Long-term perspective on wildfires in the western USA

Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400–1700 CE [Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950–1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s , human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest “fire deficit” in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.Forest fires in the western United States have been increasing in size (1) and possibly severity (2) for several decades. The increase in fire has prompted multiple investigations into both the causes (3, 4) and consequences of this shift for communities, ecosystems, and climate (5). Climate changes and human activities have both contributed to the observed changes in fire, but understanding the nature and magnitude of these impacts has been challenging first because there is substantial ecological heterogeneity and variability in terms of vegetation, soils, hydrology, topography, and other factors that affect fire regimes across the western United States, and second because most fire-history data come from recent decades and centuries when climate and human activities have both undergone rapid and unique transformations. As a result, studies tend to focus either on local ecological and anthropogenic factors that drive fire at fine scales (6, 7), or on climatic influences at broad scales (3, 4). Furthermore, the limited temporal scope of many fire-history studies does not provide adequate context for examining the joint impacts of climate and human activities on broad-scale, long-term fire regime changes. In addition, projections of future climate change and its ecosystem impacts place the expected changes well outside the range of variations in the past few centuries. Thus, coupling multi-decadal-to millennial-scale data on fire, climate changes, and human activities can reveal linkages among these components that are often missed in studies restricted to finer scales or fewer factors.Here we use sedimentary charcoal accumulation rates to construct variations in levels of burning for the past 3,000 y in the western United States (i.e., the West) and compare this record to independent fire-history data from historical records and fire scars. The long charcoal records enable identification of baseline shifts in fire regimes that cannot be detected with shorter records and allow us to view the nature and extent of human impacts on fire in a long-term context; this approach helps to distill the dominant patterns in fire activity across the West, but it does not reveal the important differences in fire controls and effects among vegetation types, ecoregions, or elevation gradients that exist at finer spatial scales (e.g., ref. 8).Our focus here is specifically on multi-decadal-to-centennial-scale variations in fire over the past few millennia and on the West as a whole. Climatic variations on this time scale are characterized by extended periods of persistent anomalies, such as the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) (9, 10), which feature broad-scale (i.e., across the whole of the western United States) anomalies of both surface climates and atmospheric circulation (10). We use temperature (10), drought (9), and population (11) data to compare with the fire-history reconstructions. We also construct a simple statistical model for predicting biomass burning from the temperature and drought data. Our analysis builds on the rich historical narratives of fire in the western United States (12) as well as on many more detailed but shorter broad-scale studies (4, 13, 14). The results illustrate the importance of climate in explaining the variations in fire over time, and show the development of a 20th century “fire deficit” related to the combined effects of fire exclusion, land-use change, and ongoing climate change.     

Health effects of the 2003 Southern California wildfires on children

RATIONALE: In late October 2003, Southern California wildfires burned more than 3,000 km2. The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS). OBJECTIVES: To study the acute effects of fire smoke on the health of CHS participants. METHODS: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr) and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level. MAIN RESULTS: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire. CONCLUSIONS: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.     

Driving forces of global wildfires over the past millennium and the forthcoming century

Recent bursts in the incidence of large wildfires worldwide have raised concerns about the influence climate change and humans might have on future fire activity. Comparatively little is known, however, about the relative importance of these factors in shaping global fire history. Here we use fire and climate modeling, combined with land cover and population estimates, to gain a better understanding of the forces driving global fire trends. Our model successfully reproduces global fire activity record over the last millennium and reveals distinct regimes in global fire behavior. We find that during the preindustrial period, the global fire regime was strongly driven by precipitation (rather than temperature), shifting to an anthropogenic-driven regime with the Industrial Revolution. Our future projections indicate an impending shift to a temperature-driven global fire regime in the 21st century, creating an unprecedentedly fire-prone environment. These results suggest a possibility that in the future climate will play a considerably stronger role in driving global fire trends, outweighing direct human influence on fire (both ignition and suppression), a reversal from the situation during the last two centuries.     

Advances in the understanding of eclampsia

Preeclampsia, a serious hypertensive complication of pregnancy characterized by new-onset hypertension and proteinuria after midpregnancy, is a multisystem disorder that often involves the central nervous system. Neurologic signs and symptoms include hyperreflexia, headaches, visual disturbance, seizures, and cerebral hemorrhage. Eclampsia—new-onset seizures in the setting of preeclampsia—usually occurs before or within 48 hours of delivery, but can present as late as 1 month postpartum (late postpartum eclampsia). Magnesium sulfate is the drug of choice to prevent and treat eclampsia, a recommendation validated through large, randomized, and placebo-controlled trials. This review describes the pathogenesis, clinical features, and treatment of eclampsia, focusing on recent observations regarding roles of circulating antiangiogenic factors in the pathogenesis of the neurologic complications of eclampsia.     

Progress in the understanding of protease-activated receptors

Thrombin results from the activation of the blood coagulation system. It is a multifunctional protein that has, besides its function in hemostasis and thrombosis, several cellular effects that link the coagulation system with the inflammatory response. Many years of investigations were necessary for the discovery of the first functional thrombin receptor, which was found to have a unique mechanism of activation. The receptor was named protease-activated receptor 1 (PAR-1) because proteolysis is necessary for its activation. Subsequent studies led to the identification of the other PARs, PAR-2, PAR-3, and PAR-4. PAR-2 is activated by trypsin, tryptase, factor Xa, or factor VIIa, but it cannot be activated by thrombin, PAR-3 and PAR-4 can also be activated by thrombin. Activation of PARs by protease involves proteolytic cleavage and unmasking of an amino-terminal receptor sequence, which acts as a tethered ligand by binding to the second extracellular loop of the receptor to initiate transmembrane signaling. Sequence analysis has shown that all PARs are members of the 7-transmembrane domain receptor superfamily. Expression of PARs has been detected in most tissues and in numerous cells, and thus these molecules have been implicated in several physiological processes and in the pathogenesis of several diseases.     

Advances in understanding the pathophysiology of spondyloarthritis

Progressive understanding of the underlying pathophysiology of axial spondyloarthritis has successfully translated into innovative therapeutic strategies and successful management of patients in the clinic. This review summarizes the key roles of the pro-inflammatory cytokines tumor necrosis factor and interleukin-17 in the onset and progression of disease and how these cytokines are instrumental in shaping the concept that enthesitis is a key feature of axial spondyloarthritis. Advances in immunological technologies have led to the important insight that different cell populations, part of both the innate and adaptive immune system, play a key role in axial spondyloarthritis. In addition to inflammation, structural damage to the axial skeleton, in particular progressive ankylosis of the sacroiliac joints and the spine, is key to the outcome of patients. Novel data integrate the role of pro-inflammatory cytokines and enthesitis in this context.     

Advances in understanding the pathogenesis of HLH

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X‐linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule‐dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi‐organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined.     

Advances in the understanding of entheseal inflammation

The importance of enthesitis in the pathogenesis of spondyloarthropathy (SpA) is now well recognized. Several entheses comprise more than simply the insertion site, and they are part of a complex biomechanical organ to resist shear and compression. It is also evident that tendons that wrap around bony pulleys form an integral part of joint capsules, and share, along with imaging abnormalities and histopathologic changes, common anatomic, histologic, and biomechanical features with classically defined entheses. Researchers have called these regions of tendons functional entheses. Furthermore, certain synovial joints have much in common with classic entheses—most notably those lined with fibrocartilage rather than hyaline cartilage. These observations provide a unifying anatomic basis for SpA. Enthesitis is associated with underlying osteitis, whether mechanically induced or inflammatory-related—with the extent of osteitis determined by the human leukocyte antigen-B27 gene. Until recently, there was no effective therapy for resistant enthesitis, but it is now evident that enthesitis responds well to biologic blockade with anti-tumor necrosis factor. Unraveling the pathogenic basis of enthesitis will have important implications for understanding and defining therapies in SpA.     

Advances in the understanding of dyskeratosis congenita

Dyskeratosis congenita (DC) is a rare inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is characterised by mucocutaneous abnormalities, bone marrow failure and a predisposition to cancer. Bone marrow failure is the principal cause of premature mortality. Studies over the last 10 years have demonstrated that DC is principally a disease of defective telomere maintenance. All DC patients have very short telomeres and the genetically characterised cases of DC have mutations in six genes which either encode components of the telomerase complex ( DKC1 , TERC , TERT , NOP10 , NHP2 ) or shelterin ( TINF2 ); these are important in the elongation and protection of the telomeric end, respectively. These advances have led to the recognition of cryptic forms of DC, such as presentations with aplastic anaemia and myelodysplasia. They have also increased our understanding of normal haematopoiesis and provided new insights to the aetiology of some cases of aplastic anaemia and related haematological disorders.     

New developments in the understanding of cholera

Recent advances in prevention and treatment of cholera have occurred in the areas of vaccine testing, modifications of oral-rehydration solutions (ORS), and antimicrobial treatment. Oral vaccines consisting of killed whole bacterial cells (WC) with and without the B-subunit of cholera toxin (BS) were shown to be effective in large trials in Bangladesh, Peru, and Vietnam. However, the trials did not resolve whether two or three doses of vaccine are required and whether BS adds significantly to the immune protection of WC. Live, attenuated bacterial vaccines that are immunogenic and have been shown protective in human volunteer studies are candidates for future field trials. Rehydration of patients is a lifesaving effort. The best ORS contains rice powder in place of glucose, and solutions with reduced osmolarity (245 mOsm/L, sodium 75 mEq/L) are as effective as standard ORS. Ciprofloxacin in a single dose is effective in adults, and erythromycin or ampicillin in multiple doses is effective in children.     

Advances in the understanding of Barth syndrome

Barth syndrome (BTHS) is an X‐linked autosomal recessive disorder characterized by neutropenia, cardiomyopathy and growth retardation. BTHS was first described as mitochondrial disease affecting neutrophils as well as cardiac and skeletal muscles. Patients with neutropenia may have extremely low levels of circulating neutrophils and suffer from recurring sometimes life‐threatening bacterial infections. Sepsis is not infrequent, may occur unexpectedly in a patient with no history for pronounced bacterial infections and may lead to death. The reduced level of circulating neutrophils suggests either a reduced production of myeloid cells in the bone marrow and premature apoptosis or aberrant clearance of neutrophils in peripheral blood. The underlying molecular defects are truncation, deletion or substitution mutations in the TAZ gene that appear to result in loss‐of‐function of the gene product tafazzin. Molecular mechanisms triggering neutropenia and cardiomyopathy in BTHS remain largely unclear. The current review focusses on recent advances in the understanding of molecular and cellular bases of neutropenia in Barth syndrome and covers the functional implications of the TAZ mutations, experimental models for neutropenia, the specific cellular abnormalities triggered by loss of TAZ function and potential novel therapeutic strategies for restoring the normal phenotype.     

Advances in understanding the leukaemia microenvironment

Dynamic interactions between leukaemic cells and cells of the bone marrow are a feature of haematological malignancies. Two distinct microenvironmental niches in the bone marrow, the ‘osteoblastic (endosteal)’ and ‘vascular’ niches, provide a sanctuary for subpopulations of leukaemic cells to evade chemotherapy‐induced death and allow acquisition of drug resistance. Key components of the bone marrow microenvironment as a home for normal haematopoietic stem cells and the leukaemia stem cell niches, and the molecular pathways critical for microenvironment/leukaemia interactions via cytokines, chemokines and adhesion molecules as well as hypoxic conditions, are described in this review. Finally, the genetic abnormalities of leukaemia‐associated stroma are discussed. Further understanding of the contribution of the bone marrow niche to the process of leukaemogenesis may provide new targets that allow destruction of leukaemia stem cells without adversely affecting normal stem cell self‐renewal.