Trends in Twentieth-Century U.S. Snowfall Using a Quality-Controlled Dataset

A quality assessment of daily manual snowfall data has been undertaken for all U.S. long-term stations and their suitability for climate research. The assessment utilized expert judgment on the quality of each station. Through this process, the authors have identified a set of stations believed to be suitable for analysis of trends. Since the 1920s, snowfall has been declining in the West and the mid-Atlantic coast. In some places during recent years the decline has been more precipitous, strongly trending downward along the southern margins of the seasonal snow region, the southern Missouri River basin, and parts of the Northeast. Snowfall has been increasing since the 1920s in the lee of the Rocky Mountains, the Great Lakes– northern Ohio Valley, and parts of the north-central United States. These areas that are in opposition to the overall pattern of declining snowfall seem to be associated with specific dynamical processes, such as upslope snow and lake-effect snow that may be responding to changes in atmospheric circulation

Trends in Twentieth-Century U.S. Extreme Snowfall Seasons

Temporal variability in the occurrence of the most extreme snowfall years, both those with abundant snowfall amounts and those lacking snowfall, was examined using a set of 440 quality-controlled, homogenous U.S. snowfall records. The frequencies with which winter-centered annual snowfall totals exceeded the 90th and 10th percentile thresholds at individual stations were calculated from 1900–01 to 2006–07 for the conterminous United States, and for 9 standard climate regions. The area-weighted conterminous U.S. results do not show a statistically significant trend in the occurrence of either high or low snowfall years for the 107-yr period, but there are regional trends. Large decreases in the frequency of low-extreme snowfall years in the west north-central and east north-central United States are balanced by large increases in the frequency of low-extreme snowfall years in the Northeast, Southeast, and Northwest. During the latter portion of the period, from 1950–51 to 2006–07, trends are much more consistent, with the United States as a whole and the central and northwest U.S. regions in particular showing significant declines in high-extreme snowfall years, and four regions showing significant increases in the frequency of low-extreme snowfall years (i.e., Northeast, Southeast, south, and Northwest). In almost all regions of the United States, temperature during November–March is more highly correlated than precipitation to the occurrence of extreme snowfall years. El Nin ̃ o events are strongly associated with an increase in low-extreme snowfall years over the United States as a whole, and in the northwest, northeast, and central regions. A reduction in low-extreme snowfall years in the Southwest is also associated with El Nin ̃ o. The impacts of La Nin ̃ a events are strongest in the south and Southeast, favoring fewer high-extreme snowfall years, and, in the case of the south, more low-extreme snowfall years occur. The Northwest also has a significant reduction in the chance of a low-extreme snowfall year during La Nin ̃ a. A combination of trends in temperature in the United States and changes in the frequency of ENSO modes influences the frequency of extreme snowfall years in the United States

High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing >160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

Trends in Twentieth-Century U.S. Extreme Snowfall Seasons

Temporal variability in the occurrence of the most extreme snowfall years, both those with abundant snowfall amounts and those lacking snowfall, was examined using a set of 440 quality-controlled, homogenous U.S. snowfall records. The frequencies with which winter-centered annual snowfall totals exceeded the 90th and 10th percentile thresholds at individual stations were calculated from 1900–01 to 2006–07 for the conterminous United States, and for 9 standard climate regions. The area-weighted conterminous U.S. results do not show a statistically significant trend in the occurrence of either high or low snowfall years for the 107-yr period, but there are regional trends. Large decreases in the frequency of low-extreme snowfall years in the west north-central and east north-central United States are balanced by large increases in the frequency of low-extreme snowfall years in the Northeast, Southeast, and Northwest. During the latter portion of the period, from 1950–51 to 2006–07, trends are much more consistent, with the United States as a whole and the central and northwest U.S. regions in particular showing significant declines in high-extreme snowfall years, and four regions showing significant increases in the frequency of low-extreme snowfall years (i.e., Northeast, Southeast, south, and Northwest). In almost all regions of the United States, temperature during November–March is more highly correlated than precipitation to the occurrence of extreme snowfall years. El Nin ̃ o events are strongly associated with an increase in low-extreme snowfall years over the United States as a whole, and in the northwest, northeast, and central regions. A reduction in low-extreme snowfall years in the Southwest is also associated with El Nin ̃ o. The impacts of La Nin ̃ a events are strongest in the south and Southeast, favoring fewer high-extreme snowfall years, and, in the case of the south, more low-extreme snowfall years occur. The Northwest also has a significant reduction in the chance of a low-extreme snowfall year during La Nin ̃ a. A combination of trends in temperature in the United States and changes in the frequency of ENSO modes influences the frequency of extreme snowfall years in the United States

Initiating advance care planning at admission: a brief intervention to increase goals of care discussions in geriatric trauma patients in an urban level I trauma center

Objectives The burden of geriatric trauma continues to rise. Older trauma patients experience higher morbidity and mortality and thus benefit from early goals of care (GOC) discussions and advance care planning (ACP). The American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) recommends holding a family meeting within 72 hours of admission when treating geriatric trauma patients. At our level I trauma center, we sought to increase early GOC discussions by implementing a new history and physical (H&P) note template for geriatric trauma patients.Methods Patients (aged >65 years) admitted to the trauma surgery service (≥24 hours) were included in the study. The intervention was a change in the H&P note template to include confirmation of code status or previous ACP and identification of a healthcare proxy. Primary outcomes were the rates of recognizing a pre-existing Do-Not-Resuscitate (DNR) status/advanced directives at admission and of documentation of a GOC discussion within 72 hours. Outcomes from a 3-month period (March–May) during the pre-intervention (2021) and post-intervention (2022) periods were compared.Results The pre-intervention and post-intervention groups had 107 and 150 patients, respectively. We observed an increase in recognition of pre-existing DNR code status at time of admission from 50% to 95% (p=0.003) and documentation of a GOC discussion within 72 hours from 17% to 83% (p<0.0001). We also observed a trend showing that new DNR orders were placed more frequently in the post-intervention period (9% vs 17%, p=0.098). The in-hospital mortality was not significantly different.Conclusions The importance of GOC discussions and ACP documentation for geriatric trauma patients is evident, but its completion can be challenging. Our intervention of a new H&P note template increased GOC discussions, and this implementation may be feasible in other trauma centers to comply with the ACS-TQIP Geriatric Trauma Management Guidelines.Level of evidence Level III