous research opportunities for faculty, along with continuing challenges for documenting
1,878 citations
TL;DR: Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable.
Abstract: Background Islet transplantation offers the potential to improve glycemic control in a subgroup of patients with type 1 diabetes mellitus who are disabled by refractory hypoglycemia. We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol). Methods We enrolled 36 subjects with type 1 diabetes mellitus, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycemic control 1 year after the final transplantation. Results Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years. Conclusions Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable. Persistent islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of glycated hemoglobin. (ClinicalTrials.gov number, NCT00014911.)
1,784 citations
Ohio State University1, Fred Hutchinson Cancer Research Center2, University of Cincinnati3, University of Iowa4, University of California, Davis5, University of Alabama at Birmingham6, University of Arizona7, University of Washington8, Rush University Medical Center9, Wake Forest University10, University of Nevada, Reno11, University of Texas at San Antonio12, Kaiser Permanente13, University of Pittsburgh14, University of California, Los Angeles15, Stony Brook University16, Baylor College of Medicine17, University of North Carolina at Chapel Hill18, Wayne State University19, Howard University20, George Washington University21, University of California, Irvine22, University of Tennessee Health Science Center23, Medical College of Wisconsin24, University of California, San Diego25, Rutgers University26, University of Florida27, National Institutes of Health28, Harvard University29, University of Minnesota30, University of Massachusetts Boston31, University of Miami32, Emory University33, University of Wisconsin-Madison34, Stanford University35, Northwestern University36, University at Buffalo37, Brown University38, Yeshiva University39
TL;DR: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones.
Abstract: Background The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. Methods We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Results Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with...
1,765 citations
Medical University of South Carolina1, Yale University2, Boston University3, University of Wisconsin–Milwaukee4, University of North Carolina at Chapel Hill5, University of Washington6, Harvard University7, University of Texas at San Antonio8, Brown University9, University of Miami10, National Institutes of Health11, University of New Mexico12, University of Pennsylvania13
TL;DR: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI.
Abstract: ContextAlcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.ObjectivesTo evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.Design, Setting, and ParticipantsRandomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.InterventionsEight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.Main Outcome MeasuresPercent days abstinent from alcohol and time to first heavy drinking day.ResultsAll groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.ConclusionsPatients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.Trial Registrationclinicaltrials.gov Identifier: NCT00006206
1,584 citations
TL;DR: This article found that older adults were less likely than younger adults to use technology in general, computers, and the World Wide Web, and that computer anxiety, fluid intelligence, and crystallized intelligence were important predictors of the use of technology.
Abstract: The successful adoption of technology is becoming increasingly important to functional independence. The present article reports findings from the Center for Research and Education on Aging and Technology Enhancement (CREATE) on the use of technology among communitydwelling adults. The sample included 1,204 individuals ranging in age from 18–91 years. All participants completed a battery that included measures of demographic characteristics, self-rated health, experience with technology, attitudes toward computers, and component cognitive abilities. Findings indicate that the older adults were less likely than younger adults to use technology in general, computers, and the World Wide Web. The results also indicate that computer anxiety, fluid intelligence, and crystallized intelligence were important predictors of the use of technology. The relationship between age and adoption of technology was mediated by cognitive abilities, computer self-efficacy, and computer anxiety. These findings are discussed in terms of training strategies to promote technology adoption.
1,447 citations
TL;DR: The results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk, however, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.
Abstract: ContextThe optimal duration of treatment of women with postmenopausal osteoporosis is uncertain.ObjectiveTo compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years.Design and SettingRandomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT).ParticipantsOne thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment.InterventionRandomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003).Main Outcome MeasuresThe primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence.ResultsCompared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (−2.4%; 95% confidence interval [CI], −2.9% to −1.8%; P<.001) and spine (−3.7%; 95% CI, −4.5% to −3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum N = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens.ConclusionsWomen who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.Trial Registrationclinicaltrials.gov Identifier: NCT 00398931
1,295 citations
Georgetown University Medical Center1, University of Modena and Reggio Emilia2, Johns Hopkins University3, University of Louisville4, French Institute of Health and Medical Research5, Martin Luther University of Halle-Wittenberg6, University of Miami7, University of Bristol8, Tel Aviv University9, National Institute of Radiological Sciences10
TL;DR: Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein, to represent more accurately its sub cellular role (or roles) and putative tissue-specific function (or functions).
