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This paper demonstrates how self-organizing maps (SOMs) can be used to evaluate the large-scale environment, in particular the synoptic circulation associated with widespread temperature extremes. The paper provides details on how SOMs are created, how they can be used to understand extreme events, and lessons learned in applying this methodology for extremes analysis. Using a SOM can be helpful in understanding the underlying physical processes that control extreme events, and how the extremes and the processes that control them may change in time or differ across space. Examples of widespread daily temperature extremes in 4 regions: 2 each in Alaska and in northern Canada during winter (December, January, and February) for 1989−2007 are presented to illustrate the application of the methodology. For the regions studied, the size of the domain over which the synoptic circulation was defined—in particular using a smaller domain focused on particular regions—and a greater number of classes to represent the archetypical synoptic patterns for the regions, give the best relationship between synoptic circulation and extremes. The results are most robust for the Alaskan domains and less so for the Canadian domains, leading to the conclusion that further study is warranted to better understand extremes in the Canadian regions.

Data from the National Centers for Environmental Prediction/National Center for Atmospheric Research and European Center for Medium‐Range Weather Forecasts 40 year reanalyses are used to relate large‐scale synoptic circulation patterns to local weather at several locations across Alaska. These results are compared to available National Weather Service observations to demonstrate the utility of this method such that it can be applied in future work at locations where local observations are not available. The focus of these comparisons is on surface observations of temperature. The results from the two reanalysis data sets match well to each other and to the observations. Synoptic patterns associated with warm/cold days at five National Weather Service stations representing different climate regions throughout Alaska are identified. In addition, a method to attribute a change in climate to circulation and noncirculation differences is applied to a known climate shift, the Pacific climate shift of 1976, which was associated with an increase in temperatures throughout Alaska. The results from this analysis show that general warming rather than changes in circulation is primarily responsible for the increase in temperatures after 1976. Key Points Reanalysis data are used to characterize synoptic patterns for Alaska Surface temperature in Alaska is related to the large‐scale synoptic patterns Temperature changes in Alaska around the 1976 Pacific climate shift are analyzed

We developed a synoptic climatology for Lake El'gygytgyn, Chukotka Russia, and explored modern climate trends affecting air temperatures there to aid in paleoclimate reconstructions of a 3.6 million-year-old sediment core taken from the lake. Our self-organized mapping (SOM) approach identified 35 synoptic weather patterns, based on sea level pressure, that span the range of synoptic patterns influencing the study domain over the 1961–2009 NCEP/NCAR analysis period. We found strong seasonality in modern weather patterns, with summer weather primarily characterized by weak low pressure systems over the Arctic Ocean or Siberia and winter weather primarily characterized by strong high pressure over the Arctic Ocean and strong low pressure in the Pacific Ocean. In general, the primary source of variation in air temperatures came from the dominant patterns in each season, which we identify in the text, and nearly all of the dominant weather patterns here have shown increasing temperatures. We found that nearly all of the warming in mean annual temperature over the past 50 yr (about 3 °C) occurred during sub-freezing conditions on either side of summer (that is, spring and fall). Here we found that the most summer-like weather patterns (low pressures to the north) in the shoulder seasons were responsible for much of the change. Finally, we compared the warmest 15 yr of the record (1995–2009) to the coolest (1961–1975) and found that changes in thermodynamics of weather were about 3 to 300 times more important than changes in frequency of weather patterns in controlling temperature variations during spring and fall, respectively. That is, in the modern record, general warming (local or advected) is more important by orders of magnitude than changes in storm tracks in controlling air temperature at Lake El'gygytgyn. We conclude with a discussion of how these results may be relevant to the paleoclimate reconstruction efforts and how this relevancy could be tested further.

