Even modest climate change may lead to major transitions in boreal forests.

The sensitivity of forests to near-term warming and associated precipitation shifts remains uncertain1-9. Herein, using a 5-year open-air experiment in southern boreal forest, we show divergent responses to modest climate alteration among juveniles of nine co-occurring North American tree species. Warming alone (+1.6 °C or +3.1 °C above ambient temperature) or combined with reduced rainfall increased the juvenile mortality of all species, especially boreal conifers. Species differed in growth responses to warming, ranging from enhanced growth in Acer rubrum and Acer saccharum to severe growth reductions in Abies balsamea, Picea glauca and Pinus strobus. Moreover, treatment-induced changes in both photosynthesis and growth help explain treatment-driven changes in survival. Treatments in which species experienced conditions warmer or drier than at their range margins resulted in the most adverse impacts on growth and survival. Species abundant in southern boreal forests had the largest reductions in growth and survival due to climate manipulations. By contrast, temperate species that experienced little mortality and substantial growth enhancement in response to warming are rare throughout southern boreal forest and unlikely to rapidly expand their density and distribution. Therefore, projected climate change will probably cause regeneration failure of currently dominant southern boreal species and, coupled with their slow replacement by temperate species, lead to tree regeneration shortfalls with potential adverse impacts on the health, diversity and ecosystem services of regional forests.

Phenological responses of temperate and boreal trees to warming depend on ambient spring temperatures, leaf habit, and geographic range.

Changes in plant phenology associated with climate change have been observed globally. What is poorly known is whether and how phenological responses to climate warming will differ from year to year, season to season, habitat to habitat, or species to species. Here, we present 5 y of phenological responses to experimental warming for 10 subboreal tree species. Research took place in the open-air B4WarmED experiment in Minnesota. The design is a two habitat (understory and open) × three warming treatments (ambient, +1.7 °C, +3.4 °C) factorial at two sites. Phenology was measured twice weekly during the growing seasons of 2009 through 2013. We found significant interannual variation in the effect of warming and differences among species in response to warming that relate to geographic origin and plant functional group. Moreover, responses to experimental temperature variation were similar to responses to natural temperature variation. Warming advanced the date of budburst more in early compared to late springs, suggesting that to simulate interannual variability in climate sensitivity of phenology, models should employ process-based or continuous development approaches. Differences among species in timing of budburst were also greater in early compared to late springs. Our results suggest that climate change-which will make most springs relatively "early"-could lead to a future with more variable phenology among years and among species, with consequences including greater risk of inappropriately early leafing and altered interactions among species.

Enhanced light interception and light use efficiency explain overyielding in young tree communities.

Diverse plant communities are often more productive than mono-specific ones. Several possible mechanisms underlie this phenomenon but their relative importance remains unknown. Here we investigated whether light interception alone or in combination with light use efficiency (LUE) of dominant and subordinate species explained greater productivity of mixtures relative to monocultures (i.e. overyielding) in 108 young experimental tree communities. We found mixed-species communities that intercepted more light than their corresponding monocultures had 84% probability of overyielding. Enhanced LUE, which arose via several pathways, also mattered: the probability of overyielding was 71% when, in a mixture, species with higher 'inherent' LUE (i.e. LUE in monoculture) intercepted more light than species with lower LUE; 94% when dominant species increased their LUE in mixture; and 79% when subordinate species increased their LUE. Our results suggest that greater light interception and greater LUE, generated by inter and intraspecific variation, together drive overyielding in mixed-species forests.

Species-specific flowering phenology responses to experimental warming and drought alter herbaceous plant species overlap in a temperate-boreal forest community.

