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Stratospheric ozone, and its response to anthropogenic forcings, provides an important pathway for the coupling between atmospheric composition and climate. In addition to stratospheric ozone's radiative impacts, recent studies have shown that changes in the ozone layer due to 4xCO2 have a considerable impact on the Northern Hemisphere (NH) tropospheric circulation, inducing an equatorward shift of the North Atlantic jet during boreal winter. Using simulations produced with the NASA Goddard Institute for Space Studies (GISS) high-top climate model (E2.2), we show that this equatorward shift of the Atlantic jet can induce a more rapid weakening of the Atlantic meridional overturning circulation (AMOC). The weaker AMOC, in turn, results in an eastward acceleration and poleward shift of the Atlantic and Pacific jets, respectively, on longer time scales. As such, coupled feedbacks from both stratospheric ozone and the AMOC result in a two-time-scale response of the NH midlatitude jet to abrupt 4xCO2 forcing: a "fast" response (5–20 years) during which it shifts equatorward and a "total" response (∼100–150 years) during which the jet accelerates and shifts poleward. The latter is driven by a weakening of the AMOC that develops in response to weaker surface zonal winds that result in reduced heat fluxes out of the subpolar gyre and reduced North Atlantic Deep Water formation. Our results suggest that stratospheric ozone changes in the lower stratosphere can have a surprisingly powerful effect on the AMOC, independent of other aspects of climate change. [ABSTRACT FROM AUTHOR]

Climate models project a future weakening of the Atlantic meridional overturning circulation (AMOC), but the impacts of this weakening on climate remain highly uncertain. A key challenge in quantifying the impact of an AMOC decline is in isolating its influence on climate, relative to other changes associated with increased greenhouse gases. Here we isolate the climate impacts of a weakened AMOC in the broader context of a warming climate using a unique ensemble of Shared Socioeconomic Pathway (SSP) 2–4.5 integrations that was performed using the Climate Model Intercomparison Project phase 6 (CMIP6) version of the NASA Goddard Institute for Space Studies ModelE (E2.1). In these runs internal variability alone results in a spontaneous bifurcation of the ocean flow, wherein 2 out of 10 ensemble members exhibit an entire AMOC collapse, while the other 8 members recover at various stages despite identical forcing of each ensemble member and with no externally prescribed freshwater perturbation. We show that an AMOC collapse results in an abrupt northward shift and strengthening of the Northern Hemisphere (NH) Hadley cell (HC) and intensification of the northern midlatitude eddy-driven jet. We then use a set of coupled atmosphere–ocean abrupt CO2 experiments spanning the range 1 times to 5 times CO2 (1x to 5xCO2) to show that this response to an AMOC collapse results in a nonlinear shift in the NH circulation moving from 2xCO2 to 3xCO2. Slab-ocean versions of these experiments, by comparison, do not capture this nonlinear behavior. Our results suggest that changes in ocean heat flux convergences associated with an AMOC collapse—while highly uncertain—can result in profound changes in the NH circulation and continued efforts to constrain the AMOC response to future climate change are needed. [ABSTRACT FROM AUTHOR]

A 10-member ensemble simulation with the NASA GISS-E2-1-G climate model shows a clear bifurcation in the Atlantic meridional overturning circulation (AMOC) strength under the SSP2–4.5 extended scenario. At 26°N, the bifurcation leads to 8 strong AMOC and 2 much weaker AMOC states, while at 48°N, it leads to 8 stable AMOC-on and 2 nearly AMOC-off states, the latter lasting approximately 800 years. A variety of fully coupled models have demonstrated tipping points in AMOC through hosing experiments, i.e., prescribing sufficient freshwater inputs in the subpolar North Atlantic. In the GISS simulations, there are no external freshwater perturbations. The bifurcation arises freely in the coupled system and is the result of stochastic variability (noise-induced bifurcation) associated with sea ice transport and melting in the Irminger Sea after a slowing of the greenhouse gas forcing. While the AMOC strength follows the near shutdown of the Labrador Sea deep convection initially, the Irminger Sea salinity and deep mixing determine the timing of the AMOC recovery or near collapse at 48°N, which varies widely across the ensemble members. Other feedbacks such as ice-albedo, ice-evaporation, E − P, and the overturning salt-advection feedback play a secondary role that may enhance or reduce the primary mechanism which is ice melt. We believe this is the first time that a coupled climate model has shown such a bifurcation across an initial condition ensemble and might imply that there is a chance for significant and prolonged AMOC slow down due to internal variability of the system. Significance Statement: We believe this is the first time that divergent AMOC behavior has been reported for an ensemble of Earth system model simulations using identical climate forcing and no prescribed freshwater perturbations. This response is a manifestation of noise-induced bifurcation, enhanced by feedbacks, revealing the role stochastic (or intrinsic) variability may play in AMOC stability. [ABSTRACT FROM AUTHOR]

This Viewpoint examines the appropriateness of FDA accelerated approval of novel gene therapies to treat boys with Duchenne muscular dystrophy following clinical trials with surrogate outcomes that did not demonstrate net benefits. [ABSTRACT FROM AUTHOR]

Standard vector calculus formulas of Cartesian three space are projected onto the surface of a sphere. This produces symmetric equations with three nonindependent horizontal velocity components. Each orthogonal axis has a velocity component that rotates around its axis (eastward velocity rotates around the north–south axis) and a specific angular momentum component that is the product of the velocity component multiplied by the cosine of axis' latitude. Angular momentum components align with the fixed axes and simplify several formulas, whereas the rotating velocity components are not orthogonal and vary with location. Three symmetric coordinates allow vector resolution and calculus operations continuously over the whole spherical surface, which is not possible with only two coordinates. The symmetric equations are applied to one-layer shallow water models on cubed-sphere and icosahedral grids, the latter being computationally simple and applicable to an ocean domain. Model results are presented for three different initial conditions and five different resolutions. [ABSTRACT FROM AUTHOR]

