Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALS.GOV IDENTIFIER: NCT01056185

Cost Analysis of Various Low Pathogenic Avian Influenza Surveillance Systems in the Dutch Egg Layer Sector

Background: As low pathogenic avian influenza viruses can mutate into high pathogenic viruses the Dutch poultry sector implemented a surveillance system for low pathogenic avian influenza (LPAI) based on blood samples. It has been suggested that egg yolk samples could be sampled instead of blood samples to survey egg layer farms. To support future decision making about AI surveillance economic criteria are important. Therefore a cost analysis is performed on systems that use either blood or eggs as sampled material. Methodology/Principal Findings: The effectiveness of surveillance using egg or blood samples was evaluated using scenario tree models. Then an economic model was developed that calculates the total costs for eight surveillance systems that have equal effectiveness. The model considers costs for sampling, sample preparation, sample transport, testing, communication of test results and for the confirmation test on false positive results. The surveillance systems varied in sampled material (eggs or blood), sampling location (farm or packing station) and location of sample preparation (laboratory or packing station). It is shown that a hypothetical system in which eggs are sampled at the packing station and samples prepared in a laboratory had the lowest total costs (i.e. J 273,393) a year. Compared to this a hypothetical system in which eggs are sampled at the farm and samples prepared at a laboratory, and the currently implemented system in which blood is sampled at the farm and samples prepared at a laboratory have 6 % and 39 % higher costs respectively

CD8+ T-Cell Interleukin-7 Receptor Alpha Expression as a Potential Indicator of Disease Status in HIV-Infected Children

Background: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease. Methods: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status. Results: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers. Conclusions: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression

Periodic trends and easy estimation of relative stabilities in 11-vertex nido-p-block-heteroboranes and -borates

Density functional theory computations were carried out for 11-vertex nido-p-block-hetero(carba)boranes and -borates containing silicon, germanium, tin, arsenic, antimony, sulfur, selenium and tellurium heteroatoms. A set of quantitative values called “estimated energy penalties” was derived by comparing the energies of two reference structures that differ with respect to one structural feature only. These energy penalties behave additively, i.e., they allow us to reproduce the DFT-computed relative stabilities of 11-vertex nido-heteroboranes in general with good accuracy and to predict the thermodynamic stabilities of unknown structures easily. Energy penalties for neighboring heteroatoms (HetHet and HetHet′) decrease down the group and increase along the period (indirectly proportional to covalent radii). Energy penalties for a five- rather than four-coordinate heteroatom, [Het5k(1) and Het5k(2)], generally, increase down group 14 but decrease down group 16, while there are mixed trends for group 15 heteroatoms. The sum of HetHet′ energy penalties results in different but easily predictable open-face heteroatom positions in the thermodynamically most stable mixed heterocarbaboranes and -borates with more than two heteroatoms

Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALSGOV IDENTIFIER: NCT01056185

The preventive services use self-efficacy (PRESS) scale in older women: development and psychometric properties

Background\ud Preventive services offered to older Americans are currently under-utilized despite considerable evidence regarding their health and economic benefits. Individuals with low self-efficacy in accessing these services need to be identified and provided self-efficacy enhancing interventions. Scales measuring self-efficacy in the management of chronic diseases exist, but do not cover the broad spectrum of preventive services and behaviors that can improve the health of older adults, particularly older women who are vulnerable to poorer health and lesser utilization of preventive services. This study aimed to evaluate the psychometric properties of a new preventive services use self-efficacy scale, by measuring its internal consistency reliability, assessing internal construct validity by exploring factor structure, and examining differences in self-efficacy scores according to participant characteristics.\ud \ud Methods\ud The Preventive Services Use Self-Efficacy (PRESS) Scale was developed by an expert panel at the University of Pittsburgh Center for Aging and Population Health - Prevention Research Center. It was administered to 242 women participating in an ongoing trial and the data were analyzed to assess its psychometric properties. An exploratory factor analysis with a principal axis factoring approach and orthogonal varimax rotation was used to explore the underlying structure of the items in the scale. The internal consistency of the subscales was assessed using Cronbach’s alpha coefficient.\ud \ud Results\ud The exploratory factor analysis defined five self-efficacy factors (self-efficacy for exercise, communication with physicians, self-management of chronic disease, obtaining screening tests, and getting vaccinations regularly) formed by 16 items from the scale. The internal consistency of the subscales ranged from .81 to .94. Participants who accessed a preventive service had higher self-efficacy scores in the corresponding sub-scale than those who did not.\ud \ud Conclusions\ud The 16-item PRESS scale demonstrates preliminary validity and reliability in measuring self-efficacy in the use of preventive services among older women. It can potentially be used to evaluate the impact of interventions designed to improve self-efficacy in the use of preventive services in community-dwelling older women

