The difference between the time series trend for temperature expected from the increasing level of atmospheric CO
2
and that for the (more slowly rising) observed temperature has been termed the ...global surface temperature slowdown. In this paper, we characterise the single time series made from the subtraction of these two time series as the ‘global surface temperature gap’. We also develop an analogous atmospheric CO
2
gap series from the difference between the level of CO
2
and first-difference CO
2
(that is, the change in CO
2
from one period to the next). This paper provides three further pieces of evidence concerning the global surface temperature slowdown. First, we find that the present size of both the global surface temperature gap and the CO
2
gap is unprecedented over a period starting at least as far back as the 1860s. Second, ARDL and Granger causality analyses involving the global surface temperature gap against the major candidate physical drivers of the ocean heat sink and biosphere evapotranspiration are conducted. In each case where ocean heat data was available, it was significant in the models: however, evapotranspiration, or its argued surrogate precipitation, also remained significant in the models alongside ocean heat. In terms of relative scale, the standardised regression coefficient for evapotranspiration was repeatedly of the same order of magnitude as—typically as much as half that for—ocean heat. The foregoing is evidence that, alongside the ocean heat sink, evapotranspiration is also likely to be making a substantial contribution to the global atmospheric temperature outcome. Third, there is evidence that both the ocean heat sink and the evapotranspiration process might be able to continue into the future to keep the temperature lower than the level-of-CO
2
models would suggest. It is shown that this means there can be benefit in using the first-difference CO
2
to temperature relationship shown in Leggett and Ball (Atmos Chem Phys 15(20):11571–11592,
2015
) to forecast future global surface temperature.
Abstract
Background
Following historically low influenza activity during the 2020–2021 season, the United States saw an increase in influenza circulating during the 2021–2022 season. Most viruses ...belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade.
Methods
We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders.
Results
In total, 86 732 ED/UC ARI-associated encounters (7696 9% cases) and 16 805 hospitalized ARI-associated encounters (649 4% cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%–29%) and 25% (95% CI, 11%–37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, −5% to 17%) or with immunocompromising conditions (4%; 95% CI, −45% to 36%).
Conclusions
During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.
During the 2021–2022 United States influenza season with predominant influenza A(H3N2) virus circulation, vaccine effectiveness against influenza-associated emergency department/urgent care encounters and hospitalizations were both 25%, with effectiveness varying by age group and presence of immunocompromising conditions.
Inherited kidney cancer syndromes Ball, Mark W; Shuch, Brian M
Current opinion in urology,
2019-July, 2019-07-00, 20190701, Letnik:
29, Številka:
4
Journal Article
PURPOSE OF REVIEWTo describe current paradigms for genetic testing, screening, and treatment of patients with inherited kidney cancer syndromes.
RECENT FINDINGSWe describe various new aspects of ...hereditary kidney cancer. Recent data now support that hereditary kidney cancer may account for 5–8% of kidney cancers diagnosed. Methods of testing have evolved including the introduction of multigene next-generation sequencing panels. We continue to learn more about the natural history and management of classic hereditary cancer syndromes. New emerging conditions with lower kidney cancer penetrance have been recognized adding the growing list of syndromes associated with kidney cancer development. The surgical management strategies of enucleation remain however systemic therapy options are being explored both for localized and advanced settings.
SUMMARYGenetic predisposition to kidney cancer is likely more common than once thought. Knowledge of clinical manifestation and genetic testing strategies are needed to properly identify and treat patient and their families.
To evaluate whether bilateral, multifocal clear cell renal cell carcinoma (ccRCC) patients can be differentiated by VHL mutation analysis into cases that represent either multiple independently ...arising primary tumors, or a single primary tumor which has spread ipsilaterally as well as to the contralateral kidney. The nature of kidney cancer multifocality outside of known hereditary syndromes is as yet poorly understood.
DNA from multiple tumors per patient were evaluated for somatic VHL gene mutation and hypermethylation. A subset of tumors with shared VHL mutations were analyzed with targeted, next-generation sequencing assays.
This cohort contained 5 patients with multiple tumors that demonstrated a shared somatic VHL mutation consistent with metastatic spread including to the contralateral kidney. In several cases this was substantiated by additional shared somatic mutations in ccRCC-associated genes. In contrast, the remaining 14 patients with multiple tumors demonstrated unique, unshared VHL alterations in every analyzed tumor, consistent with independently arising kidney tumors. None of these latter patients showed any evidence of local spread or distant metastasis.
