•We model stand development following bark beetles in three forest composition types.•We simulate burning and thinning treatment effects on each forest type.•Canopy fuels are most hazardous in ...forests mixed with subalpine fir and spruce.•Canopy fuels are least hazardous in mixed lodgepole pine and aspen forest.•Fuels reduction effects are greatest where shade-tolerant species are abundant.
Mountain pine beetle outbreaks have killed lodgepole pine on more than one million hectares of Colorado and southern Wyoming forest during the last decade and have prompted harvest operations throughout the region. In northern Colorado, lodgepole pine commonly occurs in mixed stands with subalpine fir, Engelmann spruce, and aspen. Variation in tree species composition will influence structure, fuel profiles and fire hazard as forests recover from bark beetle outbreaks, and this diversity has implications for design and implementation of fuel reduction treatments. We used stand inventory data to predict forest structure and fuel loads starting after needle fall through one century after bark beetle infestation for three lodgepole pine-dominated forest types (pine, pine with aspen, pine with fir and spruce), and compared simulated effects of no-action and fuel reduction treatments (thinning, broadcast burning). In pine stands mixed with significant density of fir and spruce, the high canopy bulk density and low canopy base height increases passive and active crown fire hazards compared to stands with few shade tolerant trees. In contrast, stands of pine mixed with aspen had lower canopy bulk density and active crown fire hazard. All three forest types had high snag and coarse woody debris loads. Thinning and broadcast burning reduced canopy fuels in all forest types for several decades, but had the largest effect in forests with abundant fir. Burning temporarily reduced fine woody fuel, and caused a longer-term reduction in coarse wood and duff. Overall, these simulations indicate that management aimed at reducing canopy fuels in beetle-killed lodgepole pine forests should prioritize stands with high densities of overstory and understory fir and spruce. Forest growth following treatment requires frequent stand manipulation (as often as every 20years) to maintain reduced fuel loads, and since such treatments are expensive and likely not analogous to natural disturbances these activities are most appropriate where resource and infrastructure protection and human safety concerns are high.
•Initial estimate of United States National Forest System (NFS) old-growth forest area.•Applied existing NFS old growth definitions to Forest Inventory and Analysis data.•We estimate there are ∼ 10 ...million hectares of National Forest System (NFS) old growth.•Estimates and methods were designed respond to Executive Order #14072 in co-production with NFS officials.
Old-growth forests are globally valued for their ecological attributes, cultural significance, and in many cases their rarity. Yet, defining and quantifying these forests has been a difficult task. This study developed an approach to consistently estimate extent of old-growth forest on United States Department of Agriculture (USDA) Forest Service National Forest System (NFS) lands, using NFS regional old-growth definitions applied to the US national forest inventory (conducted by the USDA Forest Service Forest Inventory and Analysis FIA program). This method was developed in response to a presidential order (EO#14072, April 22, 2022) and federal laws (e.g., Infrastructure Investment and Jobs Act, 2021; Inflation Reduction Act, 2022). We worked with NFS experts to obtain regionally approved criteria for establishing old growth status based on NFS definitions, assessments, and related documents. NFS regional old growth definitions focus on structural characteristics of forests with criteria for old growth status commonly including minimum abundance of large live trees (in eight of nine regions), tree or stand age (in eight of nine regions), and dead large tree density (in three of nine regions). Determining the regional criteria to use was straightforward for some NFS regions where old-growth forest definitions were specific, and in some cases, had already been applied to FIA data to quantify old-growth forest area. In other NFS regions, such as where definitions have never been applied in an operational manner, or where there were merely assessments of remnant old-growth forest conditions, determining exact criteria was more difficult. We estimate that there are approximately 10 million ha of old growth across NFS forests, as defined by NFS criteria, with the preponderance in the western US states. This study produces the first old-growth forest assessment at the national scale based on NFS definitions and FIA’s statistically-rigorous national forest inventory of the US. These methods can be repeated with future inventories or modified when definitions change to produce updated estimates of old-growth forest attributes, and such work is already underway.
To identify trends in high-dose therapy with autologous hematopoietic stem-cell support (autotransplants) for breast cancer (1989 to 1995).
