Spectrally refined unbiased Monte Carlo estimate of the Earth's global radiative cooling.

The Earth's radiative cooling is a key driver of climate. Determining how it is affected by greenhouse gas concentration is a core question in climate-change sciences. Due to the complexity of radiative transfer processes, current practices to estimate this cooling require the development and use of a suite of radiative transfer models whose accuracy diminishes as we move from local, instantaneous estimates to global estimates over the whole globe and over long periods of time (decades). Here, we show that recent advances in nonlinear Monte Carlo methods allow a paradigm shift: a completely unbiased estimate of the Earth's infrared cooling to space can be produced using a single model, integrating the most refined spectroscopic models of molecular gas energy transitions over a global scale and over years, all at a very low computational cost (a few seconds).

Spread in model climate sensitivity traced to atmospheric convective mixing.

Equilibrium climate sensitivity refers to the ultimate change in global mean temperature in response to a change in external forcing. Despite decades of research attempting to narrow uncertainties, equilibrium climate sensitivity estimates from climate models still span roughly 1.5 to 5 degrees Celsius for a doubling of atmospheric carbon dioxide concentration, precluding accurate projections of future climate. The spread arises largely from differences in the feedback from low clouds, for reasons not yet understood. Here we show that differences in the simulated strength of convective mixing between the lower and middle tropical troposphere explain about half of the variance in climate sensitivity estimated by 43 climate models. The apparent mechanism is that such mixing dehydrates the low-cloud layer at a rate that increases as the climate warms, and this rate of increase depends on the initial mixing strength, linking the mixing to cloud feedback. The mixing inferred from observations appears to be sufficiently strong to imply a climate sensitivity of more than 3 degrees for a doubling of carbon dioxide. This is significantly higher than the currently accepted lower bound of 1.5 degrees, thereby constraining model projections towards relatively severe future warming.

Radiative flux and forcing parameterization error in aerosol-free clear skies.

Radiation parameterizations in GCMs are more accurate than their predecessorsErrors in estimates of 4 ×CO2 forcing are large, especially for solar radiationErrors depend on atmospheric state, so global mean error is unknown.

Management of Oligometastatic Breast Cancer: An Expert Committee's Opinion.

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion. The experts were physicians working in the Province of Quebec (Canada) and specialized in BC care, including surgical oncologists, medical oncologists, and radiation oncologists. The experts provided their opinions about the context of the disease and therapeutic approach, local and systemic therapies, and the prognosis of oligometastatic BC. In addition to the expert panel's opinions about the management of oligometastatic disease per se, the experts stated that a prospective data registry should be implemented to collect data about oligometastatic BC to improve knowledge about oligometastatic BC and implement data-driven MDT. These data could also allow for the design of treatment algorithms. In conclusion, this paper presents the expert panel's opinions about the management of oligometastatic BC and highlights the needs to be met to improve the care of this condition.

Acute hypercalcemia and excessive bone resorption following anti-RANKL withdrawal: Case report and brief literature review.

Denosumab is an anti-RANKL antibody that is commonly used for the treatment of osteoporosis; in oncology, bisphosphonates and denosumab have become the standard therapies for the treatment and prevention of skeletal complications in patients with myeloma and solid tumors. In recent years, excessive bone remodeling following the discontinuation of denosumab has raised concerns. Several cases of hypercalcemia have been reported after the discontinuation of high-dose denosumab (120 mg every 4 weeks), mainly in children. In this study, we report a new case of severe refractory hypercalcemia in a 54-year-old woman who received high-dose denosumab for 5 years as an adjuvant therapy for breast cancer. She is currently in remission and undergoing treatment with anastrazole, an aromatase inhibitor. The peculiarities of this case are the presence of associated bone pain with subperiosteal bone resorption on hand X-rays, and diffuse, long bone diaphyseal uptake on a bone scan. Hyperparathyroidism has been ruled out, and existing evidence suggests that this high-level of bone remodeling could be due to a rebound hyperactivation of the RANKL pathway. In addition to rehydration, repeated use of i.v. bisphosphonates was required to control recurrent hypercalcemia. As hypercalcemia is a serious metabolic complication, a gradual dose reduction should be considered when interruption of high dose denosumab therapy is planned.

Retrospective Study of High Hemoglobin Levels in 56 Young Adults.

BACKGROUND: Erythrocytosis is a frequent request for consultation in the hematologic field. The diagnostic approach is well established in the general population but in a young adult, finding the etiology of erythrocytosis can be a real diagnostic challenge. METHODS: This is an observational retrospective unicentric study made at the Sherbrooke University Hospital Center, over a period of 20 years (1995 - 2015). Every patient aged between 16 and 35 years old with a significant elevation of hemoglobin or hematocrit was included (hemoglobin > 185 g/L and/or hematocrit > 0.52 in men; hemoglobin > 165 g/L and/or hematocrit > 0.48 in women). RESULTS: Totally, 426 patients met the inclusion criteria (over a total of 113,453 complete blood counts) but only 56 entered the study for investigations. The majority of patients were of male gender, 43% of the patients were obese, 59% were smokers and 38% used excess alcohol or recreational drugs. Twenty-five patients had the diagnosis of absolute erythrocytosis. Seven patients had the diagnosis of relative erythrocytosis and no cause could be identified in 24 patients. No primary erythrocytosis was found in this cohort. Among the 25 patients with secondary erythrocytosis, hypoxia was the most frequent etiology identified. Less than half of the patients in the cohort had long term follow-up. Search for JAK2 mutation and serum EPO dosage were performed in 17.9% and 23.2% of cases respectively. Seven patients were treated with aspirin and five patients had phlebotomies. CONCLUSIONS: This retrospective study reveals an actual clinical management that is often discordant with the current recommendations and a frequent lack of follow-up after initial investigations. Harmonization of management of erythrocytosis appears to be highly desirable.

