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- Aaron-Morrison, Arlene P., et al.
(author)
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State of the climate in 2014
- 2015
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In: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 96
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Journal article (peer-reviewed)abstract
- Most of the dozens of essential climate variables monitored each year in this report continued to follow their long-term trends in 2014, with several setting new records. Carbon dioxide, methane, and nitrous oxide-the major greenhouse gases released into Earth's atmosphere-once again all reached record high average atmospheric concentrations for the year. Carbon dioxide increased by 1.9 ppm to reach a globally averaged value of 397.2 ppm for 2014. Altogether, 5 major and 15 minor greenhouse gases contributed 2.94 W m-2 of direct radiative forcing, which is 36% greater than their contributions just a quarter century ago. Accompanying the record-high greenhouse gas concentrations was nominally the highest annual global surface temperature in at least 135 years of modern record keeping, according to four independent observational analyses. The warmth was distributed widely around the globe's land areas, Europe observed its warmest year on record by a large margin, with close to two dozen countries breaking their previous national temperature records; many countries in Asia had annual temperatures among their 10 warmest on record; Africa reported above-average temperatures across most of the continent throughout 2014; Australia saw its third warmest year on record, following record heat there in 2013; Mexico had its warmest year on record; and Argentina and Uruguay each had their second warmest year on record. Eastern North America was the only major region to observe a below-average annual temperature. But it was the oceans that drove the record global surface temperature in 2014. Although 2014 was largely ENSO-neutral, the globally averaged sea surface temperature (SST) was the highest on record. The warmth was particularly notable in the North Pacific Ocean where SST anomalies signaled a transition from a negative to positive phase of the Pacific decadal oscillation. In the winter of 2013/14, unusually warm water in the northeast Pacific was associated with elevated ocean heat content anomalies and elevated sea level in the region. Globally, upper ocean heat content was record high for the year, reflecting the continued increase of thermal energy in the oceans, which absorb over 90% of Earth's excess heat from greenhouse gas forcing. Owing to both ocean warming and land ice melt contributions, global mean sea level in 2014 was also record high and 67 mm greater than the 1993 annual mean, when satellite altimetry measurements began. Sea surface salinity trends over the past decade indicate that salty regions grew saltier while fresh regions became fresher, suggestive of an increased hydrological cycle over the ocean expected with global warming. As in previous years, these patterns are reflected in 2014 subsurface salinity anomalies as well. With a now decade-long trans-basin instrument array along 26°N, the Atlantic meridional overturning circulation shows a decrease in transport of-4.2 ± 2.5 Sv decade-1. Precipitation was quite variable across the globe. On balance, precipitation over the world's oceans was above average, while below average across land surfaces. Drought continued in southeastern Brazil and the western United States. Heavy rain during April-June led to devastating floods in Canada's Eastern Prairies. Above-normal summer monsoon rainfall was observed over the southern coast of West Africa, while drier conditions prevailed over the eastern Sahel. Generally, summer monsoon rainfall over eastern Africa was above normal, except in parts of western South Sudan and Ethiopia. The south Asian summer monsoon in India was below normal, with June record dry. Across the major tropical cyclone basins, 91 named storms were observed during 2014, above the 1981-2010 global average of 82. The Eastern/Central Pacific and South Indian Ocean basins experienced significantly above-normal activity in 2014; all other basins were either at or below normal. The 22 named storms in the Eastern/Central Pacific was the basin's most since 1992. Similar to 2013, the North Atlantic season was quieter than most years of the last two decades with respect to the number of storms, despite the absence of El Niño conditions during both years. In higher latitudes and at higher elevations, increased warming continued to be visible in the decline of glacier mass balance, increasing permafrost temperatures, and a deeper thawing layer in seasonally frozen soil. In the Arctic, the 2014 temperature over land areas was the fourth highest in the 115-year period of record and snow melt occurred 20-30 days earlier than the 1998-2010 average. The Greenland Ice Sheet experienced extensive melting in summer 2014. The extent of melting was above the 1981-2010 average for 90% of the melt season, contributing to the second lowest average summer albedo over Greenland since observations began in 2000 and a record-low albedo across the ice sheet for August. On the North Slope of Alaska, new record high temperatures at 20-m depth were measured at four of five permafrost observatories. In September, Arctic minimum sea ice extent was the sixth lowest since satellite records began in 1979. The eight lowest sea ice extents during this period have occurred in the last eight years. Conversely, in the Antarctic, sea ice extent countered its declining trend and set several new records in 2014, including record high monthly mean sea ice extent each month from April to November. On 20 September, a record large daily Antarctic sea ice extent of 20.14 × 106 km2 occurred. The 2014 Antarctic stratospheric ozone hole was 20.9 million km2 when averaged from 7 September to 13 October, the sixth smallest on record and continuing a decrease, albeit statistically insignificant, in area since 1998.
