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Background. Wide awake local anesthesia no tourniquet (WALANT) is an increasingly popular anesthetic technique used in hand surgery which uses local anesthetic and epinephrine, achieves adequate anesthesia, and eliminates the need for a tourniquet. Objective. This study compares the onset and duration of the three most commonly used concentrations of lidocaine and epinephrine for WALANT. Methodology. This was a randomized double-blind comparative study of 78 middle fingers subjected to either 1% lidocaine with 1:100,000 epinephrine, 0.5% lidocaine with 1:200,000 epinephrine or 0.25% lidocaine with 1:400,000 epinephrine. The pinprick test was used to measure onset time and anesthetic duration for the local effect and as a digital nerve block. Results. The contents of each treatment arm were as follows: Arm A: 0.25% lidocaine with 1:400,000 epinephrine, Arm B: 1% lidocaine with 1:100,000 epinephrine, and Arm C: 0.5% lidocaine with 1:200,000 epinephrine. Arm B had the shortest onset time (30.77 ± 10.39 seconds for local, 2.78 ± 0.69 minutes for digital block) followed by Arm C (38 ± 17.17 seconds for local, 4.30 ± 1.62 minutes for digital block) and Arm A (55.38 ± 18.48 seconds for local, 5.18 ± 1.46 minutes for digital block, p

Objectives: Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. Methods: Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV. Results: Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions. Conclusion: In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.

El crecimiento continuo del aviturismo por la oferta destacada de Colombia para el mercado especializado, es también resultado de la firma de los Acuerdos de Paz, cuya menguada implementación, exacerbada por la pandemia del Covid-19, conllevó a una profunda crisis sectorial. Reflexionando sobre el papel del medio ambiente durante y después de conflictos armados, se presentan diferentes perspectivas acerca del aviturismo en algunas regiones afectadas y las implicaciones para el Sur del Trapecio Amazónico como lugar destino, particularmente. El artículo introduce los estudios de turismo a un contexto local amazónico, intrincado en los estudios de conflictos socioambientales.

The SGLT2 inhibitor, Empagliflozin, is shown to exert cardioprotective effects by increasing mitochondrial ATP in a mouse model of diabetes.

Abstract Background Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to differentiate from benign viral infections. This leaves clinicians with the risk of missing a serious IBI diagnosis or inappropriately using antimicrobials in a child with a viral infection- contributing to the ongoing development of increased antimicrobial resistance. Hence, biomarkers which could aid in early detection of IBI and differentiation from viral infections are desirable. Mid-Regional pro-Adrenomedullin (MR-proADM) is a biomarker which has been associated with IBI. The aim of this systematic review was to determine its diagnostic accuracy in identifying children with IBI. Methods A strategy was devised to search online databases MEDLINE, Embase, Web of Science and Scopus for human clinical trials reporting the accuracy of MR-proADM in children. Against predesigned inclusion and exclusion criteria full texts were selected for inclusion and data extraction. True positives, false positives, true negatives and false negatives were extracted from each included study to fill 2 × 2 tables. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool methodological quality of each study was assessed. Results A total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed and four texts (totaling 1404 patients) were included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible. Conclusion There is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI. Trial registration PROSPERO CRD42018096295 .

Niemann–Pick disease type C1 (NP-C) is a prematurely lethal genetic lysosomal storage disorder with neurological and visceral pathology resulting from mutations in the NPC1 gene encoding the lysosomal transmembrane protein NPC1. There is currently no cure for NP-C, and the only disease modifying treatment, miglustat, slows disease progression but does not significantly attenuate neurological symptoms. AAV-mediated gene therapy is an attractive option for NP-C, but due to the large size of the human NPC1 gene, there may be packaging and truncation issues during vector manufacturing. One option is to reduce the size of DNA regulatory elements that are essential for gene expression, such as the promoter sequence. Here, we describe a novel small truncated endogenous NPC1 promoter that leads to high gene expression both in vitro and in vivo and compare its efficacy to other commonly used promoters. Following neonatal intracerebroventricular (ICV) injection into the CNS, this novel promoter provided optimal therapeutic efficacy compared to all other promoters including increased survival, improved behavioural phenotypes, and attenuated neuropathology in mouse models of NP-C. Taken together, we propose that this novel promoter can be extremely efficient in designing an optimised AAV9 vector for gene therapy for NP-C.

Abstract In US academic institutions, efforts often concentrate on enhancing the recruitment of students from underrepresented groups, focusing on gender and/or race. However, little attention has been paid to nondemographic forms of diversity, such as environmental worldviews (i.e., differences in the metaphysical, epistemological, and ethical beliefs that define how humans view, value, and interact with the natural world). Here, we present an exploratory measure of environmental worldview diversity among undergraduate students enrolled in natural resource‐related programs. We tested our procedure at Oregon State University, a large public land‐grant university in the United States. Many students reported metaphysical, epistemological, and/or ethical beliefs that deviate from what has been philosophically characterized as the dominant western worldview of natural resources (anthropocentric, dualistic, hierarchical, utilitarian, and mechanistic). Our results suggest that, although forestry students' environmental worldviews are in some ways more closely aligned with the dominant western worldview than other students in natural resources, generally student worldviews reflect a long‐term generational shift away from a strict resource‐commodity value orientation, as documented in the past research. Our findings highlight the importance of considering environmental worldviews as a dimension of diversity within the new generation of natural resource students. Future efforts toward understanding these levels of difference can be important assets in designing programs that appeal to a wide variety of students, ultimately helping efforts to recruit and retain a diverse pool of aspiring natural resource professionals.

Abstract Background Only a small fraction of the information available is generally used in the majority of camera-based sensing approaches for vital sign monitoring. Dedicated skin pixels, for example, fall into this category while other regions are often disregarded early in the processing chain. Methods We look at a simple processing chain for imaging where a video stream is converted to several other streams to investigate whether other image regions should also be considered. These streams are generated by mapping spatio-temporal and -spectral features of video segments and, thus, compressing the information contained in several seconds of video and encoding these in a new image. Two typical scenarios are provided as examples to study the applicability of these maps: face videos in a laboratory setting and measurements of a baby in the neonatal intensive care unit. Each measurement consists of the synchronous recording of photoplethysmography imaging (PPGI) and infrared thermography (IRT). We report the results of a visual inspection of those maps, evaluate the root mean square (RMS) contrast of foreground and background regions, and use histogram intersections as a tool for similarity measurements. Results The maps allow us to distinguish visually between pulsatile foreground objects and an image background, which is found to be a noisy pattern. Distortions in the maps could be localized and the origin could be discovered. The IRT highlights subject contours for the heart frequency band, while silhouettes show strong signals in PPGI. Reflections and shadows were found to be sources of signals and distortions. We can testify advantages for the use of near-infrared light for PPGI. Furthermore, a difference in RMS contrast for pulsatile and non-pulsatile regions could be demonstrated. Histogram intersections allowed us to differentiate between the background and foreground. Conclusions We introduced new maps for the two sensing modalities and presented an overview for three different wavelength ranges. The maps can be used as a tool for visualizing aspects of the dynamic information hidden in video streams without automation. We propose focusing on an indirect method to detect pulsatile regions by using the noisy background pattern characteristic, for example, based on the histogram approach introduced.

Abstract Background A Target Product Profile (TPP) outlines the necessary characteristics of an innovative product to address an unmet clinical need. TPPs could be used to better guide manufacturers in the development of ‘fit for purpose’ tests, thus increasing the likelihood that novel tests will progress from bench to bedside. However, there is currently no guidance on how to produce a TPP specifically for medical tests. Methods A systematic review was conducted to summarise the methods currently used to develop TPPs for medical tests, the sources used to inform these recommendations and the test characteristics for which targets are made. Database and website searches were conducted in November 2018. TPPs written in English for any medical test were included. Based on an existing framework, test characteristics were clustered into commonly recognised themes. Results Forty-four TPPs were identified, all of which focused on diagnostic tests for infectious diseases. Three core decision-making phases for developing TPPs were identified: scoping, drafting and consensus-building. Consultations with experts and the literature mostly informed the scoping and drafting of TPPs. All TPPs provided information on unmet clinical need and desirable analytical performance, and the majority specified clinical validity characteristics. Few TPPs described specifications for clinical utility, and none included cost-effectiveness. Conclusions We have identified a commonly used framework that could be beneficial for anyone interested in drafting a TPP for a medical test. Currently, key outcomes such as utility and cost-effectiveness are largely overlooked within TPPs though and we foresee this as an area for further improvement.