Coupling between lower-tropospheric convective mixing and low-level clouds: Physical mechanisms and dependence on convection scheme.

Several studies have pointed out the dependence of low-cloud feedbacks on the strength of the lower-tropospheric convective mixing. By analyzing a series of single-column model experiments run by a climate model using two different convective parametrizations, this study elucidates the physical mechanisms through which marine boundary-layer clouds depend on this mixing in the present-day climate and under surface warming. An increased lower-tropospheric convective mixing leads to a reduction of low-cloud fraction. However, the rate of decrease strongly depends on how the surface latent heat flux couples to the convective mixing and to boundary-layer cloud radiative effects: (i) on the one hand, the latent heat flux is enhanced by the lower-tropospheric drying induced by the convective mixing, which damps the reduction of the low-cloud fraction, (ii) on the other hand, the latent heat flux is reduced as the lower troposphere stabilizes under the effect of reduced low-cloud radiative cooling, which enhances the reduction of the low-cloud fraction. The relative importance of these two different processes depends on the closure of the convective parameterization. The convective scheme that favors the coupling between latent heat flux and low-cloud radiative cooling exhibits a stronger sensitivity of low-clouds to convective mixing in the present-day climate, and a stronger low-cloud feedback in response to surface warming. In this model, the low-cloud feedback is stronger when the present-day convective mixing is weaker and when present-day clouds are shallower and more radiatively active. The implications of these insights for constraining the strength of low-cloud feedbacks observationally is discussed.

Activity and safety of the antiestrogen EM-800, the orally active precursor of acolbifene, in tamoxifen-resistant breast cancer.

PURPOSE: To determine the efficacy and safety of EM-800 (SCH-57050), the precursor of acolbifene, a new, highly potent, orally active, pure antiestrogen in the mammary gland and endometrium, for the treatment of tamoxifen-resistant breast cancer. PATIENTS AND METHODS: Forty-three post menopausal/ovariectomized women with breast cancer who had received tamoxifen, either for metastatic disease or as adjuvant to surgery for > or = 1 year, and had relapsed were treated in a prospective, multicenter, phase II study with EM-800 (20 mg/d [n = 21] or 40 mg/d [n = 22] orally). Results Thirty-seven patients had estrogen receptor (ER)-positive tumors (>10 fmol/mg; mean, 146 fmol/mg cytosolic protein), three patients had ER-negative/progesterone receptor-positive tumors, and three patients had undetermined ER status. The objective response rate to EM-800 was 12%, with one complete response and four partial responses. Ten patients (23%) had stable disease for > or = 3 months, and 7 patients (16%) had stable disease for > or = 6 months. With a median follow-up of 29 months, median duration of response was 8 months (range, 7 to 71+ months). Treatment with EM-800 was well tolerated. No significant adverse events related to the study drug were observed clinically or biochemically. CONCLUSION: EM-800 produced responses in a significant proportion of patients with tamoxifen-resistant breast cancer, thus showing that this highly potent, selective estrogen receptor modulator, which lacks estrogenic activity in the mammary gland and endometrium, has incomplete cross-resistance with tamoxifen, thus suggesting additional benefits in the treatment of breast cancer.

Toll motorway accessibility for wheelchair users: a survey.

OBJECTIVE: To identify difficulties encountered by wheelchair users who travel on toll motorways, with the goal of defining areas for improvement. DESIGN: Survey. After observing a wheelchair user travelling on a toll motorway and using the associated services, we designed a self-questionnaire on perceptions by wheelchair users of toll motorway accessibility. SETTING: Toll motorway and rehabilitation hospital in France. SUBJECTS: We recruited 167 wheelchair users by advertisement and, to assess selection bias, 19 consecutive outpatients who visited our hospital's wheelchair showroom. INTERVENTION: None. RESULTS: Of the 186 included subjects, 91 (49%) were used to driving independently on toll motorways. Among them, only 16% used automatic toll booths and 32% reported difficulties at toll booths. Furthermore, 53% routinely asked for help at filling stations, and only 27% were aware of the availability of a free-of-charge assistance service for disabled people at some filling stations. Among the 186 toll motorway users, only 84 (45%) reported never encountering difficulties in lay-bys; 162 (87%) felt that toilet accessibility was the most important feature of lay-bys and 143 (77%) preferred the locked toilets reserved for disabled people. CONCLUSION: Wheelchair users reported difficulties on toll motorways that could be corrected fairly easily.