Search

Auditors must ensure that their audit plans budget sufficient time for key audit steps. Research has shown that insufficient audit time budgets can be detrimental to audit quality. We examine whether framing audit steps negatively (e.g., assess whether management's assumptions are not appropriate) increases time budgets—particularly for steps in which the auditor perceives that performance quality is less verifiable, and thus most at risk of being performed with low quality. First, we report the results of analyses indicating that, in practice, audit steps are predominantly framed positively, potentially resulting in smaller time budgets. We then report the results of an experiment in which 50 experienced audit managers budget time for an audit program that tests a Level-3 fair-value estimate. Prior research and Public Company Accounting Oversight Board (PCAOB) inspections indicate that this is a challenging audit area, vulnerable to allegations of low audit quality. The results support our predictions and suggest that reframing audit steps negatively would increase audit time budgets—an audit quality indicator—particularly for less-verifiable steps.

Antiretroviral therapy (ART) simplification to a single-tablet regimen can benefit HIV-1-infected, virologically suppressed, individuals on ART composed of multiple pills.We assessed long-term efficacy and safety of switching to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) from multi-tablet ritonavir-boosted protease inhibitor (PI + RTV) plus F/TDF (TVD) regimens.STRATEGY-PI was a 96-week, phase 3b, randomized (2:1), open-label, non-inferiority study examining the efficacy, safety, and tolerability of switching to E/C/F/TDF from PI + RTV + TVD regimens in virologically suppressed individuals (HIV-1 RNA 50 copies/mL). Participants were randomized to switch to E/C/F/TDF (switch group) or to continue their PI + RTV + TVD regimens (no-switch group). Eligibility criteria included no resistance to F/TDF or history of virologic failure, and estimated creatinine clearance ≥70 mL/min.At week 96, 87% (252/290) of switch and 70% (97/139) of no-switch participants maintained HIV-1 RNA 50 copies/mL (difference: 17%, 95% CI 8.7-26.0%, p 0.001). Superiority of the switch to E/C/F/TDF vs. no-switch was due to a smaller proportion of both virologic failures (switch, 1% [3/290]; no-switch, 6% [8/139]) and discontinuations for non-virologic reasons (switch, 11% [31/290]; no-switch, 24% [33/139]). No treatment-emergent resistance was observed in switch subjects with virologic failure. Discontinuation rates from adverse events were 3% in both groups (9/293, switch; 4/140, no-switch). Switching from PI + RTV + TVD to E/C/F/TDF was associated with significant improvements in patient-reported outcomes related to gastrointestinal symptoms (nausea and bloating).E/C/F/TDF is a safe, effective long-term alternative to multi-tablet PI + RTV + TVD-based regimens in virologically suppressed, HIV-1-infected adults, and improves patient-reported gastrointestinal symptoms.

Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5–80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (−72.8 ± 1.4 mV) at 20 mmHg and unaffected by increasing pressure to 80 mmHg (−74.3 ± 2.2 mV). In contrast, BFAs constricted to the thromboxane analog U-46619 (100 nM), the adrenergic agonist phenylephrine (10 µM), and KCl (60 mM). Inhibition of nitric oxide synthase or intermediate- and small-conductance Ca2+-activated K+channels did not alter arteriolar diameter, indicating that the dilated state of BFAs is not attributable to overactive endothelium-dependent dilatory influences. Myocytes isolated from BFAs exhibited BaCl2(100 µM)-sensitive K+currents consistent with strong inward-rectifier K+(KIR) channels. Notably, block of these KIRchannels “restored” pressure-induced constriction and membrane depolarization. This suggests that these channels, in part, account for hyperpolarization and associated absence of tone in BFAs. Furthermore, smooth muscle-specific knockout of KIR2.1 caused significant myogenic tone to develop at physiological pressures. This suggests that 1) the regulation of vascular tone in the bladder is independent of pressure, insofar as pressure-induced depolarizing conductances cannot overcome KIR2.1-mediated hyperpolarization; and 2) maintenance of bladder blood flow during bladder filling is likely controlled by neurohumoral influences.

Successful treatment of HIV-associated multicentric Castleman disease (HIV+MCD) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 (HHV8)-associated lymphoma. Longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. A prospective cohort of 84 patients with biopsy-proven HIV+MCD were treated with risk-stratified rituximab-based therapy. Four patients (5%) died of refractory HIV+MCD and 80 achieved clinical remission. The median follow-up for the 80 patients was 6.9 years and their 5-year overall survival was 92% (95% confidence interval [CI], 85 to 99). Eighteen have relapsed (all histologically confirmed), including 5 with concomitant HHV8-associated lymphoma and MCD at relapse. The 5-year relapse-free survival is 82% (95% CI, 72 to 92). No clinical or laboratory findings that were present at MCD diagnosis predicted subsequent relapse, and the median time to first relapse was 30 months (maximum, 10 years). There were no significant differences in clinicopathological features at initial diagnosis and at relapse. All patients were successfully retreated at relapse with rituximab-based therapy. Only 1 patient died of relapsed MCD (at fifth relapse 9.4 years after initial diagnosis). Despite the use of rituximab, the risk of developing HHV8-associated lymphoma was significantly elevated in this cohort, with an incidence of 11.4/1000 person-years. The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy; this should only be advocated in the context of a clinical trial.

Hop stunt viroid (HSVd) is an economically important pathogen that reduces growth and yield of hops. Visual symptoms of infected hop are highly dependent on cultivar. A study was conducted using six cultivars of hop to determine the impact on yield. Average dry cone yields of infected ‘Glacier’, ‘Cascade’, and ‘Willamette’ were reduced by 62, 14, and 34%, respectively, relative to noninoculated healthy plants. No significant yield reduction was observed for ‘Nugget’, ‘Columbus’, and ‘Galena’. The α-acid and β-acid contents showed a parallel pattern. Horticultural parameters of Willamette and Nugget were measured in the final year of the study. Internode length, shoot length, and side-arm length were reduced by 29, 26, and 73%, respectively, for infected Willamette bines relative to noninfected bines; no effects were observed resulting from infection of Nugget. To understand the current potential impact of HSVd, a survey was conducted to determine its distribution in central Washington. The survey revealed that 17% of hop plants tested are infected. Hop yield and hop plant longevity will be significantly affected by this level of infection. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

U.S. GAAP and IFRS require full disclosure of the effects of an accounting change in the year the change is made, but not in future years. However, some accounting changes have multi-period effects. We conduct an experiment to examine whether investors forget to adjust for an accounting change in periods subsequent to the change, and examine the effectiveness of interventions designed to mitigate that tendency. In the experiment, a company changed how it accounts for pension gains and losses, and investors value the company over three consecutive reporting periods. Results indicate that investors gradually forget to adjust for the accounting change over time under the current approach used to disclose accounting changes. These effects are mitigated in post-change periods when investors receive full disclosure of the current effect of the prior accounting change, and to a lesser extent when investors receive a disclosure that includes a simple non-quantitative disclosure that the accounting change occurred. Supplemental analyses indicate that investors rely more on memory-aiding disclosures as the time delay between valuation judgments increases.