Abstract Background Informal caregivers report substantial burden and depressive symptoms which predict higher rates of patient institutionalization. While caregiver education interventions may reduce caregiver distress and decrease the use of long-term institutional care, evidence is mixed. Inconsistent findings across studies may be the result of reporting average treatment effects which do not account for how effects differ by participant characteristics. We apply a machine-learning approach to randomized clinical trial (RCT) data of the Helping Invested Family Members Improve Veteran’s Experiences Study (HI-FIVES) intervention to explore how intervention effects vary by caregiver and patient characteristics. Methods We used model-based recursive partitioning models. Caregivers of community-residing older adult US veterans with functional or cognitive impairment at a single VA Medical Center site were randomized to receive HI-FIVES (n = 118) vs. usual care (n = 123). The outcomes included cumulative days not in the community and caregiver depressive symptoms assessed at 12 months post intervention. Potential moderating characteristics were: veteran age, caregiver age, caregiver ethnicity and race, relationship satisfaction, caregiver burden, perceived financial strain, caregiver depressive symptoms, and patient risk score. Results The effect of HI-FIVES on days not at home was moderated by caregiver burden (p

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aβ expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.

Water quality monitoring programs commonly use the Mann-Kendall test or linear regression to identify statistically significant monotonic trends in fecal indicator bacteria concentrations (typically Escherichia coli [E. coli]). The statistical power of these tests to detect trends of different magnitudes (effect size) is rarely communicated to stakeholders, and it is unlikely they are considered when designing monitoring schedules. The statistical power for detecting trends in surface water E. coli bacteria concentrations using Mann-Kendall and linear regression at water quality monitoring sites across Texas was estimated using Monte Carlo simulation. The probability that an individual water quality monitoring site in Texas had adequate statistical power was also estimated using logistic regression. Mann-Kendall and linear regression trend tests show similar statistical power. Both tests are unlikely to achieve adequate statistical power when E. coli concentrations decrease by 20% or less over 7 years under most sampling frequencies. To adequately detect concentration decreases of 30% to 40% over 7 years, monthly sampling is required. Because many sites across Texas are sampled quarterly, monotonic trends tests will not be powerful enough to detect trends of moderate magnitudes. To better facilitate stakeholder decision-making, it is important to communicate the relative power of statistical tests and detectible magnitudes of changes. I suggest data analysts conduct power analyses to improve monitoring program designs and improve communication of trend test limitations. Software and training for water quality analysts could facilitate communication of power and effect sizes. Alternative trend assessment methods may be more reliable for describing changes in fecal indicator bacteria concentrations.

Treatments with sodium–glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin–angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model.

The silicon heterojunction solar cell (SHJ) is considered the dominant state-of-the-art silicon solar cell technology due to its excellent passivation quality and high efficiency. However, SHJ’s light management performance is limited by its narrow optical absorption in long-wave near-infrared (NIR) due to the front, and back tin-doped indium oxide (ITO) layer’s free carrier absorption and reflection losses. Despite the light-trapping efficiency (LTE) schemes adopted by SHJ in terms of back surface texturing, the previous investigations highlighted the ITO layer as a reason for an essential long-wavelength light loss mechanism in SHJ solar cells. In this study, we propose the use of Molybdenum disulfide (MoS2) as a way of improving back-reflection in SHJ. The text presents simulations of the optical response in the backside of the SHJ applying the Monte-Carlo raytracing method with a web-based Sunsolve high-precision raytracing tool. The solar cells’ electrical parameters were also resolved using the standard electrical equivalent circuit model provided by Sunsolve. The proposed structure geometry slightly improved the SHJ cell optical current density by ~0.37% (rel.), and hence efficiency (η) by about 0.4% (rel.). The SHJ cell efficiency improved by 21.68% after applying thinner back ITO of about 30 nm overlayed on ~1 nm MoS2. The efficiency improvement following the application of MoS2 is tentatively attributed to the increased NIR absorption in the silicon bulk due to the light constructive interface with the backside components, namely silver (Ag) and ITO. Study outcomes showed that improved SHJ efficiency could be further optimized by addressing front cell components, mainly front ITO and MoS2 contact engineering.