BACKGROUND AND AIMS: Warmer temperatures and altered precipitation patterns are expected to continue to occur as the climate changes. How these changes will impact the flowering phenology of herbaceous perennials in northern forests is poorly understood but could have consequences for forest functioning and species interactions. Here, we examine the flowering phenology responses of five herbaceous perennials to experimental warming and reduced summer rainfall over 3 years. METHODS: This study is part of the B4WarmED experiment located at two sites in northern Minnesota, USA. Three levels of warming (ambient, +1.6 °C and +3.1 °C) were crossed with two rainfall manipulations (ambient and 27 % reduced growing season rainfall). KEY RESULTS: We observed species-specific responses to the experimental treatments. Warming alone advanced flowering for four species. Most notably, the two autumn blooming species showed the strongest advance of flowering to warming. Reduced rainfall alone advanced flowering for one autumn blooming species and delayed flowering for the other, with no significant impact on the three early blooming species. Only one species, Solidago spp., showed an interactive response to warming and rainfall manipulation by advancing in +1.6 °C warming (regardless of rainfall manipulation) but not advancing in the warmest, driest treatment. Species-specific responses led to changes in temporal overlap between species. Most notably, the two autumn blooming species diverged significantly in their flowering timing. In ambient conditions, these two species flowered within the same week. In the warmest, driest treatment, flowering occurred over a month apart. CONCLUSIONS: Herbaceous species may differ in how they respond to future climate conditions. Changes to phenology may lead to fewer resources for insects or a mismatch between plants and pollinators.

Experimental warming advances phenology of groundlayer plants at the boreal-temperate forest ecotone.

PREMISE OF THE STUDY: Changes to plant phenology have been linked to warmer temperatures caused by climate change. Despite the importance of the groundlayer to community and forest dynamics, few warming experiments have focused on herbaceous plant and shrub phenology. METHODS: Using a field study in Minnesota, United States, we investigated phenological responses of 16 species to warming over five growing seasons (2009-2013) at two sites, under two canopy covers, and in three levels of simultaneous above- and belowground warming: ambient temperature, ambient +1.7°C and ambient +3.4°C. We tested whether warming led to earlier phenology throughout the growing season and whether responses varied among species and years and depended on canopy cover. KEY RESULTS: Warming extended the growing season between 11-30 days, primarily through earlier leaf unfolding. Leaf senescence was delayed for about half of the species. Warming advanced flowering across species, especially those flowering in August, with modest impacts on fruit maturation for two species. Importantly, warming caused more than half of the species to either converge or diverge phenologically in relation to each other, suggesting that future warmed climate conditions will alter phenological relationships of the groundlayer. Warm springs elicited a stronger advance of leaf unfolding compared to cool spring years. Several species advanced leaf unfolding (in response to warming) more in the closed canopy compared to the open. CONCLUSIONS: Climate warming will extend the growing season of groundlayer species in the boreal-temperate forest ecotone and alter the synchrony of their phenology.

Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance.

BACKGROUND: The purpose of this study was to determine whether dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized non-human primate model. METHODS: We fed 112 baboons a high-cholesterol, high-fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy. RESULTS: We observed evidence of atherosclerosis in all but one baboon fed the two-year challenge diet. CVD risk biomarkers, the prevalence, size, and complexity of arterial lesions, plus consequent arterial stiffness, were increased in comparison with dietary control animals. CONCLUSIONS: Feeding baboons a high-cholesterol, high-fat diet for two years reliably induces atherosclerosis, with risk factor profiles, arterial lesions, and changes in vascular function also seen in humans.

Comparison of vitamin D metabolites in wild and captive baboons.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D3 synthesis, captive primates are supplemented with vitamin D3 (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D2&3 (25(OH)D2&3 ), and 24,25 dihydroxyvitamin D2&3 (24,25(OH)2 D2&3 ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D3 while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D3 . Further metabolic conversion of 25(OH)D3 to 24,25(OH)2 D3 indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.

A Pilot Randomized Controlled Trial of the Feasibility of a Multicomponent Delirium Prevention Intervention Versus Usual Care in Acute Stroke.