Standard vector calculus formulas of Cartesian three space are projected onto the surface of a sphere. This produces symmetric equations with three nonindependent horizontal velocity components. Each orthogonal axis has a velocity component that rotates around its axis (eastward velocity rotates around the north-south axis) and a specific angular momentum component that is the product of the velocity component times the cosine of axis' latitude. Angular momentum components align with the fixed axes and simplify several formulas, whereas the rotating velocity components are not orthogonal and vary with location. Three symmetric coordinates allow vector resolution and calculus operations continuously over the whole spherical surface, which is not possible with only two coordinates. The symmetric equations are applied to one-layer shallow water models on cubed-sphere and icosahedral grids, the latter being computationally simple and applicable to an ocean domain. Model results are presented for three different initial conditions and five different resolutions. [ABSTRACT FROM AUTHOR]

Simulations of the preindustrial and doubled CO2 climates are made with the GISS Global Climate Middle Atmosphere Model 3 using two different estimates of the absolute solar irradiance value: a higher value measured by solar radiometers in the 1990s and a lower value measured recently by the Solar Radiation and Climate Experiment. Each of the model simulations is adjusted to achieve global energy balance; without this adjustment the difference in irradiance produces a global temperature change of 0.4°C, comparable to the cooling estimated for the Maunder Minimum. The results indicate that by altering cloud cover the model properly compensates for the different absolute solar irradiance values on a global level when simulating both preindustrial and doubled CO2 climates. On a regional level, the preindustrial climate simulations and the patterns of change with doubled CO2 concentrations are again remarkably similar, but there are some differences. Using a higher absolute solar irradiance value and the requisite cloud cover affects the model's depictions of high-latitude surface air temperature, sea level pressure, and stratospheric ozone, as well as tropical precipitation. In the climate change experiments it leads to an underestimation of North Atlantic warming, reduced precipitation in the tropical western Pacific, and smaller total ozone growth at high northern latitudes. Although significant, these differences are typically modest compared with the magnitude of the regional changes expected for doubled greenhouse gas concentrations. Nevertheless, the model simulations demonstrate that achieving the highest possible fidelity when simulating regional climate change requires that climate models use as input the most accurate (lower) solar irradiance value. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the action to control cardiovascular risk in diabetes (ACCORD) eye study in an issue.

This study uses a hybrid coupled model (referred to as the general-circulation model (GCM)/Zebiak/Cane (ZC) model), which consists of the Goddard Institute for Space Studies' (GISS) Atmospheric general-circulation model (AGCM) coupled to the oceanic component of the ZC intermediate model to assess the impact of global warming on El Niño behavior, with and without the influence of heat introduced from the subtropical Pacific (via subtropical cell (STC) pathway). The baseline GCM/ZC model produces El Niño variability with a two year periodicity and an amplitude of approximately half the magnitude of observed El Niño. The GCM/ZC model also produces an appropriate atmospheric global response to El Niño/southern oscillation (ENSO) as shown by composites of 500 hPa heights, sea-level pressure (SLP), 200 hPa wind, and precipitation during El Niño and La Niña periods. To evaluate the importance of global warming on ENSO variability, 2× CO2 and 4× CO2 transient simulations were done increasing the atmospheric CO2 one percent per year, then extending the runs for an additional 70 years to obtain equilibrium climates for each run. An additional set of global-warming simulations was run after including a STC parameterization generated by computing 5-year running means of the sea-surface temperature (SST) difference between a transient run and the 1× CO2 GCM/ZC run at the anticipated subduction zones (160-130°W, 20-40°N and 20-44°S, 160-130°W) and adding it to the base of the equatorial mixed-layer of the ZC model with a time lag of 15 years. This effectively alters the vertical temperature gradient of the ZC model, which affects SST via upwelling. Two features of the GCM/ZC response to global warming are emphasized. Firstly, the inclusion of the STC results in a major redistribution of heat across the equatorial Pacific, leading to an El Niño-like response in the final equilibrium solution with less variability about the mean. The global warming aspect due to the El Niño-like response results in a positive feedback on global warming, which causes a higher global surface-air temperature (SAT) than identical transient simulations without inclusion of the STC. Secondly, including the STC effect produces a far greater magnitude of global ENSO-like impact because of the reduction of, or even the reversal of, the equatorial Pacific longitudinal SST gradient. The implications of such an extreme climate scenario are discussed. Copyright © 2006 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

Highlights from the article: Our analysis did conclude a gain of 1.3 quality-adjusted life-years (QALYs) for VN compared with SoC as stated by Buessing et al., and they conclude that this implies an 8% improvement in the patient's quality of life. Nevertheless, we did complete a scenario analysis around this assumption, available in the publicly available ICER report, which resulted in higher health gains and lower costs for VN patients relative to the base-case scenario. Future studies of long-term health outcomes, quality of life, and indirect costs for patients with RPE65-mediated inherited retinal disease would improve our understanding of the economic and health impacts of new treatments.