Abstract Ecosystems are changing in complex and unpredictable ways, and analysis of these changes is facilitated by coordinated, long‐term research. Meeting diverse societal needs requires an understanding of what populations and communities will be dominant in 20, 50, and 100 yr. This paper is a product of a synthesis effort of the U.S. National Science Foundation funded Long‐Term Ecological Research (LTER) network addressing the LTER core research area of populations and communities. This analysis revealed that each LTER site had at least one compelling story about what their site would look like in 50 or 100 yr. As the stories were prepared, themes emerged, and the stories were grouped into papers along five themes for this special issue: state change, connectivity, resilience, time lags, and cascading effects. This paper addresses the resilience theme and includes stories from the Baltimore (urban), Hubbard Brook (northern hardwood forest), Andrews (temperate rain forest), Moorea (coral reef), Cedar Creek (grassland), and North Temperate Lakes (lakes) sites. The concept of resilience (the capacity of a system to maintain structure and processes in the face of disturbance) is an old topic that has seen a resurgence of interest as the nature and extent of global environmental change have intensified. The stories we present here show the power of long‐term manipulation experiments (Cedar Creek), the value of long‐term monitoring of forests in both natural (Andrews, Hubbard Brook) and urban settings (Baltimore), and insights that can be gained from modeling and/or experimental approaches paired with long‐term observations (North Temperate Lakes, Moorea). Three main conclusions emerge from the analysis: (1) Resilience research has matured over the past 40 yr of the LTER program; (2) there are many examples of high resilience among the ecosystems in the LTER network; (3) there are also many warning signs of declining resilience of the ecosystems we study. These stories highlight the need for long‐term studies to address this complex topic and show how the diversity of sites within the LTER network facilitates the emergence of overarching concepts about this important driver of ecosystem structure, function, services, and futures.

In a response to a Formal Comment critiquing their model for classifying individualized glucose patterns into glucotypes, these authors stand by their results and conclusions, which can be reproduced using their publicly available data, and maintain that improved algorithms for analyzing CGM data will continue to emerge and enrich the field.

We consider the role information energy can play as a source of dark energy. Firstly, we note that if stars and structure had not formed in the universe, elemental bits of information describing the attributes of particles would have exhibited properties similar to the cosmological constant. The Landauer equivalent energy of such elemental bits would be defined in form and value identical to the characteristic energy of the cosmological constant. However, with the formation of stars and structure, stellar heated gas and dust now provide the dominant contribution to information energy with the characteristics of a dynamic, transitional, dark energy. At low redshift, z < ~1.35, this dark energy emulates the cosmological constant with a near-constant energy density, w = −1.03 ± 0.05, and an energy total similar to the mc2 of the universe’s ∼1053 kg of baryons. At earlier times, z > ~1.35, information energy was phantom, differing from the cosmological constant, Λ, with a CPL parameter difference of ∆wo = −0.03 ± 0.05 and ∆wa = −0.79 ± 0.08, values sufficient to account for the H0 tension. Information dark energy agrees with most phenomena as well as Λ, while exhibiting characteristics that resolve many tensions and problems of ΛCDM: the cosmological constant problem; the cosmological coincidence problem; the H0 tension, and the σ8 tension. As this proposed dark energy source is not usually considered, we identify the expected signature in H(a) that will enable the role of information dark energy to be falsified by experimental observation.

The unprecedented development of perovskite-silicon (PSC-Si) tandem solar cells in the last five years has been hindered by several challenges towards industrialization, which require further research. The combination of the low cost of perovskite and legacy silicon solar cells serve as primary drivers for PSC-Si tandem solar cell improvement. For the perovskite top-cell, the utmost concern reported in the literature is perovskite instability. Hence, proposed physical loss mechanisms for intrinsic and extrinsic instability as triggering mechanisms for hysteresis, ion segregation, and trap states, along with the latest proposed mitigation strategies in terms of stability engineering, are discussed. The silicon bottom cell, being a mature technology, is currently facing bottleneck challenges to achieve power conversion efficiencies (PCE) greater than 26.7%, which requires more understanding in the context of light management and passivation technologies. Finally, for large-scale industrialization of the PSC-Si tandem solar cell, the promising silicon wafer thinning, and large-scale film deposition technologies could cause a shift and align with a more affordable and flexible roll-to-roll PSC-Si technology. Therefore, this review aims to provide deliberate guidance on critical fundamental issues and configuration factors in current PSC-Si tandem technologies towards large-scale industrialization. to meet the 2031 PSC-Si Tandem road maps market target.