BackgroundTo analyse the effect of drug resistance mutations (DRM) on CD4+T-cell (CD4) trends in HIV-positive people maintained on virologically failing anti-retroviral therapy (ART).MethodsIndividuals from two large cohorts experiencing virological failure (VF) while maintained on ART with ≥1 CD4 count and ≥1 resistance test were included. CD4 slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 decline.Results5,357 individuals contributing 7,661 VF episodes were included: any DRM were detected in 88.8% of episodes. After adjustment, CD4 counts declined less steeply during episodes where DRM were detected compared to episodes with no DRM (difference =28 cells/mm3/year, 95% CI =18, 39; PConclusionsDetection of resistance and of certain DRM during VF of ART has a small but significant favourable effect on CD4 decline.

Background Variation in red blood cell (RBC) transfusion practices exists at cardiac surgery centers across the nation. We tested the hypothesis that significant variation in RBC transfusion practices between centers in our state's cardiac surgery quality collaborative remains even after risk adjustment. Methods Using a multiinstitutional statewide database created by the Maryland Cardiac Surgery Quality Initiative (MCSQI), we included patient-level data from 8,141 patients undergoing isolated coronary artery bypass (CAB) or aortic valve replacement at 1 of 10 centers. Risk-adjusted multivariable logistic regression models were constructed to predict the need for any intraoperative RBC transfusion, as well as for any postoperative RBC transfusion, with anonymized center number included as a factor variable. Results Unadjusted intraoperative RBC transfusion probabilities at the 10 centers ranged from 13% to 60%; postoperative RBC transfusion probabilities ranged from 16% to 41%. After risk adjustment with demographic, comorbidity, and operative data, significant intercenter variability was documented (intraoperative probability range, 4% –59%; postoperative probability range, 13%–39%). When stratifying patients by preoperative hematocrit quartiles, significant variability in intraoperative transfusion probability was seen among all quartiles (lowest quartile: mean hematocrit value, 30.5% ± 4.1%, probability range, 17%–89%; highest quartile: mean hematocrit value, 44.8% ± 2.5%; probability range, 1%–35%). Conclusions Significant variation in intercenter RBC transfusion practices exists for both intraoperative and postoperative transfusions, even after risk adjustment, among our state's centers. Variability in intraoperative RBC transfusion persisted across quartiles of preoperative hematocrit values.

Accountants making judgments with respect to a particular set of standards are increasingly aware of standards from other reporting regimes that offer additional or conflicting guidance. In fact, IFRS encourages reliance on out-of-regime standards when IFRS lacks guidance. This paper reports the results of two experiments which provide evidence that auditors in such circumstances are vulnerable to contrast effects, whereby reporting judgments under IFRS are systematically influenced away from the accounting treatment supported by standards from another regime (U.S. GAAP). Contrast effects are observed (1) when out-of-regime standards are considered before making a reporting judgment under IFRS, and (2) when out-of-regime standards are applied as local GAAP for a subsidiary of a foreign parent that reports under IFRS. We also find that contrast effects are reduced when auditors believe IFRS lacks guidance. These results have implications for financial statement preparers and auditors in the current incomplete-convergence environment. This article is protected by copyright. All rights reserved.

International audience; Changes to our climate and oceans are already affecting living marine resources (LMRs) and the people, businesses, and economies that depend on them. As a result, the U.S. National Marine Fisheries Service (NMFS) has developed a Climate Science Strategy (CSS) to increase the production and use of the climate-related information necessary to fulfill its LMR stewardship mission for fisheries management and protected species conservation. The CSS establishes seven objectives: (1) determine appropriate, climate-informed reference points; (2) identify robust strategies for managing LMRs under changing climate conditions; (3) design decision processes that are robust to climate-change scenarios; (4) predict future states of ecosystems, LMRs, and LMR-dependent human communities; (5) determine the mechanisms of climate-change related effects on ecosystems, LMRs, and LMR-dependent human communities; (6) track trends in ecosystems, LMRs, and LMR-dependent human communities and provide early warning of change; and (7) build and maintain the science infrastructure required to fulfill NMFS mandates under changing climate conditions. These objectives provide a nationally consistent approach to addressing climate-LMR science needs that supports informed decision-making and effective implementation of the NMFS legislative mandates in each region. Near term actions that will address all objectives include: (1) conducting climate vulnerability analyses in each region for all LMRs; (2) establishing and strengthening ecosystem indicators and status reports in all regions; and (3) developing a capacity to conduct management strategy evaluations of climate-related impacts on management targets, priorities, and goals. Implementation of the Strategy over the next few years and beyond is critical for effective fulfillment of the NMFS mission and mandates in a changing climate.

To investigate if there is evidence for a 'legacy effect' for blood pressure (BP) lowering treatment, that is, worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults. We systematically reviewed studies comparing the effects of delayed BP treatment (placebo/untreated during the trial or no previous treatment at trial entry) vs. early treatment (actively treated during the trial or previous BP treatment at trial entry) on mortality in the short term (5-year in-trial period) and long term (≥10 years in total period). The data were pooled using Peto ORs. A subgroup analysis by 10-year Framingham risk score was performed. Three studies (ALLHAT, Oslo and PREVEND-IT) involving 4746 participants were included. The results were heavily influenced by the ALLHAT trial. We found no significant difference in all-cause mortality between 'delayed BP' and 'early treatment' in the short-term OR 0.95 (95% CI 0.68-1.32) or long-term OR 0.90 (95% CI 0.78-1.04), with similar results for mortality from cardiovascular disease (CVD). The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD. The review showed no clinically adverse 'legacy effect' on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over. The results were consistent for all CVD risk subgroups. Although these studies are non-randomised post-hoc analyses, they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention populations.