1,264 citations
TL;DR: Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD.
Abstract: Context A history of depression may increase risk for developing Alzheimer disease (AD) later in life. Clarifying this relation might improve understanding of risk factors for and disease mechanisms in AD. Objective To systematically review and complete a meta-analysis on the relation of depression and AD. Data sources We conducted electronic bibliographic searches of MEDLINE, PsychLit, EMBASE, and BIOSIS using search terms sensitive to studies of etiology combined with searches on terms related to depression and AD and reviewed reference lists of articles. Study selection Studies with data contrasting depressed vs nondepressed patients who did and did not later develop AD were included. Studies that related continuous measures of depression and cognitive status were excluded. Data extraction Numerical data were independently extracted by 3 reviewers. They also rated studies on a scale that assessed quality indicators for observational studies. Data on the interval between observation of depression and the diagnosis of AD were collected when available. Data synthesis Meta-analytic evaluation with random-effects models resulted in pooled odds ratios of 2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95% confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk were robust to sensitivity analyses. Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD. Conclusions A history of depression may confer an increased risk for later developing AD. This relation may reflect an independent risk factor for the disease.
1,263 citations
TL;DR: Using a high-resolution biophysical model for the Caribbean region, it is reported that typical larval dispersal distances are on the scale of only 10 to 100 kilometers for a variety of reef fish species and shows the importance of the early onset of active larval movement mediating the dispersal potential.
Abstract: Defining the scale of connectivity, or exchange, among marine populations and determining the factors driving this exchange are pivotal to our understanding of the population dynamics, genetic structure, and biogeography of many coastal species. Using a high-resolution biophysical model for the Caribbean region, we report that typical larval dispersal distances of ecologically relevant magnitudes are on the scale of only 10 to 100 kilometers for a variety of reef fish species. We also show the importance of the early onset of active larval movement mediating the dispersal potential. In addition to self-recruitment, larval import from outside the local area is required to sustain most populations, although these population subsidies are very limited in particular systems. The results reveal distinct regions of population isolation based on larval dispersal that also correspond to genetic and morphological clines observed across a range of marine organisms.
TL;DR: It is concluded that the unique cellular arrangement of human islets has functional implications for islet cell function.
Abstract: The cytoarchitecture of human islets has been examined, focusing on cellular associations that provide the anatomical framework for paracrine interactions. By using confocal microscopy and multiple immunofluorescence, we found that, contrary to descriptions of prototypical islets in textbooks and in the literature, human islets did not show anatomical subdivisions. Insulin-immunoreactive β cells, glucagon-immunoreactive α cells, and somatostatin-containing δ cells were found scattered throughout the human islet. Human β cells were not clustered, and most (71%) showed associations with other endocrine cells, suggesting unique paracrine interactions in human islets. Human islets contained proportionally fewer β cells and more α cells than did mouse islets. In human islets, most β, α, and δ cells were aligned along blood vessels with no particular order or arrangement, indicating that islet microcirculation likely does not determine the order of paracrine interactions. We further investigated whether the unique human islet cytoarchitecture had functional implications. Applying imaging of cytoplasmic free Ca2+ concentration, [Ca2+]i, we found that β cell oscillatory activity was not coordinated throughout the human islet as it was in mouse islets. Furthermore, human islets responded with an increase in [Ca2+]i when lowering the glucose concentration to 1 mM, which can be attributed to the large contribution of α cells to the islet composition. We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function.