Simulation is a valid pedagogical tool used to teach students, observe student clinical skills, and to assess clinical competencies. During the COVID-19 pandemic, a lack of medical speech-language pathology placements required graduate programs to re-examine clinical training. Simulation has proven useful in providing an alternative and safe learning modality. Standardized patients, which are one simulation modality, provide increased standardization and higher fidelity than medical manikins. This is particularly true in the context of both student learning and demonstration of clinical communication skills (CCS) within a simulated learning environment where the simulated patient can interact authentically with the student clinician. CCS are important because they can lead to better treatment outcomes and strengthen the therapeutic alliance. The purpose of this study was to evaluate the evidence for a CCS training in the context of a speaking valve trial with a standardized tracheostomy patient. Results showed that students are demonstrating emerging skills or have already developed CCS in this context. Student questionnaire ratings suggest that this simulation was helpful to their learning as it provided a safe environment for them to practice valuable clinical skills. Simulation appears to be a viable modality to use when training CSD students to improve their CCS.

Es raro encontrar un ateísmo militante en la literatura inglesa de cierta calidad; hoy en día en el campo de la narrativa de ficción la religión está más ausente que satirizado o atacada. Sin embargo, hay tres familias de narración que el autor explora: primero, las novelas y los novelistas que parecen inicialmente ateos (I. McEwan, R. Ford), en segundo lugar, una familia entera de ficción que es abiertamente espiritual sin ser religiosa (Y. Mantel, D. Copland); en tercer lugar, algunos novelistas que tratan de contrarrestar el ateísmo por medio de su escritura (F. O’Connor, J. R. Tolkien). Este artículo ofrece algunas reflexiones teológicas sobre la evangelización, porque «una cierta apertura a la posibilidad de misterio» permanece como una característica de la literatura.

Keeping older adults over 65 years of age socially included is a challenge still being addressed. Older adults’ views of feeling socially included and avoiding social exclusion and isolation are individual. This ethnographic study examines the views participants have about feeling socially included in their community when attending a community healthy ageing program in Brisbane, Australia. Niche studies of social inclusion in particular settings are valuable as alternatives to large studies, because of the diversity they offer in finding out what older adults identify as making them feel socially included. Data was collected by participant observation and focus groups, with supporting member checks and brief follow-up interviews. The main finding was that the program encouraged program participants to view themselves as feeling socially mobile, mainly because of access to information resources and to the human networks the program offered. Five concerns dominated the analysis where participants felt exclusion and isolation was an issue: transport, housing and living arrangements, health, crime and personal safety, and technology use. This paper contributes to the understanding of views of social inclusion in a particular setting and brings an awareness of the types of solutions a community program can bring to older adults to help keep them socially included. Keywords: ethnography, social exclusion, social inclusion, social isolation, older adults

The purpose of this investigation was 2-fold: (1) to investigate the effects of a translational 12-week community-based multimodal exercise program on quality of life (QoL) in breast cancer survivors (BCS) and (2) to examine the influence of a start delay on physical function and QoL in BCS. Fifty-two female BCS completed a 12-week program consisting of 90-minute supervised exercise sessions at a frequency of 2 supervised sessions per week. Exercise sessions consisted of three 30-minute components: (1) aerobic conditioning, (2) resistance exercise training, and (3) balance and flexibility training. Significant ( P < .05) improvements in QoL were identified post-program completion. Cohort stratification comparison between the early start (1 year since completion of oncologic treatment) revealed no significant ( P > .05) differences between the early start and late start groups on improvements in physical function. Regarding the influence of start delay on QoL, the early start group showed significant ( P < .05) improvement in emotional well-being. No other significant differences in improvement in QoL were detected between the early start and late start groups. Regardless of start delay, meaningful improvements in physical function and QoL were found after completing the community-based multimodal exercise program. Early participation in community-based exercise programming may benefit BCS’ emotional well-being compared to later participation.