The climate during the Maunder Minimum is compared with current conditions in GCM simulations that include a full stratosphere and parameterized ozone response to solar spectral irradiance variability and trace gas changes. The Goddard Institute for Space Studies (GISS) Global Climate/Middle Atmosphere Model (GCMAM) coupled to a q-flux/mixed-layer model is used for the simulations, which begin in 1500 and extend to the present. Experiments were made to investigate the effect of total versus spectrally varying solar irradiance changes; spectrally varying solar irradiance changes on the stratospheric ozone/climate response with both preindustrial and present trace gases; and the impact on climate and stratospheric ozone of the preindustrial trace gases and aerosols by themselves. The results showed that 1) the Maunder Minimum cooling relative to today was primarily associated with reduced anthropogenic radiative forcing, although the solar reduction added 40% to the overall cooling. There is no obvious distinguishing surface climate pattern between the two forcings. 2) The global and tropical response was greater than 1°C, in a model with a sensitivity of 1.2°C (W m[sup -2] )[sup -1] . To reproduce recent low-end estimates would require a sensitivity one-fourth as large. 3) The global surface temperature change was similar when using the total and spectral irradiance prescriptions, although the tropical response was somewhat greater with the former, and the stratospheric response greater with the latter. 4) Most experiments produce a relative negative phase of the North Atlantic Oscillation/Arctic Oscillation (NAO/AO) during the Maunder Minimum, with both solar and anthropogenic forcing equally capable, associated with the tropical cooling and relative poleward Eliassen–Palm (EP) flux refraction. 5) A full stratosphere appeared to be necessary for the negative AO/NAO phase, as was the case with this model for global warming experiments, unless the cooling was very large, while the ozone response played a minor role and did not influence surface temperature significantly. 6) Stratospheric ozone was most affected by the difference between present-day and preindustrial atmospheric composition and chemistry, with increases in the upper and lower stratosphere during the Maunder Minimum. While the estimated UV reduction led to ozone decreases, this was generally less important than the anthropogenic effect except in the upper midstratosphere, as judged by two different ozone photochemistry schemes. 7) The effect of the reduced solar irradiance on stratospheric ozone and on climate was similar in Maunder Minimum and current atmospheric conditions. [ABSTRACT FROM AUTHOR]

Evaluates the global climate model simulation for climate changes. Comparison by the Atmospheric Model Intercomparison Project to provide surface boundary conditions; Sensitivity on simulated climate to sea ice concentrations; Impact of satellite inaccuracies.

Part II. Investigates how the quassi biennial oscillation (QBO) influence on wave propagation and temperatures affects the Antarctic ozone hole. Correlation between QBO and ozone hole severity; Ozone response to QBO; Discussion and conclusions.

The GISS coupled atmosphere-ocean model is used to investigate the effect of increased atmospheric CO[sub2] by comparing a compounded 1% CO[sub2] increase experiment with a control simulation. After 70 yr of integration, the global surface air temperature in the 1% CO[sub2] experiment is 1.43°C warmer. In spite of this global warming, there are two distinct regions, the northern Atlantic Ocean and the southern Pacific Ocean, where the surface air temperature is up to 4°C cooler. This situation is maintained by two positive feedbacks: a local effect on convection in the South Pacific and a nonlocal impact on the meridional circulation in the North Atlantic. The poleward transport of latent energy and dry static energy by the atmosphere is greater in the 1% CO[sub2] experiment, caused by warming and therefore increased water vapor and greater greenhouse capacity at lower latitudes. The larger atmospheric transports tend to reduce upward vertical fluxes of heat and moisture from the ocean surface at high latitudes, which has the effect of stabilizing the ocean, reducing both convection and the thermohaline circulation. With less convection, less warm water is brought up from below, and with a reduced North Atlantic thermohaline circulation (by 30% at time of CO[sub2] doubling), the poleward energy transport by the oceans decreases. The colder water then leads to further reductions in evaporation, decreases of salinity at high latitudes, continued stabilization of the ocean, and maintenance of reduced convection and meridional overturning. Although sea ice decreases globally, it increases in the cooling regions, which reduces the overall climate sensitivity, especially in the Southern Hemisphere. Tropical warming has been observed over the past several decades; if modeling studies such as this and others that have produced similar effects are valid, these processes may already be beginning. [ABSTRACT FROM AUTHOR]

By how much does changing radiation from the sun influence the earth's climate, presently and in the recent past, compared with other natural and anthropogenic processes? Current knowledge of the amplitudes and timescales of solar radiative output variability needed to address this question is described from contemporary solar monitoring and historical reconstructions. The 17-yr observational database of space-based solar monitoring exhibits an 11-yr irradiance cycle with amplitude of about 0.1%. Larger amplitude solar total radiative output changes--of 0.24% relative to present levels--are estimated for the seventeenth-century Maunder Minimum by parameterizing the variability mechanisms identified for the 11-yr cycle, using proxies of solar and stellar variability. The 11- and 22-yr periods evident in solar activity proxies appear in many climate and paleoclimate records, and some solar and climate time series correlate strongly over multidecadal and centennial timescales. These statistical relationships suggest a response of the climate system to the changing sun. The correlation of reconstructed solar irradiance and Northern Hemisphere (NH) surface temperature anomalies is 0.86 in the pre-industrial period from 1610 to 1800, implying a predominant solar influence. Extending this correlation to the present suggests that solar forcing may have contributed about half of the observed 0.558C surface warming since 1900 and one-third of the warming since 1970. Climate model simulations using irradiance reconstructions provide a tool with which to identify potential physical mechanism for these implied connections. An equilibrium simulation by the Goddard Institute for Space Studies GCM predicts an NH surface temperature change of 0.518C for a 0.25% solar irradiance reduction, in general agreement with the preindustrial parameterization. But attributing a significant fraction of recent climate warming to solar forcing presents serious ambiguities about. [ABSTRACT FROM AUTHOR]

Examines the relationships between solar cycle variability, ozone and climate. Interactive parameterization of stratospheric chemistry; Importance of the dynamical coupling between the stratosphere and troposphere; Control of geopotential heights.