BACKGROUND: Delirium after acute stroke is a serious complication. Numerous studies support a benefit of multicomponent interventions in minimizing delirium-related complications in at-risk patients, but this has not been reported in acute stroke patients. The purpose of this study was to explore the feasibility of conducting a randomized (delirium care) versus usual standardized stroke care (usual care) in reducing delirium in acute stroke. OBJECTIVE: This pilot study assessed the feasibility of (1) enrollment within the 48-hour window when delirium risk is greatest, (2) measuring cognitive function using the Montreal Cognitive Assessment, (3) delivering interventions 7 days per week, and (4) determining delirium incidence in stroke-related cognitive dysfunction. METHODS: A 2-group randomized controlled trial was conducted. Patients admitted with ischemic and hemorrhagic strokes and 50 years or older, English speaking, and without delirium on admit were recruited, consented, and randomized to usual care or delirium care groups. RESULTS: Data from 125 subjects (delirium care, n = 59; usual care, n = 66) were analyzed. All Montreal Cognitive Assessment subscales were completed by 86% of subjects (delirium care, mean [SD], 18.14 [6.03]; usual care, mean [SD], 17.61 [6.29]). Subjects in the delirium care group received a mean of 6.10 therapeutic activities (range, 2-23) and daily medication review by a clinical pharmacist using anticholinergic drug calculations. Delirium incidence was 8% (10/125), 3 in the delirium care group and 7 in the usual care group. CONCLUSION: Findings support the feasibility of delivering a multicomponent delirium prevention intervention in acute stroke and warrants testing intervention effects on delirium outcomes and anticholinergic medication administration.

Operational Failures Detected by Frontline Acute Care Nurses.

Frontline nurses encounter operational failures (OFs), or breakdowns in system processes, that hinder care, erode quality, and threaten patient safety. Previous research has relied on external observers to identify OFs; nurses have been passive participants in the identification of system failures that impede their ability to deliver safe and effective care. To better understand frontline nurses' direct experiences with OFs in hospitals, we conducted a multi-site study within a national research network to describe the rate and categories of OFs detected by nurses as they provided direct patient care. Data were collected by 774 nurses working in 67 adult and pediatric medical-surgical units in 23 hospitals. Nurses systematically recorded data about OFs encountered during 10 work shifts over a 20-day period. In total, nurses reported 27,298 OFs over 4,497 shifts, a rate of 6.07 OFs per shift. The highest rate of failures occurred in the category of Equipment/Supplies, and the lowest rate occurred in the category of Physical Unit/Layout. No differences in OF rate were detected based on hospital size, teaching status, or unit type. Given the scale of this study, we conclude that OFs are frequent and varied across system processes, and that organizations may readily obtain crucial information about OFs from frontline nurses. Nurses' detection of OFs could provide organizations with rich, real-time information about system operations to improve organizational reliability. © 2017 Wiley Periodicals, Inc.

Riverine discharges to Chesapeake Bay: Analysis of long-term (1927-2014) records and implications for future flows in the Chesapeake Bay basin.

The Chesapeake Bay (CB) basin is under a total maximum daily load (TMDL) mandate to reduce nitrogen, phosphorus, and sediment loads to the bay. Identifying shifts in the hydro-climatic regime may help explain observed trends in water quality. To identify potential shifts, hydrologic data (1927-2014) for 27 watersheds in the CB basin were analyzed to determine the relationships among long-term precipitation and stream discharge trends. The amount, frequency, and intensity of precipitation increased from 1910 to 1996 in the eastern U.S., with the observed increases greater in the northeastern U.S. than the southeastern U.S. The CB watershed spans the north-to-south gradient in precipitation increases, and hydrologic differences have been observed in watersheds north relative to watersheds south of the Pennsylvania-Maryland (PA-MD) border. Time series of monthly mean precipitation data specific to each of 27 watersheds were derived from the Precipitation-elevation Regression on Independent Slopes Model (PRISM) dataset, and monthly mean stream-discharge data were obtained from U.S. Geological Survey streamgage records. All annual precipitation trend slopes in the 18 watersheds north of the PA-MD border were greater than or equal to those of the nine south of that border. The magnitude of the trend slopes for 1927-2014 in both precipitation and discharge decreased in a north-to-south pattern. Distributions of the monthly precipitation and discharge datasets were assembled into percentiles for each year for each watershed. Multivariate correlation of precipitation and discharge within percentiles among the groups of northern and southern watersheds indicated only weak associations. Regional-scale average behaviors of trends in the distribution of precipitation and discharge annual percentiles differed between the northern and southern watersheds. In general, the linkage between precipitation and discharge was weak, with the linkage weaker in the northern watersheds compared to those in the south. On the basis of simple linear regression, 26 of the 27 watersheds are projected to have higher annual mean discharge in 2025, the target date for implementation of the TMDL for the CB basin.

Is it getting hot in here? Adjustment of hydraulic parameters in six boreal and temperate tree species after 5 years of warming.

Global temperatures (T) are rising, and for many plant species, their physiological response to this change has not been well characterized. In particular, how hydraulic parameters may change has only been examined experimentally for a few species. To address this, we measured characteristics of the hydraulic architecture of six species growing in ambient T and ambient +3.4 °C T plots in two experimentally warmed forest sites in Minnesota. These sites are at the temperate-boreal ecotone, and we measured three species from each forest type. We hypothesized that relative to boreal species, temperate species near their northern range border would increase xylem conduit diameters when grown under elevated T. We also predicted a continuum of responses among wood types, with conduit diameter increases correlating with increases in the complexity of wood structure. Finally, we predicted that increases in conduit diameter and specific hydraulic conductivity would positively affect photosynthetic rates and growth. Our results generally supported our hypotheses, and conduit diameter increased under elevated T across all species, although this pattern was driven predominantly by three species. Two of these species were temperate angiosperms, but one was a boreal conifer, contrary to predictions. We observed positive relationships between the change in specific hydraulic conductivity and both photosynthetic rate (P = 0.080) and growth (P = 0.012). Our results indicate that species differ in their ability to adjust hydraulically to increases in T. Specifically, species with more complex xylem anatomy, particularly those individuals growing near the cooler edge of their range, appeared to be better able to increase conduit diameters and specific hydraulic conductivity, which permitted increases in photosynthesis and growth. Our data support results that indicate individual's ability to physiologically adjust is related to their location within their species range, and highlight that some wood types may adjust more easily than others.

Two novel simian arteriviruses in captive and wild baboons (Papio spp.).

UNLABELLED: Since the 1960s, simian hemorrhagic fever virus (SHFV; Nidovirales, Arteriviridae) has caused highly fatal outbreaks of viral hemorrhagic fever in captive Asian macaque colonies. However, the source(s) of these outbreaks and the natural reservoir(s) of this virus remain obscure. Here we report the identification of two novel, highly divergent simian arteriviruses related to SHFV, Mikumi yellow baboon virus 1 (MYBV-1) and Southwest baboon virus 1 (SWBV-1), in wild and captive baboons, respectively, and demonstrate the recent transmission of SWBV-1 among captive baboons. These findings extend our knowledge of the genetic and geographic diversity of the simian arteriviruses, identify baboons as a natural host of these viruses, and provide further evidence that baboons may have played a role in previous outbreaks of simian hemorrhagic fever in macaques, as has long been suspected. This knowledge should aid in the prevention of disease outbreaks in captive macaques and supports the growing body of evidence that suggests that simian arterivirus infections are common in Old World monkeys of many different species throughout Africa. IMPORTANCE: Historically, the emergence of primate viruses both in humans and in other primate species has caused devastating outbreaks of disease. One strategy for preventing the emergence of novel primate pathogens is to identify microbes with the potential for cross-species transmission in their natural state within reservoir species from which they might emerge. Here, we detail the discovery and characterization of two related simian members of the Arteriviridae family that have a history of disease emergence and host switching. Our results expand the phylogenetic and geographic range of the simian arteriviruses and define baboons as a natural host for these viruses. Our findings also identify a potential threat to captive macaque colonies by showing that simian arteriviruses are actively circulating in captive baboons.

Acclimation of photosynthetic temperature optima of temperate and boreal tree species in response to experimental forest warming.

Rising temperatures caused by climate change could negatively alter plant ecosystems if temperatures exceed optimal temperatures for carbon gain. Such changes may threaten temperature-sensitive species, causing local extinctions and range migrations. This study examined the optimal temperature of net photosynthesis (Topt ) of two boreal and four temperate deciduous tree species grown in the field in northern Minnesota, United States under two contrasting temperature regimes. We hypothesized that Topt would be higher in temperate than co-occurring boreal species, with temperate species exhibiting greater plasticity in Topt , resulting in better acclimation to elevated temperatures. The chamberless experiment, located at two sites in both open and understory conditions, continuously warmed plants and soils during three growing seasons. Results show a modest, but significant shift in Topt of 1.1 ± 0.21 °C on average for plants subjected to a mean 2.9 ± 0.01 °C warming during midday hours in summer, and shifts with warming were unrelated to species native ranges. The 1.1 °C shift in Topt with 2.9 °C warming might be interpreted as suggesting limited capacity to shift temperature response functions to better match changes in temperature. However, Topt of warmed plants was as well-matched with prior midday temperatures as Topt of plants in the ambient treatment, and Topt in both treatments was at a level where realized photosynthesis was within 90-95% of maximum. These results suggest that seedlings of all species were close to optimizing photosynthetic temperature responses, and equally so in both temperature treatments. Our study suggests that temperate and boreal species have considerable capacity to match their photosynthetic temperature response functions to prevailing growing season temperatures that occur today and to those that will likely occur in the coming decades under climate change.