Conservation triage, as a concept, seems to have been born from analogizing circumstances that characterize conservation with triage, as the concept applies to emergency medicine. Careful consideration—facilitated through the aid of formal argumentation—demonstrates the critical limitations of the analogy. Those limitations reveal how the concept of conservation triage falls short. For example, medical triage presupposes that resources available for an emergency are limited and fixed. By contrast, the resources available for conservation are not fixed. Moreover, the ethics of prioritization in medical triage is characterized by there being universal agreement on the moral value of the patients. However, in conservation there is not universal agreement on the value of various objects of conservation concern. The looming importance of those features of conservation—disputed values and unfixed resources—make conservation triage a largely un-useful concept.

The 2013 cosmology results from the European Space Agency Planck spacecraft provide new limits to the dark energy equation of state parameter. Here we show that Holographic Dark Information Energy (HDIE), a dynamic dark energy model, achieves an optimal fit to the published datasets where Planck data is combined with other astrophysical measurements. HDIE uses Landauer’s principle to account for dark energy by the energy equivalent of information, or entropy, of stellar heated gas and dust. Combining Landauer’s principle with the Holographic principle yields an equation of state parameter determined solely by star formation history, effectively solving the “cosmic coincidence problem”. While HDIE mimics a cosmological constant at low red-shifts, z < 1, the small difference from a cosmological constant expected at higher red-shifts will only be resolved by the next generation of dark energy instrumentation. The HDIE model is shown to provide a viable alternative to the main cosmological constant/vacuum energy and scalar field/ quintessence explanations.

Clinical simulations, in a variety of forms, is a viable educational tool, allowing CSD students to acquire professional competencies and skills. Simucase is a computer-based simulation program designed for this objective. The goal of this study was to determine what elements of simulation engagement predicted success on a student's overall ability to make the correct recommendation for patient care, and what those predictors can tell us about how students navigate computer-based simulations. The data set used for this study comprised 149 graduate students in communication sciences and disorders (CSD) programs who completed a computer-based assessment simulation for a patient with aphasia. To determine which areas of the simulation predicted student success, a logistic regression was performed to determine which of the 12 types of decision points offered predictive data for making the correct final recommendation. The 12 types of decisions used comprised case history, collaborator, assessment, and diagnosis sections with reflective, acceptable, and rejected options in each. Results indicate that student patterns of case engagement can predict overall case success. The overall model was significant and individual predictors were significantly responsible for predicting which students would choose the correct outcome at the end of the case. This study revealed that students who engage in more careful navigation of preliminary assessment steps such as case history and collaborators were more likely to reach the correct recommendation at the end of the case. This finding has implications for the implementation of computer-based simulations for clinical education.

Apple production in the UK is worth over £100 million per annum and this production is heavily dependent on insect pollination. Despite its importance, it is not clear which insect pollinators carry out the majority of this pollination. Furthermore, it is unknown whether current UK apple production, in terms of both yield and quality, suffers pollination deficits and whether production value could be increased through effective management of pollination services. The present study set out to address some of these unknowns and showed that solitary bee activity is high in orchards and that they could be making a valuable contribution to pollination. Furthermore, fruit set and apple seed number were found to be suffering potential pollination deficits although these were not reflected in apple quality. Deficits could be addressed through orchard management practices to improve the abundance and diversity of wild pollinators. Such practices include provision of additional floral resources and nesting habitats as well as preservation of semi-natural areas. The cost effectiveness of such strategies would need to be understood taking into account the potential gains to the apple industry.

Several models have been proposed to explain the dark energy that is causing universe expansion to accelerate. Here the acceleration predicted by the Holographic Dark Information Energy (HDIE) model is compared to the acceleration that would be produced by a cosmological constant. While identical to a cosmological constant at low redshifts, z < 1, the HDIE model results in smaller Hubble parameter values at higher redshifts, z > 1, reaching a maximum difference of 2.6 ± 0.5% around z ~ 1.7. The next generation of dark energy measurements, both those scheduled to be made in space (ESA’s Euclid and NASA’s WFIRST missions) and those to be made on the ground (BigBOSS, LSST and Dark Energy Survey), should be capable of determining whether such a difference exists or not. In addition a computer simulation thought experiment is used to show that the algorithmic entropy of the universe always increases because the extra states produced by the accelerating expansion compensate for the loss of entropy from star formation.

