Public Perceptions of Wind Energy in Vermont: The Role of Physical, Social, and Environmental Parameters in the Vermont Wind Energy Debate

This research examines how proximity to wind farms influences public perceptions of wind energy in Vermont. Despite overall public support for wind energy in Vermont, opposition to specific utility-scale wind energy facilities arises, commonly by those people living adjacent to the site of the proposed development. Often, the NIMBY explanation is used to characterize the geographic schism that emerges. Under this explanation, it is theorized that the closer an individual is in proximity to a wind farm, the greater their opposition or negative attitudes towards it will be, referred to as the ‘proximity hypothesis.’ A questionnaire was developed to determine what influence proximity has on public perceptions of wind energy in Vermont. Results indicate that the majority of respondents support wind energy; further, distance to Georgia Mountain Community Wind farm was not found to influence attitudes towards wind energy. Further, environmental and political factors shape local perceptions of wind energy. As Vermont transitions to a local, renewable energy system, managing public perception and addressing municipal concerns towards wind energy will become increasingly important. While tradeoffs are inherent with any energy-generation facility, utility-scale wind energy facilities will increasingly expand to locations that Vermont communities value for aesthetic or environmental reasons; consequently, a degree of public resistance is unavoidable. Thus, decision-making that engages individuals from different interests in Vermont is necessary to determine the future of wind energy in Vermont

Sirolimus as Primary Treatment of Acute Graft-versus-Host Disease following Allogeneic Hematopoietic Cell Transplantation

Glucocorticoids have gone unchallenged as an essential component of primary therapy for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) despite limited complete response rates and adverse effects from this therapy. The role for alternate immunosuppressive agents as primary aGHVD treatment remains unexamined. In a series of 10 patients at high risk for corticosteroid toxicity or leukemia relapse who developed biopsy-proven grade II-III aGVHD after hematopoietic cell transplantation, we report that primary therapy with sirolimus resulted in durable complete remission of aGVHD in 5 (50%) without requirement for glucocorticoids. Mild chronic GVHD (cGVHD) developed in 4 (40%). Projected overall survival (OS) at 18 months is 79% (95% confidence interval [CI]: 38.1%-94.3%), and projected relapse-free survival (RFS) at 15 months is 70% (95% CI: 32.9%-89.2%). Sirolimus was well tolerated with mild and reversible thrombotic microangiopathy occurring in 2 patients. This experience provides preliminary evidence for the efficacy of sirolimus as a sole primary therapy in the treatment of aGVHD

Le coste dei Nebrodi tra mosaico paesaggistico, beni culturali e criticità complesse. Visioni e Scenari Strategici progettuali nel paradigma della sostenibiltà

The coastline that delimits and separates (or joins) the geographical area of the Nebrodi (Eastern Sicily) from (or with) the Mediterranean Sea, includes beaches, coastlines and areas now more or less urbanized along a border section of about 104 km. Along this coastline there are (mainly in a linear way) 15 urban centers going towards Messina-Palermo, and precisely they are: Oliveri, Patti, Gioiosa Marea, Piraino, Brolo, Naso, Capo d’Orlando, Torrenova, Sant’Agata di Militello, Acquedolci, Caronia, Santo Stefano di Camastra, Reitano, Motta d’Affermo, Tusa, all falling (due to administrative competence) in the Metropolitan City of Messina. The composition of the coastline is divided into three macro dimensions: 1) the beaches (understood as the space that includes the movement of the sea); the dunes (intended as the most natural space and not directly touched by the movement of the waves but where there are valuable environmental assets); the "waterfront" (which instead reflects the composition and organization of human activity eg infrastructure, building, landscape, ...). Thus it is possible to clearly understand that the coastline defines a "wider" territory that has its own complexity where natural activities (eg the water cycle) and human activities (eg building constructions) intertwine and develop giving different shape to the places. However, in this mosaic the peculiar relationship between man and nature emerges, a relationship that has not always guaranteed, in recent years, the right balance of the two dimensions and has increasingly raised environmental criticalities (with negative effects also on human activities) that they require strategic and structural interventions according to a holistic and / or integrated vision. In this sense the progressive urbanization of the coastal areas (often pushed up to the shoreline and even to the river beds) with coastal roads, second homes, tourist villages, purifiers, ... (now a common situation in Italy) has produced the real stiffening of the coastline and questioning of ecological cycles. In this framework it is necessary to start again with new visions and scenarios (for the Nebrodi coasts) that have their own foundation in the sustainability paradigm

A combined biomarker and clinical panel for chronic graft versus host disease diagnosis.

Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers

Improved Survival After Acute Graft-Versus-Host Disease Diagnosis in the Modern Era

Acute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft-versus-host disease (n=497 for 1999–2001, n=962 for 2002–2005, n=1,446 for 2006–2010). The median (range) follow-up was 144 (4–174), 97 (4–147) and 60 (8–99) months for 1999–2001, 2002–2005, and 2006–2010, respectively. Among the cohort with grade II-IV acute graft-versus-host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999–2001, 2002–2005, and 2006–2012, respectively (P\u3c0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease

GvHD After Umbilical Cord Blood Transplantation for Acute Leukemia: an Analysis of Risk Factors and Effect on Outcomes

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord bloodtransplantation (UCBT) patients (single (\u3c18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acuteGvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD

A Systematic Review and Meta-Analysis of Changes in Cognitive Functioning in Adults Undergoing Hematopoietic Cell Transplantation

Evidence is mixed regarding the effects of hematopoietic cell transplantation (HCT) on changes in cognitive functioning among adults. Meta-analysis, which is designed to help reconcile conflicting findings, has not yet been conducted on studies of adults receiving HCT. To fill this gap, the current study provides a systematic review and meta-analysis of cognitive functioning in adults receiving HCT. A search of PubMed, PsycInfo, CINAHL, and Cochrane Library yielded 732 abstracts, which were independently evaluated by pairs of raters. Seventeen studies were systematically reviewed; eleven were retained for meta-analysis. There was agreement that cognitive impairments are evident for a subset of patients prior to HCT. Meta-analytic findings of 404 patients revealed no significant changes in cognitive functioning pre- to post-HCT (P values > .05). Age, time since transplant, and total body irradiation were not associated with changes in cognitive functioning. Patients who received autologous transplants were more likely to demonstrate improvements in attention (P = .004). The systematic review identified several limitations of existing literature, including small, clinically heterogeneous samples. Large, cooperative group studies are needed to address these design limitations. Nevertheless, results from the current meta-analysis suggest that cognitive functioning does not significantly change following HCT

Feasibility of Frequent Patient-Reported Outcome Surveillance in Patients Undergoing Hematopoietic Cell Transplantation

Patient-reported outcomes (PROs), including symptoms and health-related quality of life (HRQOL), provide a patient-centered description of hematopoietic cell transplantation (HCT)-related toxicity. These data characterize the patient experience after HCT and may have prognostic usefulness for long-term outcomes after HCT. We conducted a study of 32 patients after HCT (10 autologous HCT recipients, 11 full-intensity conditioning allogeneic HCT recipients, and 11 reduced-intensity conditioning allogeneic HCT recipients) to determine the feasibility of weekly electronic PRO collection from HCT until day (D) +100. We used questions from the PRO version of the Common Terminology Criteria for Adverse Events to capture symptoms, and the Patient-Reported Outcomes Measurement Information System Global Health scale to measure physical and mental HRQOL. The vast majority (94%) of patients used the electronic PRO system, with only 6% opting for paper-and-pencil only. The median weekly percentage of participants who completed the surveys was 100% in all cohorts through hospital discharge, and remained 100% for the autologous HCT and reduced-intensity allogeneic HCT cohorts through D+100. Patients were satisfied with the electronic system, giving high marks for readability, comfort, and questionnaire length. Symptom severity varied by absolute level and type of symptom across the 3 cohorts, with the full-intensity allogeneic HCT cohort exhibiting the greatest median overall symptom severity, peaking at D+7. Median physical health HRQOL scores decreased with time in the 3 cohorts, and HRQOL was generally correlated with overall symptom severity. Our results demonstrate the feasibility of frequent electronic PROs in the early post-HCT period. Future studies in larger populations to explore predictive models using frequent PRO data for outcomes, including long-term HRQOL and survival, are warranted

Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: A Chronic Graft-versus-Host Disease Consortium study

Background The National Institutes of Health Consensus Conference proposed the term “overlap” graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present. Design and Methods We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to “classic” chronic graft-versus-host disease without any acute features. Results Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P\u3c0.001), and had a lower platelet count at onset of the graft-versus-host disease (P\u3c0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1–4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2–8.3; P=0.02) than classic chronic graft-versus-host disease. Conclusions These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved