Nine states' use of collaboratives to improve children's health care quality in medicaid and CHIP.
We examine quality improvement (QI) collaboratives underway in 9 states participating in the Children's Health Insurance Program Reauthorization Act (CHIPRA) Quality Demonstration Grant Program. A total of 147 diverse, child-serving practices were participating in the collaboratives. We conducted 256 semistructured interviews with key stakeholders from March to August 2012-2 years into the 5-year demonstration projects-and analyzed states' grant applications, operating plans, and progress reports. The collaboratives have multiple complex aims. In addition to developing patient-centered medical home (PCMH) capability, some states use collaboratives to familiarize practices with CMS's Initial Core Set of Children's Health Care Quality Measures, practice-level quality measurement, and improving QI knowledge and skills. The duration of the collaboratives is longer than other well-known collaborative models. Collaboratives also vary in their methods for targeting areas for improvement and strategies for motivating practice recruitment and engagement. States also vary with respect to the other strategies they use to support QI and PCMH development. All states supplement the collaboratives with practice facilitation; the majority utilized practice-level parent engagement, but only 4 used workforce augmentation (ie, providing care coordinators and QI specialists). Practice staff highly valued aspects of the collaboratives and supplemental strategies, including the opportunity to work with experts and other child-serving practices; states' efforts to provide stipends and align demonstration efforts with other professional requirements or programs; receipt of relevant, customized QI materials; opportunities to learn how care coordinators or QI specialists might work in their practice without the risk of hiring them; and satisfaction from learning more about quality measures, QI concepts and techniques, critical medical home components, and how to identify PCMH capacity and performance gaps. However, practice staff also reported a variety of challenges, including difficulty learning from other practices that have very different preexisting QI and PCMH capacity and patient populations, or that are working on different topic areas and measures; a sometimes overwhelming amount of materials and ideas covered during in-person meetings; difficulty keeping up with Webinars, calls, and Web sites/blogs; and trouble motivating and sharing information with other practice staff not attending collaborative activities. As the demonstration projects continue, states and the national evaluation team will learn more about how best to use collaboratives and complementary strategies to support child-serving practices in QI and PCMH development. States will also search for ways to sustain and spread these activities after the demonstration ends, if they prove effective.


Time-Course Analysis of Early Meiotic Prophase Events Informs Mechanisms of Homolog Pairing and Synapsis in Caenorhabditis elegans.
Segregation of homologous chromosomes during meiosis depends on their ability to reorganize within the nucleus, discriminate among potential partners, and stabilize pairwise associations through assembly of the synaptonemal complex (SC). Here we report a high-resolution time-course analysis of these key early events during Caenorhabditis elegans meiosis. Labeled nucleotides are incorporated specifically into the X chromosomes during the last 2 hr of S phase, a property we exploit to identify a highly synchronous cohort of nuclei. By tracking X-labeled nuclei through early meiotic prophase, we define the sequence and duration of chromosome movement, nuclear reorganization, pairing at pairing centers (PCs), and SC assembly. Appearance of ZYG-12 foci (marking attachment of PCs to the nuclear envelope) and onset of active mobilization occur within an hour after S-phase completion. Movement occurs for nearly 2 hr before stable pairing is observed at PCs, and autosome movement continues for ∼4 hr thereafter. Chromosomes are tightly clustered during a 2-3 hr postpairing window, during which the bulk of SC assembly occurs; however, initiation of SC assembly can precede evident chromosome clustering. SC assembly on autosomes begins immediately after PC pairing is detected and is completed within ∼3.5 hr. For the X chromosomes, PC pairing is contemporaneous with autosomal pairing, but autosomes complete synapsis earlier (on average) than X chromosomes, implying that X chromosomes have a delay in onset and/or a slower rate of SC assembly. Additional evidence suggests that transient association among chromosomes sharing the same PC protein may contribute to partner discrimination.


Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial.
Antibiotic-associated diarrhea is an important problem in hospitalized patients. The use of probiotics is gaining interest in the scientific community as a potential measure to prevent this complication. The main objective of the present study was to assess the efficacy and safety of a fermented milk combining Lactobacillus acidophilus and Lactobacillus casei that is widely available in Canada, in the prevention of antibiotic-associated diarrhea. In this double-blind, randomized study, hospitalized patients were randomly assigned to receive either a lactobacilli-fermented milk or a placebo on a daily basis. Among 89 randomized patients, antibiotic-associated diarrhea occurred in seven of 44 patients (15.9%) in the lactobacilli group and in 16 of 45 patients (35.6%) in the placebo group (OR 0.34, 95% CI 0.125 to 0.944; P=0.05). The median hospitalization duration was eight days in the lactobacilli group, compared with 10 days in the placebo group (P=0.09). Overall, the lactobacilli-fermented milk was well tolerated. The daily administration of a lactobacilli-fermented milk was safe and effective in the prevention of antibiotic-associated diarrhea in hospitalized patients.


Spectral line interferometry: a proposed means of selectively measuring the change in the density of a specific atomic population.
An extension of the two-wavelength interferogram technique is proposed that will enable selective measurements to be made of the variation in the density of a specific atomic population. One wavelength should be chosen to closely coincide with the wavelength associated with an absorption line of the species of interest, whereas the other wavelength should be displaced by several angstroms from the line. The difference between the fringe shifts on the two interferograms would then enable the density variation of the specific atomic population of interest to be measured with high sensitivity. Two criteria are established that ascertain for any system the minimum density that could be detected, and the range in density variation for which the interferograms should be discernible.


Impact of pre-injury family functioning and resources on self-reported post-concussive symptoms and functional outcomes in persons with mild TBI.
This study investigates the contribution of pre-injury family functioning and resources on self-reported post-concussive symptoms and functional outcomes in persons with mild TBI (mTBI). Participants with uncomplicated or complicated mTBIs were recruited from consecutive admissions to the emergency department of a level 1 trauma centre. Patients completed baseline assessments within 2 weeks of injury and an outcomes assessment at 3 months post-injury. One hundred and sixty-six adults with mTBI were included. Baseline measures of pre-injury history, family functioning and resources were obtained. Functional status assessments and self-reported measures of health, common TBI symptoms and psychological problems were administered at 3-months post-injury. Data reduction of outcome measures using principle components analysis revealed two factors: self-reported post-concussive symptoms and current functional/participation status, explaining 60.53% of the variance. Family resources (β = -0.239, t(150) = -2.84, p = 0.005) and age (β = -0.170, t(150) = -2.19, p = 0.030), but not family functioning, were significant predictors of self-reported post-concussive symptoms at follow-up, R2 = 0.051, F(5, 150) = 4.09, p = 0.002. Neither family resources nor functioning predicted current functional/participation status. Fewer family resources and younger age were associated with increased self-reported post-concussive symptoms. Fewer resources may be a potential risk factor to heightened perception of post-concussive symptoms. Providing low-cost counselling or resource facilitation services may improve outcomes for those with limited resources after mTBI.


High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children.
Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma. To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS. We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: January 2003 Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS. Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies). 31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV(1) ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ). Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS. For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.


A Nearly Complete Genome of Ciona intestinalis Type A (C. robusta) Reveals the Contribution of Inversion to Chromosomal Evolution in the Genus Ciona.
Since its initial publication in 2002, the genome of Ciona intestinalis type A (Ciona robusta), the first genome sequence of an invertebrate chordate, has provided a valuable resource for a wide range of biological studies, including developmental biology, evolutionary biology, and neuroscience. The genome assembly was updated in 2008, and it included 68% of the sequence information in 14 pairs of chromosomes. However, a more contiguous genome is required for analyses of higher order genomic structure and of chromosomal evolution. Here, we provide a new genome assembly for an inbred line of this animal, constructed with short and long sequencing reads and Hi-C data. In this latest assembly, over 95% of the 123 Mb of sequence data was included in the chromosomes. Short sequencing reads predicted a genome size of 114-120 Mb; therefore, it is likely that the current assembly contains almost the entire genome, although this estimate of genome size was smaller than previous estimates. Remapping of the Hi-C data onto the new assembly revealed a large inversion in the genome of the inbred line. Moreover, a comparison of this genome assembly with that of Ciona savignyi, a different species in the same genus, revealed many chromosomal inversions between these two Ciona species, suggesting that such inversions have occurred frequently and have contributed to chromosomal evolution of Ciona species. Thus, the present assembly greatly improves an essential resource for genome-wide studies of ascidians.


Development of inpatient risk stratification models of acute kidney injury for use in electronic health records.
Patients with hospital-acquired acute kidney injury (AKI) are at risk for increased mortality and further medical complications. Evaluating these patients with a prediction tool easily implemented within an electronic health record (EHR) would identify high-risk patients prior to the development of AKI and could prevent iatrogenically induced episodes of AKI and improve clinical management. The authors used structured clinical data acquired from an EHR to identify patients with normal kidney function for admissions from 1 August 1999 to 31 July 2003. Using administrative, computerized provider order entry and laboratory test data, they developed a 3-level risk stratification model to predict each of 2 severity levels of in-hospital AKI as defined by RIFLE criteria. The severity levels were defined as 150% or 200% of baseline serum creatinine. Model discrimination and calibration were evaluated using 10-fold cross-validation. Cross-validation of the models resulted in area under the receiver operating characteristic (AUC) curves of 0.75 (150% elevation) and 0.78 (200% elevation). Both models were adequately calibrated as measured by the Hosmer-Lemeshow goodness-of-fit test chi-squared values of 9.7 (P = 0.29) and 12.7 (P = 0.12), respectively. The authors generated risk prediction models for hospital-acquired AKI using only commonly available electronic data. The models identify patients at high risk for AKI who might benefit from early intervention or increased monitoring.


Lack of iNOS facilitates MCMV spread in the retina.
The purposes of this study were to identify iNOS-producing retinal cells and to determine whether lack of iNOS facilitates MCMV spread and replication in the retina. Immunosuppressed (IS) iNOS(-/-) mice or C57BL/6 (wild-type) mice were inoculated with 5 x 10(4) PFU of MCMV K181 strain (K181) via the supraciliary route. Injected eyes were collected at several times after inoculation and examined by plaque assay for replicating virus, RT-PCR for iNOS RNA, Western blot for iNOS protein and by staining for MCMV early antigen (EA), iNOS, and retinal cell antigens. iNOS mRNA and iNOS proteins were expressed in the MCMV-injected eye of wild-type mice. Most iNOS-producing cells were F4/80-positive, including macrophages, RPE-derived macrophages, and resident microglia. Significantly higher titers of virus were recovered from the injected eyes, and more infected cells were detected in the retina of IS iNOS(-/-) mice than in IS wild-type mice. Retinal necrosis and loss of retinal architecture throughout the retina were noted in IS iNOS(-/-) mice, whereas cytomegalic cells and retinitis were present only in the peripheral retina of IS wild-type mice. iNOS produced by macrophages, especially resident macrophages including microglia and RPE derived macrophages, plays an important role in limiting spread of MCMV in the retina.


Deintensification of Treatment With Sulfonylurea and Insulin After Severe Hypoglycemia Among Older Adults With Diabetes.
Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated emergency department (ED) visit or hospitalization among older adults with diabetes and to identify factors associated with deintensification of treatment. This retrospective cohort study included a random sample of 20% of nationwide fee-for-service US Medicare beneficiaries aged 65 years and older with concurrent Medicare parts A, B, and D coverage between January 1, 2007, and December 31, 2017. Individuals with diabetes who had at least 1 hypoglycemia-associated ED visit or hospitalization were included. Data were analyzed from August 1, 2020, to August 1, 2021. Baseline medication for the treatment of diabetes (sulfonylurea, insulin, or both). Incidence of treatment deintensification (yes or no) in the 100 days after a severe hypoglycemic episode requiring an ED visit or hospitalization, with treatment deintensification defined as (1) a decrease in sulfonylurea dose, (2) a change from long-acting to short-acting sulfonylurea (glipizide), (3) discontinuation of sulfonylurea, or (4) discontinuation of insulin based on pharmacy dispensing claims. Among 76 278 distinct Medicare beneficiaries who had a hypoglycemia-associated ED visit or hospitalization, the mean (SD) age was 76.6 (7.6) years. Of 106 293 total hypoglycemic episodes requiring hospital attention, 69 084 (65.0%) occurred among women, 26 056 (24.5%) among Black individuals; 4761 (4.5%) among Hispanic individuals; 69 704 (65.6%) among White individuals; and 5772 (5.4%) among individuals of other races and ethnicities (comprising Asian, North American Native, unknown race or ethnicity, and unspecified race or ethnicity). A total of 32 074 episodes (30.2%) occurred among those receiving sulfonylurea only, 60 350 (56.8%) occurred among those receiving insulin only, and 13 869 (13.0%) occurred among those receiving both sulfonylurea and insulin. Treatment deintensification rates were highest among individuals receiving both sulfonylurea and insulin therapies at the time of their hypoglycemic episode (6677 episodes [48.1%]), followed by individuals receiving sulfonylurea only (14 192 episodes [44.2%]) and insulin only (14 495 episodes [24.0%]). Treatment deintensification rates increased between 2007 and 2017 (sulfonylurea only: from 41.4% to 49.7%; P < .001 for trend; insulin only: from 21.3% to 25.9%; P < .001 for trend; sulfonylurea and insulin: from 45.9% to 49.6%; P = .005 for trend). Lower socioeconomic status (as indicated by the receipt of low-income subsidies) was associated with lower odds of deintensification, regardless of baseline hypoglycemic regimen (sulfonylurea only: adjusted odds ratio [AOR], 0.74 [95% CI, 0.70-0.78]; insulin only: AOR, 0.71 [95% CI, 0.68-0.75]; sulfonylurea and insulin: AOR, 0.72 [95% CI, 0.66-0.78]). A number of patient factors were associated with higher odds of treatment deintensification: higher frailty (eg, ≥40% probability of needing assistance with activities of daily living among those receiving sulfonylurea and insulin: AOR, 1.50; 95% CI, 1.32-1.71), chronic kidney disease (eg, sulfonylurea and insulin: AOR, 1.29; 95% CI, 1.19-1.40), a history of falls (eg, sulfonylurea and insulin: AOR, 1.20; 95% CI, 1.09-1.33), and depression (eg, sulfonylurea and insulin: AOR, 1.11; 95% CI, 1.02-1.20). In this cohort study, deintensification of sulfonylurea and/or insulin therapy within 100 days after a hypoglycemia-associated ED visit or hospitalization occurred in fewer than 50% of older adults with diabetes; however, these deintensification rates may be increasing over time, and deintensification of insulin was likely underestimated because of challenges in capturing changes to insulin dosing using administrative claims data. These results suggest that greater efforts are needed to identify individuals at high risk of hypoglycemia to encourage appropriate treatment deintensification in accordance with current evidence.


Fenugreek powder exerts protective effects on alcoholised rats' kidney, highlighted using ultrastructural studies.
Trigonella foenum-graecum (TFG) seeds exert a protective antioxidant effect and membrane protector through their rich content in polyphenolic flavonoids. The previous research focused on the hypoglycemic action of the seeds, with scarce studies on the preventive effects in the pathology of the kidney. Our work was conducted on an experimental in vivo model; the animals were given two different concentrations of TFG seeds, consequently to alcohol intoxication. Transmission electron microscopy (TEM) analysis showed vacuolation in cytoplasm, edemas at the apical pole of the nephrocytes, diffusion of the cytoplasmic and mitochondrial matrix and the increase in number of the lysozymes and especially peroxisomes, as well as the congestion of blood capillaries. In the case of the groups T5R and T10R, which received Trigonella powder together with ethanol, the structural and ultrastructural changes produced by the ethylic intoxication were more reduced, being somewhat improved in the T5R group. Therefore, the majority of the cells nuclei have retained their spherical shape, being at the same time predominantly euchromatic, with little heterochromatin and evenly dispersed. Our results suggest the use of Trigonella seeds as a food supplement to prevent cellular deterioration and improve renal morphology and function.


PPARs in atherosclerosis: the clot thickens.
Cardiovascular disease is the leading cause of morbidity and mortality in Western countries. Previous studies have highlighted the beneficial effects of PPARgamma activators on cardiovascular disease; however, the role of other PPAR family members in atherosclerosis is less clear. A report in this issue of the JCI expands our understanding of PPARs in vascular biology and highlights the potential use of multiple PPAR agonists to limit lipid accumulation in macrophages.


Erinacine A-enriched Hericium erinaceus mycelia promotes longevity in Drosophila melanogaster and aged mice.
Erinacine A-enriched Hericium erinaceus mycelia is a well-established potential therapeutic agent for neurodegenerative disorders. However, the effect of erinacine A-enriched H. erinaceus mycelia on promoting longevity remains unclear. This is the first study to investigate the effect of erinacine A-enriched H. erinaceus mycelia on lifespan-prolonging activity in Drosophila melanogaster and senescence-accelerated P8 (SAMP8) mice. Two hundred D. melanogaster and 80 SAMP8 mice of both sexes were randomly divided into four groups and were administered with either the standard, low-dose, mid-dose, or high-dose erinacine A-enriched H. erinaceus mycelia. After treatment, the lifespan was measured in D. melanogaster, and the lifespan, food intake and oxidative damage were evaluated in SAMP8 mice. Results showed that supplementation with erinacine A-enriched H. erinaceus mycelia extended the lifespan in both D. melanogaster and SAMP8 by a maximum of 32% and 23%, respectively, compared to the untreated controls. Moreover, erinacine A-enriched H. erinaceus mycelia decreased TBARS levels and induced the anti-oxidative enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Together, these findings suggest that erinacine A-enriched H. erinaceus mycelia supplement could promote longevity, mediated partly through the induction of endogenous antioxidants enzymes.


The Greek Goddess, Artemis, reveals the secrets of her cleavage.
A recent paper in Cell by Ma et al. [Cell 8 (2002) 781] showed that the protein Artemis cleaves a hairpin intermediate during V(D)J recombination. Peter O'Neill and Penny Jeggo discuss this finding in the light of evidence that Artemis also functions to repair radiation damage [Cell 105 (2001) 177]. The findings suggest that Artemis may function in double strand break repair by "tidying up" double strand ends with associated base damage. The development of genetic diversity during immune development, therefore, seems to exploit damage response mechanisms that function to maintain genetic stability in other cell lineages.