Cyclosporine A (CsA) is one of the most effective systemic drugs available for the treatment of psoriasis, as evidenced by the results of several randomized studies and by a prolonged experience in dermatological setting. In clinical practice, CsA is usually used for the induction of psoriasis remission at a daily dose included in the range of 2.5–5 mg/kg and with intermittent short-term regimens, lasting on average 3–6 months. The magnitude and rapidity of response are dose dependent, as well as the risk of development of adverse events. Therefore, the dose should be tailored to patient’s needs and general characteristics and adjusted during the treatment course according to both the efficacy and tolerability. Some studies support the feasibility of pulse administration of CsA for a few days per week for both the induction and the maintenance of response in psoriasis patients. This paper will review the data on CsA regimens for plaque-type psoriasis and will focus the attention on dose, treatment duration, novel schedules, and role in combination therapies, including the association with biologicals.

This article sets the near-surface meteorological conditions during the Multidisciplinary drifting Observatory for the Study of Arctic Climate expedition in the context of the interannual variability and extremes within the past 4 decades. Hourly ERA5 reanalysis data for the Polarstern trajectory for 1979–2020 are analyzed. The conditions were relatively normal given that they were mostly within the interquartile range of the preceding 4 decades. Nevertheless, some anomalous and even record-breaking conditions did occur, particularly during synoptic events. Extreme cases of warm, moist air transported from the northern North Atlantic or northwestern Siberia into the Arctic were identified from late fall until early spring. Daily temperature and total column water vapor were classified as being among the top-ranking warmest/wettest days or even record-breaking based on the full record. Associated with this, the longwave radiative fluxes at the surface were extremely anomalous for these winter cases. The winter and spring period was characterized by more frequent storm events and median cyclone intensity ranking in the top 25th percentile of the full record. During summer, near melting point conditions were more than a month longer than usual, and the July and August 2020 mean conditions were the all-time warmest and wettest. These record conditions near the Polarstern were embedded in large positive temperature and moisture anomalies over the whole central Arctic. In contrast, unusually cold conditions occurred during the beginning of November 2019 and in early March 2020, related to the Arctic Oscillation. In March, this was linked with anomalously strong and persistent northerly winds associated with frequent cyclone occurrence to the southeast of the Polarstern.

This article sets the near-surface meteorological conditions during the Multidisciplinary drifting Observatory for the Study of Arctic Climate expedition in the context of the interannual variability and extremes within the past 4 decades. Hourly ERA5 reanalysis data for the Polarstern trajectory for 1979–2020 are analyzed. The conditions were relatively normal given that they were mostly within the interquartile range of the preceding 4 decades. Nevertheless, some anomalous and even record-breaking conditions did occur, particularly during synoptic events. Extreme cases of warm, moist air transported from the northern North Atlantic or northwestern Siberia into the Arctic were identified from late fall until early spring. Daily temperature and total column water vapor were classified as being among the top-ranking warmest/wettest days or even record-breaking based on the full record. Associated with this, the longwave radiative fluxes at the surface were extremely anomalous for these winter cases. The winter and spring period was characterized by more frequent storm events and median cyclone intensity ranking in the top 25th percentile of the full record. During summer, near melting point conditions were more than a month longer than usual, and the July and August 2020 mean conditions were the all-time warmest and wettest. These record conditions near the Polarstern were embedded in large positive temperature and moisture anomalies over the whole central Arctic. In contrast, unusually cold conditions occurred during the beginning of November 2019 and in early March 2020, related to the Arctic Oscillation. In March, this was linked with anomalously strong and persistent northerly winds associated with frequent cyclone occurrence to the southeast of the Polarstern.

The coastal geography of Barrow, Alaska, makes the city vulnerable to weather events that cause flooding and erosion. This study uses the self-organizing map (SOM) algorithm, an unsupervised learning process that codifies large, multivariate datasets onto a 2-dimensional array, or map, to study large-scale circulation patterns associated with temperature and high wind extremes at Barrow. The analysis first uses the SOM algorithm to produce an automated 55 yr synoptic climatology of daily sea level pressure patterns for the western Arctic for August to November, when the area is potentially ice free. The results are in agreement with previous Arctic climatologies, showing the Aleutian Low to be dominant in southern Alaska, and high pressure prevalent over the Beaufort and Chukchi Seas. The SOM algorithm is then used to study circulation patterns associated with temperature and high wind extremes at Barrow. These results show that high winds are associated with patterns containing a strong pressure gradient between the Aleutian Low and the Beaufort and Chukchi Seas and also with patterns that contain a low pressure system to the north of Barrow. High (low) air temperature extreme anomalies are associated with patterns that produce strong, southerly (northerly) air flow at Barrow. This study demonstrates the utility of using SOMs to investigate the relationship between local weather conditions and large-scale patterns. This approach can be applied to future global climate model (GCM) simulations to investigate the impact of changes in large-scale circulation patterns to local extreme events.

A new class of drugs, produced with the hybridoma technique, has been introduced and employed to treat many immunological diseases. This class consists of recombinant monoclonal antibodies, which can be chimeric, humanized or human. Predictably, there has been a rise in adverse hypersensitivity reactions to these therapeutic agents, whose pathogenic mechanisms are not yet well understood. Specific IgE has been demonstrated in a very few cases, and only in some of these recombinant antibodies. Skin tests are not done as a clinical routine screening. In the present article the mechanisms underlying hypersensitivity reactions to these drugs are analyzed, also in the light of the personal experience and that reported in the literature, with the aim of identifying potential risk factors and means of prevention of these reactions. For some drugs, infusion reactions may be prevented thanks to the the use of premedication. Moreover, symptoms of acute hypersensitivity during infusion can be successfully managed in the majority of cases by slowing the speed of administration. All these findings seem to confirm that the pathogenesis is not related to a true immediate (IgE-mediated) hypersensitivity in most cases. When the substitution of the drug that has triggered a hypersensitivity reaction is required, this is only possible if such an alternative drug exists (i.e., replacement of a chimeric antibody with a humanized or human antibody sharing the same target). As an alternative, desensitization protocols have been employed to induce a state of temporary tolerance to the drug in some cases, yielding successful results for infliximab and trastuzumab.

Signs supporting antiinflammatory effects of H1-antihistamines were first reported long ago, but their clinical relevance remains controversial, especially with respect to their ability to inhibit the release of histamine and other preformed mediators. Experimental studies have documented that H1-antihistamines may affect several inflammatory events, including chemotaxis and the survival of eosinophils, the expression of adhesion molecules, and the release of chemokines and cytokines from different sources, thus highlighting the potential for a modulation of chronic inflammation and immune responses. Interestingly, a specific inhibitory effect on Th2-type cytokine secretion has been demonstrated for some new generation antihistamines. The mechanisms responsible for the antiinflammatory activity of H1-antihistamines are still unclear, but are presumed to be both receptor-dependent and receptor-independent. Recent findings have indicated the ability of these drugs to down-regulate intracellular signaling pathways, i.e., NF-κB. In this article, the current knowledge and novel findings about the antiinflammatory action and mechanisms of H1-antihistamines are briefly reviewed and critically analyzed, from the standpoint of possible clinical implications with special reference to skin disorders.

This paper describes work to improve the understanding of the broad range of factors affecting the occurrence of flooding in Barrow, Alaska, using as a basis the series of extreme events that have affected the community over the past 50 years. A numerical weather prediction model and a storm surge inundation model have been applied to the 21 case studies identified in National Weather Service data as high wind events. Based on this simulation work flow, a reduced-form model that adequately describes the flooding response has been developed. Specifically, it was found that when wind is forecast to be greater than 13 m s−1 (30 mph) for at least 20 h, this is the most accurate predictor of the possibility of damaging flood. It was found that wind direction, the magnitude of fetch to the sea ice edge (when present), and maximum wind speed were in contrast relatively small contributors to the likelihood of flooding.