University of Edinburgh1, Max Planck Society2, University of Oslo3, Royal Netherlands Meteorological Institute4, University of Cambridge5, International Institute for Applied Systems Analysis6, Lawrence Livermore National Laboratory7, Goddard Institute for Space Studies8, École Polytechnique Fédérale de Lausanne9, Hadley Centre for Climate Prediction and Research10, Newbury College11, Geophysical Fluid Dynamics Laboratory12, Belgian Institute for Space Aeronomy13, University of California, Irvine14, Goddard Space Flight Center15, University of Miami16
TL;DR: In this article, an ensemble of 26 state-of-the-art atmospheric chemistry models have been compared and synthesized as part of a wider study into both the air quality and climate roles of ozone.
Abstract: Global tropospheric ozone distributions, budgets, and radiative forcings from an ensemble of 26 state-of-the-art atmospheric chemistry models have been intercompared and synthesized as part of a wider study into both the air quality and climate roles of ozone. Results from three 2030 emissions scenarios, broadly representing optimistic, likely, and pessimistic options, are compared to a base year 2000 simulation. This base case realistically represents the current global distribution of tropospheric ozone. A further set of simulations considers the influence of climate change over the same time period by forcing the central emissions scenario with a surface warming of around 0.7K. The use of a large multimodel ensemble allows us to identify key areas of uncertainty and improves the robustness of the results. Ensemble mean changes in tropospheric ozone burden between 2000 and 2030 for the 3 scenarios range from a 5% decrease, through a 6% increase, to a 15% increase. The intermodel uncertainty (±1 standard deviation) associated with these values is about ±25%. Model outliers have no significant influence on the ensemble mean results. Combining ozone and methane changes, the three scenarios produce radiative forcings of -50, 180, and 300 mW m-2, compared to a CO 2 forcing over the same time period of 800-1100 mW m-2. These values indicate the importance of air pollution emissions in short- to medium-term climate forcing and the potential for stringent/lax control measures to improve/worsen future climate forcing. The model sensitivity of ozone to imposed climate change varies between models but modulates zonal mean mixing ratios by ±5 ppbv via a variety of feedback mechanisms, in particular those involving water vapor and stratosphere-troposphere exchange. This level of climate change also reduces the methane lifetime by around 4%. The ensemble mean year 2000 tropospheric ozone budget indicates chemical production, chemical destruction, dry deposition and stratospheric input fluxes of 5100, 4650, 1000 and 550 Tg(O 3 ) yr-1, respectively. These values are significantly different to the mean budget documented by the Intergovernmental Panel on Climate Change (IPCC) Third Assessment Report (TAR). The mean ozone burden (340 Tg(O 3 )) is 10% larger than the IPCC TAR estimate, while the mean ozone lifetime (22 days) is 10% shorter. Results from individual models show a correlation between ozone burden and lifetime, and each model's ozone burden and lifetime respond in similar ways across the emissions scenarios. The response to climate change is much less consistent. Models show more variability in the tropics compared to midlatitudes. Some of the most uncertain areas of the models include treatments of deep tropical convection, including lightning NO x production; isoprene emissions from vegetation and isoprene's degradation chemistry; stratosphere-troposphere exchange; biomass burning; and water vapor concentrations. Copyright 2006 by the American Geophysical Union.
TL;DR: It is found that MM cells have a lower threshold for PI-induced UPR induction and ER stress-induced apoptosis because they constitutively express ER stress survival factors to function as secretory cells.
Memorial Hospital of South Bend1, Howard University2, Northwestern University3, George Washington University4, Harvard University5, Stanford University6, Yeshiva University7, University of Pittsburgh8, Fred Hutchinson Cancer Research Center9, University of California, San Diego10, Rutgers University11, University of Alabama at Birmingham12, University of Florida13, University of Minnesota14, Ohio State University15, University of Massachusetts Medical School16, University of Miami17, Emory University18, University of California, Davis19, National Institutes of Health20, University of Wisconsin-Madison21, University of Iowa22, Kaiser Permanente23, University at Buffalo24, Wake Forest University25, Brown University26, Pfizer27, University of Arizona28, Rush University Medical Center29, University of Nevada, Reno30, University of Texas at San Antonio31, University of California, Los Angeles32, University of Cincinnati33, Stony Brook University34, Baylor College of Medicine35, University of North Carolina at Chapel Hill36, Wayne State University37, University of California, Irvine38, University of Tennessee Health Science Center39, Medical College of Wisconsin40
TL;DR: A dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVDrisk.