Effects of Maternal Singing Style on Mother-Infant Arousal and Behavior.
Mothers around the world sing to infants, presumably to regulate their mood and arousal. Lullabies and playsongs differ stylistically and have distinctive goals. Mothers sing lullabies to soothe and calm infants and playsongs to engage and excite infants. In this study, mothers repeatedly sang Twinkle, Twinkle, Little Star to their infants (n = 30 dyads), alternating between soothing and playful renditions. Infant attention and mother-infant arousal (i.e., skin conductivity) were recorded continuously. During soothing renditions, mother and infant arousal decreased below initial levels as the singing progressed. During playful renditions, maternal and infant arousal remained stable. Moreover, infants exhibited greater attention to mother during playful renditions than during soothing renditions. Mothers' playful renditions were faster, higher in pitch, louder, and characterized by greater pulse clarity than their soothing renditions. Mothers also produced more energetic rhythmic movements during their playful renditions. These findings highlight the contrastive nature and consequences of lullabies and playsongs.


Highly active electrolytes for rechargeable Mg batteries based on a [Mg2(μ-Cl)2](2+) cation complex in dimethoxyethane.
A novel [Mg2(μ-Cl)2](2+) cation complex, which is highly active for reversible Mg electrodeposition, was identified for the first time in this work. This complex was found to be present in electrolytes formulated in dimethoxyethane (DME) through dehalodimerization of non-nucleophilic MgCl2 by reacting with either Mg salts (such as Mg(TFSI)2, TFSI = bis(trifluoromethane)sulfonylimide) or Lewis acid salts (such as AlEtCl2 or AlCl3). The molecular structure of the cation complex was characterized by single crystal X-ray diffraction, Raman spectroscopy and NMR. The electrolyte synthesis process was studied and rational approaches for formulating highly active electrolytes were proposed. Through control of the anions, electrolytes with an efficiency close to 100%, a wide electrochemical window (up to 3.5 V) and a high ionic conductivity (>6 mS cm(-1)) were obtained. The understanding of electrolyte synthesis in DME developed in this work could bring significant opportunities for the rational formulation of electrolytes of the general formula [Mg2(μ-Cl)2][anion]x for practical Mg batteries.


5-Iodo-A-85380, an alpha4beta2 subtype-selective ligand for nicotinic acetylcholine receptors.
In an effort to develop selective radioligands for in vivo imaging of neuronal nicotinic acetylcholine receptors (nAChRs), we synthesized 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with (125)I and (123)I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[(125)I]iodo-A-85380 for alpha4beta2 nAChRs in rat and human brain is defined by K(d) values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the alpha4beta2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing alpha3 and beta4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at alpha7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[(125)I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the beta2 subunit of nAChRs. Binding of 5-[(125)I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate of dissociation of the receptor-ligand complex (t(1/2) for dissociation approximately 2 h). These properties, along with other features observed previously in in vivo experiments (low toxicity, rapid penetration of the blood-brain barrier, and a high ratio of specific to nonspecific binding), suggest that this compound, labeled with (125)I or (123)I, is superior to other radioligands available for in vitro and in vivo studies of alpha4beta2 nAChRs, respectively.


CONFOUNDER ADJUSTMENT IN MULTIPLE HYPOTHESIS TESTING.
We consider large-scale studies in which thousands of significance tests are performed simultaneously. In some of these studies, the multiple testing procedure can be severely biased by latent confounding factors such as batch effects and unmeasured covariates that correlate with both primary variable(s) of interest (e.g., treatment variable, phenotype) and the outcome. Over the past decade, many statistical methods have been proposed to adjust for the confounders in hypothesis testing. We unify these methods in the same framework, generalize them to include multiple primary variables and multiple nuisance variables, and analyze their statistical properties. In particular, we provide theoretical guarantees for RUV-4 [Gagnon-Bartsch, Jacob and Speed (2013)] and LEAPP [Ann. Appl. Stat. 6 (2012) 1664-1688], which correspond to two different identification conditions in the framework: the first requires a set of "negative controls" that are known a priori to follow the null distribution; the second requires the true nonnulls to be sparse. Two different estimators which are based on RUV-4 and LEAPP are then applied to these two scenarios. We show that if the confounding factors are strong, the resulting estimators can be asymptotically as powerful as the oracle estimator which observes the latent confounding factors. For hypothesis testing, we show the asymptotic z-tests based on the estimators can control the type I error. Numerical experiments show that the false discovery rate is also controlled by the Benjamini-Hochberg procedure when the sample size is reasonably large.


Knowledge, attitudes, and practice of medical students regarding occupational risks of hepatitis B virus in college of medicine, aljouf university.
Medical students represent a population that is at high-risk group for acquiring and spreading hepatitis B infection (HBV). This study was designed to evaluate the knowledge and attitudes among male student regarding occupational risks of HBV infection. During March 2013, a descriptive cross-sectional study was conducted on medical students of AlJouf University College of Medicine. Structured questionnaires of 16 different statements concerning knowledge base of HBV, attitudes as well as practices toward occupational risks of hepatitis B were distributed to 120 students. Response rate of 76.7% (92/120) yielded 92 questionnaires for analysis. Majority of the students surveyed 62.0% (57/92) perceived that they are at high risk of contracting and spreading HBV. The rate of this perception among students who had a history of training on universal precautions was more than that found among those who did not have (70.8% vs. 58.8%; P < 0.01). Most of the students surveyed 63.0% (58/92) considered vaccine is safe and more than half 52.2% (48/92) were vaccinated against HBV. There were a very strong agreement about needlestick 92.4% (85/92) and blood 87.0% (80/92) as efficient modes of HBV transmission. Seventy-two percent of the participants did not have any knowledge about post-exposure prophylaxis for hepatitis B. A significant relationship was found between students who had a history of training on universal precautions and knowledge about post needlestick injury (P < 0.01). Infectious occupational risk of hepatitis B remains a challenge for medical students and the foundations of the medical institutes. Students must complete an infection control training before they start their clinical education.


Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial.
The RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 ( www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8-12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8-12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months. Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory.


Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort.
Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days). With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.