Responses of two understory herbs, Maianthemum canadense and Eurybia macrophylla, to experimental forest warming: early emergence is the key to enhanced reproductive output.

PREMISE OF THE STUDY: Understory herbs might be the most sensitive plant form to global warming in deciduous forests, yet they have been little studied in the context of climate change. METHODS: A field experiment set up in Minnesota, United States simulated global warming in a forest setting and provided the opportunity to study the responses of Maianthemum canadense and Eurybia macrophylla in their natural environment in interaction with other components of the ecosystem. Effects of +1.7° and +3.4°C treatments on growth, reproduction, phenology, and gas exchange were evaluated along with treatment effects on light, water, and nutrient availability, potential drivers of herb responses. KEY RESULTS: Overall, growth and gas exchanges of these two species were modestly affected by warming. They emerged up to 16 (E. macrophylla) to 17 d (M. canadense) earlier in the heated plots than in control plots, supporting early-season carbon gain under high light conditions before canopy closure. This additional carbon gain in spring likely supported reproduction. Eurybia macrophylla only flowered in the heated plots, and both species had some aspect of reproduction that was highest in the +1.7°C treatment. The reduced reproductive effort in the +3.4°C plots was likely due to reduced soil water availability, counteracting positive effects of warming. CONCLUSIONS: Global warming might improve fitness of herbaceous species in deciduous forests, mainly by advancing their spring emergence. However, other impacts of global warming such as drier soils in the summer might partly reduce the carbon gain associated with early emergence.

Decreased atmospheric sulfur deposition across the Southeastern U.S.: when will watersheds release stored sulfate?

Emissions of sulfur dioxide (SO2) to the atmosphere lead to atmospheric deposition of sulfate (SO4(2-)), which is the dominant strong acid anion causing acidification of surface waters and soils in the eastern United States. Since passage of the Clean Air Act and its Amendments, atmospheric deposition of SO2 in this region has declined by over 80%, but few corresponding decreases in streamwater SO4(2-) concentrations have been observed in unglaciated watersheds. We calculated SO4(2-) mass balances for 27 forested, unglaciated watersheds from Pennsylvania to Georgia, by using total atmospheric deposition (wet plus dry) as input. Many of these watersheds still retain SO4(2-), unlike their counterparts in the northeastern U.S. and southern Canada. Our analysis showed that many of these watersheds should convert from retaining to releasing SO4(2-) over the next two decades. The specific years when the watersheds crossover from retaining to releasing SO4(2-) correspond to a general geographical pattern of later net watershed release from north to south. The single most important variable that explained the crossover year was the runoff ratio, defined as the ratio of annual mean stream discharge to precipitation. Percent clay content and mean soil depth were secondary factors in predicting crossover year. The conversion of watersheds from net SO4(2-) retention to release anticipates more widespread reductions in streamwater SO4(2-) concentrations in this region.

Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism.

Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry body composition scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, high-density lipoprotein, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ± 6.4 vs. 6.9 ± 4.0, P = 0.01). Although C-peptide, fasting glucose, and %HbA1c did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r = 0.61, P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.

Mixed-methods approach to understanding nurses' clinical reasoning in recognizing delirium in hospitalized older adults.

A mixed-methods study was conducted to enhance understanding of nurses' clinical reasoning in recognizing delirium in the hospitalized older adult. Paired nurse and researcher ratings of the confusion assessment method in 103 medical-surgical patients were analyzed to determine the rate of agreement in detecting delirium and to identify a purposive sample of nurses to be interviewed about the patients with delirium who were under their care. Nurses' clinical reasoning in recognizing and underrecognizing delirium was investigated using semistructured interviews. The incidence of delirium was 13%, with poor agreement (95% CI [0.05, 0.64], p < 0.05) between the researchers and the nurses in detecting delirium. Sixteen nurses were interviewed and transcripts were analyzed with grounded theory. Confusion was the primary causal factor for recognizing symptoms of delirium. The findings explicated a framework that forms the basis for generating testable assumptions to improve nurses' recognition of delirium.

Balloon catheter delivery of helper-dependent adenoviral vector results in sustained, therapeutic hFIX expression in rhesus macaques.

Hemophilia B is an excellent candidate for gene therapy because low levels of factor IX (FIX) (≥1%) result in clinically significant improvement of the bleeding diathesis. Helper-dependent adenoviral (HDAd) vectors can mediate long-term transgene expression without chronic toxicity. To determine the potential for HDAd-mediated liver-directed hemophilia B gene therapy, we administered an HDAd expressing hFIX into rhesus macaques through a novel and minimally invasive balloon occlusion catheter-based method that permits preferential, high-efficiency hepatocyte transduction with low, subtoxic vector doses. Animals given 1 × 10(12) and 1 × 10(11) virus particle (vp)/kg achieved therapeutic hFIX levels for the entire observation period (up to 1,029 days). At 3 × 10(10) and 1 × 10(10) vp/kg, only subtherapeutic hFIX levels were achieved which were not sustained long-term. Balloon occlusion administration of HDAd was well tolerated with negligible toxicity. Five of six animals developed inhibitors to hFIX. These results provide important information in assessing the clinical utility of HDAd for hemophilia B gene therapy.

Strategies to improve delirium recognition in hospitalized older adults.

As 24-hour caregivers, nurses' detection of delirium is critical to physician diagnosis because of the waxing and waning of delirium-related clinical features. However, nurses fail to accurately interpret delirium-related clinical features more than 30% of the time.

Patients with Low Vision Struggle with Placing Eye Drops and Benefit from an Eye Drop Aid.

PURPOSE: To evaluate eye drop self-administration in a low-vision patient population and test whether a nose-pivoted drop delivery device (NPDD, GentleDrop) can improve eye drop delivery in these patients. DESIGN: Repeated-measures case series. PARTICIPANTS: Thirty subjects (58 eyes) with low vision, defined as best-corrected visual acuity worse than 20/60 or visual field worse than 20° in the better-seeing eye. METHODS: We video-recorded subjects while self-administering eye drops using their own traditional delivery at baseline, after a standardized teaching, and with an NPDD. Two masked graders independently reviewed each drop delivery. Primary success was defined as the drop reaching the eye without the bottle touching the eye or eyelids. Subjects rated ease-of-use (1-10 scale, 10 = easiest) after each drop delivery and completed a satisfaction survey, which included asking whether subjects could place drops independently (1-5 scale, 5 = most independent). MAIN OUTCOME MEASURES: Logistic-transformed generalized estimating equation regression to compare technique satisfaction, ease-of-use, independence, no contact, and success. RESULTS: Primary success was observed in 30 (52%) of 58 eyes at baseline and increased to 44 eyes (76%) with an NPDD (P = 0.013). Bottle tip contact occurred in 23 (40%) of 58 eyes at baseline and 8 eyes (14%) with an NPDD (P = 0.004). Mean ease-of-use scores were 6.7 ± 3.1 at baseline and 8.3 ± 1.8 (P < 0.001) with an NPDD. Likewise, the NPDD improved success, bottle tip contact, and ease-of-use compared with post-teaching traditional delivery (P < 0.01). Twenty-two (73%) of 30 subjects preferred the NPDD to traditional delivery. Twenty-nine (97%) thought the NPDD was comfortable to use, and all would recommend the device. A subgroup analysis was performed on 16 subjects that self-reported difficulty instilling drops at baseline. The NPDD showed similar results, and it increased confidence in placing drops independently (4.6 ± 0.9) compared with baseline (2.7 ± 1.6, P < 0.001). Fifteen (94%) subjects in this subgroup preferred the NPDD. CONCLUSIONS: Low-vision subjects struggled to self-administer eye drops. An NPDD can improve bottle tip contact, ease-of-use, satisfaction, and independence. Eye care providers could consider screening low-vision patients about difficulty with eye drop self-administration and recommending eye drop aids. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.