Parameterized stratospheric ozone photochemistry has been included in the Goddard Institute for Space Studies (GISS) GCM to investigate the coupling between chemistry and climate change for the doubled CO[sub2] climate. The chemical ozone response is of opposite sign to temperature changes, so that radiative cooling in the upper stratosphere results in increased ozone, while warming reduces ozone in the lower stratosphere. The increased overhead column reduces the amount of UV reaching the lower stratosphere, resulting in further ozone decreases there. Changes of up to 15% are seen, including both photochemistry and transport. Good agreement is found between the authors' results and those in other models for tropical latitudes where the stratospheric temperature responses are similar. However, in the extratropics, there are large differences between present results and those of the other models due to differences in tropospheric warming and tropospheric forcing of the stratospheric residual circulation. A net decrease in column ozone at midlatitudes is seen in this climate model, in contrast to the other models that showed an increase in column ozone everywhere. These ozone reductions lead to an increase of 10% in UV radiation reaching the surface at northern midlatitudes. The authors find significantly less of an increase in the high-latitude ozone column than in the other models. When parameterized heterogeneous chemistry on polar stratospheric clouds is also included, while maintaining current chlorine loading, it is found that the Antarctic ozone hole becomes significantly larger and of longer duration. In addition, an ozone hole of approximately half the depth in percent of the current Antarctic ozone hole forms in the Arctic due to both chemistry and transport changes resulting from a reduction of sudden warmings seen in the doubled CO[sub2] atmosphere. [ABSTRACT FROM AUTHOR]

Presents research which studied the interplay between projected future emissions of greenhouse gases and levels of ozone-depleting halogen species. Chemical reactions responsible for ozone depletion; Impact of greenhouse gases; Use of a global climate model with ozone-depletion chemistry; Results; Arctic losses of ozone; Predicted increase in severity and duration of the Antarctic ozone hole.

Uses a series of climate simulations to show that maintaining ocean heat transport at close to present-day values leads to enhanced cooling, particularly in the tropics. The suggestion that near-modern ocean heat transport may have been sustained in all ocean basins during the Last Glacial Maximum; How the climate model simulations were created. INSET: Ocean heat convergence and transport calculations..

Presents a study regarding physician and nurse practitioners' use of electronic medical records when caring for patients with HIV infection in a primary care practice. Response times to situations that triggered alerts and reminders; Lack of visitation effect to primary care practice; Admission rate patterns.

Describes a protocol developed to protect the confidentiality of patient medical records by the Boston Electronic Medical Record Collaborative. Benefits of using this protocol; Problems experienced in the use of previous systems; Details on how patient care should be improved through the interinstitutional transfer of records.

Objectives: This study aimed to estimate the cost-effectiveness of remdesivir, the first novel therapeutic to receive Emergency Use Authorization for the treatment of hospitalized patients with COVID-19, and identify key drivers of value to guide future pricing and reimbursement efforts.Methods: A Markov model evaluated the cost-effectiveness of remdesivir in patients hospitalized with COVID-19 from a US healthcare sector perspective. A lifetime time horizon captured potential long-term costs and outcomes. Model outcomes included discounted total costs, life-years, and quality-adjusted life-years (QALYs). Remdesivir was modeled as an addition to standard of care and compared with standard of care alone, including dexamethasone for patients requiring respiratory support. COVID-19 hospitalizations were assumed to be reimbursed through a single payment based on the respiratory support received alongside a remdesivir carveout payment in the base case. Sensitivity and scenario analyses identified key drivers.Results: At a unit price of $520 per vial and assuming no survival benefit with remdesivir, the incremental cost-effectiveness was $298 200/QALY for patients with moderate to severe COVID-19 and $1 847 000/QALY for patients with mild COVID-19. Although current data do not support a survival benefit, if one was assumed, the cost-effectiveness estimate was $50 100/QALY for the moderate to severe population and $103 400/QALY for the mild population. Another key driver included the hospitalization payment structure (per diem vs bundled payment).Conclusions: With the current evidence available, remdesivir's price is too high to align with its expected health gains for hospitalized patients with COVID-19. Results from this study provide a rationale for iterative health technology assessment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in reply to the article "Challenges in using observational studies to evaluate the adverse effects of treatment," by M.D. Hughes and P.L. Williams in the April 26, 2007 issue.

Suggests that high glacial dust loading may have caused significant, episodic regional warming downwind of major Asian and ice-margin dust sources during the last glacial period. The association of abrupt changes in dust loading with the Dansgaard-Oeschger and Heinrich climate events and with glacial termination; The suggestion that dust-induced warming may have played a role in triggering large shifts in Pleistocene climate.

This study aimed to evaluate the diversity of clinical trials informing assessments conducted by the Institute for Clinical and Economic Review. This was a cross-sectional study of pivotal trials included in completed Institute for Clinical and Economic Review assessments over 5 years (2017-2021). Representation of racial/ethnic minority groups, females, and older adults was compared with the disease-specific and US population, using a relative representation cutoff of 0.8 for adequate representation. A total of 208 trials, evaluating 112 interventions for 31 unique conditions, were examined. Race/ethnicity data were inconsistently reported. The median participant-to-disease representative ratio (PDRR) for Blacks/African Americans (0.43 [interquartile range (IQR) 0.24-0.75]), American Indians/Alaska Natives (0.37 [IQR 0.09-0.77]), and Hispanics/Latinos (0.79 [IQR 0.30-1.22]) were below the adequate representation cutoff. In contrast, Whites (1.06 [IQR 0.92-1.2]), Asians (1.71 [IQR 0.50-3.75]), and Native Hawaiian/Other Pacific Islanders (1.61 [IQR 0.77-2.81]) were adequately represented. Findings were similar when compared with the US Census, except for Native Hawaiian/Pacific Islanders, which was substantially worse. Relative to all trials, a higher proportion of US-based trials adequately represented Blacks/African Americans (61% vs 23%, P <.0001) and Hispanics/Latinos (68% vs 50%; P =.047), but a lower proportion adequately represented Asians (15% vs 67%, P <.0001). Females were adequately represented in 74% of trials (PDRR: 1.02 [IQR 0.79-1.14]). Nevertheless, older adults were adequately represented in only 20% of trials (PDRR: 0.30 [IQR 0.13-0.64]). The representation of racial/ethnic minorities and older adults was inadequate. Efforts are needed to enhance the diversity of clinical trials. Standardized and transparent evaluation of trial diversity should be part of the health technology assessment process. • Lack of diversity in clinical trial populations, particularly in pivotal trials that serve as the key source of evidence for regulatory, clinical, and policy decisions, has implications for generalizability and fairness. • Based on the US Census and disease-specific prevalence estimates, this study showed that racial/ethnic minorities and older adults were underrepresented in the majority of the trials that serve as the major source of evidence for health technology assessment in the United States and further highlighted the disparity in the racial diversity of US-based trials versus global trials. • Given the changing US population and the current trend of global trials, clinical trial diversity may worsen if proactive steps are not taken to mitigate this. Although investigators and clinical trial developers are at the front line of recruiting diverse participants, regulators and health technology assessment bodies have a role in enhancing transparency and accountability by developing standardized approaches to evaluating clinical trial diversity. [ABSTRACT FROM AUTHOR]

Nadofaragene firadenovec is a gene therapy for bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) undergoing Food and Drug Administration review. Pembrolizumab is approved for treating patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS). We evaluated the cost-effectiveness of these treatments compared with a hypothetical therapeutic alternative, at a willingness-to-pay threshold of $150 000 per quality-adjusted life-year (QALY) gained, in CIS and non-CIS BCG-unresponsive NMIBC populations. We developed a Markov cohort simulation model with a 3-month cycle length and lifetime horizon to estimate the total costs, QALYs, and cost per additional QALY from the health sector perspective. Clinical inputs were informed by results of single-arm clinical trials evaluating the treatments, and systematic literature reviews were conducted to obtain other model inputs. Sensitivity analyses were conducted to assess uncertainty in model results. Nadofaragene firadenovec, at a placeholder price 10% higher than the price of pembrolizumab, had an incremental cost-effectiveness ratio of $263 000 and $145 000 per QALY gained in CIS and non-CIS populations, respectively. Pembrolizumab had an incremental cost-effectiveness ratio of $168 000 per QALY gained for CIS. A 5.4% reduction in pembrolizumab's price would make it cost-effective. The model was sensitive to many inputs, especially to the probabilities of disease progression, initial treatment response and durability, and drug price. The cost-effectiveness of nadofaragene firadenovec will depend upon its price. Pembrolizumab, although not cost-effective in our base-case analysis, is an important alternative in this population with an unmet medical need. Comparative trials of these treatments are warranted to better estimate cost-effectiveness. • There are few therapeutic alternatives for the treatment of bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer. Although cystectomy is potentially curative, many patients are ineligible for or unwilling to undergo cystectomy. Nadofaragene firadenovec and pembrolizumab are new bladder-sparing treatments. • This study evaluated the lifetime cost-effectiveness of nadofaragene firadenovec and pembrolizumab from the US health sector perspective. • Using a placeholder price, nadofaragene firadenovec was cost-effective in the non–carcinoma in situ (CIS) population but not in the CIS population. Pembrolizumab, at its current price, was not cost-effective in the CIS population. Cost per quality-adjusted life-year gained and threshold price estimates can aid drug pricing negotiations between payers and drug manufacturers. [ABSTRACT FROM AUTHOR]

Both the Greenland and Antarctic ice sheets have been melting at an accelerating rate over recent decades. Meltwater from Greenland might be expected to initiate a climate response that is distinct, and perhaps different from, that associated with Antarctic meltwater. Which one might elicit a greater climate response, and what mechanisms are involved? To explore these questions, we apply climate response functions (CRFs) to guide a series of meltwater-perturbation experiments using a fully coupled climate model. In both hemispheres, meltwater drives atmospheric cooling, sea ice expansion, and strengthened Hadley and Ferrel cells. Greenland meltwater induces a slowdown of the Atlantic meridional overturning circulation (AMOC) and a cooling of the subsurface ocean in the northern high latitudes. Antarctic meltwater, instead, induces a slowdown of the Antarctic Bottom Water formation and a warming of the subsurface ocean around Antarctica. For melt rates up to 2000 Gt yr−1, the climate response is rather linear. However, as melt rates increase to 5000 Gt yr−1, the climate response becomes nonlinear. Due to a collapsed AMOC, the climate response is superlinear at high Greenland melt rates. Instead, the climate response is sublinear at high Antarctic melt rates, due to the halting of the northward expansion of Antarctic sea ice by warm surface waters. Finally, in the linear limit, we use CRFs and linear convolution theory to make projections of important climate parameters in response to meltwater scenarios, which suggest that Antarctic meltwater will become a major driver of climate change, dominating that of Greenland meltwater, as the current century proceeds. Significance Statement: Melting of the Greenland and Antarctic ice sheets is one of the most uncertain potential contributors to future climate change. In this study, we address the comparative role of Greenland and Antarctic meltwater in the climate system and explore the differing mechanisms at work in each hemisphere. We find that the climate response is linear for low melt rates but becomes nonlinear for high melt rates. As the century proceeds, we speculate that Antarctic meltwater will increasingly dominate that of Greenland meltwater, leading to atmospheric cooling, Antarctic sea ice expansion, and contraction and warming of the Antarctic Bottom Water. Greenland meltwater will, instead, affect smaller changes in the Northern Hemisphere. [ABSTRACT FROM AUTHOR]

Analyzes the tie between the behavior of water in the atmosphere and global climate models. Impact of global warming; Lower tropospheric water vapor concentration; Likelihood of reductions in high-altitude moisture; Measuring water vapor values; Use of satellites, and their drawbacks; Possible amplification of the greenhouse effect; How researchers are addressing the problem.

Comments on discussions held at a recent mini-conference on `Uplift, Erosion and Climate.' Projections of a rapid warming of the climate over the next century; Increased greenhouse gases; The Tertiary Period, 63-2.5 millions years ago; Relation between the rapid development of the great mountain belts and the onset of the modern alternation between glacial and interglacial climes following the end of the Tertiary era; Study by P. Molnar; Late Cenozoic; Study by T. Volk; More.

The prevalence of diabetes in the United States is rising. Twelve percent of U.S. adults have diabetes and another 37% have impaired fasting glucose or impaired glucose tolerance. Diabetes is a major risk factor for such outcomes as cardiovascular disease, blindness, chronic kidney disease, and limb amputation. An important consideration is whether screening for abnormal glucose levels or diabetes reduces cardiovascular or all-cause morbidity and mortality. In October 2015, the U.S. Preventive Services Task Force published recommendations on screening for abnormal blood glucose and concluded that intensive lifestyle interventions have a moderate benefit in reducing progression to diabetes in patients who have abnormal blood glucose levels detected by screening. It found inadequate evidence that such screening reduces cardiovascular or all-cause mortality and no evidence of psychological or other harms from screening. The Task Force recommends glucose screening every 3 years for adults aged 40 to 70 years who are overweight or obese and do not have symptoms of diabetes. In this article, we present the case of a man who meets these criteria and explore his preferences and concerns regarding screening. Two experts then debate screening merits and benefits, the significance of abnormal blood glucose levels and diabetes as cardiovascular risk factors, and application of the guidelines to this particular patient. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The computer-based patient record and confidentiality," by B. Woodward in the November 23, 1995 issue.

A letter to the editor is presented in response to the article "Why We Need Medical Savings Accounts," by U.S. Senator Phil Gramm in the June 16, 1994 issue.

Presents an abstract of the study `Effect of Computer-Based Alerts on the Treatment and Outcomes of Hospitalized Patients,' by David M. Rind et al.

This paper presents the response to anthropogenic forcing in the GISS‐E2.1 climate models for the 21st century Shared Socioeconomic Pathways emission scenarios within the Coupled Model Intercomparison Project Phase 6 (CMIP6). The experiments were performed using an updated and improved version of the NASA Goddard Institute for Space Studies (GISS) coupled general circulation model that includes two different versions for atmospheric composition: A non‐interactive version (NINT) with prescribed composition and a tuned aerosol indirect effect and the One‐Moment Aerosol model (OMA) version with fully interactive aerosols which includes a parameterized first indirect aerosol effect on clouds. The effective climate sensitivities are 3.0°C and 2.9°C for the NINT and OMA models, respectively. Each atmospheric version is coupled to two different ocean general circulation models: The GISS ocean model (E2.1‐G) and HYCOM (E2.1‐H). We describe the global mean responses for all future scenarios and spatial patterns of change for surface air temperature and precipitation for four of the marker scenarios: SSP1‐2.6, SSP2‐4.5, SSP4‐6.0, and SSP5‐8.5. By 2100, global mean warming ranges from 1.5°C to 5.2°C relative to 1,850–1,880 mean temperature. Two high‐mitigation scenarios SSP1‐1.9 and SSP1‐2.6 limit the surface warming to below 2°C by the end of the 21st century, except for the NINT E2.1‐H model that simulates 2.2°C of surface warming. For the high emission scenario SSP5‐8.5, the range is 4.6–5.2°C at 2100. Due to about 15% larger effective climate sensitivity and stronger transient climate response in both NINT and OMA CMIP6 models compared to CMIP5 versions, there is a stronger warming by 2100 in the SSP emission scenarios than in the comparable Representative Concentration Pathway (RCP) scenarios in CMIP5. Changes in sea ice area are highly correlated to global mean surface air temperature anomalies and show steep declines in both hemispheres, with the largest sea ice area decreases occurring during September in the Northern Hemisphere in both E2.1‐G (−1.21 × 106 km2/°C) and E2.1‐H models (−0.94 × 106 km2/°C). Both coupled models project decreases in the Atlantic overturning stream function by 2100. The largest decrease of 56%–65% in the 21st century overturning stream function is produced in the warmest scenario SSP5‐8.5 in the E2.1‐G model, comparable to the reduction in the corresponding CMIP5 GISS‐E2 RCP8.5 simulation. Both low‐end scenarios SSP1‐1.9 and SSP1‐2.6 also simulate substantial reductions of the overturning (9%–37%) with slow recovery of about 10% by the end of the 21st century (relative to the maximum decrease at the middle of the 21st century). Plain Language Summary: The projections of future climate change are uncertain because they are dependent on different possible scenarios of human‐caused emissions and their interaction with natural forcings, internal climate variability, and inter‐model differences. This paper presents the results of the climate model of the NASA Goddard Institute for Space Studies, GISS‐E2.1, for the anthropogenically forced climate response for the twenty first century Shared Socioeconomic Pathways emission scenarios within the Coupled Model Intercomparison Project Phase 6 (CMIP6). The sensitivity of the model response to different magnitudes of anthropogenic forcings in the twenty‐first‐century scenarios were performed using two different versions for the atmospheric composition and two different ocean general circulation models. Compared to CMIP5 GISS‐E2 versions, the CMIP6 GISS‐E2.1 climate model shows a stronger warming by 2100 in comparable scenarios due to larger effective climate sensitivity and transient climate response. Both climate models with two different ocean components project decreases in the Atlantic overturning stream function by 2100. Key Points: GISS E2.1 model with different configurations is used to carry out 134 Shared Socioeconomic Pathway (SSP) experimentsGISS‐E2.1 climate model shows a stronger warming by 2,100 in comparable Representative Concentration Pathway scenarios in CMIP5 due to larger effective climate sensitivity and stronger transient climate responseBoth coupled models, E2.1‐G and E2.1‐H, project decreases in the Atlantic overturning stream function by 2100 with the largest decrease in the warmest scenario SSP5‐8.5 in the E2.1‐G model [ABSTRACT FROM AUTHOR]