Abstract: ContextMultiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.ObjectiveTo test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Design, Setting, and ParticipantsRandomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.InterventionIntensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Main Outcome MeasuresFatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).ResultsBy year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.ConclusionsOver a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
TL;DR: In this article, the climate feedbacks in coupled ocean-atmosphere models are compared using a coordinated set of twenty-first-century climate change experiments, and it is found that water vapor is the largest positive feedback in all models and its strength is consistent with that expected from constant relative humidity changes in the water vapor mixing ratio.
Abstract: The climate feedbacks in coupled ocean–atmosphere models are compared using a coordinated set of twenty-first-century climate change experiments Water vapor is found to provide the largest positive feedback in all models and its strength is consistent with that expected from constant relative humidity changes in the water vapor mixing ratio The feedbacks from clouds and surface albedo are also found to be positive in all models, while the only stabilizing (negative) feedback comes from the temperature response Large intermodel differences in the lapse rate feedback are observed and shown to be associated with differing regional patterns of surface warming Consistent with previous studies, it is found that the vertical changes in temperature and water vapor are tightly coupled in all models and, importantly, demonstrate that intermodel differences in the sum of lapse rate and water vapor feedbacks are small In contrast, intermodel differences in cloud feedback are found to provide the largest
University at Buffalo1, Medical College of Wisconsin2, Fred Hutchinson Cancer Research Center3, Memorial Hospital of Rhode Island4, Pfizer5, University of Nevada, Reno6, University of Miami7, University of Minnesota8, University of Massachusetts Medical School9, Emory University10, National Institutes of Health11, University of California, Davis12, Yeshiva University13, University of Wisconsin-Madison14, Stanford University15, Northwestern University16, University of Iowa17, Kaiser Permanente18, University of Arizona19, University of Washington20, Rush University Medical Center21, Wake Forest University22, University of Texas at San Antonio23, University of California, Los Angeles24, University of California, San Diego25, University of Cincinnati26, Baylor College of Medicine27, University of North Carolina at Chapel Hill28, Wayne State University29, Howard University30, George Washington University31, University of California, Irvine32, Ohio State University33, University of Tennessee Health Science Center34, University of Pittsburgh35, Stony Brook University36, Rutgers University37, University of Alabama at Birmingham38, University of Florida39, Harvard University40
TL;DR: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women, and the long latency associated with the development of colorescopy cancer, along with the seven-year duration of the trial, may have contributed to this null finding.
Abstract: Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study. Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.)
TL;DR: Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation, and the climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean.
Abstract: Since the mid-nineteenth century the Earth's surface has warmed, and models indicate that human activities have caused part of the warming by altering the radiative balance of the atmosphere. Simple theories suggest that global warming will reduce the strength of the mean tropical atmospheric circulation. An important aspect of this tropical circulation is a large-scale zonal (east-west) overturning of air across the equatorial Pacific Ocean--driven by convection to the west and subsidence to the east--known as the Walker circulation. Here we explore changes in tropical Pacific circulation since the mid-nineteenth century using observations and a suite of global climate model experiments. Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation. The size of this trend is consistent with theoretical predictions, is accurately reproduced by climate model simulations and, within the climate models, is largely due to anthropogenic forcing. The climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean. These results support model projections of further weakening of tropical atmospheric circulation during the twenty-first century.
TL;DR: In this paper, a review of recent observational, numerical, and theoretical studies of climate feedbacks is presented, showing that there has been progress since the Third Assessment Report of the Intergovernmental Panel on Climate Change in (i) the understanding of the physical mechanisms involved in these feedbacks, (ii) the interpretation of intermodel differences in global estimates of the feedbacks associated with water vapor, lapse rate, clouds, snow, and sea ice, and (iii) the development of methodologies of evaluation of these inputs using observations.
Abstract: Processes in the climate system that can either amplify or dampen the climate response to an external perturbation are referred to as climate feedbacks. Climate sensitivity estimates depend critically on radiative feedbacks associated with water vapor, lapse rate, clouds, snow, and sea ice, and global estimates of these feedbacks differ among general circulation models. By reviewing recent observational, numerical, and theoretical studies, this paper shows that there has been progress since the Third Assessment Report of the Intergovernmental Panel on Climate Change in (i) the understanding of the physical mechanisms involved in these feedbacks, (ii) the interpretation of intermodel differences in global estimates of these feedbacks, and (iii) the development of methodologies of evaluation of these feedbacks ( or of some components) using observations. This suggests that continuing developments in climate feedback research will progressively help make it possible to constrain the GCMs' range of climate feedbacks and climate sensitivity through an ensemble of diagnostics based on physical understanding and observations.
TL;DR: The combination of tenofovir DF and emtricitabineplus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efvirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs.
Abstract: background Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere. methods We conducted an open-label, noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were randomly assigned to receive either a regimen of tenofovir disoproxil fumarate (DF), emtricitabine, and efavirenz once daily (tenofovir–emtricitabine group) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily (zidovudine–lamivudine group). The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study. results Through week 48, significantly more patients in the tenofovir–emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine–lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P = 0.002). This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen. Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in the tenofovir– emtricitabine group vs. 70 percent in the zidovudine–lamivudine group; 95 percent confidence interval for the difference, 2 to 17 percent; P = 0.02) and in increases in CD4 cell counts (190 vs. 158 cells per cubic millimeter, respectively; 95 percent confidence interval for the difference, 9 to 55; P = 0.002). More patients in the zidovudine–lamivudine group than in the tenofovir–emtricitabine group had adverse events resulting in discontinuation of the study drugs (9 percent vs. 4 percent, respectively; P = 0.02). In none of the patients did the K65R mutation develop. conclusions Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs. (ClinicalTrials. gov number, NCT00112047.)
TL;DR: This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
Abstract: Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
TL;DR: In children, DCM is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation, and race, sex, and age affect the incidence of disease.
Abstract: ContextDilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and cause of cardiac transplantation in children. However, the epidemiology and clinical course of DCM in children are not well established.ObjectiveTo provide a detailed description of the incidence, causes, outcomes, and related risk factors for DCM in children.Design and SettingLongitudinal study based on a population-based, prospective cohort of children diagnosed as having DCM since January 1, 1996, at 89 pediatric cardiac centers and a retrospectively collected cohort of patients seen primarily at large tertiary care centers in North America and who had diagnoses between January 1, 1990, and December 31, 1995, and were enrolled through February 2003.ParticipantsA total of 1426 children from the United States and Canada diagnosed as having DCM at younger than 18 years. Primary DCM was determined by strict echocardiographic and/or pathologic criteria. Patients with disease due to endocrine, immunologic, drug toxicity, and other causes were excluded.Main Outcome MeasuresAnnual incidence per 100 000 children; mortality; cardiac transplantation.ResultsThe annual incidence of DCM in children younger than 18 years was 0.57 cases per 100 000 per year overall. The annual incidence was higher in boys than in girls (0.66 vs 0.47 cases per 100 000; P<.001), in blacks than in whites (0.98 vs 0.46 cases per 100 000; P<.001), and in infants (<1 year) than in children (4.40 vs 0.34 cases per 100 000; P<.001). The majority of children (66%) had idiopathic disease. The most common known causes were myocarditis (46%) and neuromuscular disease (26%). The 1- and 5-year rates of death or transplantation were 31% and 46%, respectively. Independent risk factors at DCM diagnosis for subsequent death or transplantation were older age, congestive heart failure, lower left ventricular fractional shortening Z score, and cause of DCM (P<.001 for all).ConclusionsIn children, DCM is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation. Race, sex, and age affect the incidence of disease. Most children do not have a known cause of DCM, which limits the potential for disease-specific therapies.
