Weather and Climate Change Drive Annual Variation of Reproduction by an Aerial Insectivore

For many bird species, but especially aerial insectivores, reproduction depends on weather. Climate change is likely to intensify effects, but with uncertain consequences. We report 22 years of data on Eastern Kingbird (Tyrannus tyrannus) reproduction for two populations located in different hygric environments undergoing climate change; mesic central New York, USA, (NY; 12 years) and xeric southeastern Oregon, USA, (OR: 10 years). Laying date became earlier with increasing temperature in the 30-day period preceding laying in identical fashion at both sites, and in years of early laying, clutch size was larger, length of laying season increased, and failed initial nesting attempts were more often replaced. High temperature in the 10-days preceding mean laying date was associated with shorter laying seasons, while a site by 10-day temperature interaction reflected an increase and decrease of clutch size with increasing 10-day temperature in NY and OR, respectively. Seasonal rate of clutch size decline was higher when the laying season was short but also slowed in xeric OR when rain was abundant in the 10-days prior to mean laying date. Nest predation drove annual variation in young fledged/nest, but the latter also increased and decreased with increasing maximum temperature during the nestling phase in mesic NY and xeric OR, respectively. Potential effects of climate change on kingbird populations are thus high given the dependence of reproduction on weather, and climate change likely contributed to declines of kingbirds in OR. Declines of kingbirds in NY appear unrelated to warming climates because higher temperatures advanced laying dates and yielded greater nest productivity. However, length of laying season declined across years at both sites, and thus early season gains may be negated by poor conditions late in the season that may be causing shorter laying seasons. Further work is needed to identify causes for the latter changes

Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration.

Recessive Stargardt disease (STGD1) is an inherited blinding disorder caused by mutations in the Abca4 gene. ABCA4 is a flippase in photoreceptor outer segments (OS) that translocates retinaldehyde conjugated to phosphatidylethanolamine across OS disc membranes. Loss of ABCA4 in Abca4 -/- mice and STGD1 patients causes buildup of lipofuscin in the retinal pigment epithelium (RPE) and degeneration of photoreceptors, leading to blindness. No effective treatment currently exists for STGD1. Here we show by several approaches that ABCA4 is additionally expressed in RPE cells. (i) By in situ hybridization analysis and by RNA-sequencing analysis, we show the Abca4 mRNA is expressed in human and mouse RPE cells. (ii) By quantitative immunoblotting, we show that the level of ABCA4 protein in homogenates of wild-type mouse RPE is about 1% of the level in neural retina homogenates. (iii) ABCA4 immunofluorescence is present in RPE cells of wild-type and Mertk -/- but not Abca4 -/- mouse retina sections, where it colocalizes with endolysosomal proteins. To elucidate the role of ABCA4 in RPE cells, we generated a line of genetically modified mice that express ABCA4 in RPE cells but not in photoreceptors. Mice from this line on the Abca4 -/- background showed partial rescue of photoreceptor degeneration and decreased lipofuscin accumulation compared with nontransgenic Abca4 -/- mice. We propose that ABCA4 functions to recycle retinaldehyde released during proteolysis of rhodopsin in RPE endolysosomes following daily phagocytosis of distal photoreceptor OS. ABCA4 deficiency in the RPE may play a role in the pathogenesis of STGD1

Formed Metal Products and Methods of Making the Same

Provided herein are methods of forming a metal product, including applying a water soluble formability film to the metal blank and/or applying a network polymer preprime (e.g., a hybrid organic-inorganic preprime, or a heat-resistant hybrid preprime) to the metal blank, forming the metal blank into a formed metal product, and optionally removing the formability film. A removable formability film and/or a preprime can improve the formability of an aluminum alloy and replace lubricants that used for forming processes by reducing the coefficient of friction of the metal product surface. Further, employing a water soluble polymer film eliminates lubricant removal for downstream processing. The formability film and/or preprime can include chemical additives that provide additional surface properties. The methods of processing the aluminum alloy products described herein provide a more efficient method for producing aluminum alloy products, as required by end users (e.g., original equipment manufacturers (OEMs))