Derived structure of the putative sialic acid transporter from Escherichia coli predicts a novel sugar permease domain.
Catabolism of sialic acids by Escherichia coli requires the genes nanA and nanT, which were previously mapped between argG and rpoN (E.R. Vimr and F.A. Troy, J. Bacteriol. 164:845-853, 1985). This organization is confirmed and extended by physical mapping techniques. An open reading frame beginning 135 bp from the nanA translational stop codon could code for a 53,547-Da hydrophobic polypeptide predicted to contain 14 transmembrane segments. Complementation analysis confirmed that nanT is required for sialic acid uptake when expressed in trans. NanT is homologous to a putative permease encoded by open reading frame 425, which maps between leuX and fecE in the E. coli chromosome. However, unlike this hypothetical permease or previously reported monosaccharide transporters, NanT contains a centrally located domain with two additional potential membrane-spanning segments plus one amphiphilic alpha-helix that may be important for the structure and function of sialic acid-permease.


Bone morphogenetic protein promotes vascularization and osteoinduction in preformed hydroxyapatite in the rabbit.
Early reconstruction of large osseous defects in children is often delayed due to limited availability of autogenous bone graft donor sites. With the advent of growth factors, osteoinductive proteins, and delivery matrices, it is possible to fabricate new bone at extraskeletal sites. Due to their own blood supply, adequate bony volume, and decreased resorption, vascularized bone flaps have demonstrated greater success in restoring large bony defects compared with nonvascularized bone grafts. The purpose of this study is to prefabricate a vascularized bone flap in the immature-age rabbit using the auricularis anterior muscle as a muscle pedicle. Sixteen female New Zealand White rabbits, 2.0 to 2.5 kg, were divided into two groups. Group 1 contained 8 animals that had T-shaped, 10 x 6 x 4-mm hydroxyapatite (HA) implants combined with 100-microgram bovine-derived bone morphogenetic protein (BMP) placed supraperiosteally and fixed deep to the auricularis anterior muscle. Implants with HA alone were placed in the same animal and secured to the contralateral auricularis anterior muscle. Group 2 contained 8 animals that had HA/BMP placed subperiosteally and fixed deep to the auricularis anterior muscle, while implants with HA alone were secured in the same animal to the contralateral auricularis anterior muscle. In each group, 4 animals were sacrificed at 4 and 8 weeks. The animals underwent randomized bilateral carotid artery injection with micropaque barium suspension just prior to sacrifice to help maintain vascularity. At harvest the implants and surrounding muscle and cranium were removed en bloc. New bone formation in the HA implants was examined by using routine histology and scanning electron microscopic backscattering image (quantitative) analysis. Microradiographs were performed on representative specimens. At 4 weeks postimplantation, backscattering analysis in the subperiosteal HA/BMP showed a mean 17.1% bone ingrowth vs. 11.3% of HA alone (p < 0.05). Supraperiosteal HA/BMP showed a mean 12.9% bone ingrowth vs. 0% of HA alone (p < 0.05). At 8 weeks, backscatter analysis of supraperiosteal HA/BMP showed a mean 19.33% bone ingrowth vs. 0% of HA alone (p < 0.05). Subperiosteal HA/BMP showed a mean 22% bone ingrowth vs. 20.85% of HA alone. This was the only group that did not have statistically significant results. Implant histology demonstrated woven bone within the interstices of HA/BMP placed either supra- or subperiosteally. In the HA-alone implants placed supraperiosteally, fibrovascular ingrowth was seen without any evidence of bone formation. In the HA-alone implant placed subperiosteally, woven bone was seen at the calvarium-implant junction. Microradiographs also demonstrated vascularization and bone formation similar to that seen on scanning electron microscopy. BMP-treated specimens appeared to have slightly greater vascularity than the nontreated specimens. The greatest bone formation occurred with the HA/BMP implant placed subperiosteally in the immature rabbit. Furthermore, these results demonstrate the potential prefabrication of vascularized bone flaps as early as 4 to 8 weeks. The clinical advantage of HA permits the surgeon to design osseous flaps that are customized in shape, fill all contour defects, and have little resorptive properties. Such prefabricated bone with an axial blood supply may allow for ultimate transfer as a pedicle or free flap to reconstruct osseous defects in children.


Single-image separation measurements of two unresolved fluorophores.
Measuring subdiffraction separations between single fluorescent particles is important for biological, nano-, and medical-technology studies. Major challenges include (i) measuring changing molecular separations with high temporal resolution while (ii) using identical fluorescent labels. Here we report a method that measures subdiffraction separations between two identical fluorophores by using a single image of milliseconds exposure time and a standard single-molecule fluorescent imaging setup. The fluorophores do not need to be bleached and the separations can be measured down to 40 nm with nanometer precision. The method is called single-molecule image deconvolution--SMID, and in this article it measures the standard deviation (SD) of Gaussian-approximated combined fluorescent intensity profiles of the two subdiffraction-separated fluorophores. This study enables measurements of (i) subdiffraction dimolecular separations using a single image, lifting the temporal resolution of seconds to milliseconds, while (ii) using identical fluorophores. The single-image nature of this dimer separation study makes it a single-image molecular analysis (SIMA) study.


Effect of surface preparation on bond strength of resin luting cements to dentin.
This study examined the effects of using two different burs for dentin surface preparation on the microtensile bond strength (microTBS) of three resin luting cements. Flat, deep dentin surfaces from 45 extracted human third molars were divided into three groups (n = 15) according to bur type: (i) diamond bur and (ii) tungsten carbide bur. The controls were abraded with #600-grit SiC paper. Both burs operated in a high-speed handpiece under water-cooling. Composite blocks were luted onto the dentin using one of three cements: RelyX ARC (ARC, 3M ESPE), Panavia F2.0 (PF, Kuraray) and RelyX Unicem (UN, 3M ESPE) following the manufacturers' instructions. For ARC, the dentin surface was treated with 32% phosphoric acid. The bonded specimens were stored at 37 degrees C for 24 hours and sectioned into 0.9 x 0.9 mm beams for microTBS testing. The data were analyzed using the two-way ANOVA and Student-Newman-Keuls tests. Representative fractured beams from each group were prepared for fractographic analysis under SEM. Two-way ANOVA revealed that the effects of "dentin surface preparation" and "luting cement" were statistically significant (p < 0.001); however, the interaction of these two factors was not significant (p > 0.05). ARC showed no significant difference in microTBS among the three differently prepared dentin surfaces. The microTBS of PF and UN was significantly lower when bonding to dentin prepared with a diamond bur (p < 0.05), compared to the control. For Panavia F2.0, higher bond strengths were achieved on the dentin surface prepared with a tungsten carbide bur. Proper bur selection is essential to optimizing the dentin adhesion of self-etch resin luting cements.


Admixture facilitates adaptation from standing variation in the European aspen (Populus tremula L.), a widespread forest tree.
Adaptation to new environments can start from new mutations or from standing variation already present in natural populations. Whether admixture constrains or facilitates adaptation from standing variation is largely unknown, especially in ecological keystone or foundation species. We examined patterns of neutral and adaptive population divergence in Populus tremula L., a widespread forest tree, using mapped molecular genetic markers. We detected the genetic signature of postglacial admixture between a Western and an Eastern lineage of P. tremula in Scandinavia, an area suspected to represent a zone of postglacial contact for many species of animals and plants. Stringent divergence-based neutrality tests provided clear indications for locally varying selection at the European scale. Six of 12 polymorphisms under selection were located less than 1 kb away from the nearest gene predicted by the Populus trichocarpa genome sequence. Few of these loci exhibited a signature of 'selective sweeps' in diversity-based tests, which is to be expected if adaptation occurs primarily from standing variation. In Scandinavia, admixture explained genomic patterns of ancestry and the nature of clinal variation and strength of selection for bud set, a phenological trait of great adaptive significance in temperate trees, measured in a common garden trial. Our data provide a hitherto missing direct link between past range shifts because of climatic oscillations, and levels of standing variation currently available for selection and adaptation in a terrestrial foundation species.


Stem cells, cancer, and cancer stem cells.
Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis.


Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis.
Resistance and aerobic exercises are both recommended as effective treatments for people with type 2 diabetes. However, the optimum type of exercise for the disease remains to be determined to inform clinical decision-making and facilitate personalized exercise prescription. Our objective was to investigate whether resistance exercise is comparable to aerobic exercise in terms of effectiveness and safety in people with type 2 diabetes. PubMed, EMBASE, CENTRAL, CINAHL, and SPORTdiscus were systematically searched up to March 2013. The reference lists of eligible studies and relevant reviews were also checked. We used the following criteria to select studies for inclusion in the review: (i) the study was a randomized controlled trial; (ii) the participants were people with type 2 diabetes aged 18 years or more; (iii) the trial compared resistance exercise with aerobic exercise for a duration of at least 8 weeks, with pre-determined frequency, intensity, and duration; and (iv) the trial provided relevant data on at least one of the following: glycaemic control, blood lipids, anthropometric measures, blood pressure, fitness, health status, and adverse events. The assessment of study quality was based on the Cochrane Risk of Bias tool. For effectiveness measures, differences (resistance group minus aerobic group) in the changes from baseline with the two exercises were combined, using a random-effects model wherever possible. For adverse events, the relative risks (resistance group vs. aerobic group) were combined. Twelve trials (n = 626) were included. Following the exercise interventions, there was a greater reduction of glycosylated hemoglobin with aerobic exercise than with resistance exercise (difference 0.18% (1.97 mmol/mol), 95% confidence interval (CI) 0.01, 0.36). This difference became non-significant with sensitivity analysis (p = 0.14). The differences in changes from baseline were also statistically significant for body mass index (difference 0.22, 95% CI 0.06, 0.39), peak oxygen consumption (difference -1.84 mL/kg/min, 95% CI -3.07, -0.62), and maximum heart rate (difference 3.44 beats per minute, 95% CI 2.49, 4.39). Relative risks for adverse events (all) and serious adverse events were 1.17 (95% CI 0.77, 1.79) and 0.89 (95% CI 0.18, 4.39), respectively. Most included trials were short term (8 weeks to 6 months), and seven had important methodological limitations. Additionally, the meta-analyses for some of the secondary outcomes had a small number of participants or substantial statistical heterogeneity. Although differences in some diabetic control and physical fitness measures between resistance exercise and aerobic exercise groups reached statistical significance, there is no evidence that they are of clinical importance. There is also no evidence that resistance exercise differs from aerobic exercise in impact on cardiovascular risk markers or safety. Using one or the other type of exercise for type 2 diabetes may be less important than doing some form of physical activity. Future long-term studies focusing on patient-relevant outcomes are warranted.


Changes in dispersal during species' range expansions.
Explanations for rapid species' range expansions have typically been purely ecological, with little attention given to evolutionary processes. We tested predictions for the evolution of dispersal during range expansion using four species of wing-dimorphic bush cricket (Conocephalus discolor, Conocephalus dorsalis, Metrioptera roeselii, and Metrioptera brachyptera). We observed distinct changes in dispersal in the two species with expanding ranges. Recently colonized populations at the range margin showed increased frequencies of dispersive, long-winged (macropterous) individuals, compared with longer-established populations in the range core. This increase in dispersal appeared to be short-lived because 5-10 years after colonization populations showed similar incidences of macroptery to populations in the range core. These changes are consistent with evolutionary change; field patterns persisted when nymphs were reared under controlled environmental conditions, and range margin individuals reared in the laboratory flew farther than range core individuals in a wind tunnel. There was also a reproductive trade-off with dispersal in both females and males, which could explain the rapid reversion to lower rates of dispersal once populations become established. The effect of population density on wing morphology differed between populations from the range core (no significant effect of density) and expanding range margins (negative density dependence), which we propose is part of the mechanism of the changes in dispersal. Transient changes in dispersal are likely to be common in many species undergoing range expansion and can have major population and biogeographic consequences.


Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population.
Hereditary fructose intolerance (HFI) causes severe and sometimes fatal metabolic disturbances in infants and children but responds to dietary treatment. To determine the practicability of screening newborn infants for HFI, we have investigated the frequency of the most common and widespread mutant allele of aldolase B, A149P, in the neonatal population. The polymerase chain reaction was used to amplify aldolase B exon 5 genomic sequences in DNA present in dried blood specimens preserved on Guthrie cards. The A149P mutation was identified by discriminatory hybridisation to allele specific oligonucleotides and confirmed independently by digestion with the restriction endonuclease BsaHI. Twenty-seven A149P heterozygotes were identified by the molecular analysis of aldolase B genes in blood samples obtained from a random cohort of 2050 subjects born in 1994 and 1995, 1.32 +/- 0.49% (95% confidence level). Although no A149P homozygotes were identified, the data allow the frequency of 1 in 23,000 homozygotes for this allele to be predicted. Our findings have implications for establishing an interventional mass screening programme to identify newborn infants with HFI in the UK.


Revisiting the notion of deleterious sweeps.
It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites-both in the presence and absence of interference amongst deleterious mutations-and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.


Does the Medicare Part D Decision-Making Experience Differ by Rural/Urban Location?
Although much has been written about Medicare Part D enrollment, much less is known about beneficiaries' personal experiences with choosing a Part D plan, especially among rural residents. This study sought to address this gap by examining geographic differences in Part D enrollees' perceptions of the plan decision-making process, including their confidence in their choice, their knowledge about the program, and their satisfaction with available information. We used data from the 2012 Medicare Current Beneficiary Survey and included adults ages 65 and older who were enrolled in Part D at the time of the survey (n = 3,706). We used ordered logistic regression to model 4 outcomes based on beneficiaries' perceptions of the Part D decision-making and enrollment process, first accounting only for differences by rurality, then adjusting for sociodemographic, health, and coverage characteristics. Overall, half of all beneficiaries were not very confident in their Part D knowledge. Rural beneficiaries had lower odds of being confident in the plan they chose and in being satisfied with the amount of information available to them during the decision-making process. After adjusting for all covariates, micropolitan residents continued to have lower odds of being confident in the plan that they chose. Policy-makers should pay particular attention to making information about Part D easily accessible for all beneficiaries and to addressing unique barriers that rural residents have in accessing information while making decisions, such as reduced Internet availability. Furthermore, confidence in the decision-making process may be improved by simplifying the Part D program.


Cross-sensitization of histamine-independent itch in mouse primary sensory neurons.
Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and -independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8-22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8-22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8-22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8-22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8-22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.


Pre-dialysis hospital use and late referrals in incident dialysis patients in England: a retrospective cohort study.
Timely referral to specialist kidney care can improve outcomes for patients and delay the onset of dialysis, yet late referral (LR) remains a problem in many countries. We aimed to estimate the proportion of LRs that could potentially have been detected earlier because of increases in patients' general hospital activity. A cohort of patients starting dialysis in the English NHS (National Health Service) during 2010/11 was approximated using hospital administrative data. The time between first recorded contact with a consultant nephrologist and starting dialysis was used to categorize the timeliness of referral. Monthly rates of inpatient activity prior to starting dialysis for both referral types were compared with the national average. A cohort of 3928 patients was detected. One-third (34%) of the cohort started dialysis <90 days after their first referral to a nephrologist. Rates were higher for patients starting haemodialysis than peritoneal dialysis. The proportion of patients receiving their first dialysis as an emergency rises from 27% for those referred before 3 months to 67% for those referred on or after the day of starting dialysis. Half of the late referred patients (49%) have hospital activity rates more than double the national average (adjusted for age and sex) at 90 days before they start dialysis. A substantial proportion of patients (49%) referred late for specialist kidney care have had regular contact with other hospital services. This could represent a missed opportunity to improve outcomes by timely management of their kidney disease.


Application of the microarray technology to the transcriptional analysis of muscle phenotypes in pigs.
The transcriptome refers to the collection of all transcripts present in a cell. Gene expression has a very dynamic nature; it acts as a bridge between epigenetic marks, DNA sequence and proteins and changes to accommodate the requirements of the cell at each given time. Recent technological advances have created new opportunities to study complex phenotypes from a global point of view. From an animal production perspective, muscle transcriptomics has been investigated in relation to muscle growth, carcass fattening and meat quality traits. In this review, we discuss the impact of nutritional, anatomical and genetic factors on muscle gene expression and meat quality of pigs assessed by microarray technologies. Altogether, several common themes have been revealed by the in-depth analysis of the current body of knowledge, for instance, the involvement of genes related to energy balance and substrate turnover in the oxidative/glycolytic phenotype of red/white muscle fibre types and in the storage of intramuscular fat. The review also covers recent advances in the discovery of expression QTL and regulatory RNAs in porcine breeds as well as technical developments in the field of deep-sequencing technologies that are expected to substantially increase our knowledge about the genetic architecture of meat quality and production traits.


Validation of image-based method for extraction of coronary morphometry.
An accurate analysis of the spatial distribution of blood flow in any organ must be based on detailed morphometry (diameters, lengths, vessel numbers, and branching pattern) of the organ vasculature. Despite the significance of detailed morphometric data, there is relative scarcity of data on 3D vascular anatomy. One of the major reasons is that the process of morphometric data collection is labor intensive. The objective of this study is to validate a novel segmentation algorithm for semi-automation of morphometric data extraction. The utility of the method is demonstrated in porcine coronary arteries imaged by computerized tomography (CT). The coronary arteries of five porcine hearts were injected with a contrast-enhancing polymer. The coronary arterial tree proximal to 1 mm was extracted from the 3D CT images. By determining the centerlines of the extracted vessels, the vessel radii and lengths were identified for various vessel segments. The extraction algorithm described in this paper is based on a topological analysis of a vector field generated by normal vectors of the extracted vessel wall. With this approach, special focus is placed on achieving the highest accuracy of the measured values. To validate the algorithm, the results were compared to optical measurements of the main trunk of the coronary arteries with microscopy. The agreement was found to be excellent with a root mean square deviation between computed vessel diameters and optical measurements of 0.16 mm (<10% of the mean value) and an average deviation of 0.08 mm. The utility and future applications of the proposed method to speed up morphometric measurements of vascular trees are discussed.


Immunotherapy for food allergy.
Although the current standard care for patients with food allergy is based on avoidance of the trigger foods with hope of possible gain of tolerance, increasing number of studies have shown that oral immunotherapy is a promising approach. Understanding the transcutaneous sensitization and oral immune tolerance to food antigens has shifted focus of treatment and prevention. However, more studies are warranted to elucidate the underlying mechanisms and to clarify the indication criteria to which type of patients this therapy should be applied. Easy and uncontrolled use of elimination diets for atopic dermatitis might have increased and exacerbated food allergy, and thorough innovation of our whole concept for food allergy is now required.


