Heart failure (HF) has been recognized as a common complication of diabetes, with a prevalence of up to 22% in individuals with diabetes and increasing incidence rates. Data also suggest that HF may ...develop in individuals with diabetes even in the absence of hypertension, coronary heart disease, or valvular heart disease and, as such, represents a major cardiovascular complication in this vulnerable population; HF may also be the first presentation of cardiovascular disease in many individuals with diabetes. Given that during the past decade, the prevalence of diabetes (particularly type 2 diabetes) has risen by 30% globally (with prevalence expected to increase further), the burden of HF on the health care system will continue to rise. The scope of this American Diabetes Association consensus report with designated representation from the American College of Cardiology is to provide clear guidance to practitioners on the best approaches for screening and diagnosing HF in individuals with diabetes or prediabetes, with the goal to ensure access to optimal, evidence-based management for all and to mitigate the risks of serious complications, leveraging prior policy statements by the American College of Cardiology and American Heart Association.
Mangroves under sea level rise
The rate of sea level rise has doubled from 1.8 millimeters per year over the 20th century to ∼3.4 millimeters per year in recent years. Saintilan
et al.
investigated ...the likely effects of this increasing rate of rise on coastal mangrove forest, a tropical ecosystem of key importance for coastal protection (see the Perspective by Lovelock). They reviewed data on mangrove accretion 10,000 to 7000 years before present, when the rate of sea level rise was even higher than today as a result of glacial ice melt. Their analysis suggests an upper threshold of 7 millimeters per year as the maximum rate of sea level rise associated with mangrove vertical development, beyond which the ecosystem fails to keep up with the change. Under projected rates of sea level rise, they predict that a deficit between accretion and sea level rise is likely to commence in the next 30 years.
Science
, this issue p.
1118
; see also p.
1050
Mangrove response to sea level rise in the final stages of deglaciation reveals survival thresholds that may be exceeded within 30 years.
The response of mangroves to high rates of relative sea level rise (RSLR) is poorly understood. We explore the limits of mangrove vertical accretion to sustained periods of RSLR in the final stages of deglaciation. The timing of initiation and rate of mangrove vertical accretion were compared with independently modeled rates of RSLR for 78 locations. Mangrove forests expanded between 9800 and 7500 years ago, vertically accreting thick sequences of organic sediments at a rate principally driven by the rate of RSLR, representing an important carbon sink. We found it very likely (>90% probability) that mangroves were unable to initiate sustained accretion when RSLR rates exceeded 6.1 millimeters per year. This threshold is likely to be surpassed on tropical coastlines within 30 years under high-emissions scenarios.
Warming climate, melting ice, rising seas
We know that the sea level will rise as climate warms. Nevertheless, accurate projections of how much sea-level rise will occur are difficult to make based ...solely on modern observations. Determining how ice sheets and sea level have varied in past warm periods can help us better understand how sensitive ice sheets are to higher temperatures. Dutton
et al.
review recent interdisciplinary progress in understanding this issue, based on data from four different warm intervals over the past 3 million years. Their synthesis provides a clear picture of the progress we have made and the hurdles that still exist.
Science
, this issue
10.1126/science.aaa4019
Reconstructing past magnitudes, rates, and sources of sea-level rise can help project what our warmer future may hold.
BACKGROUND
Although thermal expansion of seawater and melting of mountain glaciers have dominated global mean sea level (GMSL) rise over the last century, mass loss from the Greenland and Antarctic ice sheets is expected to exceed other contributions to GMSL rise under future warming. To better constrain polar ice-sheet response to warmer temperatures, we draw on evidence from interglacial periods in the geologic record that experienced warmer polar temperatures and higher GMSLs than present. Coastal records of sea level from these previous warm periods demonstrate geographic variability because of the influence of several geophysical processes that operate across a range of magnitudes and time scales. Inferring GMSL and ice-volume changes from these reconstructions is nontrivial and generally requires the use of geophysical models.
ADVANCES
Interdisciplinary studies of geologic archives have ushered in a new era of deciphering magnitudes, rates, and sources of sea-level rise. Advances in our understanding of polar ice-sheet response to warmer climates have been made through an increase in the number and geographic distribution of sea-level reconstructions, better ice-sheet constraints, and the recognition that several geophysical processes cause spatially complex patterns in sea level. In particular, accounting for glacial isostatic processes helps to decipher spatial variability in coastal sea-level records and has reconciled a number of site-specific sea-level reconstructions for warm periods that have occurred within the past several hundred thousand years. This enables us to infer that during recent interglacial periods, small increases in global mean temperature and just a few degrees of polar warming relative to the preindustrial period resulted in ≥6 m of GMSL rise. Mantle-driven dynamic topography introduces large uncertainties on longer time scales, affecting reconstructions for time periods such as the Pliocene (~3 million years ago), when atmospheric CO
2
was ~400 parts per million (ppm), similar to that of the present. Both modeling and field evidence suggest that polar ice sheets were smaller during this time period, but because dynamic topography can cause tens of meters of vertical displacement at Earth’s surface on million-year time scales and uncertainty in model predictions of this signal are large, it is currently not possible to make a precise estimate of peak GMSL during the Pliocene.
OUTLOOK
Our present climate is warming to a level associated with significant polar ice-sheet loss in the past, but a number of challenges remain to further constrain ice-sheet sensitivity to climate change using paleo–sea level records. Improving our understanding of rates of GMSL rise due to polar ice-mass loss is perhaps the most societally relevant information the paleorecord can provide, yet robust estimates of rates of GMSL rise associated with polar ice-sheet retreat and/or collapse remain a weakness in existing sea-level reconstructions. Improving existing magnitudes, rates, and sources of GMSL rise will require a better (global) distribution of sea-level reconstructions with high temporal resolution and precise elevations and should include sites close to present and former ice sheets. Translating such sea-level data into a robust GMSL signal demands integration with geophysical models, which in turn can be tested through improved spatial and temporal sampling of coastal records.
Further development is needed to refine estimates of past sea level from geochemical proxies. In particular, paired oxygen isotope and Mg/Ca data are currently unable to provide confident, quantitative estimates of peak sea level during these past warm periods. In some GMSL reconstructions, polar ice-sheet retreat is inferred from the total GMSL budget, but identifying the specific ice-sheet sources is currently hindered by limited field evidence at high latitudes. Given the paucity of such data, emerging geochemical and geophysical techniques show promise for identifying the sectors of the ice sheets that were most vulnerable to collapse in the past and perhaps will be again in the future.
Peak global mean temperature, atmospheric CO
2
, maximum global mean sea level (GMSL), and source(s) of meltwater.
Light blue shading indicates uncertainty of GMSL maximum. Red pie charts over Greenland and Antarctica denote fraction (not location) of ice retreat.
Interdisciplinary studies of geologic archives have ushered in a new era of deciphering magnitudes, rates, and sources of sea-level rise from polar ice-sheet loss during past warm periods. Accounting for glacial isostatic processes helps to reconcile spatial variability in peak sea level during marine isotope stages 5e and 11, when the global mean reached 6 to 9 meters and 6 to 13 meters higher than present, respectively. Dynamic topography introduces large uncertainties on longer time scales, precluding robust sea-level estimates for intervals such as the Pliocene. Present climate is warming to a level associated with significant polar ice-sheet loss in the past. Here, we outline advances and challenges involved in constraining ice-sheet sensitivity to climate change with use of paleo–sea level records.
Off-label drug use in children is common and potentially harmful. In most previous off-label use research, authors studied hospitalized children, specific drug classes, or non-US settings. We ...characterized frequencies, trends, and reasons for off-label systemic drug orders for children in ambulatory US settings.
Using nationally representative surveys of office-based physicians (National Ambulatory Medical Care Surveys, 2006-2015), we studied off-label orders of systemic drugs for children age <18 based on US Food and Drug Administration-approved labeling for age, weight, and indication. We characterized the top classes and diagnoses with off-label orders and analyzed factors and trends of off-label orders using logistic regression.
Physicians ordered ≥1 off-label systemic drug at 18.5% (95% confidence interval: 17.7%-19.3%) of visits, usually (74.6%) because of unapproved conditions. Off-label ordering was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders out of 1000 visits). Off-label ordering was associated with female sex, subspecialists, polypharmacy, and chronic conditions. Rates and reasons for off-label orders varied considerably by age. Relative and absolute rates of off-label orders rose over time. Among common classes, off-label orders for antihistamines and several psychotropics increased over time, whereas off-label orders for several classes of antibiotics were stable or declined.
US office-based physicians have ordered systemic drugs off label for children at increasing rates, most often for unapproved conditions, despite recent efforts to increase evidence and drug approvals for children. These findings can help inform education, research, and policies around effective, safe use of medications in children.
Handbook of Sea-Level Research Ian Shennan, Antony J. Long, Benjamin P. Horton / Ian Shennan, Antony J. Long, Benjamin P. Horton
2015, 2014-12-17, 2015-02-19
eBook
Measuring sea-level change – be that rise or fall – is one of the most pressing scientific goals of our time and requires robust scientific approaches and techniques. This Handbook aims to provide a ...practical guide to readers interested in this challenge, from the initial design of research approaches through to the practical issues of data collection and interpretation from a diverse range of coastal environments. Building on thirty years of international research, the Handbook comprises 38 chapters that are authored by leading experts from around the world. The Handbook will be an important resource to scientists interested and involved in understanding sea-level changes across a broad range of disciplines, policy makers wanting to appreciate our current state of knowledge of sea-level change over different timescales, and many teachers at the university level, as well as advanced-level undergraduates and postgraduate research students, wanting to learn more about sea-level change. Additional resources for this book can be found at: www.wiley.com\go\shennan\sealevel
Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN ...are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance.
This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease.
Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin.
Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Activation induces a programmed timed division burst before return to quiescence.•Clonal integration of activation signals, stochastic probabilities and ongoing signals.•Signals are integrated by ...each cell in a cumulative manner.•Clonal inheritance and interclonal variation shape the response.
Activation induced proliferation and clonal expansion of antigen specific lymphocytes is a hallmark of the adaptive immune response to pathogens. Recent studies identify two distinct control phases. In the first T and B lymphocytes integrate antigen and additional costimuli to motivate a programmed proliferative burst that ceases with a return to cell quiescence and eventual death. This proliferative burst is autonomously timed, ensuring an appropriate response magnitude whilst preventing uncontrolled expansion. This initial response is subject to further modification and extension by a range of signals that modify, expand and direct the emergence of a rich array of new cell types. Thus, both robust clonal expansion of a small number of antigen specific T cells, and the concurrent emergence of extensive cellular diversity, confers immunity to a vast array of different pathogens. The in vivo response to a given pathogen is made up by the sum of all responding clones and is reproducible and pathogen specific. Thus, a precise description of the regulatory principles governing lymphocyte proliferation, differentiation and survival is essential to a unified understanding of the immune system.
Heatwaves kill more people than floods, tornadoes, and earthquakes combined and disproportionally affect older persons and those with chronic conditions. Commonly used medications for chronic ...conditions, e.g., diuretics, antipsychotics disrupt thermoregulation or fluid/electrolyte balance and may sensitive patients to heat. However, the effect of heat-sensitizing medications and their interactions with heatwaves are not well-quantified. We evaluated effects of potentially heat-sensitizing medications in vulnerable older patients.
US Medicare data were linked at the zip code level to climate data with surface air temperatures for June-August of 2007-2012. Patients were Medicare beneficiaries aged ≥65 years with chronic conditions including diabetes, dementia, and cardiovascular, lung, or kidney disease. Exposures were potentially heat-sensitizing medications including diuretics, anticholinergics, antipsychotics, beta blockers, stimulants, and anti-hypertensives. A heatwave was defined as ≥2 days above the 95th percentile of historical zip code-specific surface air temperatures. We estimated associations of heat-sensitizing medications and heatwaves with heat-related hospitalization using self-controlled case series analysis.
We identified 9,721 patients with at least one chronic condition and heat-related hospitalization; 42.1% of these patients experienced a heatwave. Heatwaves were associated with an increase in heat-related hospitalizations ranging from 21% (95% CI: 7% to 38%) to 33% (95% CI: 14% to 55%) across medication classes. Several drug classes were associated with moderately elevated risk of heat-related hospitalization in the absence of heatwaves, with rate ratios ranging from 1.16 (95% CI: 1.00 to 1.35) to 1.37 (95% CI: 1.14 to 1.66). We did not observe meaningful synergistic interactions between heatwaves and medications.
Older patients with chronic conditions may be at heightened risk for heat-related hospitalization due to the use of heat-sensitizing medications throughout the summer months, even in the absence of heatwaves. Further studies are needed to confirm these findings and also to understand the effect of milder and shorter heat exposure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and ...systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
Methods
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
Conclusion
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision‐making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision‐making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Healthcare workers (HCW) are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, ...there has been little epidemiological research to assess these risks.
We conducted a prospective cohort study of HCW (n = 546) and non-healthcare workers (NHCW; n = 283) with no known prior SARS-CoV-2 infection who were recruited from a large U.S. university and two affiliated university hospitals. In this cross-sectional analysis of data collected at baseline, we examined SARS-CoV-2 infection status (as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs) by healthcare worker status and role.
At baseline, 41 (5.0%) of the participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among HCW (7.3%) than in NHCW (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7, 9.3%). The majority of infected HCW (62.5%) were nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties.
Overall, our results demonstrate that HCW had a higher prevalence of SARS-CoV-2 infection than NHCW. Continued follow-up of this cohort will enable us to monitor infection rates and examine risk factors for transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