Biodiversity and Health: Implications for Conservation

The human health and well-being benefits of contact with nature are becoming increasingly recognised and well understood, yet the implications of nature experiences for biodiversity conservation are far less clear. Theoretically, there are two plausible pathways that could lead to positive conservation outcomes. The first is a direct win-win scenario where biodiverse areas of high conservation value are also disproportionately beneficial to human health and well-being, meaning that the two sets of objectives can be simultaneously and directly achieved, as long as such green spaces are safeguarded appropriately. The second is that experiencing nature can stimulate people’s interest in biodiversity, concern for its fate, and willingness to take action to protect it, therefore generating conservation gains indirectly. To date, the two pathways have rarely been distinguished and scarcely studied. Here we consider how they may potentially operate in practice, while acknowledging that the mechanisms by which biodiversity might underpin human health and well-being benefits are still being determined

B(C6F5)3 as C6F5 Transfer Agent in Zirconium Chemistry: Borole Sandwich and Borole-Bridged Triple-Decker Complexes

Treatment of Cp‘‘Zr(C6F5)(OEt2){?5-(3-RC4H3BC6F5)} ( 1H , R = H; 1Me , R = Me; Cp‘‘ = 1,3-C5H3(SiMe3)2) in toluene with nitriles R‘CN gives rise to the adducts Cp‘‘Zr(C6F5)(NCR‘){?5-(3-RC4H3BC6F5)} ( 2H , R = H, R‘ = Me; 3H , R = H, R‘ = tBu; 3Me , R = Me, R‘ = tBu) in high yields. The reaction of 1H and 1Me with a 4-fold excess of tert-butylisocyanide in toluene at -20 °C leads to the formation of Cp‘‘Zr(C6F5)(CNtBu)2{?5-(3-RC4H3BC6F5)} ( 4H , R = H; 4Me , R = Me), while warming to room temperature results in the insertion of one molecule of isocyanide into the zirconium-C6F5 bond to give the ?2-iminoacyl complexes Cp‘‘Zr{?2-(C6F5CNtBu)}(CNtBu){?5-(3-RC4H3BC6F5)} ( 5H , R = H; 5Me , R = Me). The structures of 3H and 5H were confirmed by X-ray diffraction. The reaction of the diene complexes CpRZr(?3-crotyl)(?4-butadiene) ( 6a , CpR = C5H4SiMe3; 6b , C5H4Me; 6c , Cp; 6d , Cp‘‘) with B(C6F5)3 in toluene solution at room temperature proceeds quantitatively with C-H activation, butene elimination, and C6F5 transfer to generate CpRZr(C6F5){?4-CH2CHCHCHB(C6F5)2} ( 7a - d ). These boryldiene complexes are thermally unstable and smoothly rearrange to give the triple-decker complexes Zr2(CpR)2(C6F5)2{µ-?5:?5-C4H4BCH2-?3,?F-CHCHCHB(C6F5)3} ( 8a - d ). The formation of these complexes involves the complete transfer of all three C6F5 substituents of one B(C6F5)3 molecule, as well as C-H activation and the loss of one C6F5 group as pentafluorobenzene. The triple-decker complexes feature a Zr2C4B core, a zwitterionic structure, and an unusually strong Zr-F donor interaction. On activation with methylalumoxane (MAO), 8a - d polymerize ethene

Assessing the ecological and societal impacts of alien parrots in Europe using a transparent and inclusive evidence-mapping scheme

Globally, the number of invasive alien species (IAS) continues to increase, and management and policy responses typically need to be adopted before conclusive empirical evidence on their environmental and socioeconomic impacts are available. Consequently, numerous protocols exist for assessing IAS impacts, and differ considerably in which evidence they include. However, inclusive strategies for building a transparent evidence base underlying IAS impact assessments are lacking, potentially affecting our ability to reliably identify priority IAS. Using alien parrots in Europe as a case study, here we apply an evidence-mapping scheme to classify impact evidence and evaluate the consequences of accepting different subsets of available evidence on impact assessment outcomes. We collected environmental and socioeconomic impact data in multiple languages using a “wiki-review” process, comprising a systematic evidence search and an online editing and consultation phase. Evidence was classified by parrot species, impact category (e.g. infrastructure), geographical area (e.g. native range), source type (e.g. peer-review), study design (e.g. experimental), and impact direction (deleterious, beneficial and no impact). Our comprehensive database comprised 386 impact entries from 233 sources. Most evidence was anecdotal (50%). 42% of entries reported damage to agriculture (mainly in native ranges), while within Europe most entries concerned interspecific competition (39%). We demonstrate that the types of evidence included in assessments can strongly influence impact severity scores. For example, including evidence from the native range or anecdotal evidence resulted in an overall switch from minimal-moderate to moderate-major overall impact scores. We advise using such an evidence-mapping approach to create an inclusive and updatable database as the foundation for more transparent IAS impact assessments. When openly shared, such evidence-mapping can help better inform IAS research, management and policy