We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca2+ sparks and Ca2+ transients within vascular smooth muscle cells of intact arteries were characterized using high‐speed confocal microscopy of intact arteries. Arteries were studied under conditions of varying intraluminal pressure and oxidation. Intraluminal pressure specifically, rather than the generic stretch of the artery, was necessary to activate the oxidative pathway. We demonstrated a graded step activation profile for the generation of Ca2+ sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca2+ sensitive‐K+ channel functional availability was independent of oxidant activated PKG. There was an increase in the amplitude, but not the Area under the Curve (AUC) of the caffeine‐induced Ca2+ transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ spark vasoregulation through a tightly controlled pathway with a graded onset switch. The pathway, underpinned by oxidant activation of PKG, cannot be further boosted by additional pressure or oxidation once active. We propose that these restrictive characteristics of pressure‐induced Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants., Intraluminal pressure within resistance arteries triggers a binary activation of an oxidant‐driven pathway whereby protein kinase G regulates calcium spark vasoregulation. Once activated, the pathway cannot be boosted by additional pressure or oxidants and we propose this confers stability upon the pressure‐induced constriction of the artery.

Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people&rsquo, s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla&trade, ) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera&trade, ). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p &lt, 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms.

Trait-based climate vulnerability assessments based on expert evaluation have emerged as a rapid tool to assess biological vulnerability when detailed correlative or mechanistic studies are not feasible. Trait-based assessments typically view vulnerability as a combination of sensitivity and exposure to climate change. However, in some locations, a substantial amount of information may exist on system productivity and environmental conditions (both current and projected), with potential disparities in the information available for data-rich and data-poor stocks. Incorporating this level of detailed information poses challenges when conducting, and communicating uncertainty from, rapid vulnerability assessments. We applied a trait-based vulnerability assessment to 36 fish and invertebrate stocks in the eastern Bering Sea (EBS), a data-rich ecosystem. In recent years, the living marine resources of the EBS and Aleutian Islands have supported fisheries worth more than US $1 billion of annual ex-vessel value. Our vulnerability assessment uses projections (to 2039) from three downscaled climate models, and graphically characterizes the variation in climate projections between climate models and between seasons. Bootstrapping was used to characterize uncertainty in specific biological traits and environmental variables, and in the scores for sensitivity, exposure, and vulnerability. The sensitivity of EBS stocks to climate change ranged from "low" to "high," but vulnerability ranged between "low" and "moderate" due to limited exposure to climate change. Comparison with more detailed studies reveals that water temperature is an important variable for projecting climate impacts on stocks such as walleye pollock (Gadus chalcogrammus), and sensitivity analyses revealed that modifying the rule for determining vulnerability increased the vulnerability scores. This study demonstrates the importance of considering several uncertainties (e.g., climate projections, biological, and model structure) when conducting climate vulnerability assessments, and can be extended in future research to consider the vulnerability of user groups dependent on these stocks.

—The design process is often characterized by and realized through the iterative steps of evaluation and refinement. When the process is based on a single creative domain such as visual art or audio production, designers primarily take inspiration from work within their domain and refine it based on their own intuitions or feedback from an audience of experts from within the same domain. What happens, however, when the creative process involves more than one creative domain such as in a digital game? How should the different domains influence each other so that the final outcome achieves a harmonized and fruitful communication across domains? How can a computational process orchestrate the various computational creators of the corresponding domains so that the final game has the desired functional and aesthetic characteristics? To address these questions, this paper identifies game facet orchestration as the central challenge for artificial-intelligence-based game generation, discusses its dimensions, and reviews research in automated game generation that has aimed to tackle it. In particular, we identify the different creative facets of games, propose how orchestration can be facilitated in a top-down or bottom-up fashion, review indicative preliminary examples of orchestration, and conclude by discussing the open questions and challenges ahead.

TAF1/MRSX33 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these mutations cause dysmorphology, hypotonia, intellectual and motor defects is unknown. Mouse models which have embryonically targeted TAF1 have failed, possibly due to TAF1 being essential for viability, preferentially expressed in early brain development, and intolerant of mutation. Novel animal models are valuable tools for understanding neuronal pathology. Here, we report the development and characterization of a novel animal model for TAF1 ID syndrome in which the TAF1 gene is deleted in embryonic rats using clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) technology and somatic brain transgenesis mediated by lentiviral transduction. Rat pups, post-natal day 3, were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 vectors. Rats were subjected to a battery of behavioral tests followed by histopathological analyses of brains at post-natal day 14 and day 35. TAF1-edited rats exhibited behavioral deficits at both the neonatal and juvenile stages of development. Deletion of TAF1 lead to a hypoplasia and loss of the Purkinje cells. We also observed a decreased in GFAP positive astrocytes and an increase in Iba1 positive microglia within the granular layer of the cerebellum in TAF1-edited animals. Immunostaining revealed a reduction in the expression of the CaV3.1 T-type calcium channel. Abnormal motor symptoms in TAF1-edited rats were associated with irregular cerebellar output caused by changes in the intrinsic activity of the Purkinje cells due to loss of pre-synaptic CaV3.1. This animal model provides a powerful new tool for studies of neuronal dysfunction in conditions associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.

Background: Chronic Disease Management (CDM) plans are usually administered by general practitioners (GPs) to assist those with a chronic medical condition, such as stroke, and provide better management of risk factors. Despite the prevalent use of CDM plans, its comprehensiveness and the fact that there is a government commitment to fund it, there is limited evidence of its effectiveness in Australian survivors of stroke. We aimed to assess the effectiveness of CDM plans on preventing the recurrence of CVD-related serious adverse events. Methods: Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Poisson regression models were used to determine the incidence rate ratio (IRRs) of increasing exposure to being on a CDM plan over 3 years, while adjusting for confounding factors. We used the total count of CVD-related events and deaths within 3 years after stroke/TIA, based on either hospital discharge codes or adjudication by two independent stroke specialists. Results: Five hundred and sixty-three patients were included (median age 70; 36% female). There were 305 CVD-related events over the three years (mean 0.54), in which a third (104) were adjudicated and two-thirds (201) were derived from hospital discharge codes alone. Nearly a quarter (27%) did not take up a CDM plan over the three years, a third (33%) were on plans for less than 1.5 years and 40% were on plans from 1.5 years to 3 years. The factors most strongly associated with decreased incidence of CVD-related events were duration on a CDM plan (Adjusted IRR (aIRR) 0.85, 95% confidence interval (95%CI) 0.77-0.93; p Conclusion: Being on a CDM plan for a longer duration appeared to reduce the occurrence of CVD-related events within 3 years after stroke, potentially via more closely controlled risk factors. Patients should be encouraged to return for regular reviews of their CDM plans to enhance secondary prevention strategies, and maintain a better quality of life.