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- Uzunel, M, et al.
(author)
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Kinetics of minimal residual disease and chimerism in patients with chronic myeloid leukemia after nonmyeloablative conditioning and allogeneic stem cell transplantation
- 2003
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 101:2, s. 469-472
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Journal article (peer-reviewed)abstract
- The kinetics of minimal residual disease (MRD) and chimerism were studied in 15 patients with chronic myeloid leukemia (CML) receiving nonmyeloablative stem cell transplantation (NST) and in 10 patients receiving conventional stem cell transplantation (CST). All NST patients showed T-cell mixed chimerism (MC) while granulocyte and B-cell MC occurred in 80% and 60% of the NST patients, respectively. In CST patients, T-cell MC was detected in 5 patients, of whom 3 were mixed only during the first month. MRD was detected in all NST patients. During the first 3 months the median BCR-ABL/ABL ratio was 0.2% in NST patients compared with 0.01% in CST patients (P < .01). However, 12 months after transplantation, the percentage of reverse transcriptase–polymerase chain reaction (RT-PCR)–positive patients was 20% in NST patients and 50% in CST patients. In conclusion, molecular remission can be induced in most patients after NST, albeit with different kinetics from CST.
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- Barkholt, L, et al.
(author)
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Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study
- 2009
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In: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 1:5, s. 753-764
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Journal article (peer-reviewed)abstract
- The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum α-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
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- Dregan, A, et al.
(author)
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Common mental disorders within chronic inflammatory disorders: a primary care database prospective investigation
- 2019
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:5, s. 688-695
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Journal article (peer-reviewed)abstract
- There is inconsistent evidence about the association between inflammatory disorders and depression and anxiety onset in a primary care context. The study aimed to evaluate the risk of depression and anxiety within multisystem and organ-specific inflammatory disorders.MethodsThis is a prospective cohort study with primary care patients from the UK Clinical Practice Research Datalink diagnosed with an inflammatory disorder between 1 January 2001 and 31 December 2016. These patients were matched on age, gender, practice and index date with patients without an inflammatory disorder. The study exposures were seven chronic inflammatory disorders. Clinical diagnosis of depression and anxiety represented the outcome measures of interest.ResultsAmong 538 707 participants, the incidence of depression ranged from 14 per 1000 person-years (severe psoriasis) to 9 per 1000 person-years (systemic vasculitis), substantively higher compared with their comparison group (5–7 per 1000 person-years). HRs of multiple depression and anxiety events were 16% higher within inflammatory disorders (HR, 1.16, 95% CI 1.12 to 1.21, p<0.001) compared with the matched comparison group. The incidence of depression and anxiety was strongly associated with the age at inflammatory disorder onset. The overall HR estimate for depression was 1.90 (95% CI 1.66 to 2.17, p<0.001) within early-onset disorder (<40 years of age) and 0.93 (95% CI 0.90 to 1.09, p=0.80) within late-onset disorder (≥60 years of age).ConclusionsPrimary care patients with inflammatory disorders have elevated rates of depression and anxiety incidence, particularly those patients with early-onset inflammatory disorders. This finding may reflect the impact of the underlying disease on patients’ quality of life, although the precise mechanisms require further investigation.
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- Ghaderi, A, et al.
(author)
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A ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Mantle Cell Lymphoma (MCL) Cells
- 2022
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:10
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Journal article (peer-reviewed)abstract
- The receptor tyrosine kinase orphan receptor 1 (ROR1) is absent in most normal adult tissues but overexpressed in various malignancies and is of importance for tumor cell survival, proliferation, and metastasis. In this study, we evaluated the apoptotic effects of a novel small molecule inhibitor of ROR1 (KAN0441571C) as well as venetoclax (BCL-2 inhibitor), bendamustine, idelalisib (PI3Kδ inhibitor), everolimus (mTOR inhibitor), and ibrutinib (BTK inhibitor) alone or in combination in human MCL primary cells and cell lines. ROR1 expression was evaluated by flow cytometry and Western blot (WB). Cytotoxicity was analyzed by MTT and apoptosis by Annexin V/PI staining as well as signaling and apoptotic proteins (WB). ROR1 was expressed both in patient-derived MCL cells and human MCL cell lines. KAN0441571C alone induced significant time- and dose-dependent apoptosis of MCL cells. Apoptosis was accompanied by decreased expression of MCL-1 and BCL-2 and cleavage of PARP and caspase 3. ROR1 was dephosphorylated as well as ROR1-associated signaling pathway molecules, including the non-canonical WNT signaling pathway (PI3Kδ/AKT/mTOR). The combination of KAN0441571C and ibrutinib, venetoclax, idelalisib, everolimus, or bendamustine had a synergistic apoptotic effect and significantly prevented phosphorylation of ROR1-associated signaling molecules as compared to KAN0441571C alone. Our results suggest that targeting ROR1 by a small molecule inhibitor, KAN0441571C, should be further evaluated particularly in combination with other targeting drugs as a new therapeutic approach for MCL.
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- Harber-Aschan, Lisa, 1987-, et al.
(author)
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Cardiometabolic risk profiles in a Sri Lankan twin and singleton sample
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Journal article (peer-reviewed)abstract
- IntroductionPrevention of cardiovascular disease and diabetes is a priority in low- and middle-income countries, especially in South Asia where these are leading causes of morbidity and mortality. The metabolic syndrome is a tool to identify cardiometabolic risk, but the validity of the metabolic syndrome as a clinical construct is debated. This study tested the existence of the metabolic syndrome, explored alternative cardiometabolic risk characterisations, and examined genetic and environmental factors in a South Asian population sample.MethodsData came from the Colombo Twin and Singleton follow-up Study, which recruited twins and singletons in Colombo, Sri Lanka, in 2012–2015 (n = 3476). Latent class analysis tested the clustering of metabolic syndrome indicators (waist circumference, high-density lipoprotein cholesterol, triglycerides, blood pressure, fasting plasma glucose, medications, and diabetes). Regression analyses tested cross-sectional associations between the identified latent cardiometabolic classes and sociodemographic covariates and health behaviours. Structural equation modelling estimated genetic and environmental contributions to cardiometabolic risk profiles. All analyses were stratified by sex (n = 1509 men, n = 1967 women).ResultsThree classes were identified in men: 1) “Healthy” (52.3%), 2) “Central obesity, high triglycerides, high fasting plasma glucose” (40.2%), and 3) “Central obesity, high triglycerides, diabetes” (7.6%). Four classes were identified in women: 1) “Healthy” (53.2%), 2) “Very high central obesity, low high-density lipoprotein cholesterol, raised fasting plasma glucose” (32.8%), 3) “Very high central obesity, diabetes” (7.2%) and 4) “Central obesity, hypertension, raised fasting plasma glucose” (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk classes, compared to the “Healthy” classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In women, genetic differences predicted class membership.ConclusionThe findings did not support the metabolic syndrome construct. Instead, distinct clinical profiles were identified for men and women, suggesting different aetiological pathways.
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- Hassan, Z, et al.
(author)
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Pharmacokinetics of liposomal busulphan in man
- 2001
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 27:5, s. 479-485
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Journal article (peer-reviewed)
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