The spectrum of VHL alterations within evaluated bilateral, multifocal ccRCC tumors from a single patient can distinguish between multiple independent tumor growth and metastasis. This can be performed using currently available clinical genetic tests and will improve the accuracy of patient diagnosis and prognosis, as well as informing appropriate management.
To characterize the clinical manifestations and genetic basis of a familial cancer syndrome in patients with lipomas and Birt-Hogg-Dubé-like clinical manifestations including fibrofolliculomas and ...trichodiscomas and kidney cancer.
Genomic analysis of blood and renal tumor DNA was performed. Inheritance pattern, phenotypic manifestations, and clinical and surgical management were documented. Cutaneous, subcutaneous, and renal tumor pathologic features were characterized.
Affected individuals were found to be at risk for a highly penetrant and lethal form of bilateral, multifocal papillary renal cell carcinoma. Whole genome sequencing identified a germline pathogenic variant in PRDM10 (c.2029 T>C, p.Cys677Arg), which cosegregated with disease. PRDM10 loss of heterozygosity was identified in kidney tumors. PRDM10 was predicted to abrogate expression of FLCN, a transcriptional target of PRDM10, which was confirmed by tumor expression of GPNMB, a TFE3/TFEB target and downstream biomarker of FLCN loss. In addition, a sporadic papillary RCC from the TCGA cohort was identified with a somatic PRDM10 mutation.
We identified a germline PRDM10 pathogenic variant in association with a highly penetrant, aggressive form of familial papillary RCC, lipomas, and fibrofolliculomas/trichodiscomas. PRDM10 loss of heterozygosity and elevated GPNMB expression in renal tumors indicate that PRDM10 alteration leads to reduced FLCN expression, driving TFE3-induced tumor formation. These findings suggest that individuals with Birt-Hogg-Dubé-like manifestations and subcutaneous lipomas, but without a germline pathogenic FLCN variant, should be screened for germline PRDM10 variants. Importantly, kidney tumors identified in patients with a pathogenic PRDM10 variant should be managed with surgical resection instead of active surveillance.
Climate change, and more recently, the risk of fossil fuel production being unable to keep pace with demand (peak fossil fuel) are both considered as risks to civilisation, or global risks. In an ...initial empirical analysis, this paper attempts to answer the following questions, which have often been posed but have not, to our knowledge, been answered empirically at global level. At which date, if unaddressed, will the risks become critical? Given that the substitution of fossil fuels by wind and solar energy is often proposed as a solution to these problems, what is its current aggregate growth rate and is there a plausible future growth rate which would substitute it for fossil fuels before the risks become critical? The study finds that the peak fossil fuel risk will start to be critical by 2020. If however the future growth rate of wind and solar energy production follows that already achieved for the world mobile phone system or the Chinese National Expressway Network the peak fossil fuel risk can be prevented completely. For global warming, the same growth rate provides significant mitigation by reducing carbon dioxide emissions from fossil fuels to zero by the early 2030s.
► Converging studies show the peak fossil fuel risk likely to be critical by 2020. ► We model the future growth rate of wind and solar energy based on analogous precedents. ► These are the growth rates already achieved by the world mobile phone system and the Chinese National Expressway Network. ► We show that wind and solar energy growth at these rates averts the peak fossil fuel risk. ► For global warming, the scenarios make fossil-fuel CO2 emissions zero by 2030.
The aim of this study was to assess the interreader reliability and per-RCC sensitivity of high-resolution photon-counting computed tomography (PCCT) in the detection and characterization of renal ...masses in comparison to MRI.
This prospective study included 24 adult patients (mean age, 52 ± 14 years; 14 females) who underwent PCCT (using an investigational whole-body CT scanner) and abdominal MRI within a 3-month time interval and underwent surgical resection (partial or radical nephrectomy) with histopathology (n = 70 lesions). Of the 24 patients, 17 had a germline mutation and the remainder were sporadic cases. Two radiologists (R1 and R2) assessed the PCCT and corresponding MRI studies with a 3-week washout period between reviews. Readers recorded the number of lesions in each patient and graded each targeted lesion's characteristic features, dimensions, and location. Data were analyzed using a 2-sample t test, Fisher exact test, and weighted kappa.
In patients with von Hippel-Lindau mutation, R1 identified a similar number of lesions suspicious for neoplasm on both modalities (51 vs 50, P = 0.94), whereas R2 identified more suspicious lesions on PCCT scans as compared with MRI studies (80 vs 56, P = 0.12). R1 and R2 characterized more lesions as predominantly solid in MRIs (R1: 58/70 in MRI vs 52/70 in PCCT, P < 0.001; R2: 60/70 in MRI vs 55/70 in PCCT, P < 0.001). R1 and R2 performed similarly in detecting neoplastic lesions on PCCT and MRI studies (R1: 94% vs 90%, P = 0.5; R2: 73% vs 79%, P = 0.13).
The interreader reliability and per-RCC sensitivity of PCCT scans acquired on an investigational whole-body PCCT were comparable to MRI scans in detecting and characterizing renal masses.
PCCT scans have comparable performance to MRI studies while allowing for improved characterization of the internal composition of lesions due to material decomposition analysis. Future generations of this imaging modality may reveal additional advantages of PCCT over MRI.
Objective
The objectives of the present study were analyze specific comorbidities associated with survival and actual causes of death for patients with small renal masses, and to suggest a simplified ...measure associated with decreased overall survival specific to this population.
Methods
The Surveillance, Epidemiology and End Results‐Medicare database (1995–2007) was queried to identify patients with localized T1a kidney cancer undergoing partial nephrectomy, radical nephrectomy or deferring therapy. We explored independent associations of specific comorbidities with causes of death, and developed a simplified cardiovascular index. Cox proportional hazards, and Fine and Gray competing risks regression were used.
Results
Of 7177 Medicare beneficiaries in the study population, 754 (10.5%) deferred therapy, 1849 (25.8%) underwent partial nephrectomy and 4574 (63.7%) underwent radical nephrectomy with none of the selected comorbidities identified in 3682 (51.3%) patients. Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival. The cardiovascular index provided good survival risk stratification, and reclassified 1427 (41%) patients with a score ≥1 on the Charlson Comorbidity Index to a 0 on the cardiovascular index with minimal concession of 5‐year survival.
Conclusions
Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival among Medicare beneficiaries with small renal masses. The cardiovascular index could serve as a clinically useful prognostic aid when advising older patients that are borderline candidates for surgery or active surveillance.
Von Hippel-Lindau (VHL) is a hereditary cancer syndrome characterized by bilateral, multifocal renal masses. The cumulative impact of extirpative surgery can depreciate renal function and render ...patients anephric. In the larger end-stage renal disease population, renal transplant offers both excellent quality of life and functional renal replacement. This case control study aims to examine and compare oncologic and functional outcomes of patients who have undergone renal transplant as renal replacement therapy (RRT) to those who remain anephric.
Patient charts were retrospectively reviewed of patients with germline testing confirmed VHL between 1980 and 2022 for transplant, all prior surgical history (within and outside the NCI), renal function and graft outcomes. Overall survival (OS) was determined from years after radical nephrectomy, and graft time was defined as years of graft function from initial transplant until failure or patient death. Graft survival was determined as time between transplant(s) to last follow up. Kaplan-Meier analysis was conducted to compare graft times of anephric VHL patients to those with transplanted kidneys.
A total of 23 VHLD patients were identified as either anephric or candidates for transplant. Out of this cohort, 11 total VHLD received 12 total kidney grafts. Median wait time from nephrectomy to transplant was 22.6 months (IQR: 1.02-40.25 months). Median age at transplant was 32 years (IQR: 23-54 years). OS at 5 and 10 years of anephric patients who did not receive a transplant was 33% and 16.7%, respectively. OS rates of the transplant cohort at 10, 15, and 20 years were 91%, 78%, and 58% years, respectively. Median graft time was 161 months (IQR: 56-214 months). Graft survival at 10, 15, and 20 years was 69.8%, 69.8%, and 26.2%, respectively.
We demonstrate that transplant recipients have decreased mortality with no difference in cancer recurrence compared to those who do not receive renal transplant for RRT. This data can aid in informing providers of the optimal window for early RRT planning in VHL, while also improving patient counseling.
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