Background: Prognostic performances of models predicting risk of recurrent events of cardiovascular disease (CVD) are not adequate for use in clinical settings. We aimed to determine whether adapting the Framingham Risk Score (FRS) to an Australian population could effectively predict recurrent cardiovascular outcomes. Methods: Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Cox proportional hazards regression models were used to determine the risk of recurrence of CVD-related events and deaths within 3 years after stroke/TIA; adjudicated by two independent stroke specialists. Regression estimates were then used to recalibrate the coefficients used by the FRS, and performance of the model assessed. Results: In women, the recalibrated FRS model had poor discrimination (C-statistic = 0.634) and appeared to better predict CVD recurrence (AUC = 0.664) than the original FRS model (AUC = 0.598). However in men, the recalibrated FRS model had poor discrimination (C-statistic = 0.604) and prediction of CVD recurrence (AUC = 0.632) similar to the original FRS model (AUC = 0.606). Conclusion: The original FRS and recalibrated FRS models appeared to perform poorly in Australian men and women with stroke. The identification of relevant risk factors, easily measured in a clinical setting, may help clinicians better monitor the risks of their patients and enhance secondary prevention strategies.

The incidences of Hop latent virus (HpLV), Hop mosaic virus (HpMV), and American hop latent virus (AHLV), members of the genus Carlavirus, and Prunus necrotic ringspot virus and Apple mosaic virus, members of the genus Ilarvirus, were assessed for two hop cultivars, Horizon and Nugget, in Washington State. The spatial distribution of plants infected by the carlaviruses was assessed in two Horizon gardens in 2000 and one Nugget garden in 1993, 1994, and 1995. In the first Horizon garden (garden 1) and the Nugget garden, plants were separated by 2.1 m within and between rows. In these gardens, cultivation and the wide plant spacing discouraged contact between plants in either direction. In the second Horizon garden (garden 2), plants were separated by 4.3 m between rows and 1.0 m within rows. In all gardens, mechanical operations operated predominantly along rows; however, the closer plant spacing within rows in garden 2 permitted contact between adjacent plants within rows. In both Horizon gardens, the distribution of plants infected with HpMV was aggregated within rows. However, the distribution of plants infected with HpLV and AHLV was strongly influenced by contact between plants. In the Nugget garden, the distribution of plants infected by all three carlaviruses was autocorrelated within rows by 1995.

A novel Bacillus thuringiensis Cry protein, Cry8Hb, active against Diabrotica virgifera virgifera (Western corn rootworm, WCRW) was discovered. Unexpectedly, the anti-rootworm activity of the Cry8Hb toxin was enhanced significantly by fusing Escherichia coli maltose binding protein (MBP) to this Cry toxin. While the exact mechanism of the activity enhancement remains indefinite, it is probable that the enhancement is a result of increased solubility of the MBP-Cry8Hb fusion in the rootworm midgut. This hypothesis was examined using a synthetic Cry3 protein called IP3-1, which was not soluble at a neutral pH like Cry8Hb and marginally active to WCRW. When IP3-1 was fused to MBP, its anti-WCRW activity was enhanced 13-fold. To further test the hypothesis, DNA shuffling was performed on IP3-1 to increase the solubility without MBP. Screening of shuffled libraries found six new IP3 variants showing very high anti-WCRW activity without MBP. Sequence and 3D structure analysis of those highly active, shuffled IP3 variants revealed several charge-altering mutations such as Lys to Glu on the putative MBP-attaching side of the IP3 molecule. It is likely that those mutations make the protein acidic to substitute the functions of MBP including enhancing the solubility of IP3 at a neutral pH.

Pseudoperonospora humuli populations from Oregon and Washington were analyzed for genetic variation using random amplified polymorphic DNA (RAPD) and DNA amplification fingerprinting (DAF) markers. The genetic structure of the Oregon and Washington populations differed considerably. There was little genetic diversity in Washington, with only five RAPD and six DAF groups detected among 40 isolates tested. One genotype was predominant in Washing-ton. In contrast, 18 RAPD and 34 DAF groups were found among the 40 isolates tested from Oregon. No unique band profile associated with host cultivar was observed. It is suggested that the distinct difference in population structure between the two geographic regions might be due to climatic differences resulting in a higher frequency of sexual reproduction of P. humuli in Oregon than in Washington.

Gent, D. H., Nelson, M. E., and Grove, G. G. 2008. Persistence of phenylamide insensitivity in Pseudoperonospora humuli. Plant Dis. 92:463-468. Downy mildew, caused by Pseudoperonospora humuli, is an important disease of hop in most production regions in the northern hemisphere. Insensitivity to phenylamide fungicides was detected in isolates of P. humuli in production regions in Oregon and Idaho in 1992, and these fungicides since have been used on a limited basis. In this study, the prevalence of phenylamide insensitivity among isolates of P. humuli collected from 2005 to 2007 in the northwestern United States was quantified using a leaf disk assay with a discriminating dose (25 µg/ml) of either metalaxyl or mefenoxam with inoculum derived from 201 systemically infected diseased shoots (basal spikes) collected from 6, 10, and 11 hop yards in Idaho, Washington, and Oregon, respectively. A subset of 47 basal spike isolates and 42 monosporic isolates collected from two yards in Idaho and nine yards in Oregon during 2006 and 2007 were assayed using a dilution series of metalaxyl to determine the effective dose that inhibited 50% of the incidence of sporulation (ED50). Insensitivity to mefenoxam was detected in 31 of 74 (41.9%) basal spikes collected from 13 hop yards. Insensitivity to the related compound metalaxyl was detected in 52 of 80 (65%) spikes collected from nine hop yards, including four hop yards in Washington. Log ED50 values ranged from –2.25 to 2.67 for basal spike isolates and –2.27 to 2.98 for monosporic isolates and had a similar distribution. Log ED50 values for monosporic isolates and entire basal spike isolates were significantly associated. However, the slope of the regression line was less than 1, indicating that the log ED50 values obtained from entire basal spike isolates were greater than the corresponding log ED50 values obtained from a monosporic isolate obtained from that spike. This research suggests that insensitivity to phenylamide fungicides is a stable phenotype in P. humuli. Management of downy mildew should rely on measures other than these fungicides in yards or regions where phenylamide insensitivity is prevalent, which is now known to include certain hop yards in Idaho, Oregon, and Washington.