Extreme monsoon rainfall in India has disastrous consequences, including significant socioeconomic impacts. However, little is known about the overall trends and climate factors associated with extreme rainfall because rainfall greatly varies across India and because few appropriate methods are available to measure extreme rainfall in the context of such heterogeneity. To provide a comprehensive assessment of extreme monsoon rainfall, the authors developed a metric using record rainfall data to measure the changes in the likelihood of extreme high and extreme low rainfall over time; this metric is independent of the characteristics of the underlying rainfall distributions. Hence, the metric is ideally suited to aggregate extreme rainfall information across heterogeneous regions covering India. The authors found that from 1930 to 2013, the likelihood of extreme high and extreme low rainfall increases 2-fold and 4-fold, respectively. These overall trend increases are driven by anomalous increases, particularly in the early 2000s; the likelihood of extreme high and extreme low rainfall increases 5-fold and 18-fold in 2005 and 2002, respectively. These findings imply a broadening of the underlying monsoon rainfall distribution over the past century. The authors also show that the time patterns of the likelihood of extreme rainfall in recent decades are correlated with El Niño-Southern Oscillation, especially when it is in the same phase with the Pacific decadal oscillation and Indian Ocean dipole. [ABSTRACT FROM AUTHOR]

Consensus on global warming is the result of multiple and varying lines of evidence, and one key ramification is the increase in frequency of extreme climate events including record high temperatures. Here we develop a metric-called 'record equivalent draws' (RED)-based on record high (low) temperature observations, and show that changes in RED approximate changes in the likelihood of extreme high (low) temperatures. Since we also show that this metric is independent of the specifics of the underlying temperature distributions, RED estimates can be aggregated across different climates to provide a genuinely global assessment of climate change. Using data on monthly average temperatures across the global landmass we find that the frequency of extreme high temperatures increased 10-fold between the first three decades of the last century (1900-1929) and the most recent decade (1999-2008). A more disaggregated analysis shows that the increase in frequency of extreme high temperatures is greater in the tropics than in higher latitudes, a pattern that is not indicated by changes in mean temperature. Our RED estimates also suggest concurrent increases in the frequency of both extreme high and extreme low temperatures during 2002-2008, a period when we observe a plateauing of global mean temperature. Using daily extreme temperature observations, we find that the frequency of extreme high temperatures is greater in the daily minimum temperature time-series compared to the daily maximum temperature time-series. There is no such observable difference in the frequency of extreme low temperatures between the daily minimum and daily maximum. [ABSTRACT FROM AUTHOR]

Migrations toward altered sea surface temperature (SST) patterns in the Indo-Pacific region are present in the recent observational record and in future global warming projections. These SSTs are in the form of 'permanent' El Niño-like (herein termed 'El Padre') and Indian Ocean Dipole (IOD)-like patterns. The Early Pliocene Warm Period, which bears similarity to future warming projections, may have also exhibited these Indo-Pacific SST patterns, as suggested by regional terrestrial paleo-climatic data and general circulation model studies. The ability to corroborate this assessment with paleo-data reconstructions is an advantage of the warm Pliocene period that is not afforded by future warming scenarios. Thus, the Pliocene period provides us with a warm-climate perspective and test bed for understanding potential changes to future atmospheric interactions given these altered SST states. This study specifically assesses how atmospheric teleconnections from El Padre/IOD SST patterns are generated and propagate to create the regional climate signals of the Pliocene period, as these signals may be representative of future regional climatic changes as well. To do this, we construct a holistic diagnostic rubric that allows us to examine atmospheric teleconnections, both energetically and dynamically, as produced by a general circulation model. We incorporate KE′, a diagnostic adapted from the eddy kinetic energy generation field, to assess the available energy transferred to these teleconnections. Using this methodology, we found that relative to our Modern Control experiments, weaker atmospheric teleconnections prevail under warm Pliocene conditions, although pathways of propagation still appear directed toward the southwestern United States from our tropical Pacific sector forcing. Propagation directly emanating from the Indian Ocean forcing sector appears to be largely blocked, although indirect teleconnective pathways appear traversing the Asian continent toward the North Pacific. The changes in the atmospheric circulation of Indian Ocean region in response to the underlying specified SST forcing (and indicated by Pliocene paleo-data) may have a host of implications for energy transfer out of and into the region, including interactions with the Asian jet stream and changes to the seasonal monsoon cycle. These interactions warrant further study in both past and future warm climate scenarios. [ABSTRACT FROM AUTHOR]

