Deer Damage Control in Pennsylvania Agriculture

Deer damage to crops has been and continues to be a serious problem for many Pennsylvania farmers. In 1978 wildlife scientists at Penn State began a 4-year study on deer damage to Pennsylvania agriculture. The research project was funded by the PA Department of Agriculture. The objectives were to determine the extent and distribution of the damage, and to evaluate methods of damage control

Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.

Relationship of Race/Ethnicity and Survival after Single Umbilical Cord Blood Transplantation for Adults and Children with Leukemia and Myelodysplastic Syndromes

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 107/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used

The Microbiome and Hematopoietic Cell Transplantation: Past, Present, and Future

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Defining Responses to Therapy and Study Outcomes in Clinical Trials of Invasive Fungal Diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledg

Medical school faculty discontent: prevalence and predictors of intent to leave academic careers

<p>Abstract</p> <p>Background</p> <p>Medical school faculty are less enthusiastic about their academic careers than ever before. In this study, we measured the prevalence and determinants of intent to leave academic medicine.</p> <p>Methods</p> <p>A 75-question survey was administered to faculty at a School of Medicine. Questions addressed quality of life, faculty responsibilities, support for teaching, clinical work and scholarship, mentoring and participation in governance.</p> <p>Results</p> <p>Of 1,408 eligible faculty members, 532 (38%) participated. Among respondents, 224 (40%; CI95: 0.35, 0.44) reported that their careers were not progressing satisfactorily; 236 (42%; CI95: 0.38, 0.46) were "seriously considering leaving academic medicine in the next five years." Members of clinical departments (OR = 1.71; CI95: 1.01, 2.91) were more likely to consider leaving; members of inter-disciplinary centers were less likely (OR = 0.68; CI95: 0.47, 0.98). The predictors of "serious intent to leave" included: Difficulties balancing work and family (OR = 3.52; CI95: 2.34, 5.30); inability to comment on performance of institutional leaders (OR = 3.08; CI95: 2.07, 4.72); absence of faculty development programs (OR = 3.03; CI95: 2.00, 4.60); lack of recognition of clinical work (OR = 2.73; CI95: 1.60, 4.68) and teaching (OR = 2.47; CI95: 1.59, 3.83) in promotion evaluations; absence of "academic community" (OR = 2.67; CI95: 1.86, 3.83); and failure of chairs to evaluate academic progress regularly (OR = 2.60; CI95: 1.80, 3.74).</p> <p>Conclusion</p> <p>Faculty are a medical school's key resource, but 42 percent are seriously considering leaving. Medical schools should refocus faculty retention efforts on professional development programs, regular performance feedback, balancing career and family, tangible recognition of teaching and clinical service and meaningful faculty participation in institutional governance.</p

Hyperinsulinaemia as long-term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project.

Objectives. Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow-up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long-term total mortality. Setting. Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. Subjects. A total of 6074 nondiabetic, middle-aged, healthy Swedish males. Screening examination. We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow-up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration. Main outcome measures. Total mortality and cardiac event (CE) rate for IHD. Results. Unadjusted relative risks (RRs) for both death and CE were J-shaped with the highest relative risk (RR: 1.4-1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow-up. The risk of death in hyperinsulinaemic men, defined on the basis of 2-h insulin level, increased with time of follow-up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05-1.65], even after adjustment for other risk factors. Conclusions. Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow-up time. The 2-h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long-term follow-up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long-term risk of mortality and IHD

Delineation of Stage Specific Expression of Plasmodium falciparum EBA-175 by Biologically Functional Region II Monoclonal Antibodies

EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains..The role of the F1 and F2 domains in erythrocyte invasion and binding was elucidated with mAbs. These mAbs interfere with native EBA-175 binding to erythrocyte in a synergistic fashion. The stage specific expression of EBA-175 showed that the primary focus of activity was the merozoite stage. A recombinant RII protein vaccine consisting of both F1 and F2 domains that could induce synergistic activity should be optimal for induction of antibody responses that interfere with merozoite invasion of erythrocytes