TAF1 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these mutations cause dysmorphology, hypotonia, intellectual and motor defects is unknown. Mouse models which have embryonically targeted TAF1 have failed, possibly due to TAF1 being essential for viability, preferentially expressed in early brain development, and intolerant of mutation. Novel animal models are valuable tools for understanding neuronal pathology. Here, we report the development and characterization of a novel animal model for TAF1 ID syndrome in which theTAF1gene is deleted in embryonic rats using clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) technology and somatic brain transgenesis mediated by lentiviral transduction. Rat pups, post-natal day 3, were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 vectors. Rats were subjected to a battery of behavioral tests followed by histopathological analyses of brains at post-natal day 14 and day 35.TAF1-edited rats exhibited behavioral deficits at both the neonatal and juvenile stages of development. Deletion of TAF1 lead to a hypoplasia and loss of the Purkinje cells. Abnormal motor symptoms in TAF1-edited rats were associated with irregular cerebellar output caused by changes in the intrinsic activity of the Purkinje cells. Immunostaining revealed a reduction in the expression of the CaV3.1 T-type calcium channel. This animal model provides a powerful new tool for studies of neuronal dysfunction in conditions associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.Significance StatementIntellectual disability (ID) syndrome is an X-linked rare disorder caused by loss-of-function mutations in theTAF1gene. There is no animal model for understanding neuronal pathology and to facilitate development of new therapeutics for this X-linked intellectual disability syndrome. Novel animal models are valuable tools for understanding neuronal pathology and to facilitate development of new therapeutics for diseases. Here we developed a novel animal model for TAF1 ID syndrome in which theTAF1gene is deleted by CRISPR-Cas9 editing and lentiviral transduction. This animal model provides a powerful new tool for studies of neuronal dysfunction associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.

Gent, D. H., Nelson, M. E., Grove, G. G., Mahaffee, W. F., Turechek, W. W., and Woods, J. L. 2012. Association of spring pruning practices with severity of powdery mildew and downy mildew on hop. Plant Dis. 96:1343-1351. Downy mildew (caused by Pseudoperonospora humuli) and powdery mildew (caused by Podosphaera macularis) are important diseases of hop in the Pacific Northwest United States, and cultural practices may affect the severity of both diseases. The association of spring pruning quality and timing with severity of downy mildew and powdery mildew was assessed through analysis of survey data collected from commercial hop yards in Oregon and Washington. Among 149 hop yards surveyed, the most common pruning method was chemical desiccation (48% of yards), mechanical pruning (23%), or a combination of these practices (15%). The quality of pruning was assessed using a threecategory ordinal scale (“excellent”, “moderate”, or “poor”) based on the amount of foliage remaining on plants following pruning. Excellent pruning quality was attained more often in yards pruned twice (74.6 to 82.1% of yards) versus once (33.8% of yards), independent of pruning method. Seasonal severity of downy mildew in Oregon increased approximately twofold with reduction in pruning quality from excellent to moderate to poor. Pruning quality was not significantly related to levels of powdery mildew on leaves or cones in Oregon. Under more severe disease pressure in Washington, however, seasonal severity of powdery mildew on leaves and the incidence of cones with powdery mildew were significantly greater in yards that had poor pruning compared with excellent pruning. Moreover, yards that had excellent pruning quality received, on average, 1.1 to 1.5 fewer fungicide applications per season for downy mildew or powdery mildew compared with yards that had moderate or poor pruning quality. This savings was associated with delayed initiation of the first application by 7.5 to 14.2 days in yards with excellent pruning quality. Replicated experiments in commercial yards in Oregon quantified the effect of delaying pruning timing 5 to 21 days compared with growers’ standard practices on the diseases and yield. Downy mildew suppression by delayed pruning was dependent on cultivar and year of sampling, being significantly reduced fivefold only in ‘Willamette’ in 2007. Severity of powdery mildew and cone yield was similar between plots that received the delayed or standard pruning timing treatments. Collectively, these studies emphasize that early spring sanitation measures are associated with reduced primary inoculum and are critically important for managing both downy mildew and powdery mildew. A savings of at least one fungicide application per year appears achievable when spring pruning is conducted thoroughly and slightly delayed compared with growers’ current practices. Cultural disease management practices are actions that involve the manipulation of the plant, its components, crop refuse, and the environment to reduce or prevent disease (5,26,31,34). In hop (Humulus lupulus L.), cultural practices are an important component of integrated management of the two most important foliar diseases of

Resistant cultivars of hop (Humulus lupulus) have been grown, with the aim of helping to manage powdery mildew in the Pacific Northwest since the first report of the disease in the field in 1997 (4). A major objective of many breeding programs is development of resistance to powdery mildew, and this has generally been achieved by single resistance genes (qualitative resistance). One such gene, R6 (3), has been utilized extensively in new cultivars and has prevented epidemics of the disease in those cultivars across the Pacific Northwestern United States for approximately 15 years. In 2011, a grower in Washington State reported outbreaks of powdery mildew on cv. Apollo, which is thought to possess powdery mildew resistance derived from R6. Fungicides and cultural control measures were applied, and the grower reported no substantial crop damage from the disease. During the winter of 2012, the same grower planted rhizomes of cv. Apollo in a greenhouse in the Yakima Valley of Washington State and later found the plants to be affected by powdery mildew. Affected leaves from plants of cvs. Apollo, Newport, and Nugget (all reported [3] or assumed to possess R6 based on pedigree) grown in the same greenhouse were later provided to the authors. Conidia obtained from each affected plants were transferred to plants of the highly susceptible cv. Symphony, which is not known to contain any resistance genes. After 10 to 14 days of incubation, resultant conidia from each cultivar above (total of three isolates) were transferred to greenhouse grown plants of cvs. Nugget and Symphony and incubated at 18°C. Within 7 days, all three isolates produced powdery mildew colonies characteristic of P. macularis (2) on both cultivars. Cleistothecia did not develop in any colonies. In addition, Nugget and Symphony plants were inoculated with a field population of P. macularis originating from cultivars lacking R6 in Oregon. These inoculations on Nugget did not develop powdery mildew whereas Symphony plants did. Non-inoculated controls remained free of powdery mildew. Results were identical in two additional experiments. The sequence of the mating type idiomorph, MAT1-1, was obtained to confirm identity of the pathogen as P. macularis as described previously (1). The sequences were identical among the three isolates obtained from the greenhouse in Washington and isolates of P. macularis obtained previously from Oregon and Washington. MAT1-2 idiomorph was not detected in the isolates collected. While R6-virulent strains have been detected previously in race characterization experiments, these strains have not caused widespread epidemics of powdery mildew. The increasing prevalence of virulent strains of P. macularis and outbreaks of powdery mildew on formerly resistant cultivars necessitates changes in breeding strategies and disease management efforts to minimize damage resulting from the disease. The distribution of virulent strains of the pathogen and susceptibility of formerly resistance cultivars to powdery mildew are currently under investigation. References: (1) B. Asalfet et al. Phytopathology 103:717, 2013. (2) R. Bélanger et al. The Powdery Mildews: a Comprehensive Treatise. APS Press, St. Paul, MN, 2002. (3) P. Darby. Brew Hist. 121:94, 2005. (4) C. Ocamb et al. Plant Dis. 83:1072, 1999.

Background: Hospital, emergency presentation and death databases are frequently used to research outcomes after stroke. The reliability of diagnostic coding for cardiovascular disease (CVD) in these administrative data remains uncertain. We aimed to determine the reliability of these data in Australia using an existing clinical trial cohort. Methods: Patients with stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563, recruited from 4 hospitals within Victoria). We used diagnostic ICD-10-AM coded data from hospital, emergency department and death databases within 2 years after stroke/TIA. Medical records for these potential CVD-related events were reviewed by two independent stroke specialists and adjudicated according to strict criteria. We then estimated sensitivity and specificity of using either primary or both primary and secondary diagnoses fields (obtained for all adjudicated records), against the events adjudicated by the specialists (gold standard). False positives were CVD-events defined by ICD-10-AM diagnostic codes that were adjudicated as not being a CVD-event. False negatives were true CVD-events that were misclassified as not being CVD-related when using ICD-10-AM codes. Results: We identified 261 events for medical review. After adjudication, 65 were classified as CVD-events (cases) and 196 were not CVD-events. Using both primary and secondary diagnoses, 55 true positives were correctly identified among the cases (sensitivity = 84.6%) and 129 true negatives among the non-cases (specificity = 65.8%). Using only primary diagnoses, 48 true positives were identified (sensitivity = 73.9%) and 171 true negatives (specificity = 87.2%). Using both primary and secondary diagnoses had an increased sensitivity, but decreased specificity (area under the Receiver Operating Characteristic curve (AUC) = 0.75; 95% CI, 0.70, 0.81) when compared with using only primary diagnoses (AUC = 0.81; 95% CI, 0.75, 0.86; p = 0.028). Conclusion: Both primary and secondary diagnoses should be used to identify true CVD-events and minimise misclassifying these in administrative databases.

Podosphaera macularis, the causal agent of hop powdery mildew, is a recurrent threat to hops in the Pacific Northwest because of the potential to reduce cone yield and quality. Early-season pruning is a common practice in hop production for horticultural reasons. Studies were conducted over a 3-year period in a commercial hop yard to quantify the effect of pruning method and timing on disease development, yield, and cone quality factors. A 4-week delay in pruning reduced the incidence of leaves with powdery mildew from 46 to 10% and cones from 9 to 1%, with the specific effect being season dependent. Pruning using chemical desiccants rather than by mechanical means had similar effects on disease levels on leaves. On cones, though, chemical pruning had a small but significant reduction in the incidence of powdery mildew compared with mechanical pruning. Cone yield, levels of bittering-acids, and color were not negatively affected in any individual year or cumulatively over three seasons when pruning treatments were applied repeatedly to the same plots during the study period. Delayed pruning may offer a low-cost means of reducing both the incidence of powdery mildew and early-season fungicide inputs in certain cultivars.

Canopy management is an important aspect of control of powdery mildew diseases and may influence the intensity of fungicide applications required to suppress disease. In hop, powdery mildew (caused by Podosphaera macularis) is most damaging to cones when infection occurs during bloom and the juvenile stages of cone development. Experiments were conducted over 3 years to evaluate whether fungicide applications could be ceased after the most susceptible stages of cone development (late July) without unduly affecting crop yield and quality when disease pressure was moderated with varying levels of basal foliage removal. In experimental plots of ‘Galena’ hop, the incidence of leaves with powdery mildew was similar whether fungicides were ceased in late July or made in late August. Disease levels on leaves were unaffected by the intensity of basal foliage removal, whereas the intensity of basal foliage removal interacted with the duration of fungicide applications to affect disease levels on cones. Similar experiments conducted in large plots of ‘Tomahawk’ hop in a commercial hop yard similarly found no significant impact on disease levels on leaves from either the duration of fungicide applications or intensity of basal foliage removal. In contrast, on cones, application of fungicides into August had a modest, suppressive effect on powdery mildew. There was also some evidence that the level of powdery mildew on cones associated with fungicide treatment was influenced by the intensity of basal foliage removal. When fungicide applications ceased in late July, there was a progressive decrease in the incidence of cones with powdery mildew with increasing intensity of basal foliage removal. Removing basal foliage two to three times allowed fungicide applications to be terminated in late July rather than late August without diminishing disease control on cones, yield, or cone quality factors. Thus, this study further establishes that fungicide applications made during the early stages of hop cone development have the strongest effect on suppression of powdery mildew on cones. The additive effect of fungicide applications targeted to the periods of greatest cone susceptibility and canopy management to reduce disease favorability may obviate the need for fungicide applications later in the season. This appears to be a viable strategy in mature hop yards of certain cultivars when disease pressure is not excessively high.

The American Woodcock Conservation Plan calls for halting and reversing declines of American woodcock (Scolopax minor) populations through creation and management of early successional forest (ESF). Counts of displaying male woodcock along routes of the American woodcock singing-ground survey (SGS) are used to assess regional population status and trends, and there is a need to assess whether SGS routes represent the region. We assessed whether individual SGS routes (330-m buffers) in the Boreal-Hardwood and Prairie-Hardwood Transitions of Minnesota, USA, represented land covers within local landscapes, defined using simulated 10-minute blocks, and whether the routes, in aggregate, represented land covers of our study region. Our land covers included non-forest classes, age-based ESF (20 years), and persisting classes for deciduous-mixed and evergreen forests and woody wetlands. We found that the median value of mean absolute differences (MAD) between percentages for route buffer and block cover classes was 3.78 percentage points. Twenty-two of 81 (27%) route buffers had MAD values 5 percentage points. Within Minnesota, more of these routes (19 of 22) occurred in the Boreal-Hardwood Transition than in the Prairie-Hardwood Transition. Relative to local landscapes, route buffers most frequently and strongly underrepresented open water, barren land, evergreen ESF, persisting woody wetlands, and woody wetland ESF and over-represented developed land and grassland-pasture. When we compared routes in aggregate to our study region, the magnitude of percentage point differences for individual covers did not exceed 5, except for open water. Given the relatively small differences we observed, we conclude that SGS routes well represent land covers within our study region.

This experimental study examines whether requiring auditors to report risks of material misstatement (and related auditor findings) affects audit adjustments. Experienced audit partners and senior managers in the United Kingdom proposed audit adjustments under three different reporting regimes: (a) an audit report where no risks are disclosed, (b) a report where risks of material misstatement are disclosed, and (c) a report where risks of misstatement are disclosed, augmented with the auditor’s findings with respect to those risks. Our results indicate that disclosing risks of material misstatement without findings has no effect on audit adjustments, but that lower audit adjustments occur when the disclosure also includes findings, and that this result is driven by auditors requiring particularly low adjustments when they indicate a finding that the post-audit account balance is “mildly optimistic” (as opposed to “reasonable”). Results also suggest that this tendency is unintentional. Overall, these findings indicate that auditors unintentionally trade off audit adjustments for disclosures, consistent with increased detailed disclosure providing an opportunity for “moral licensing” that enables auditors to satisfy client demands while also complying with professional standards. From a practice perspective, these results suggest that disclosure of critical or key audit matters as recently required by U.S. and international standard setters may not affect auditor behavior, but that allowing disclosure of additional findings as done voluntarily in some jurisdictions may have the unintended consequence of reducing the size of audit adjustments that auditors require.

OBJECTIVE: Definitions of virological response vary from

Antimicrobial photodynamic inactivation (aPDI) employs the combination of non-toxic photosensitizing dyes and visible light to kill pathogenic microorganisms regardless of drug-resistance, and can be used to treat localized infections. A meso-substituted tetra-methylpyridinium porphyrin with one methyl group replaced by a C12 alkyl chain (FS111) and its Pd-derivative (FS111-Pd) were synthesized and tested as broad-spectrum antimicrobial photosensitizers when excited by blue light (5 or 10 J/cm(2)). Both compounds showed unprecedented activity, with the superior FS111-Pd giving 3 logs of killing at 1 nM, and eradication at 10 nM for Gram-positive methicillin-resistant Staphylococcus aureus. For the Gram-negative Escherichia coli, both compounds produced eradication at 100 nM, while against the fungal yeast Candida albicans, both compounds produced eradication at 500 nM. Both compounds could be categorized as generators of singlet oxygen (Φ(Δ) = 0.62 for FS111 and 0.71 for FS111-Pd). An in vivo study was carried out using a mouse model of localized infection in a partial thickness skin abrasion caused by bioluminescent Gram-negative uropathogenic E. coli. Both compounds were effective in reducing bioluminescent signal in a dose-dependent manner when excited by blue light (405 nm), but aPDI with FS111-Pd was somewhat superior both during light and in preventing recurrence during the six days following PDT.

The western corn rootworm (WCR, Diabrotica virgifera virgifera) gene, dvssj1, is a putative homolog of the Drosophila melanogaster gene, snakeskin (ssk). This gene encodes a membrane protein associated with the smooth septate junction (SSJ) which is required for the proper barrier function of the epithelial lining of insect intestines. Disruption of DVSSJ integrity by RNAi technique has been shown previously to be an effective approach for corn rootworm control, by apparent suppression of production of DVSSJ1 protein leading to growth inhibition and mortality. To understand the mechanism that leads to the death of WCR larvae by dvssj1 double-stranded RNA, we examined the molecular characteristics associated with SSJ functions during larval development. Dvssj1 dsRNA diet feeding results in dose-dependent suppression of mRNA and protein; this impairs SSJ formation and barrier function of the midgut and results in larval mortality. These findings suggest that the malfunctioning of the SSJ complex in midgut triggered by dvssj1 silencing is the principal cause of WCR death. This study also illustrates that dvssj1 is a midgut-specific gene in WCR and its functions are consistent with biological functions described for ssk.

The western corn rootworm (WCR) Diabrotica virgifera virgifera causes substantial damage in corn. Genetically modified (GM) plants expressing some Bacillus thuringiensis (Bt) insecticidal Cry proteins efficiently controlled this pest. However, changes in WCR susceptibility to these Bt traits have evolved and identification of insecticidal proteins with different modes of action against WCR is necessary. We show here for the first time that Cyt1Aa from Bt exhibits toxicity against WCR besides to the dipteran Aedes aegypti larvae. Cyt1Aa is a pore-forming toxin that shows no cross-resistance with mosquitocidal Cry toxins. We characterized different mutations in helix α-A from Cyt1Aa. Two mutants (A61C and A59C) exhibited reduced or absent hemolytic activity but retained toxicity to A. aegypti larvae, suggesting that insecticidal and hemolytic activities of Cyt1Aa are independent activities. These mutants were still able to form oligomers in synthetic lipid vesicles and to synergize Cry11Aa toxicity. Remarkably, mutant A61C showed a five-fold increase insecticidal activity against mosquito and almost 11-fold higher activity against WCR. Cyt1Aa A61C mutant was as potent in killing WCR that were selected for resistance to mCry3A as it was against unselected WCR indicating that this toxin could be a useful resistance management option in the control of WCR.