Invasive adenoma and pituitary carcinoma: a SEER database analysis

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5 years (p=0.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (p=0.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30 years (p=0.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches

A comparison of magnetic resonance imaging and neuropsychological examination in the diagnostic distinction of Alzheimer’s disease and behavioral variant frontotemporal dementia

The clinical distinction between Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) remains challenging and largely dependent on the experience of the clinician. This study investigates whether objective machine learning algorithms using supportive neuroimaging and neuropsychological clinical features can aid the distinction between both diseases. Retrospective neuroimaging and neuropsychological data of 166 participants (54 AD; 55 bvFTD; 57 healthy controls) was analyzed via a Naïve Bayes classification model. A subgroup of patients (n = 22) had pathologically-confirmed diagnoses. Results show that a combination of gray matter atrophy and neuropsychological features allowed a correct classification of 61.47% of cases at clinical presentation. More importantly, there was a clear dissociation between imaging and neuropsychological features, with the latter having the greater diagnostic accuracy (respectively 51.38 vs. 62.39%). These findings indicate that, at presentation, machine learning classification of bvFTD and AD is mostly based on cognitive and not imaging features. This clearly highlights the urgent need to develop better biomarkers for both diseases, but also emphasizes the value of machine learning in determining the predictive diagnostic features in neurodegeneration

Miniaturization optimized weapon killing power during the social stress of late pre-contact North America (AD 600-1600)

Before Europeans arrived to Eastern North America, prehistoric, indigenous peoples experienced a number of changes that culminated in the development of sedentary, maize agricultural lifeways of varying complexity. Inherent to these lifeways were several triggers of social stress including population nucleation and increase, intergroup conflict (warfare), and increased territoriality. Here, we examine whether this period of social stress co-varied with deadlier weaponry, specifically, the design of the most commonly found prehistoric archery component in late pre-contact North America: triangular stone arrow tips (TSAT). The examination of modern metal or carbon projectiles, arrows, and arrowheads has demonstrated that smaller arrow tips penetrate deeper into a target than do larger ones. We first experimentally confirm that this relationship applies to arrow tips made from stone hafted onto shafts made from wood. We then statistically assess a large sample (n = 742) of late pre-contact TSAT and show that these specimens are extraordinarily small. Thus, by miniaturizing their arrow tips, prehistoric people in Eastern North America optimized their projectile weaponry for maximum penetration and killing power in warfare and hunting. Finally, we verify that these functional advantages were selected across environmental and cultural boundaries. Thus, while we cannot and should not rule out stochastic, production economizing, or non-adaptive cultural processes as an explanation for TSAT, overall our results are consistent with the hypothesis that broad, socially stressful demographic changes in late pre-contact Eastern North America resulted in the miniaturization–and augmented lethality–of stone tools across the region

Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs

A major limitation of pulmonary delivery is that drugs can exhibit suboptimal pharmacokinetic profiles resulting from rapid elimination from the pulmonary tissue. This can lead to systemic side effects and a short duration of action. A series of dibasic dipeptides attached to the poorly lung-retentive muscarinic M3 receptor antagonist piperidin-4-yl 2-hydroxy-2,2-diphenylacetate (1) through a pH-sensitive-linking group have been evaluated. Extensive optimization resulted in 1-(((R)-2-((S)-2,6-diaminohexanamido)-3,3-dimethylbutanoyl)oxy)ethyl 4-(2-hydroxy-2,2-diphenylacetoxy)piperidine-1-carboxylate (23), which combined very good in vitro stability and very high rat lung binding. Compound 23 progressed to pharmacokinetic studies in rats, where, at 24 h post dosing in the rat lung, the total lung concentration of 23 was 31.2 μM. In addition, high levels of liberated drug 1 were still detected locally, demonstrating the benefit of this novel prodrug approach for increasing the apparent pharmacokinetic half-life of drugs in the lungs following pulmonary dosing

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe