Caffeic acid protects against IL-1β-induced inflammatory responses and cartilage degradation in articular chondrocytes.
Osteoarthritis (OA) is a common articular disease that features cartilage loss and destruction. It has been confirmed that inflammation plays major roles in the progression of osteoarthritis. Caffeic acid (CA), a key dietary nutrient commonly found in coffee, has shown its anti-inflammatory properties in various inflammation diseases. However, the effects of CA in osteoarthritis remain explored. Here we investigated the effects of CA on IL-1β induced increased expression of inflammatory factors as well as the degradation of Collagen II and aggrecan in rat chondrocytes. CA prevented the cartilage damage induced by IL-1β in vivo organ culture of articular cartilage. Besides, the IL-1β induced increased production of inflammation factors such as iNOS and COX2 could be inhibited by CA. Additionally, CA could also suppress IL-1β induced expression of cartilage matrix catabolic enzymes such as ADAMTS5 and MMPs. Moreover, CA could prevent IL-1β induced degradation of Collagen II and aggrecan in chondrocytes. Furthermore, CA inhibited NF-κB activity and the activation of JNK pathway. This study reveals that CA inhibits IL-1β induced inflammation responses through suppression of NF-κB and MAPK related JNK signaling pathways. These results demonstrate that CA may provide new avenues for osteoarthritis treatment in future.


The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms.
The 25-kb linear plasmid lp25 and one of the 28-kb linear plasmids (lp28-1) are required for experimental infection in Borrelia burgdorferi, the etiologic agent of Lyme disease. The loss of these plasmids either eliminates infectivity (lp25) or significantly increases the 50% infective dose during a 2-week infection period (lp28-1). This study assessed the kinetics of bacterial dissemination in C3H/HeN mice infected with B. burgdorferi lacking either lp25 or lp28-1, as well as their wild-type parent, and tracked the development of specific borrelial antibodies over a 3-week period. The results indicated that the wild type and the lp28-1(-) strains were able to disseminate throughout the host, whereas the lp25(-) strain was cleared within 48 h of inoculation. While the wild-type B. burgdorferi persisted in tissues for the duration of the study, the lp28-1(-) mutant began clearing at day 8, with no detectable bacteria present by day 18. As expected, the wild-type strain persisted in C3H/HeN mice despite a strong humoral response; however, the lp28-1(-) mutant was cleared coincidently with the development of a modest immunoglobulin M response. The lp28-1(-) mutant was able to disseminate and persist in C3H-scid mice at a level indistinguishable from that of wild-type cells, confirming that acquired immunity was required for clearance in C3H/HeN mice. Thus, within an immunocompetent host, lp28-1-encoded proteins are not required for dissemination but are essential for persistence associated with Lyme borreliosis.


A comparison of psychological functioning in women at different stages of in vitro fertilization treatment using the mean affect adjective check list.
The objectives were to identify the stage/s of IVF treatment where a woman is most vulnerable to psychological stress, and to assess the Mean Affect Adjective Check List (MAACL) as a measure of psychological functioning during IVF treatment, which has hitherto not been reported. Thirty-seven women undergoing IVF treatment according to the long protocol of controlled ovarian stimulation completed the MAACL questionnaire at the following stages: (a) before treatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). Apart from anxiety scores for visit 2, the hostility, depression, and state anxiety scores for visit 3 were higher than the corresponding scores for visits 1 and 2 (P < 0.001). Anxiety scores for visits 2 and 3 were similar. Psychological counseling should be targeted at women after embryo transfer and leading up to the pregnancy test. The MAACL is a useful method for measuring psychological stress in women during IVF treatment.


Structure of ribose 5-phosphate isomerase from the probiotic bacterium Lactobacillus salivarius UCC118.
The structure of ribose 5-phosphate isomerase from the probiotic bacterium Lactobacillus salivarius UCC188 has been determined at 1.72 Å resolution. The structure was solved by molecular replacement, which identified the functional homodimer in the asymmetric unit. Despite only showing 57% sequence identity to its closest homologue, the structure adopted the typical α and β D-ribose 5-phosphate isomerase fold. Comparison to other related structures revealed high homology in the active site, allowing a model of the substrate-bound protein to be proposed. The determination of the structure was expedited by the use of in situ crystallization-plate screening on beamline I04-1 at Diamond Light Source to identify well diffracting protein crystals prior to routine cryocrystallography.


Sensorimotor control during peripheral muscle vibration: an experimental study.
The aims of this study were to determine whether the application of vibration on a postural lower limb muscle altered the sensorimotor control of its joint as measured by isometric force production parameters and to compare present findings with previous work conducted on trunk muscle. Twenty healthy adults were asked to reproduce submaximal isometric plantar flexion under 3 different conditions: no vibration and vibration frequencies of 30 and 80 Hz on the soleus muscle. Time to peak torque, variable error, as well as constant error and absolute error in peak torque were calculated and compared across conditions. Under vibration, participants were significantly less accurate in the force reproduction task, as they mainly undershot the target torque. Applying an 80-Hz vibration resulted in a significantly higher negative constant error than lower-frequency vibration (30 Hz) or no-vibration condition. Decreases in isometric force production accuracy under vibration influence were also observed in a previous study conducted on trunk muscle. However, no difference in constant error was found between 30- and 80-Hz vibration conditions. The results suggest that acute soleus muscle vibration interferes with plantar flexion torque generation by distorting proprioceptive information, leading to decreases in accuracy of a force reproduction task. Similar results in an isometric trunk extension force reproduction task were found with vibration applied on erector spinae muscle. However, high-frequency vibration applied on soleus muscle elicited higher force reproduction errors than low-frequency stimulation.


Patterns of morbidity and multimorbidity associated with early and late readmissions in an Australian regional health service.
To describe morbidity and multimorbidity patterns among adults readmitted to an Australian regional health service, in terms of occurrence of the same and different morbidities at index admission and readmission. This cohort study used hospital admissions data for patients admitted between 1 July 2014 and 30 June 2016 to estimate proportions of unplanned readmissions ('early' within 30 days and 'late' within 1-6 months) with the same and different morbidities as the index admission. Readmission rates were estimated by selected sociodemographic, admission and diagnostic characteristics. The majority of early and late readmissions were in different diagnostic groups and for different primary morbidities to the index admission. Only 38.8% of readmissions were in the same major diagnostic group as the index admission and 18.4% in the same Adjacent Diagnosis-Related Group. Twenty one percent of admitted patients were readmitted within six months, with this increasing to 35.3% among multimorbid patients. With increasing prevalence of multimorbidity, particularly among those at increased risk of readmission, it is essential to step away from a single disease focus in the design of both hospital avoidance and chronic disease management programmes. Holistic interventions and strategies that address multiple chronic conditions are required.


Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis.
Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.


Live imaging of chronic inflammation caused by mutation of zebrafish Hai1.
The hallmark of chronic inflammation is the infiltration and persistence of leukocytes within inflamed tissue. Here, we describe the first zebrafish chronic inflammation mutant identified in an insertional mutagenesis screen for mutants that exhibit abnormal tissue distribution of neutrophils. We identified a mutant line with an insertion in the Hepatocyte growth factor activator inhibitor 1 gene (hai1; also known as Spint1) that showed accumulation of neutrophils in the fin. The mutant embryos exhibited inflammation in areas of epidermal hyperproliferation that was rescued by knock-down of the type II transmembrane serine protease Matriptase 1 (also known as St14), suggesting a novel role for Hai1-Matriptase 1 pathway in regulating inflammation. Using time-lapse microscopy of mutant embryos that express GFP from a neutrophil-specific promoter, we found that individual neutrophils in inflamed tissue displayed random motility characterized by periods of pausing alternating with periods of motility. During periods of persistent movement the cells were highly polarized, while the pausing modes were characterized by a loss of cell polarity. In contrast to responses to acute injury, neutrophils did not exhibit clear retrograde chemotaxis or resolution of inflammation in the mutant. These findings illustrate the utility of zebrafish as a new model system to study chronic inflammation and to visualize immune responses with high resolution in vivo.


The chronic indwelling catheter and urinary infection in long-term-care facility residents.
From 5% to 10% of residents of long-term-care facilities have urinary drainage managed with chronic indwelling catheters. These residents are always bacteriuric, usually with a complex microbiological flora of two to five organisms and a biofilm on the catheter that may contribute to obstruction. Residents with chronic indwelling catheters have increased morbidity from urinary infection compared to bacteriuric residents without chronic catheters. The most effective means to prevent infection is limitation of chronic indwelling catheter use. While appropriate catheter care and infection control precautions are recommended in managing these patients, the impact of these practices on the occurrence of urinary infection or prevention of symptomatic episodes has not been evaluated. Symptomatic infection can likely be prevented by attention to catheter care, including early recognition and replacement of obstructed catheters and prevention of catheter trauma. Appropriate use of prophylactic antimicrobial therapy prior to invasive genitourinary procedures is also necessary. Asymptomatic bacteriuria should not be treated. When symptomatic episodes occur, patients should be evaluated clinically and microbiologically and treated with appropriate antimicrobial therapy. Further technological advances in catheter material and urine drainage will be needed to have a substantial impact on the frequency of urinary infection with chronic catheter use.


Compared to men, women view professional advancement as equally attainable, but less desirable.
Women are underrepresented in most high-level positions in organizations. Though a great deal of research has provided evidence that bias and discrimination give rise to and perpetuate this gender disparity, in the current research we explore another explanation: men and women view professional advancement differently, and their views affect their decisions to climb the corporate ladder (or not). In studies 1 and 2, when asked to list their core goals in life, women listed more life goals overall than men, and a smaller proportion of their goals related to achieving power at work. In studies 3 and 4, compared to men, women viewed high-level positions as less desirable yet equally attainable. In studies 5-7, when faced with the possibility of receiving a promotion at their current place of employment or obtaining a high-power position after graduating from college, women and men anticipated similar levels of positive outcomes (e.g., prestige and money), but women anticipated more negative outcomes (e.g., conflict and tradeoffs). In these studies, women associated high-level positions with conflict, which explained the relationship between gender and the desirability of professional advancement. Finally, in studies 8 and 9, men and women alike rated power as one of the main consequences of professional advancement. Our findings reveal that men and women have different perceptions of what the experience of holding a high-level position will be like, with meaningful implications for the perpetuation of the gender disparity that exists at the top of organizational hierarchies.


IEEE Committee on Man and Radiation--COMAR technical information statement radiofrequency safety and utility Smart Meters.
This Technical Information Statement describes Smart Meter technology as used with modern electric power metering systems and focuses on the radio frequency (RF) emissions associated with their operation relative to human RF exposure limits. Smart Meters typically employ low power (-1 W or less) transmitters that wirelessly send electric energy usage data to the utility company several times per day in the form of brief, pulsed emissions in the unlicensed frequency bands of 902-928 MHz and 2.4-2.48 GHz or on other nearby frequencies. Most Smart Meters operate as wireless mesh networks where each Smart Meter can communicate with other neighboring meters to relay data to a data collection point in the region. This communication process includes RF emissions from Smart Meters representing energy usage as well as the relaying of data from other meters and emissions associated with maintaining the meter's hierarchy within the wireless network. As a consequence, most Smart Meters emit RF pulses throughout the day, more at certain times and less at others. However, the duty cycle associated with all of these emissions is very small, typically less than 1%, and most of the time far less than 1%, meaning that most Smart Meters actually transmit RF fields for only a few minutes per day at most. The low peak power of Smart Meters and the very low duty cycles lead to the fact that accessible RF fields near Smart Meters are far below both U.S. and international RF safety limits whether judged on the basis of instantaneous peak power densities or time-averaged exposures. This conclusion holds for Smart Meters alone or installed in large banks of meters.


Myzobdella platensis (Hirundinida: Piscicolidae) is true parasite of blue crabs (Crustacea: Portunidae).
Leeches exhibit a marked scope of diversity, including different kinds of symbiosis. The aim of the present study was to demonstrate through biochemical and histological analysis that a species of piscicolid leech, Myzobdella platensis, is a true parasite of blue crabs, feeding on their hemolymph and using them as a site for cocoon deposition. In a total of 48 blue crabs collected on October 2007 at 3 sites of the São Vicente Estuary, 12 specimens were infested with leeches. Callinectes bocourti (n = 7) was the most infested species with leeches and cocoons; it was chosen for biochemical and histological assays. The immunoblotting assays showed a positive reaction of the proteins in the intestinal samples of leeches collected from crabs using antihemocyanin polyclonal antibody of Ampullaria canaliculata. In addition, leech intestinal samples were recognized by antihemolymph polyclonal antibody of nonparasitized blue crabs. Histological sections of leech gut showed hemocytes and a granular matrix similar to those found in crab blood vessels. Collectively, this evidence strongly suggests a parasitic interaction between the leech M. platensis and the blue crab C. bocourti, in which the former utilizes the latter as a site for cocoon deposition and possibly for dispersal similar to that proposed for Myzobdella lugubris in Callinectes sapidus in North America.


Realistic 3D coherent transfer function inverse filtering of complex fields.
We present a novel technique for three-dimensional (3D) image processing of complex fields. It consists in inverting the coherent image formation by filtering the complex spectrum with a realistic 3D coherent transfer function (CTF) of a high-NA digital holographic microscope. By combining scattering theory and signal processing, the method is demonstrated to yield the reconstruction of a scattering object field. Experimental reconstructions in phase and amplitude are presented under non-design imaging conditions. The suggested technique is best suited for an implementation in high-resolution diffraction tomography based on sample or illumination rotation.


Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats.
A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.


Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates.
The breast epithelium has two major compartments, luminal and basal cells, that are established and maintained by poorly understood mechanisms. The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown. We show that in primary human breast epithelial cells, maintenance of basal cell characteristics depends on continued expression of the p63 isoform, ΔNp63, which is expressed in the basal compartment. Forced expression of ΔNp63 in purified luminal cells confers a basal phenotype. Notch signaling downmodulates ΔNp63 expression and mimics ΔNp63 depletion, whereas forced expression of ΔNp63 partially counteracts the effects of Notch. Consistent with Notch activation specifying luminal cell fate in the mammary gland, Notch signaling activity is specifically detected in mice at sites of pubertal ductal morphogenesis where luminal cell fate is determined. Basal cells in which Notch signaling is active show decreased p63 expression. Both constitutive expression of ΔNp63 and ablation of Notch signaling are incompatible with luminal cell fate. Thus, the balance between basal and luminal cell compartments of the breast is regulated by antagonistic functions of ΔNp63 and Notch.


Genomics of Three New Bacteriophages Useful in the Biocontrol of Salmonella.
Non-typhoid Salmonella is the principal pathogen related to food-borne diseases throughout the world. Widespread antibiotic resistance has adversely affected human health and has encouraged the search for alternative antimicrobial agents. The advances in bacteriophage therapy highlight their use in controlling a broad spectrum of food-borne pathogens. One requirement for the use of bacteriophages as antibacterials is the characterization of their genomes. In this work, complete genome sequencing and molecular analyses were carried out for three new virulent Salmonella-specific bacteriophages (UAB_Phi20, UAB_Phi78, and UAB_Phi87) able to infect a broad range of Salmonella strains. Sequence analysis of the genomes of UAB_Phi20, UAB_Phi78, and UAB_Phi87 bacteriophages did not evidence the presence of known virulence-associated and antibiotic resistance genes, and potential immunoreactive food allergens. The UAB_Phi20 genome comprised 41,809 base pairs with 80 open reading frames (ORFs); 24 of them with assigned function. Genome sequence showed a high homology of UAB_Phi20 with Salmonella bacteriophage P22 and other P22likeviruses genus of the Podoviridae family, including ST64T and ST104. The DNA of UAB_Phi78 contained 44,110 bp including direct terminal repeats (DTR) of 179 bp and 58 putative ORFs were predicted and 20 were assigned function. This bacteriophage was assigned to the SP6likeviruses genus of the Podoviridae family based on its high similarity not only with SP6 but also with the K1-5, K1E, and K1F bacteriophages, all of which infect Escherichia coli. The UAB_Phi87 genome sequence consisted of 87,669 bp with terminal direct repeats of 608 bp; although 148 ORFs were identified, putative functions could be assigned to only 29 of them. Sequence comparisons revealed the mosaic structure of UAB_Phi87 and its high similarity with bacteriophages Felix O1 and wV8 of E. coli with respect to genetic content and functional organization. Phylogenetic analysis of large terminase subunits confirms their packaging strategies and grouping to the different phage genus type. All these studies are necessary for the development and the use of an efficient cocktail with commercial applications in bacteriophage therapy against Salmonella.


Urban consumption of meat and milk and its green and blue water footprints-Patterns in the 1980s and 2000s for Nairobi, Kenya.
Various studies show that the developing world experiences and will continue to experience a rise in consumption of animal proteins, particularly in cities, as a result of continued urbanization and income growth. Given the relatively large water footprint (WF) of animal products, this trend is likely to increase the pressure on already scarce water resources. We estimate, analyse and interpret the changes in consumption of meat and milk between the 1980s and 2000s for three income classes in Nairobi, the ratio of domestic production to imports, and the WF (the volume of freshwater consumed) to produce these commodities in Kenya and abroad. Nairobi's middle-income class grew much faster than the overall population. In addition, milk consumption per capita by the middle-income group grew faster than for the city's population as a whole. Contrary to expectation, average meat consumption per capita across all income groups in Nairobi declined by 11%. Nevertheless, total meat consumption increased by a factor 2.2 as a result of population growth, while total milk consumption grew by a factor 5. As a result, the total WF of meat consumption increased by a factor 2.3 and the total WF of milk consumption by a factor 4.2. The increase in milk consumption was met by increased domestic production, whereas the growth in meat consumption was partly met through imports and an enlargement of the footprint in the countries neighbouring Kenya. A likely future rise in the consumption of meat and milk in Nairobi will further enlarge the city's WF. Given Kenya's looming blue water scarcity, it is anticipated that this WF will increasingly spill over the borders of the country. Accordingly, policies aimed at meeting the rise in demand for meat and milk should consider the associated environmental constraints and the economic implications both nationally and internationally.


Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice.
Narcolepsy-cataplexy is a neurological disorder associated with the inability to maintain wakefulness and abnormal intrusions of rapid eye movement sleep-related phenomena into wakefulness such as cataplexy. The vast majority of narcoleptic-cataplectic individuals have low or undetectable levels of orexin (hypocretin) neuropeptides in the cerebrospinal fluid, likely due to specific loss of the hypothalamic orexin-producing neurons. Currently available treatments for narcolepsy are only palliative, symptom-oriented pharmacotherapies. Here, we demonstrate rescue of the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means. Ectopic expression of a prepro-orexin transgene in the brain completely prevented cataplectic arrests and other abnormalities of rapid eye movement sleep in the absence of endogenous orexin neurons. Central administration of orexin-A acutely suppressed cataplectic behavioral arrests and increased wakefulness for 3 h. These results indicate that orexin neuron-ablated mice retain the ability to respond to orexin neuropeptides and that a temporally regulated and spatially targeted secretion of orexins is not necessary to prevent narcoleptic symptoms. Orexin receptor agonists would be of potential value for treating human narcolepsy.


Entrepreneurs and Environmental Sustainability in the Digital Era: Regional and Institutional Perspectives.
Climate change and environmental degradation have negatively affected the sustainable development of mankind. The "green" concept has been gradually accepted by the public, thereby strongly promoting "green" business forms and social innovation. This study adopts related information and technology knowledge and experience and warm glow (altruistic value) for business initiatives as push factors, market opportunity (MO) and personal innovativeness (PI) in technology as pull factors, and institutional theory (regulatory support and normative support) as mooring factors. These factors are employed to analyze the switching intentions of individuals toward green entrepreneurship, which is a new persuasive psychological model based on Push-Pull-Mooring model (PPM). The survey questionnaires are collected from a total of 1562 respondents through WeChat in mainland China. The study findings present all variables that significantly affect individuals' switching intentions toward green entrepreneurs. PI exhibits the most significant impact on intention of individuals toward green entrepreneurship, while the interaction between the mooring factor and MO on switching intentions to green entrepreneurship is relatively weak. Finally, the study contributes theoretical and practical implications for increasing intentions toward green entrepreneurship.


6-pyruvoyl-tetrahydropterin synthase deficiency with mild hyperphenylalaninemia.
Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening programs. We describe an 8-year-old girl with delay, seizures, and dystonia with mild hyperphenylalaninemia detected in late childhood. The diagnosis of 6-pyruvoyl-tetrahydrobiopterin synthase deficiency was made by analysis of pterins in urine, pterins and neurotransmitters in cerebrospinal fluid, and enzyme assay. The patient improved clinically taking oral tetrahydrobiopterin, levodopa/carbidopa, and 5-hydroxytryptophan. This treatable condition may not always be detected by routine population screening for hyperphenylalaninemia.


The Impact of Medical Students Teaching Basic Life Support to Laypersons.
Basic life support (BLS) courses for laypersons, including cardiopulmonary resuscitation (CPR) training, is known to improve outcomes of out-of-hospital cardiac events. We asked medical students to provide BLS training for laypersons as a part of their emergency medicine education and evaluated the effects of training on the BLS skills of laypersons. We also used a questionnaire to determine whether the medical students who provided the BLS training were themselves more confident and motivated to perform BLS compared to students who did not provide BLS training. The proportions of laypersons who reported confidence in checking for a response, performing chest compressions, and automated external defibrillator (AED) use were significantly increased after the BLS training. The proportions of medical students who reported increased confidence/motivation in terms of understanding BLS, checking for a response, chest compression, use of AED, and willingness to perform BLS were significantly greater among medical students who provided BLS instructions compared to those who did not. BLS instruction by medical students was associated with an improvement in laypersons' CPR accuracy and confidence in responding to cardiac arrest. The results indicate that medical students could gain understanding, confidence, and motivation in regard to their BLS skills by teaching BLS to laypersons.


The skin microbiome in healthy and allergic dogs.
Changes in the microbial populations on the skin of animals have traditionally been evaluated using conventional microbiology techniques. The sequencing of bacterial 16S rRNA genes has revealed that the human skin is inhabited by a highly diverse and variable microbiome that had previously not been demonstrated by culture-based methods. The goals of this study were to describe the microbiome inhabiting different areas of the canine skin, and to compare the skin microbiome of healthy and allergic dogs. DNA extracted from superficial skin swabs from healthy (n = 12) and allergic dogs (n = 6) from different regions of haired skin and mucosal surfaces were used for 454-pyrosequencing of the 16S rRNA gene. Principal coordinates analysis revealed clustering for the different skin sites across all dogs, with some mucosal sites and the perianal regions clustering separately from the haired skin sites. The rarefaction analysis revealed high individual variability between samples collected from healthy dogs and between the different skin sites. Higher species richness and microbial diversity were observed in the samples from haired skin when compared to mucosal surfaces or mucocutaneous junctions. In all examined regions, the most abundant phylum and family identified in the different regions of skin and mucosal surfaces were Proteobacteria and Oxalobacteriaceae. The skin of allergic dogs had lower species richness when compared to the healthy dogs. The allergic dogs had lower proportions of the Betaproteobacteria Ralstonia spp. when compared to the healthy dogs. The study demonstrates that the skin of dogs is inhabited by much more rich and diverse microbial communities than previously thought using culture-based methods. Our sequence data reveal high individual variability between samples collected from different patients. Differences in species richness was also seen between healthy and allergic dogs, with allergic dogs having lower species richness when compared to healthy dogs.


What does global mean temperature tell us about local climate?
The subject of climate feedbacks focuses attention on global mean surface air temperature (GMST) as the key metric of climate change. But what does knowledge of past and future GMST tell us about the climate of specific regions? In the context of the ongoing UNFCCC process, this is an important question for policy-makers as well as for scientists. The answer depends on many factors, including the mechanisms causing changes, the timescale of the changes, and the variables and regions of interest. This paper provides a review and analysis of the relationship between changes in GMST and changes in local climate, first in observational records and then in a range of climate model simulations, which are used to interpret the observations. The focus is on decadal timescales, which are of particular interest in relation to recent and near-future anthropogenic climate change. It is shown that GMST primarily provides information about forced responses, but that understanding and quantifying internal variability is essential to projecting climate and climate impacts on regional-to-local scales. The relationship between local forced responses and GMST is often linear but may be nonlinear, and can be greatly complicated by competition between different forcing factors. Climate projections are limited not only by uncertainties in the signal of climate change but also by uncertainties in the characteristics of real-world internal variability. Finally, it is shown that the relationship between GMST and local climate provides a simple approach to climate change detection, and a useful guide to attribution studies.


Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome.
Green tea (Camellia sinensis) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects. We conducted a randomized controlled trial in obese subjects with metabolic syndrome. Thirty-five subjects [(mean ± SE) age 42.5 ± 1.7 y, body mass index 36.1 ± 1.3 kg/m(2)] completed the 8-wk study and were randomly assigned to receive green tea (4 cups/d), green tea extract (2 capsules and 4 cups water/d), or no treatment (4 cups water/d). Both the beverage and extract groups had similar dosing of epigallocatechin-3-gallate, the active green tea polyphenol. Fasting blood samples were collected at screening, 4 and 8 wk of the study. Green tea beverage or extract supplementation did not significantly alter features of metabolic syndrome or biomarkers of inflammation including adiponectin, C-reactive protein, interleukin-6, interleukin-1β, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, leptin, or leptin:adiponectin ratio. However, both green tea beverage and extracts significantly reduced plasma serum amyloid alpha versus no treatment (P < 0.005). This study suggests that the daily consumption of green tea beverage or extracts for 8 wk was well tolerated but did not affect the features of metabolic syndrome. However, green tea significantly reduced plasma serum amyloid alpha, an independent cardiovascular disease risk factor, in obese subjects with metabolic syndrome.


Fostering and assessing professionalism and communication skills in neurosurgical education.
Incorporation of the 6 ACGME core competencies into surgical training has proven a considerable challenge particularly for the two primarily behavioral competencies, professionalism and interpersonal and communication skills. We report on experience with two specific interventions to foster the teaching and continuous evaluation of these competencies for neurosurgery residents. In 2010, the Society of Neurological Surgeons (SNS) organized the first comprehensive Neurosurgery Boot Camp courses, held at six locations throughout the US and designed to assess and teach not only psychomotor skills but also components of all six Accreditation Council for Graduate Medical Education (ACGME) core competencies. These courses are comprised of various educational methodologies, including online material, faculty lectures, clinical scenario and group discussions, manual skills stations, and pre- and post-course assessments. Resident progress in each of the 6 ACGME competencies is now tracked using the neurosurgical Milestones, developed by the ACGME in collaboration with the SNS. In addition, the Milestones drafting group for neurosurgery has formulated a milestone-compatible evaluation system to directly populate Milestone reports. These evaluations utilize formative, summative, and 360-degree evaluations that are considered by a faculty core competency committee in finalizing milestones levels for each resident. Initial attendance at the 2010 Boot Camp course was 94% of the incoming resident class and in subsequent years, 100%. Pre- and post-course surveys demonstrated a significant and sustained increase in knowledge. The value of these courses has been recognized by the ACGME, which requires Boot Camp or equivalent participation prior to acting with indirect supervision during clinical activities. Neurosurgery was one of 7 early Milestone adopter specialties, beginning use in July, 2013. Early milestone data will establish benchmarks prior to utilization for "high stake" decisions such as promotion, graduation, and termination. The full impact of the neurosurgical Boot Camps and Milestones on residency education remains to be measured, although published data from the first years of the Boot Camp Courses demonstrate broad acceptance and early effectiveness. A complementary junior resident course has now been introduced for rising second-year residents. The Milestones compatible evaluation system now provides for multi-source formative and summative evaluation of neurosurgical residents within the new ACGME reporting rubric. Combined with consensus milestone assignments, this system provides new specificity and objectivity to resident evaluations. The correlation of milestone level assignments with other measurements of educational outcome awaits further study.


Prudent use guidelines: a review of existing veterinary guidelines.
The World Organisation for Animal Health (OIE) TerrestrialAnimal Health Code considers the prudent use of antimicrobial agents in veterinary medicine to comprise a series of practical measures and recommendations which confer benefits to animal and public health while preserving and maintaining the therapeutic efficacy of antimicrobials. This paper reviews some of the main veterinary prudent use guidelines which have been published in English and the responsibilities of those involved at all levels in the administration of antimicrobials to animals, including national regulatory authorities. The OIE guidelines are considered comprehensive and cover all of those levels, from regulatory authorities to veterinarians and food producers. Guidelines produced by national authorities, professional veterinary associations or farming associations and which are targeted at particular individuals, for example veterinarians or food animal producers, will, obviously, restrict their coverage to those aspects considered relevant for their target audience.


gSG6-P1 salivary biomarker discriminates micro-geographical heterogeneity of human exposure to Anopheles bites in low and seasonal malaria areas.
Over the past decade, a sharp decline of malaria burden has been observed in several countries. Consequently, the conventional entomological methods have become insufficiently sensitive and probably under-estimate micro-geographical heterogeneity of exposure and subsequent risk of malaria transmission. In this study, we investigated whether the human antibody (Ab) response to Anopheles salivary gSG6-P1 peptide, known as a biomarker of Anopheles exposure, could be a sensitive and reliable tool for discriminating human exposure to Anopheles bites in area of low and seasonal malaria transmission. A multi-disciplinary survey was performed in Northern Senegal where An. gambiae s.l. is the main malaria vector. Human IgG Ab response to gSG6-P1 salivary peptide was compared according to the season and villages in children from five villages in the middle Senegal River valley, known as a low malaria transmission area. IgG levels to gSG6-P1 varied considerably according to the villages, discriminating the heterogeneity of Anopheles exposure between villages. Significant increase of IgG levels to gSG6-P1 was observed during the peak of exposure to Anopheles bites, and decreased immediately after the end of the exposure season. In addition, differences in the season-dependent specific IgG levels between villages were observed after the implementation of Long-Lasting Insecticidal Nets by The National Malaria Control Program in this area. The gSG6-P1 salivary peptide seems to be a reliable tool to discriminate the micro-geographical heterogeneity of human exposure to Anopheles bites in areas of very low and seasonal malaria transmission. A biomarker such as this could also be used to monitor and evaluate the possible heterogeneous effectiveness of operational vector control programs in low-exposure areas.


Medial amygdala lesions differentially influence stress responsivity and sensorimotor gating in rats.
The amygdala is involved in the coordination of stress but is also an important gatekeeper involved in the regulation of vigilance. The amygdala is structurally complex, consisting of several nuclei with specific functions in the affective response to environmental stimuli. There are indications that the medial amygdaloid nucleus may be a pivotal player in acute responses to emotional environmental stimuli. The present study therefore aimed to study the effects of bilateral electrolytic lesions of the medial amygdala on unconditioned anxiety-related behavior as well as a sensorimotor gating parameter (prepulse inhibition, PPI) in rats. Anxiety-related behavior was assessed with the use of stress-induced hyperthermia (SIH), light-enhanced startle (LES) and open field behavior. Bilateral electrolytic lesions of the medial amygdala decreased the SIH response and anxiety-related open field behavior. In contrast, lesioned animals displayed augmented LES and disrupted PPI. No changes in basal locomotor activity, body temperature and acoustic startle were found between lesioned and sham animals. The present study suggests that the medial amygdala is an important player in response to acute environmental stimuli. Decreased unconditioned psychological stress responses were found, whereas LES was enhanced and sensorimotor processing was disrupted. However, considering the existing data on basolateral amygdala involvement in PPI and bed nucleus of the stria terminalis involvement in LES, local infusion studies into the MeA should be performed to further substantiate these findings.


Modified Two-Stage Exchange for Periprosthetic Joint Infection in UKA.
Periprosthetic joint infection (PJI) is a rare complication following unicompartmental knee arthroplasty (UKA), and current management guidelines are still evolving. This report presents a novel surgical technique of resection arthroplasty with an articulated hemispacer as part of a 2-stage exchange protocol. A 66-year-old man developed a culture-negative PJI four months after a medial UKA. Rather than conventional full resection arthroplasty, the patient underwent partial resection with preservation of the lateral and patellofemoral compartments to maintain vascularized bone stock. An articulating hemispacer fashioned from the old implants after sterilization was reimplanted medially to preserve function during the course of antibiotic treatment. After successful eradication of infection, the patient underwent an uncomplicated conversion total knee replacement facilitated by prior preservation of bone stock. No stems or augments were needed. Therefore, a partial resection arthroplasty with an articulating hemispacer used in a 2-stage exchange protocol may be a reasonable option to eradicate infection and maintain function. In future cases of infected UKA, this technique warrants further consideration and investigation.


Brain and psychological determinants of placebo pill response in chronic pain patients.
The placebo response is universally observed in clinical trials of pain treatments, yet the individual characteristics rendering a patient a 'placebo responder' remain unclear. Here, in chronic back pain patients, we demonstrate using MRI and fMRI that the response to placebo 'analgesic' pills depends on brain structure and function. Subcortical limbic volume asymmetry, sensorimotor cortical thickness, and functional coupling of prefrontal regions, anterior cingulate, and periaqueductal gray were predictive of response. These neural traits were present before exposure to the pill and most remained stable across treatment and washout periods. Further, psychological traits, including interoceptive awareness and openness, were also predictive of the magnitude of response. These results shed light on psychological, neuroanatomical, and neurophysiological principles determining placebo response in RCTs in chronic pain patients, and they suggest that the long-term beneficial effects of placebo, as observed in clinical settings, are partially predictable.


Selection bias in family reports on end of life with dementia in nursing homes.
Selective participation in retrospective studies of families recruited after the patient's death may threaten generalizability of reports on end-of-life experiences. To assess possible selection bias in retrospective study of dementia at the end of life using family reports. Two physician teams covering six nursing home facilities in the Netherlands reported on 117 of 119 consecutive decedents within two weeks after death unaware of after-death family participation in the study. They reported on characteristics; treatment and care; overall patient outcomes such as comfort, nursing care, and outcomes; and their own perspectives on the experience. We compared results between decedents with and without family participation. The family response rate was 55%. There were no significant differences based on participation versus nonparticipation in demographics and other nursing home resident characteristics, treatment and care, or overall resident outcome. However, among participating families, physicians perceived higher-quality aspects of nursing care and outcome, better consensus between staff and family on treatment, and a more peaceful death. Participation was less likely with involvement of a new family member in the last month. Families may be more likely to participate in research with more harmonious teamwork in end-of-life caregiving. Where family participation is an enrollment criterion, comparing demographics alone may not capture possible selection bias, especially in more subjective measures. Selection bias toward more positive experiences, which may include the physician's and probably also the family's experiences, should be considered if representativeness is aimed for. Future work should address selection bias in other palliative settings and countries, and with prospective recruitment.


Detection limit concepts: foundations, myths, and utilization.
Detection limit parameters such as the minimum detectable concentration have been widely discussed in the literature for more than 30 y. Misunderstanding and misapplication of these parameters continue to be widespread and, indeed, even encoded into computer programs, especially those developed in recent years for use with PC-based analyzer boards. This brief review of the principal concepts related to the most common types of detection limits provides guidance for correctly using these parameters. In particular, several myths concerning issues such as the "sample-specific minimum detectable concentration" and the "unreliability" of measurements made below this concentration are discussed.


Computer-Based Cognitive Training for Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors.
Advancements in chemotherapy have greatly increased breast cancer survival, leading to an increased focus on the management of long-term effects of treatment. Chemotherapy-related cognitive impairment, one such long-term effect, is experienced by as many as 90% of breast cancer survivors (BCS) and negatively affects employment, daily function, and quality of life. Chemotherapy-related cognitive impairment is a top research and clinical practice priority. The aim of this article is to review computer-based cognitive training intervention studies tested in BCS, present implications for practice and directions for future research, and discuss neuroplasticity and cognitive reserve, the mechanisms by which computer-based cognitive training produces physiologic changes in the brain. A search of PubMed, CINAHL®, and PsycINFO® databases yielded two computer-based cognitive training intervention studies in BCS. This review suggests that computer-based cognitive training may enhance cognitive function in BCS with chemotherapy-related cognitive impairment. Oncology nurses are in a unique position to support BCS experiencing chemotherapy-related cognitive impairment. In addition to acknowledging BCS' concerns, screening for other potential factors, and providing education on healthy living, nurses may suggest computer-based cognitive training as an approach to managing chemotherapy-related cognitive impairment. Future research should use imaging and larger populations.


A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism.
Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode's dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted Gr(Δ) (SP) UBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that Gr(Δ) (SP) UBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in Gr(Δ) (SP) UBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, Gr(Δ) (SP) UBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation.


Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.
In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L-arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit+-cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF-1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial adhesion of c-kit+ cells was entirely abrogated, while EL adhesion was significantly increased. The chemokine SDF-1alpha mediates firm adhesion c-kit+ cells only in the presence of TNF-alpha stimulation via an ICAM-1- and CXCR4-dependent mechanism. The presence of eNOS appears to be a crucial and specific factor for firm c-kit+-cell adhesion to the vascular endothelium.


Workflow for the Supervised Learning of Chemical Data: Efficient Data Reduction-Multivariate Curve Resolution (EDR-MCR).
A new method termed efficient data reduction-multivariate curve resolution (EDR-MCR) has been devised for classification of high-dimensional data. The method introduces the coupling of EDR and MCR as a new strategy for data splitting, variable selection, and supervised classification of high dimensionality data. The method reduces data dimensionality and selects the training set using principal component analysis (PCA) and convex geometry prior to data classification. Then, the reduced data are categorized using an MCR model, in which numerical constraints are imposed to resolve the data into classes and readily interpretable pure component signal weights. The performance of the EDR and supervised MCR methods were tested for their ability to enable discrimination between the constituents of two benchmark and two high-dimensional data sets. The results were compared with the output of the application of different data splitting methods including iterative random selection (IRS), Kennard-Stone (KS), and discrimination methods including partial least-squares-discriminant analysis (PLS-DA) and the ensemble-learning frameworks of linear discriminant analysis (LDA), k-nearest neighbors (KNN), classification and regression trees (CART), and support vector machine (SVM). Overall, EDR resulted in comparable results with other data splitting methods despite the small size of the training set samples that it created. The proposed MCR approach, in comparison with other commonly used supervised techniques, has the advantages of speed in implementation, tuning of fewer parameters, flexibility in the analysis of data characterized by low sample numbers and class imbalances, improved accuracy from the inclusion of additional system information in the form of numerical constraints, and the ability to resolve pure components signal weights.


General dentists' attitudes toward delegation, information, and patient influence in a prosthodontic context.
The aim of this study was to investigate attitudes among general dentists in Sweden in relation to gender, age, prosthodontic activity, and dental delivery system (private or public). Questionnaires were sent to a random sample of 2,059 dentists, and a response rate of 76% (1,567 dentists) was achieved. Among those who responded, 50% were private practitioners and 50% were publicly employed practitioners; 42% were female and 58% were male. The questionnaire contained 10 statements aimed at measuring attitudes. Their dimensionality was analyzed using principal components analysis. The resulting factors were related to delivery system (public or private), gender, age, job satisfaction, and weekly working hours used for prosthodontics in multiple regression models. There was a wide variation in the answers to the statements, indicating great individual differences in opinions among dentists. Several distributions differed with respect to gender and delivery system, but the mean differences between various groups of dentists were small. The most affirmative attitude was shown for delegation of impression taking to auxiliaries (mean 6.7; SD 1.8), and the most negative attitude was shown for close cooperation between dentists (mean 1.8; SD 1.4). The factor analysis gave 3 factors, with a variance explanation of 57%. Regression models for the 3 attitude dimensions ("patient influence," "delegation," and "patient information") showed that female dentists felt more positive about delegation and information than male dentists. The explained variance was very low for all 3 models and varied from 0.01 to 0.05. Although the differences in attitudes between various groups of dentists were statistically significant, these differences were small in relation to the large variation in attitudes among individual dentists.


Investigation of the thermally induced laser beam distortion associated with vacuum compressor gratings in high energy and high average power femtosecond laser systems.
We report successful compensation of the thermally induced laser beam distortion associated with high energy 110 mJ and high average power femtosecond laser system of 11 Watts operated with vacuum compressor gratings. To enhance laser-based light source brightness requires development of laser systems with higher energy and higher average power. Managing the high thermal loading on vacuum optical components is a key issue in the implementation of this approach. To our knowledge this is the first time that such thermal induced distortions on the vacuum compressor gratings are characterized and compensated.


Casual Sexual Scripts on the Screen: A Quantitative Content Analysis.
While existing content analyses have provided insightful information in terms of contextual factors and frequency of sexual behaviors, not much is known about the relational context in which sexual depictions generally occur. The current study addresses this void by employing content analytic methods to measure the frequency and context of depictions of sexual behavior within nine popular television shows produced in the U.S., while taking into account the type of sexual behavior. The results suggest that, in the analyzed television shows, sexual behaviors within a casual sexual context were almost as frequently shown as sexual behaviors within a committed relationship context. Whereas sexual behaviors within a committed relationship context were mainly limited to passionate kissing, sexual behaviors within a casual sexual context mostly consisted of explicit portrayals of sexual intercourse. Additionally, genre seemed to be an important factor when examining casual sexual television content. The situational comedy genre, for example, had no explicit portrayals of intercourse and mainly portrayed kissing couples within a committed relationship. The comedy drama genre, on the contrary, had the largest proportion of explicit sexual portrayals, usually between casual sexual partners. A second goal of this study was to analyze the portrayals of the typical casual sexual experience script and the typical casual sexual relationship script in which these sexual behaviors often occur. For instance, our analyses revealed that female characters were more likely to initiate casual sex compared to male characters. Moreover, casual sex often occurred between former partners.


Small-angle measurement with highly sensitive total-internal-reflection heterodyne interferometer.
In this paper, a high-sensitivity total-internal-reflection (TIR) heterodyne interferometer is proposed for measuring small angles. In the proposed interferometer, a half-wave plate and two quarter-wave plates that exhibit specific optic-axis azimuths are combined to form a phase shifter. When a rhomboid prism is placed between the phase shifter and an analyzer that exhibits suitable transmission-axis azimuth, it shifts and enhances the phase difference of the s- and p-polarization states at double TIR. The enhanced phase difference is dependent on the incident angle; thus small angles can be easily and accurately measured by estimating the phase difference. The experimental results demonstrate the feasibility of this method. Angular resolution and sensitivity levels superior to 1.2×10⁻⁴ deg (2.1×10⁻⁶ rad) and 100 (deg/deg), respectively, were attainable in a dynamic range of 0.5 deg.


Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates.
Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.


Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival.
Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors. The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors. Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples). Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.


Awareness of Dental Trauma Management among School Teachers of Kannur, Kerala, India.
Dental trauma can overtake dental caries and periodontal disease as the most significant threat to dental health among young people. The prognosis of traumatized teeth depends on prompt and appropriate treatment. The role of school teachers in the prevention of traumatic dental injuries is a topic that has received a great deal of attention in recent years. However, studies conducted in different regions of the world have demonstrated that teachers and other lay people's knowledge about traumatic dental injuries is inadequate and their behavior does not contribute to reduce the sequelae. The purpose of this study was to evaluate the knowledge of school teachers about dental trauma and its management in Kannur district. The survey was conducted under the Department of Paedodontics and Preventive Dentistry; Kannur Dental College among 303 school teachers randomly selected from 16 schools. Four schools were selected from 16 schools using stratified cluster sampling technique. A cross sectional study design was used. A stratified cluster sampling method was done to select the study subjects. The nature and purpose of the study was first explained to the teachers in local language. Following this the printed questionnaire was distributed to school teachers. The questionnaire was prepared based on the needs of the study after referring similar questionnaires used in studies conducted in different parts of the world. A statistically significant association was found between the teacher's knowledge regarding trauma and their teaching experience. Out of the total school teachers who participated in the study, 90.1% responded correctly that the teeth most frequently affected by traumatic accidents are the upper front teeth. Nearly 23.4% responded correctly regarding management of traumatic tooth fracture. Almost 46.5% had correct knowledge regarding the reimplantation of avulsed permanent teeth. Only 14.2% responded correctly to the proper storage medium for avulsed teeth. It was concluded from the study that among the school teachers surveyed there was significantly very low knowledge of emergency management of dental trauma.


Knowledge of health professional students on waterpipe tobacco smoking: curricula implications.
Tobacco prevention research traditionally focuses upon cigarette smoking, but there is also a need to implement and evaluate the usefulness of waterpipe tobacco smoking (WTS) interventions since it is considered less harmful than cigarettes. This study aimed to assess the impact of an educational intervention on WTS knowledge of health professional students in three academic health institutions in Bahrain. A quasi-experimental design was used to include medical students from the Arabian Gulf University, medical and nursing students from the Royal College of Surgeons in Ireland-Bahrain and nursing students from the University of Bahrain. Two hundred fifty students participated in the three phases of the study during October 2015-June 2016 from an original sample of 335. The participants answered knowledge questions on WTS before and after an intervention, which included a lecture by an expert and a video on the awareness about the health hazards of WTS. The mean age of starting cigarette and WTS was 16.8 ± 2.8 and 17.5 ± 1.7 years, respectively. The prevalence of ever smoking any type of tobacco among students was 22.4% (medical 25.8% and nursing 37.5%) and that of WTS, 17.7% (medical 20.0%, nursing 13.6%). The prevalence of current cigarette smoking was 9.6% among medical and nursing students combined with 10.3 and 8.5% for medical and nursing students, respectively. WTS was prevalent at a proportion of 6.8% among medical and nursing students combined with 6.5% in medical and 14.8% in nursing students. The university curriculum as the main source of knowledge on WTS increased from 14.2 to 33.3% after the intervention (p < 0.005). Knowledge about the hazards of WTS increased in 16 of the 20 statements. The difference in overall knowledge score was significant (p < 0.05) for nursing (77. 5 ± 1.5 vs 85.8 ± 2.2) compared to medical students (85.3 ± 1.0 vs 87.3 ± 0.9) after the intervention. Our educational intervention with health professional students improved their knowledge about the health effects of WTS. Medical and nursing institutions may consider using various methods such as informative videos and expert lectures to include in their teaching curricula as part of WTS prevention strategies.


Clearing the air: a model for investigating indoor air quality in Texas schools.
This pilot project focused on the assessment of indoor air quality at a local high school in Galveston, Texas, using methods based on guidelines for the U.S. Environmental Protection Agency's Indoor Air Quality Tools for Schools program. Tools for Schools, developed for evaluating and ensuring acceptable air quality for schools, takes a low-cost, minimal-involvement, primarily educational approach. The authors also compared the findings from this approach with the results of an air-sampling program. The overall goal was to determine if use of Tools for Schools was sufficient to identify conditions with the potential to cause adverse health effects. The primary objectives were to 1) establish an indoor air quality committee for the school to implement Tools for Schools assessments and management strategies, 2) collect air quality data in high-risk areas identified within the school by the indoor air quality committee, 3) collect outdoor air quality data at or in close proximity to the school, and 4) develop methods and instruments for assessing environmental risks associated with daily school attendance. Data were gathered on levels of formaldehyde and other volatile organic compounds (VOCs), ozone, particulate matter (PM10), mold, relative humidity, and temperature. Data values for each sampled pollutant were compared with federal standards, recommended values established by the American Conference of Governmental Industrial Hygienists for non-industrial populations, and effects screening levels developed by the Texas Commission on Environmental Quality. Levels of all VOCs except formaldehyde were found to be well within guidelines, as were ozone and particulate-matter levels. Mold, however, was widespread, including both common species and species associated with allergy and asthma, such as Aspergillus and Alternaria. In general, Tools for Schools provides an excellent foundation for a school indoor air quality program, although the authors did find it necessary to streamline data collection and did find that mold with the potential for adverse health effects was present, albeit not visible in some areas.


Early and presenting symptoms of dementia with lewy bodies.
To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer's disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. DLB should be suspected in predementia cases with visual hallucinations.


Diabetes is related to cerebral infarction but not to AD pathology in older persons.
To examine the potential relation of diabetes to common neuropathologic causes of dementia, cerebral infarction and Alzheimer disease (AD) neuropathology. Subjects were 233 older Catholic clergy in the Religious Orders Study, who underwent detailed annual evaluations, including neuropsychological testing, and brain autopsy at time of death (mean age 86 years, 45% men). Diabetes was identified by annual direct medication inspection and history. Cognitive function proximate to death was summarized into five cognitive domains, based on 19 neuropsychological tests. Macroscopic cerebral infarctions were recorded from 1 cm coronal slabs. Neuritic plaques, diffuse plaques, and neurofibrillary tangles were counted in Bielschowsky silver-stained sections and summarized to yield composite measures of neuritic plaques, diffuse plaques, tangles, and overall AD pathology. We also used immunohistochemistry with antibodies to amyloid-beta and PHF-tau to obtain quantitative measures of amyloid burden and neurofibrillary tangle density. Multiple logistic and linear regression analyses were used to examine the relation of diabetes to cerebral infarctions and AD pathology, controlling for age, sex, and education. AD pathology was related to all five cognitive domains (p < 0.01) and infarctions were related to perceptual speed (p < 0.001). Diabetes (present in 15% subjects) was associated with an increased odds of infarction (OR = 2.47, 95% CI: 1.16, 5.24). Diabetes was not related to global AD pathology score, or to specific measures of neuritic plaques, diffuse plaques or tangles, or to amyloid burden or tangle density. We found a relation between diabetes and cerebral infarction but not between diabetes and Alzheimer disease pathology in older persons.


Epilepsy Benchmarks Area III: Improved Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects.
The goals of Epilepsy Benchmark Area III involve identifying areas that are ripe for progress in terms of controlling seizures and patient symptoms in light of the most recent advances in both basic and clinical research. These goals were developed with an emphasis on potential new therapeutic strategies that will reduce seizure burden and improve quality of life for patients with epilepsy. In particular, we continue to support the proposition that a better understanding of how seizures are initiated, propagated, and terminated in different forms of epilepsy is central to enabling new approaches to treatment, including pharmacological as well as surgical and device-oriented approaches. The stubbornly high rate of treatment-resistant epilepsy-one-third of patients-emphasizes the urgent need for new therapeutic strategies, including pharmacological, procedural, device linked, and genetic. The development of new approaches can be advanced by better animal models of seizure initiation that represent salient features of human epilepsy, as well as humanized models such as induced pluripotent stem cells and organoids. The rapid advances in genetic understanding of a subset of epilepsies provide a path to new and direct patient-relevant cellular and animal models, which could catalyze conceptualization of new treatments that may be broadly applicable across multiple forms of epilepsies beyond those arising from variation in a single gene. Remarkable advances in machine learning algorithms and miniaturization of devices and increases in computational power together provide an enhanced opportunity to detect and mitigate seizures in real time via devices that interrupt electrical activity directly or administer effective pharmaceuticals. Each of these potential areas for advance will be discussed in turn.


Identification and characterization of 2'-deoxyuridine from the supernatant of conidial suspensions of rice blast fungus as an infection-promoting factor in rice plants.
We previously detected infection-promoting activity in the supernatant of the conidial suspension (SCS) of the rice blast fungus. In the present study, a molecule carrying the activity was purified and identified as 2'-deoxyuridine (dU). The infection-promoting activity of dU was strictly dependent on its chemical structure and displayed characteristics consistent with those of the SCS. Notably, the activity of dU was exclusively detected during interactions between rice and virulent isolates of the fungus, the number of susceptible lesions in leaf blades was increased by dU, and nonhost resistance in rice plants was not affected by treatment with dU. In addition, the expression of pathogensis-related genes, accumulation of H(2)O(2), and production of phytoalexins in rice in response to inoculation with virulent fungal isolates was not suppressed by dU. The infection-promoting activity of dU was not accompanied by elevated levels of endogenous abscissic acid, which is known to modify plant-pathogen interactions, and was not detected in interactions between oat plants and a virulent oat blast fungus isolate. Taken together, these results demonstrate that dU is a novel infection-promoting factor that acts specifically during compatible interactions between rice plants and rice blast fungus in a mode distinct from that of toxins and suppressors.


Engrailed expression in the anterior lineage compartment of the developing wing blade of Drosophila.
The developing wing of Drosophila melanogaster was examined at larval and pupal stages of development to determine whether the anterior-posterior lineage boundary, as identified by lineage restrictions, was congruent with the boundaries defined by the expression of posterior-specific (engrailed, invected), and anterior-specific (cubitus interruptus-D) genes. The lineage boundary was identified by marking mitotic recombinant clones, using an enhancer trap line with ubiquitous beta-gal expression in imaginal tissues; clones of +/+ cells were identified by their lack of beta-gal expression. Domains of gene expression were localized using antibodies and gene specific lacZ constructs. Surprisingly, it was found that engrailed expression extended a small distance into the anterior lineage compartment of the wing blade, as identified with anti-en/inv mAb, anti-en polyclonal antiserum, or an en-promoter-lacZ insert, ryxho25. This anterior expression was not present in early third instar discs, but appeared during subsequent larval and pupal development. In contrast, the expression of cubitus interruptus-D, as identified using the ci-Dplac insert, appeared to be limited to the anterior lineage compartment. Thus, en expression is not limited to cells from the posterior lineage compartment, and en and ci-D activities can overlap in a region just anterior to the lineage compartment boundary in the developing wing. The lineage boundary could also be identified by a line of aligned cells in the prospective wing blade region of wandering third instar discs. A decapentaplegic-lacZ construct was expressed in a stripe several cells anterior to the lineage boundary, and did not define or overlap into the posterior lineage compartment.


Primary central nervous system lymphomas: a validation study of array-based comparative genomic hybridization in formalin-fixed paraffin-embedded tumor specimens.
Only a limited number of genetic studies have been conducted in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization (aCGH) in formalin-fixed paraffin-embedded (FFPE) specimens and compare the results with matched, frozen tumor specimens. We conducted aCGH in FFPE tissues from PCNSL. Results were compared with matched, paired, frozen tumors. Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes, with a median of 23 CNAs per patient (range, 17-47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, and 9p21.3 and gain of 12q12-q24.33 were the commonest CNAs. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX). The results obtained are encouraging. Larger archival tissue collections can now be analyzed to complement the still fragmented knowledge we have of the genetic basis of the PCNSL.


Enhancing Healthcare Provider Feedback and Personal Health Literacy: Dual Use of a Decision Quality Measure.
In this protocol for a pilot study we seek to establish the feasibility of using a web-based survey to simultaneously supply healthcare organisations and agencies with feedback on a key aspect of the care experience they provide and increase the generic health decision literacy of the individuals responding. The focus is on the person's involvement in decision making, an aspect of care which is seriously under-represented in current surveys if one adopts the perspective of person-centred care. By engaging with an instrument to assess decision quality the person can, in the one action, provide a retrospective evaluation of a past decision making experience in a specific provider context and enhance their competency in future decision making in any setting. We see this as an exercise in context-sensitive educational health informatics.


Impact of feeding and post prandial time on plasma ketone bodies in sows during transition and lactation.
Two experiments were conducted with the aim of studying how dietary fat source, reproductive stage (Exp. 1), and diurnal variation (Exp. 2) affect plasma ketone bodies in sows. In Exp. 1, 40 second-parity sows were fed 1 of 5 lactation diets from 7 d prepartum until 28 d postpartum, with low or high levels (3% or 8%) of dietary fats with different proportions of medium- and long-chain fatty acids. Blood was obtained by jugular venipuncture on d 3 and 7 prepartum, and d 1, 10, 17, and 28 postpartum, and concentrations of plasma beta-hydroxy butyric acid (BHBA), acetoacetate + acetone (AcAc+Ac), glucose, NEFA, lactate, acetate, and butyrate were determined. For 4 out of 5 treatments, plasma BHBA decreased slightly, whereas plasma AcAc+Ac remained stable. However, plasma BHBA (P < 0.01) and AcAc+Ac (P < 0.001) doubled after d 10 of lactation in sows fed 4% octanoic acid and 4% fish oil diet (4+4% FO; P < 0.001), compared with earlier in lactation (P < 0.001). Plasma AcAc+Ac was positively related to BHBA (P < 0.01), glucose (P < 0.05), and butyrate (P < 0.001), and negatively related to the acetate:butyrate ratio (P < 0.001). In addition, plasma BHBA was positively related to lactate (P < 0.01), acetate, and butyrate (P < 0.05). In Exp. 2, diurnal variations of plasma metabolites were studied in 5 sows sampled every second hour from a jugular catheter throughout a 24-h period on d 5 and 17 of lactation and analyzed as in Exp. 1. In addition, milk and urine samples were collected and analyzed for BHBA and AcAc+Ac. No diurnal variations in plasma BHBA or AcAc+Ac were observed and plasma AcAc+Ac was unchanged from d 5 to 17 of lactation (3.7 μM), whereas BHBA declined from 58 μM on d 5 of lactation to 52 μM on d 17 of lactation (P < 0.05). Minor amounts of AcAc+Ac were found in urine (8.6 μM) and this was not affected by days in milk, whereas the content of AcAc+Ac in milk and BHBA in milk and urine were less than the detection limit in 4 of 5 sows. In conclusion, dietary fat source affected plasma concentrations of ketone bodies, but the concentrations were much less than normally observed in dairy cows and, therefore, primary ketosis does not appear to be a major problem in sows. In addition, this study indicates that the intermediary metabolism of sows was challenged when sows were exposed to high fat diets in late gestation.


The missing link: paediatric to adult transition in diabetes services.
Childhood diabetes is a chronic and life-changing condition requiring careful management by clinicians, the child and family. During childhood, care is provided by the paediatric team, which is then transferred to the adult diabetes team during adolescence. This literature review identified five themes in the literature: adolescence as a time of transition; adolescent needs during transition; barriers; facilitators; and models of transition. Key findings suggest that the transition process remains problematic with a gap between paediatric and adult services being identified, including significant differences in clinical practice and culture. Although there is a growing body of knowledge around the reasons behind this phenomenon, research into effective models of transition to address these problems is still lacking. A period of managed transition between the two services has been recommended, with evidence that the nurse has the potential to develop a coordinating role, to assist in bridging the gap between paediatric and adult services.


JACUSA: site-specific identification of RNA editing events from replicate sequencing data.
RNA editing is a co-transcriptional modification that increases the molecular diversity, alters secondary structure and protein coding sequences by changing the sequence of transcripts. The most common RNA editing modification is the single base substitution (A→I) that is catalyzed by the members of the Adenosine deaminases that act on RNA (ADAR) family. Typically, editing sites are identified as RNA-DNA-differences (RDDs) in a comparison of genome and transcriptome data from next-generation sequencing experiments. However, a method for robust detection of site-specific editing events from replicate RNA-seq data has not been published so far. Even more surprising, condition-specific editing events, which would show up as differences in RNA-RNA comparisons (RRDs) and depend on particular cellular states, are rarely discussed in the literature. We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples. The performance of JACUSA has been carefully evaluated and compared to other variant callers in an in silico benchmark. JACUSA outperforms other algorithms in terms of the F measure, which combines precision and recall, in all benchmark scenarios. This performance margin is highest for the RNA-RNA comparison scenario. We further validated JACUSA's performance by testing its ability to detect A→I events using sequencing data from a human cell culture experiment and publicly available RNA-seq data from Drosophila melanogaster heads. To this end, we performed whole genome and RNA sequencing of HEK-293 cells on samples with lowered activity of candidate RNA editing enzymes. JACUSA has a higher recall and comparable precision for detecting true editing sites in RDD comparisons of HEK-293 data. Intriguingly, JACUSA captures most A→I events from RRD comparisons of RNA sequencing data derived from Drosophila and HEK-293 data sets. Our software JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In practice, JACUSA shows higher recall and comparable precision in detecting A→I sites from RNA-DNA comparisons, while showing higher precision and recall in RNA-RNA comparisons.


Deficits in adult neurogenesis, contextual fear conditioning, and spatial learning in a Gfap mutant mouse model of Alexander disease.
Glial fibrillary acidic protein (GFAP) is the major intermediate filament of mature astrocytes in the mammalian CNS. Dominant gain of function mutations in GFAP lead to the fatal neurodegenerative disorder, Alexander disease (AxD), which is characterized by cytoplasmic protein aggregates known as Rosenthal fibers along with variable degrees of leukodystrophy and intellectual disability. The mechanisms by which mutant GFAP leads to these pleiotropic effects are unknown. In addition to astrocytes, GFAP is also expressed in other cell types, particularly neural stem cells that form the reservoir supporting adult neurogenesis in the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Here, we show that mouse models of AxD exhibit significant pathology in GFAP-positive radial glia-like cells in the dentate gyrus, and suffer from deficits in adult neurogenesis. In addition, they display impairments in contextual learning and spatial memory. This is the first demonstration of cognitive phenotypes in a model of primary astrocyte disease.


Benefits and harms of mammography screening after age 74 years: model estimates of overdiagnosis.
The aim of this study was to quantify the benefits and harms of mammography screening after age 74 years, focusing on the amount of overdiagnosis of invasive breast cancer and ductal carcinoma in situ (DCIS). Three well-established microsimulation models were used to simulate a cohort of American women born in 1960. All women received biennial screening starting at age 50 years with cessation ages varying from 74 up to 96 years. We estimated the number of life-years gained (LYG), quality-adjusted life-years, breast cancer deaths averted, false-positives, and overdiagnosed women per 1000 screens. The models predicted that there were 7.8 to 11.4 LYG per 1000 screens at age 74 years (range across models), decreasing to 4.8 to 7.8 LYG per 1000 screens at age 80 years, and 1.4 to 2.4 LYG per 1000 screens at age 90 years. When adjusted for quality-of-life decrements, the LYG decreased by 5% to 13% at age 74 years and 11% to 22% at age 80 years. At age 90 to 92 years, all LYG were counterbalanced by a loss in quality-of-life, mainly because of the increasing number of overdiagnosed breast cancers per 1000 screens: 1.2 to 5.0 at age 74 years, 1.8 to 6.0 at age 80 years, and 3.7 to 7.5 at age 90 years. The age at which harms began to outweigh benefits shifted to a younger age when larger or longer utility losses because of a breast cancer diagnosis were assumed. The balance between screening benefits and harms becomes less favorable after age 74 years. At age 90 years, harms outweigh benefits, largely as a consequence of overdiagnosis. This age was the same across the three models, despite important model differences in assumptions on DCIS.


Using Regional Climate Projections to Guide Grassland Community Restoration in the Face of Climate Change.
Grassland loss has been extensive worldwide, endangering the associated biodiversity and human well-being that are both dependent on these ecosystems. Ecologists have developed approaches to restore grassland communities and many have been successful, particularly where soils are rich, precipitation is abundant, and seeds of native plant species can be obtained. However, climate change adds a new filter needed in planning grassland restoration efforts. Potential responses of species to future climate conditions must also be considered in planning for long-term resilience. We demonstrate this methodology using a site-specific model and a maximum entropy approach to predict changes in habitat suitability for 33 grassland plant species in the tallgrass prairie region of the U.S. using the Intergovernmental Panel on Climate Change scenarios A1B and A2. The A1B scenario predicts an increase in temperature from 1.4 to 6.4°C, whereas the A2 scenario predicts temperature increases from 2 to 5.4°C and much greater CO2 emissions than the A1B scenario. Both scenarios predict these changes to occur by the year 2100. Model projections for 2040 under the A1B scenario predict that all but three modeled species will lose ~90% of their suitable habitat. Then by 2080, all species except for one will lose ~90% of their suitable habitat. Models run using the A2 scenario predict declines in habitat for just four species by 2040, but models predict that by 2080, habitat suitability will decline for all species. The A2 scenario appears based on our results to be the less severe climate change scenario for our species. Our results demonstrate that many common species, including grasses, forbs, and shrubs, are sensitive to climate change. Thus, grassland restoration alternatives should be evaluated based upon the long-term viability in the context of climate change projections and risk of plant species loss.


Specialist paediatric dentistry in Sweden 2008 - a 25-year perspective.
International Journal of Paediatric Dentistry 2010; 20: 313-321 Background. Paediatric dentistry in Sweden has been surveyed four times over the past 25 years. During this period postgraduate training, dental health, and the organization of child dental care have changed considerably. Aim. To investigate services provided by specialists in paediatric dentistry in Sweden in 2008, and to compare with data from previous surveys. Design. The same questionnaire was sent to all 30 specialist paediatric dental clinics in Sweden that had been used in previous surveys. Comparisons were made with data from 1983, 1989, 1996 and 2003. Results. Despite an unchanged number of specialists (N = 81 in 2008), the number of referrals had increased by 16% since 2003 and by almost 50% since 1983. There was greater variation in reasons for referrals. The main reason was still dental anxiety/behaviour management problems in combination with dental treatment needs (27%), followed by medical conditions/disability (18%), and high caries activity (15%). The use of different techniques for conscious sedation as well as general anaesthesia had also increased. Conclusions. The referrals to paediatric dentistry continue to increase, leading to a heavy work load for the same number of specialists. Thus, the need for more paediatric dentists remains.


Presentation of Human Neural Stem Cell Antigens Drives Regulatory T Cell Induction.
Transplantation of human neural stem cells (hNSCs) is a promising regenerative therapy to promote remyelination in patients with multiple sclerosis (MS). Transplantation of hNSCs has been shown to increase the number of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in the spinal cords of murine models of MS, which is correlated with a strong localized remyelination response. However, the mechanisms by which hNSC transplantation leads to an increase in Tregs in the CNS remains unclear. We report that hNSCs drive the conversion of T conventional (Tconv) cells into Tregs in vitro. Conversion of Tconv cells is Ag driven and fails to occur in the absence of TCR stimulation by cognate antigenic self-peptides. Furthermore, CNS Ags are sufficient to drive this conversion in the absence of hNSCs in vitro and in vivo. Importantly, only Ags presented in the thymus during T cell selection drive this Treg response. In this study, we investigate the mechanisms by which hNSC Ags drive the conversion of Tconv cells into Tregs and may provide key insight needed for the development of MS therapies.