The United Nations Framework Convention on Climate Change requires annual estimates for forestry and ecological indicators to monitor the change in forest resources, the sustainability of forest management, and the emission and sink of forest carbon. It is particularly important to update estimates of forestland area in a timely fashion and at flexible geographical scales, not only for its value in monitoring biological diversity at the ecosystem scale, but also because of its close association with other indicators such as forest biomass and carbon. However, in the US, the Forest Survey Handbook advises that the sampling error should not exceed 3% per 404686 ha (one million acres) of forestland area, a demanding standard barely met by pooling the Forest Inventory and Analysis (FIA) panel data measured in an inventory cycle of 5–10 years. Consequently, this study aims to propose and illustrate an updating procedure using data assimilation that integrates a design-based estimator with a model-based mixed estimator for updating annual estimates at two population levels, the state- and county-levels. The three states in the USA, Minnesota (MN), Georgia (GA) and California (CA), representing the Northern, the Southern and the Pacific Northwest FIA programs, constitute the study areas. FIA data collected were based on a 5-year inventory cycle for MN (2006–2010) and GA (2005–2009), and a 10-year cycle for CA (2001–2010). The total number of sample plots was 17764 for MN, 6323 for GA, and 16740 for CA. Distinguishing features attribute to this procedure include: (1) unbiasedness: the integration of design-based estimates into the mixed estimator introduces a favorable property – unbiasedness, which could be the property national forest inventories concern the most; (2) efficiency: considerable improvements in estimation precision greater than 55%, achieving sampling errors as small as those relying on using 5–10 years pooled FIA data; (3) time: compared with the temporal trends reflected by design-based estimates, the updated trends were of much smoother trend lines and narrower confidence intervals that would better depict temporal changes for a population at flexible spatial scales; (4) space: this procedure is scale-invariant, meaning its efficiency is not affected by an inventory employing either a large- or small-area estimation, which was demonstrated at the two population levels; and (5) generalizability: this procedure is unbiased and efficient, 100% compatible with the FIA database which is readily available to the public, and thus suitable for various official reporting instruments.

Cerebral ischemia triggers a cascade of neuroinflammatory and peripheral immune responses that contribute to post-ischemic reperfusion injury. Prior work conducted in CNS ischemia models underscore the potential to harness non-antibiotic properties of tetracycline antibiotics for therapeutic benefit. In the present study, we explored the immunomodulatory effects of the tetracycline derivative 9-tert-butyl doxycycline (9-TB) in a mouse model of transient global ischemia that mimics immunologic aspects of the post-cardiac arrest syndrome. Pharmacokinetic studies performed in C57BL/6 mice demonstrate that within four hours after delivery, levels of 9-TB in the brain were 1.6 and 9.5-fold higher than those obtained using minocycline and doxycycline, respectively. Minocycline and 9-TB also dampened inflammation, measured by reduced TNFα-inducible, NF-κβ-dependent luciferase activity in a microglial reporter line. Notably, daily 9-TB treatment following ischemia-reperfusion injury in vivo induced the retention of polymorphonuclear neutrophils (PMNs) within the spleen while simultaneously biasing CNS PMNs towards an anti-inflammatory (CD11b(Low)Ym1(High)) phenotype. These studies indicate that aside from exhibiting enhanced CNS delivery, 9-TB alters both the trafficking and polarization of PMNs in the context of CNS ischemia-reperfusion injury.

Globally, forests are a crucial natural resource, and their sound management is critical for human and ecosystem health and well-being. Efforts to manage forests depend upon reliable data on the status of and trends in forest resources. When these data come from well-designed natural resource monitoring (NRM) systems, decision makers can make science-informed decisions. National forest inventories (NFIs) are a cornerstone of NRM systems, but require capacity and skills to implement. Efficiencies can be gained by incorporating auxiliary information derived from remote sensing (RS) into ground-based forest inventories. However, it can be difficult for countries embarking on NFI development to choose among the various RS integration options, and to develop a harmonized vision of how NFI and RS data can work together to meet monitoring needs. The NFI of the United States, which has been conducted by the USDA Forest Service’s (USFS) Forest Inventory and Analysis (FIA) program for nearly a century, uses RS technology extensively. Here we review the history of the use of RS in FIA, beginning with general background on NFI, FIA, and sampling statistics, followed by a description of the evolution of RS technology usage, beginning with paper aerial photography and ending with present day applications and future directions. The goal of this review is to offer FIA’s experience with NFI-RS integration as a case study for other countries wishing to improve the efficiency of their NFI programs.

Long-term management planning for conservation-reliant migratory songbirds is particularly challenging because habitat quality in different stages and geographic locations of the annual cycle can have direct and carry-over effects that influence the population dynamics. The Neotropical migratory songbird Kirtland's warbler Setophaga kirtlandii (Baird 1852) is listed as endangered under the U.S. Endangered Species Act and Near Threatened under the IUCN Red List. This conservation-reliant species is being considered for U.S. federal delisting because the species has surpassed the designated 1000 breeding pairs recovery threshold since 2001. To help inform the delisting decision and long-term management efforts, we developed a population simulation model for the Kirtland's warbler that incorporated both breeding and wintering grounds habitat dynamics, and projected population viability based on current environmental conditions and potential future management scenarios. Future management scenarios included the continuation of current management conditions, reduced productivity and carrying capacity due to the changes in habitat suitability from the creation of experimental jack pine Pinus banksiana (Lamb.) plantations, and reduced productivity from alteration of the brown-headed cowbird Molothrus ater (Boddaert 1783) removal programme. Linking wintering grounds precipitation to productivity improved the accuracy of the model for replicating past observed population dynamics. Our future simulations indicate that the Kirtland's warbler population is stable under two potential future management scenarios: (i) continuation of current management practices and (ii) spatially restricting cowbird removal to the core breeding area, assuming that cowbirds reduce productivity in the remaining patches by =41%. The additional future management scenarios we assessed resulted in population declines. Synthesis and applications. Our study indicates that the Kirtland’s warbler population is stable under current management conditions and that the jack pine plantation and cowbird removal programmes continue to be necessary for the long-term persistence of the species. This study represents one of the first attempts to incorporate full annual cycle dynamics into a population viability analysis for a migratory bird, and our results indicate that incorporating wintering grounds dynamics improved the model performance.