National Oceanic and Atmospheric Administration1, University of Miami2, Lawrence Livermore National Laboratory3, State University of New York System4, Goddard Space Flight Center5, Goddard Institute for Space Studies6, Geophysical Fluid Dynamics Laboratory7, National Institute for Environmental Studies8, University of Paris9, National Center for Atmospheric Research10, Max Planck Society11
TL;DR: In this paper, the authors evaluate the tropical intraseasonal variability, especially the fidelity of Madden-Julian oscillation (MJO) simulations, in 14 coupled general circulation models participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4).
Abstract: This study evaluates the tropical intraseasonal variability, especially the fidelity of Madden–Julian oscillation (MJO) simulations, in 14 coupled general circulation models (GCMs) participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). Eight years of daily precipitation from each model’s twentieth-century climate simulation are analyzed and compared with daily satellite-retrieved precipitation. Space–time spectral analysis is used to obtain the variance and phase speed of dominant convectively coupled equatorial waves, including the MJO, Kelvin, equatorial Rossby (ER), mixed Rossby–gravity (MRG), and eastward inertio–gravity (EIG) and westward inertio–gravity (WIG) waves. The variance and propagation of the MJO, defined as the eastward wavenumbers 1–6, 30–70-day mode, are examined in detail. The results show that current state-of-the-art GCMs still have significant problems and display a wide range of skill in simulating the tropical intraseasonal va...
TL;DR: Data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory 'neuroprotective' strategies should be directed at preventing early neutrophil influx and modifying microglial activation.
Abstract: Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were ‘dead at the scene’ or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1–3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil α-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1–3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1–3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8+ lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative enzymes myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate oxidase (gp91phox), and of the pro-inflammatory matrix metalloproteinase (MMP)-9, was analysed to determine their potential to cause oxidative and proteolytic damage. Oxidative activity, inferred from MPO and gp91phox immunoreactivity, was primarily associated with neutrophils and activated microglia. Phagocytic macrophages had weak or no expression of MPO or gp91phox. Only neutrophils expressed MMP-9. These data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory ‘neuroprotective’ strategies should be directed at preventing early neutrophil influx and modifying microglial activation.
Fred Hutchinson Cancer Research Center1, Kaiser Permanente2, University of California, Los Angeles3, University of Pittsburgh4, University of Massachusetts Medical School5, University of Minnesota6, University of Florida7, Harvard University8, University of Miami9, Ohio State University10, Emory University11, University of California, Davis12, National Institutes of Health13, University of Wisconsin-Madison14, University of Alabama at Birmingham15, Stanford University16, University of Arizona17, Northwestern University18, Wake Forest University19, University at Buffalo20, University of Iowa21, Yeshiva University22, Howard University23, Pfizer24, Brown University25, University of Washington26, Rush University Medical Center27, University of Nevada, Reno28, University of Texas at San Antonio29, University of Cincinnati30, Baylor College of Medicine31, University of North Carolina at Chapel Hill32, Wayne State University33, George Washington University34, University of California, Irvine35, University of Tennessee Health Science Center36, Medical College of Wisconsin37, Stony Brook University38, University of California, San Diego39, Rutgers University40
TL;DR: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period, and the nonsignificant trends observed indicate that longer, planned, nonintervention follow- up may yield a more definitive comparison.
Abstract: ContextThe hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.ObjectiveTo assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.Design and SettingA randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.ParticipantsA total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.InterventionsWomen were randomly assigned to the dietary modification intervention group (40% [n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Main Outcome MeasureInvasive breast cancer incidence.ResultsDietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.ConclusionsAmong postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
University of Buenos Aires1, National Oceanic and Atmospheric Administration2, University of Costa Rica3, University of São Paulo4, University of Chile5, National Center for Atmospheric Research6, University of New Mexico7, University of Washington8, National Institute for Space Research9, University of California, Los Angeles10, University of Utah11, University of Miami12
TL;DR: This paper reviewed recent progress in the understanding of the American monsoon systems and identified some of the future challenges that remain to improve warm season climate prediction, including new insights into moisture transport processes, description of the structure and variability of the South American low level jet, and resolution of the diurnal cycle of precipitation in the core monsoon regions.