INTRODUCTION: water related diseases constitute a significant proportion of the burden of disease in Kenya. Water, sanitation and hygiene (WASH) programs are in operation nation-wide to address these challenges. This study evaluated the impact of the Sombeza Water and Sanitation Improvement Program (SWASIP) in Coast Province, Kenya. METHODS: this study is a cluster randomized, follow-up evaluation that compared baseline (2007) to follow-up (2013) indicators from 250 households. Twenty-five villages were selected with probability proportional to size sampling, and ten households were selected randomly from each village. Follow-up data were collected by in-person interviews using pre-tested questionnaires, and analyzed to compare indicators collected at baseline. Cross-sectional results from the follow-up data were also reported. RESULTS: statistically significant improvements from baseline were observed in the proportions of respondents with latrine access at home, who washed their hands after defecation, who treated their household drinking water and the average time to collect water in the dry season. However, this study also observed significant decreases in the proportion of respondents who washed their hands before preparing their food, or feeding their children, and after attending to a child who has defecated. The analysis also revealed a knowledge-behavior gap in WASH behaviors. CONCLUSION: SWASIP contributed to improvements from baseline, but further progress still needs to be seen. The findings challenge the assumption that providing infrastructure and knowledge will result in behavior change. Further understanding of specific, non-knowledge predictors of WASH related behavior is needed.

IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh) increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A) to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation), Bay11-7082 (inhibitor of IkBα phosphorylation), Hemicholinium-3 (HCh-3) (choline uptake blocker), and Tiotropium bromide (Spiriva®) (anticholinergic drug) was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

Developmental disorders (DD), including autism spectrum disorder (ASD) and intellectual disability (ID), are a common group of clinical manifestations caused by a variety of genetic abnormalities. Genetic testing, including chromosomal microarray (CMA), plays an important role in diagnosing these conditions, but CMA can be limited by incomplete coverage of genetic abnormalities and lack of guidance for conditions rarely seen by treating physicians.We conducted a longitudinal, randomized controlled trial investigating the impact of a higher resolution 2.8 million (MM) probe-CMA test on the quality of care delivered by practicing general pediatricians and specialists. To overcome the twin problems of finding an adequate sample size of multiple rare conditions and under/incorrect diagnoses, we used standardized simulated patients known as CPVs. Physicians, randomized into control and intervention groups, cared for the CPV pediatric patients with DD/ASD/ID. Care responses were scored against evidence-based criteria. In round one, participants could order diagnostic tests including existing CMA tests. In round two, intervention physicians could order the 2.8MM probe-CMA test. Outcome measures included overall quality of care and quality of the diagnosis and treatment plan.Physicians ordering CMA testing had 5.43% (p

Landauer’s principle and the Holographic principle are used to derive the holographic information energy contribution to the Universe. Information energy density has increased with star formation until sufficient to start accelerating the expansion of the universe. The resulting reduction in the rate of star formation due to the accelerated expansion may provide a feedback that limits the information energy density to a constant level. The characteristics of the universe’s holographic information energy then closely match those required to explain dark energy and also answer the cosmic coincidence problem. Furthermore the era of acceleration will be clearly limited in time.

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

Arginine vasopressin (AVP) is synthesised in magnocellular neurons (MCNs) of supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. In response to the hyperosmotic stressors of dehydration (complete fluid deprivation, DH) or salt loading (drinking 2% salt solution, SL), AVP synthesis increases in MCNs, which over-burdens the protein folding machinery in the endoplasmic reticulum (ER). ER stress and the unfolded protein response (UPR) are signaling pathways that improve ER function in response to the accumulation of misfold/unfold protein. We asked whether an ER stress response was activated in the SON and PVN of DH and SL rats. We observed increased mRNA expression for the immunoglobulin heavy chain binding protein (BiP), activating transcription factor 4 (Atf4), C/EBP-homologous protein (Chop), and cAMP responsive element binding protein 3 like 1 (Creb3l1) in both SON and PVN of DH and SL rats. Although we found no changes in the splicing pattern of X box-binding protein 1 (Xbp1), an increase in the level of the unspliced form of Xbp1 (Xbp1U) was observed in DH and SL rats. CREB3L1, a novel ER stress inducer, has been shown to be activated by ER stress to regulate the expression of target genes. We have previously shown that CREB3L1 is a transcriptional regulator of the AVP gene; however, a role for CREB3L1 in the response to ER stress has yet to be investigated in MCNs. Here, we used lentiviral vectors to introduce a dominant negative form of CREB3L1 (CREB3L1DN) in the rat SON. Expression of CREB3L1DN in the SON decreased Chop and Xbp1U mRNA levels, but not BiP and Atf4 transcript expression. CREB3L1 is thus implicated as a transcriptional mediator of the ER stress response in the osmotically stimulated SON.

Self-enucleation is a very unusual form of self-mutilation directly linked to mental illness. In this case we present a 26-year-old schizophrenic patient who attempted to enucleate his eye with a rollerball pen. Antipsychotic therapy and emergency surgery saved the patient eye and emphasize the importance of quick response and good collaboration between psychiatric and ophthalmic teams.

A total of 100 Sporisorium scitamineum isolates were investigated by inter simple sequence repeat (ISSR) and single primer-sequence related amplified polymorphism (SP-SRAP) markers. These isolates were clearly assorted into three distinct clusters regardless of method used: either cluster analysis or by principal component analysis (PCA) of the ISSR, SP-SRAP, or ISSR + SP-SRAP data set. The total gene diversity (Ht) and gene diversity between subpopulations (Hs) were estimated to be 0.34 to 0.38 and 0.22 to 0.29, respectively, by analyzing separately the ISSR and SP-SRAP data sets, and to be 0.26–0.36 by analyzing ISSR + SP-SRAP data set. The gene diversity attributable to differentiation among populations (Gst) was estimated to be 0.35 and 0.22, and the gene flow (Nm) was 0.94 and 1.78, respectively, when analyzing separately ISSR and SP-SRAP data set, and was 0.27 and 1.33, respectively, when analyzing ISSR + SP-SRAP data set. Our study showed that there is considerable genetic variation in the analyzed 100 isolates, and the environmental heterogeneity has played an important role for this observed high degree of variation. The genetic differentiation of sugarcane smut fungus depends to a large extent on the heterogeneity of their habitats and is the result of long-term adaptations of pathogens to their ecological environments.

This paper explores a conflict a pre-service physics teacher experienced while completing a teaching practicum at a religious high school that supported creationism. As a result of the conflict, the pre-service teacher was scapegoated by the staff and students at the school. An analysis of the projective dynamics involved in this conflict are explored including scapegoating, psychic inflation, fanaticism for science, and what was constellated in the pre-service teacher's personal, familial, and cultural unconscious. In examining the pre-service teacher's unconscious, it will be suggested that religion is part of the pre-service teacher's repressed shadow and the cooperating/mentor teacher's religious projections helped to constellate this shadow element. By examining the conflicts that arise between pre-service teachers and their cooperating teachers as a result of psychodynamics and differing worldviews, educators can begin to understand how analytical psychology may be applied so that such conflicts may be depotentiated in the future.

Noise can compromise the extraction of some fundamental and important features from biomedical signals and hence prohibit accurate analysis of these signals. Baseline wander in electrocardiogram (ECG) signals is one such example, which can be caused by factors such as respiration, variations in electrode impedance, and excessive body movements. Unless baseline wander is effectively removed, the accuracy of any feature extracted from the ECG, such as timing and duration of the ST-segment, is compromised. This paper approaches this filtering task from a novel standpoint by assuming that the ECG baseline wander comes from an independent and unknown source. The technique utilizes a hierarchical method including a blind source separation (BSS) step, in particular independent component analysis, to eliminate the effect of the baseline wander. We examine the specifics of the components causing the baseline wander and the factors that affect the separation process. Experimental results reveal the superiority of the proposed algorithm in removing the baseline wander.

Insulin-like growth factor 1 (IGF-1) has been shown to be associated with fertility, growth and development in cattle. The aim of this study was to 1) identify novel single nucleotide polymorphisms (SNPs) in the bovine IGF-1 gene and alongside previously identified SNPs 2) determine their association with traits of economic importance in Holstein-Friesian dairy cattle. Nine novel SNPs were identified across a panel of 22 beef and dairy cattle by sequence analysis of the 5’ promoter, intronic and 3’ regulatory regions, encompassing ~ 5 kb of the IGF-1 gene. Genotyping and associations with daughter performance for milk production, fertility, survival and measures of body size were undertaken on 848 Holstein-Friesian AI sires. Using multiple regression analysis nominal associations (P