Analysis of patients who received autotransplants and were ...reported to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989 and June 30, 1995, 19,291 autotransplants were reviewed; 5,886 were for breast cancer. Main outcomes were progression-free survival (PFS) and survival.
Between 1989 and 1995, autotransplants for breast cancer increased sixfold. After 1992, breast cancer was the most common indication for autotransplant. Significant trends included increasing use for locally advanced rather than metastatic disease (P < .00001) and use of blood-derived rather than marrow-derived stem cells (P < .00001). One-hundred-day mortality decreased from 22% to 5% (P < .0001). Three-year PFS probabilities were 65% (95% confidence intervals Cls, 59 to 71) for stage 2 disease, and 60% (95% Cl, 53 to 67) for stage 3 disease. In metastatic breast cancer, 3-year probabilities of PFS were 7% (95% Cl, 4 to 10) for women with no response to conventional dose chemotherapy; 13% (95% Cl, 9 to 17) for those with partial response; and 32% (95% Cl, 27 to 37) for those with complete response. Eleven percent of women with stage 2/3 disease and less than 1% of those with stage 4 disease participated in national cooperative group randomized trials.
Autotransplants increasingly are used to treat breast cancer. One-hundred-day mortality has decreased substantially. Three-year survival is better in women with earlier stage disease and in those who respond to pretransplant chemotherapy.
The significance of small intestinal bacterial overgrowth in patients with cirrhosis is not fully understood and its diagnostic criteria are not uniform. We examined the association of small ...intestinal bacterial overgrowth with spontaneous bacterial peritonitis and compared various microbiological criteria.
Jejunal secretions from 70 patients with cirrhosis were cultivated quantitatively and classified according to various definitions. Clinical characteristics of patients were evaluated and the incidence of spontaneous bacterial peritonitis was monitored during a 1-yr follow-up.
Small intestinal bacterial overgrowth, defined as > or = 10(5) total colony-forming units/ml jejunal secretions, was present in 61% of patients. Small intestinal bacterial overgrowth was associated with acid-suppressive therapy (p = 0.01) and hypochlorhydria (p < 0.001). Twenty-nine patients with persistent ascites were observed. Six episodes of spontaneous bacterial peritonitis occurred after an average 12.8 wk. Occurence of spontaneous bacterial peritonitis correlated with ascitic fluid protein concentration (p = 0.01) and serum bilirubin (p = 0.04) but not with small intestinal bacterial overgrowth (p = 0.39). Its association with acid-suppressive therapy was of borderline significance (hazard ratio = 7.0, p = 0.08).
Small intestinal bacterial overgrowth in cirrhotic patients is associated with acid-suppressive therapy and hypochlorhydria, but not with spontaneous bacterial peritonitis. The potential role of acid-suppressive therapy in the pathogenesis of spontaneous bacterial peritonitis merits further studies.
T-cell depletion of donor marrow decreases graft-versus-host disease resulting from transplants from unrelated and human leukocyte antigen (HLA)-mismatched related donors. However, there are diverse ...strategies for T-cell-depleted transplantation, and it is uncertain whether any improve leukemia-free survival (LFS). To compare strategies for T-cell-depleted alternative donor transplants and to compare T-cell depleted with non-T-cell-depleted transplants, we studied 870 patients with leukemia who received T-cell-depleted transplants from unrelated or HLA-mismatched related donors from 1982 to 1994. Outcomes were compared with those of 998 non-T-cell-depleted transplants. We compared LFS using different strategies for T-cell-depleted transplantation considering T-cell depletion technique, intensity of pretransplant conditioning, and posttransplant immune suppression using proportional hazards regression to adjust for other prognostic variables. Five categories of T-cell depletion techniques were considered: narrow-specificity antibodies, broad-specificity antibodies, Campath antibodies, elutriation, and lectins. Strategies resulting in similar LFS were pooled to compare T-cell-depleted with non-T-cell-depleted transplants. Recipients of transplants T-cell depleted by narrow-specificity antibodies had lower treatment failure risk (higher LFS) than recipients of transplants T-cell depleted by other techniques. Compared with non-T-cell-depleted transplants (5-year probability +/- 95% confidence interval CI of LFS, 31% +/- 4%), 5-year LFS was 29% +/- 5% (P = NS) after transplants T-cell depleted by narrow-specificity antibodies and 16% +/- 4% (P <.0001) after transplants T-cell depleted by other techniques. After alternative donor transplantation, T-cell depletion of donor marrow by narrow-specificity antibodies resulted in LFS rates that were higher than those for transplants T-cell depleted using other techniques but similar to those for non-T-cell-depleted transplants. (Blood. 2000;95:3996-4003)
Human leukocyte antigen (HLA)–identical sibling bone marrow transplantation is an effective treatment for Wiskott-Aldrich syndrome. However, most children with this disease lack such donors and many ...patients receive transplants from alternative donors. This study compared outcomes of HLA-identical sibling, other related donor, and unrelated donor transplantation for Wiskott-Aldrich syndrome. The outcome of 170 transplantations for Wiskott-Aldrich syndrome, from 1968 to 1996, reported to the International Bone Marrow Transplant Registry and/or National Marrow Donor Program were assessed. Fifty-five were from HLA-identical sibling donors, 48 from other relatives, and 67 from unrelated donors. Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non–T-cell–depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLA-identical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P = .0006). Multivariate analysis indicated significantly lower survival using related donors other than HLA-identical siblings (P = .0004) or unrelated donors in boys older than 5 years (P = .0001), compared to HLA-identical sibling transplants. Boys receiving an unrelated donor transplant before age 5 had survivals similar to those receiving HLA-identical sibling transplants. The best transplantation outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling donors. Equivalent survivals are possible with unrelated donors in young children.
The duration of the evolutionary association between a pathogen and vector can be inferred based on the strength of their mutualistic interactions. A well-adapted pathogen is likely to confer some ...benefit or, at a minimum, exhibit low pathogenicity toward its host vector. Coevolution of the two toward a mutually beneficial association appears to have occurred between the citrus greening disease pathogen, Candidatus Liberibacter asiaticus (Las), and its insect vector, the Asian citrus psyllid, Diaphorina citri (Kuwayama). To better understand the dynamics facilitating transmission, we evaluated the effects of Las infection on the fitness of its vector. Diaphorina citri harboring Las were more fecund than their uninfected counterparts; however, their nymphal development rate and adult survival were comparatively reduced. The finite rate of population increase and net reproductive rate were both greater among Las-infected D. citri as compared with uninfected counterparts, indicating that overall population fitness of infected psyllids was improved given the greater number of offspring produced. Previous reports of transovarial transmission, in conjunction with increased fecundity and population growth rates of Las-positive D. citri found in the current investigation, suggest a long evolutionary relationship between pathogen and vector. The survival of Las-infected adult D. citri was lower compared with uninfected D. citri, which suggests that there may be a fitness trade-off in response to Las infection. A beneficial effect of a plant pathogen on vector fitness may indicate that the pathogen developed a relationship with the insect before secondarily moving to plants.
Systemic endotoxemia has been implicated in various pathophysiological sequelae of chronic liver disease. One of its potential causes is increased intestinal absorption of endotoxin. We therefore ...examined the association of small intestinal bacterial overgrowth with systemic endotoxemia in patients with cirrhosis.
Fifty-three consecutive patients with cirrhosis (Child-Pugh group A, 23; group B, 18; group C, 12) were included. Jejunal secretions were cultivated quantitatively and systemic endotoxemia determined by the chromogenic Limulus amoebocyte assay. Patients were followed up for 1 yr.
Small intestinal bacterial overgrowth, defined as > or = 10(5) total colony forming units per milliliter of jejunal secretions, was present in 59% of patients and strongly associated with acid suppressive therapy. The mean plasma endotoxin level was 0.86 +/- 0.48 endotoxin units/ml (range = 0.03-1.44) and was significantly associated with small intestinal bacterial overgrowth (0.99 vs 0.60 endotoxin units/ml, p = 0.03). During the 1-yr follow-up, seven patients were lost to follow up or underwent liver transplantation and 12 patients died. Multivariate Cox regression showed Child-Pugh group to be the only predictor for survival.
Small intestinal bacterial overgrowth in cirrhotic patients is common and associated with systemic endotoxemia. The clinical relevance of this association remains to be defined.
A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. ...We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8
T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia.
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