Abstract: An important goal of the Climate Variability and Predictability (CLIVAR) research on the American monsoon systems is to determine the sources and limits of predictability of warm season precipitation, with emphasis on weekly to interannual time scales. This paper reviews recent progress in the understanding of the American monsoon systems and identifies some of the future challenges that remain to improve warm season climate prediction. Much of the recent progress is derived from complementary international programs in North and South America, namely, the North American Monsoon Experiment (NAME) and the Monsoon Experiment South America (MESA), with the following common objectives: 1) to understand the key components of the American monsoon systems and their variability, 2) to determine the role of these systems in the global water cycle, 3) to improve observational datasets, and 4) to improve simulation and monthly-to-seasonal prediction of the monsoons and regional water resources. Among the recent observational advances highlighted in this paper are new insights into moisture transport processes, description of the structure and variability of the South American low-level jet, and resolution of the diurnal cycle of precipitation in the core monsoon regions. NAME and MESA are also driving major efforts in model development and hydrologic applications. Incorporated into the postfield phases of these projects are assessments of atmosphere–land surface interactions and model-based climate predictability experiments. As CLIVAR research on American monsoon systems evolves, a unified view of the climatic processes modulating continental warm season precipitation is beginning to emerge.
University of Washington1, University of Tennessee Health Science Center2, University of Arizona3, Rutgers University4, University of Iowa5, Rush University Medical Center6, Fred Hutchinson Cancer Research Center7, Brown University8, Pfizer9, University of Nevada, Reno10, University of Texas at San Antonio11, Kaiser Permanente12, University of California, Los Angeles13, University of Cincinnati14, Baylor College of Medicine15, University of North Carolina at Chapel Hill16, Wayne State University17, Howard University18, George Washington University19, University of California, Irvine20, Ohio State University21, Medical College of Wisconsin22, University of Pittsburgh23, Stony Brook University24, University of California, San Diego25, University of Alabama at Birmingham26, Harvard University27, University of Minnesota28, Yeshiva University29, University of Massachusetts Medical School30, University of Miami31, University of Florida32, Emory University33, University of California, Davis34, National Institutes of Health35, University of Wisconsin-Madison36, Stanford University37, Northwestern University38, Wake Forest University39, University at Buffalo40
TL;DR: A low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up, and secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status.
Abstract: ContextObservational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.ObjectiveTo evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.Design, Setting, and ParticipantsThe Women’s Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48 835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.InterventionsParticipants were randomly assigned to the dietary modification intervention (n = 19 541; 40%) or the comparison group (n = 29 294; 60%).The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Main Outcome MeasureInvasive colorectal cancer incidence.ResultsA total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.ConclusionIn this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611
TL;DR: Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis ≥70%, after recent symptoms, and in women.
Abstract: Background— Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy. Methods and Results— WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke ...
Mayo Clinic1, University of Miami2, Centers for Disease Control and Prevention3, March of Dimes4, Genetic Alliance5, Ohio State University6, California Health and Human Services Agency7, Washington University in St. Louis8, Indiana University9, University of Michigan10, Anschutz Medical Campus11, National Institutes of Health12, United States Department of the Army13, Agency for Healthcare Research and Quality14, University of Louisville15, Oregon Health & Science University16, George Washington University17, University of Texas Health Science Center at San Antonio18, New Mexico Department of Health19, University of North Carolina at Chapel Hill20, New York State Department of Health21, Rutgers University22, University of Wisconsin-Madison23, Vanderbilt University24, Harvard University25, Emory University26, Icahn School of Medicine at Mount Sinai27, American Academy of Family Physicians28, United States Department of Health and Human Services29
TL;DR: The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process of standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screenings programs.
Abstract: The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process of standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screening programs. The expert panel identified 29 conditions for which screening should be mandated. An additional 25 conditions were identified because they are part of the differential diagnosis of a condition in the core panel, they are clinically significant and revealed with screening technology but lack an efficacious treatment, or they represent incidental findings for which there is potential clinical significance. The process of identification is described, and recommendations are provided.
TL;DR: The findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications and suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.
Abstract: Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.