Ample physical evidence shows that carbon dioxide (CO²) is the single most important climate-relevant greenhouse gas in Earth's atmosphere. This is because CO², like ozone, N²O, CH4, and chlorofluorocarbons, does not condense and precipitate from the atmosphere at current climate temperatures, whereas water vapor can and does. Noncondensing greenhouse gases, which account for 25% of the total terrestrial greenhouse effect, thus serve to provide the stable temperature structure that sustains the current levels of atmospheric water vapor and clouds via feedback processes that account for the remaining 75% of the greenhouse effect. Without the radiative forcing supplied by CO²; and the other noncondensing greenhouse gases, the terrestrial greenhouse would collapse, plunging the global climate into an icebound Earth state. [ABSTRACT FROM AUTHOR]

Each year, irrigated Saharan- and Australian-desert forests could sequester amounts of atmospheric CO2 at least equal to that from burning fossil fuels. Without any rain, to capture CO2 produced from gasoline requires adding about $1 to the per-gallon pump-price to cover irrigation costs, using reverse osmosis (RO), desalinated, sea water. Such mature technology is economically competitive with the currently favored, untested, power-plant Carbon Capture (and deep underground, or under-ocean) Sequestration (CCS). Afforestation sequesters CO2, mostly as easily stored wood, both from distributed sources (automotive, aviation, etc., that CCS cannot address) and from power plants. Climatological feasibility and sustainability of such irrigated forests, and their potential global impacts are explored using a general circulation model (GCM). Biogeophysical feedback is shown to stimulate considerable rainfall over these forests, reducing desalination and irrigation costs; economic value of marketed, renewable, forest biomass, further reduces costs; and separately, energy conservation also reduces the size of the required forests and therefore their total capital and operating costs. The few negative climate impacts outside of the forests are discussed, with caveats. If confirmed with other GCMs, such irrigated, subtropical afforestation probably provides the best, near-term route to complete control of green-house-gas-induced, global warming. [ABSTRACT FROM AUTHOR]

Abstract: Background: Electronic clinical knowledge support systems have decreased barriers to answering clinical questions but there is little evidence as to whether they have an impact on health outcomes. Methods: We compared hospitals with online access to UpToDate® with other acute care hospitals included in the Thomson 100 Top Hospitals® Database (Thomson database). Metrics used in the Thomson database differentiate hospitals on a variety of performance dimensions such as quality and efficiency. Prespecified outcomes were risk-adjusted mortality, complications, the Agency of Healthcare Research and Quality Patient Safety Indicators, and hospital length of stay among Medicare beneficiaries. Linear regression models were developed that included adjustment for hospital region, teaching status, and discharge volume. Results: Hospitals with access to UpToDate® (n =424) were associated with significantly better performance than other hospitals in the Thomson database (n =3091) on risk-adjusted measures of patient safety (P =0.0163) and complications (P =0.0012) and had significantly shorter length of stay (by on average 0.167 days per discharge, 95% confidence interval 0.081–0.252 days, P <0.0001). All of these associations correlated significantly with how much UpToDate® was used at each hospital. Mortality was not significantly different between UpToDate® and non-UpToDate® hospitals. Limitations: The study was retrospective and observational and could not fully account for additional features at the included hospitals that may also have been associated with better health outcomes. Conclusions: An electronic clinical knowledge support system (UpToDate®) was associated with improved health outcomes and shorter length of stay among Medicare beneficiaries in acute care hospitals in the United States. Additional studies are needed to clarify whether use of UpToDate® is a marker for the better performance, an independent cause of it, or a synergistic part of other quality improvement characteristics at better-performing hospitals. [Copyright &y& Elsevier]

Analyzes the data from the International Satellite Cloud Climatology Project on the relationship between low-cloud optical thickness and cloud temperature implying a positive feedback between clouds and climate. Use of a two-dimensional radiative-convective model to assess feedback the effect of the on climate change; Positive feedback in the Northern Hemisphere.

Objective: The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration-approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC).Study Design: A 2-state Markov model, alive and dead, with a lifetime horizon.Methods: Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs.Results: VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective.Conclusions: At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered. [ABSTRACT FROM AUTHOR]

Background: Overdose deaths have increased dramatically in the United States, including in Rhode Island. In July 2021, the Rhode Island government passed legislation supporting a two-year pilot program authorizing supervised consumption sites (SCSs) in response to this crisis. We estimated the costs and benefits of a hypothetical SCS in Providence, Rhode Island.Methods: We utilized a decision analytic mathematical model to compare costs and outcomes for people who inject drugs under two scenarios: (1) a SCS that includes syringe services provision, and (2) a syringe service program only (i.e., status quo). We assumed 0.95% of injections result in overdose, the SCS would serve 400 clients monthly and have a net cost of $783,899 annually, 46% of overdoses occurring outside of the SCS result in an ambulance run and 43% result in an emergency department (ED) visit, 0.79% of overdoses occurring within the SCS result in an ambulance run and ED visit, and the SCS would lead to a 25.7% reduction in fatal overdoses near the site. The model was developed from a modified societal perspective with a one-year time horizon.Results: A hypothetical SCS in Providence would prevent approximately 2 overdose deaths, 261 ambulance runs, 244 ED visits, and 117 inpatient hospitalizations for emergency overdose care annually compared to a scenario that includes a syringe service program only. The SCS would save $1,104,454 annually compared to the syringe service program only, accounting only for facility costs and short-term costs of emergency overdose care and ignoring savings associated with averted deaths. Influential parameters included the percentage of injections resulting in overdose, the total annual injections at the SCS, and the percentage of overdoses outside of the SCS that result in an ED visit.Conclusion: A SCS in would result in substantial cost savings due to prevention of costly emergency overdose care. [ABSTRACT FROM AUTHOR]