Impacts of increasing typhoons on the structure and function of a subtropical forest: reflections of a changing climate.
Due to their destructive and sporadic nature, it is often difficult to evaluate and predict the effects of typhoon on forest ecosystem patterns and processes. We used a 21-yr record of litterfall rates to explore the influence of typhoon frequency and intensity, along with other meteorological variables, on ecosystem dynamics in a subtropical rainforest. Over the past half century there has been an increasing frequency of strong typhoons (category 3; >49.6 m s-1; increase of 1.5 typhoons/decade) impacting the Fushan Experimental Forest, Taiwan. At Fushan strong typhoons drive total litterfall mass with an average of 1100 kg ha-1 litterfall typhoon-1. While mean typhoon season litterfall has been observed to vary by an order of magnitude, mean litterfall rates associated with annual leaf senescence vary by <20%. In response to increasing typhoon frequency, total annual litter mass increased gradually over the 21-year record following three major typhoons in 1994. Monthly maximum wind speed was predictive of monthly litterfall, yet the influence of precipitation and temperature was only evident in non-typhoon affected months. The response of this subtropical forest to strong typhoons suggests that increasing typhoon frequency has already shifted ecosystem structure and function (declining carbon sequestration and forest stature).


Coronary artery Calcium predicts Cardiovascular events in participants with a low lifetime risk of Cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA).
Patients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA). MESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol ≤ 200 mg/dL, systolic BP ≤ 139 mmHg, and diastolic BP ≤ 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100. Over 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively. While 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications.


454-pyrosequencing: a molecular battiscope for freshwater viral ecology.
Viruses, the most abundant biological entities on the planet, are capable of infecting organisms from all three branches of life, although the majority infect bacteria where the greatest degree of cellular diversity lies. However, the characterization and assessment of viral diversity in natural environments is only beginning to become a possibility. Through the development of a novel technique for the harvest of viral DNA and the application of 454 pyrosequencing, a snapshot of the diversity of the DNA viruses harvested from a standing pond on a cattle farm has been obtained. A high abundance of viral genotypes (785) were present within the virome. The absolute numbers of lambdoid and Shiga toxin (Stx) encoding phages detected suggested that the depth of sequencing had enabled recovery of only ca. 8% of the total virus population, numbers that agreed within less than an order of magnitude with predictions made by rarefaction analysis. The most abundant viral genotypes in the pond were bacteriophages (93.7%). The predominant viral genotypes infecting higher life forms found in association with the farm were pathogens that cause disease in cattle and humans, e.g. members of the Herpesviridae. The techniques and analysis described here provide a fresh approach to the monitoring of viral populations in the aquatic environment, with the potential to become integral to the development of risk analysis tools for monitoring the dissemination of viral agents of animal, plant and human diseases.


Serine-threonine protein kinase activity of Elm1p, a regulator of morphologic differentiation in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae gene ELM1 regulates morphologic differentiation and its nucleotide sequence predicts a novel protein kinase. Elm1p was expressed in yeast and insect cells and purified. Elm1p displayed protein kinase activity in autophosphorylation assays and towards exogenous substrates. Serine and threonine residues were identified as the acceptors in these reactions. These data together with previous genetic analysis of ELM1 function indicate that phosphorylation on serine and/or threonine residues of a particular substrate or set of substrates by Elm1p is required for repression of the filamentous growth differentiation state.


Economic evaluations of adult weight management interventions: a systematic literature review focusing on methods used for determining health impacts.
One of the challenges when undertaking economic evaluations of weight management interventions is to adequately assess future health impacts. Clinical trials commonly measure impacts using surrogate outcomes, such as reductions in body mass index, and investigators need to decide how these can best be used to predict future health effects. Since obesity is associated with an increased risk of numerous chronic diseases occurring at different future time points, modelling is needed for predictions. To assess the methods used in economic evaluations to determine health impacts of weight management interventions and to investigate whether differences in methods affect the cost-effectiveness estimates. Eight databases were systematically searched. Included studies were categorized according to a decision analytic approach and effect measures incorporated. A total of 44 articles were included; 21 evaluated behavioural interventions, 12 evaluated surgical procedures and 11 evaluated pharmacological compounds. Of the 27 papers that estimated future impacts, eleven used Markov modelling, seven used a decision tree, five used a mathematical application, two used patient-level simulation and the modelling method was unclear in two papers. The most common types of effects included were co-morbidity treatment costs, heath-related quality of life due to weight loss and gain in survival. Only 12 of the studies included heath-related quality of life gains due to reduced co-morbidities and only one study included productivity gains. Despite consensus that trial-based analysis on its own is inadequate in guiding resource allocation decisions, it was used in 39% of the studies. Several of the modelling papers used model structures not suitable for chronic diseases with changing health risks. Three studies concluded that the intervention dominated standard care; meaning that it generated more quality-adjusted life-years (QALYs) for less cost. The incremental costs per QALY gained varied from $US235 to $US56,836 in the remaining studies using this outcome measure. An implicit hypothesis of the review was that studies including long-term health effects would illustrate greater cost effectiveness compared with trial-based studies. This hypothesis is partly confirmed with three studies arriving at dominating results, as these reach their conclusion from modelling future co-morbidity treatment cost savings. However, for the remaining studies there is little indication that decision-analytic modelling disparities explain the differences. This is the first literature review comparing methods used in economic evaluations of weight management interventions, and it is the first time that observed differences in study results are addressed with a view to methodological explanations. We conclude that many studies have methodological deficiencies and we urge analysts to follow recommended practices and use models capable of depicting long-term health consequences.


Ethnic differences in the prevalence of myopia and ocular biometry in 10- and 11-year-old children: the Child Heart and Health Study in England (CHASE).
Ethnic differences in childhood prevalence of myopia have not been well characterized in the United Kingdom. In this study, ethnic differences in refractive status and ocular biometry were examined in a multiethnic sample of British children. This was a cross-sectional study of 10- and 11-year-old school children of South Asian, black African Caribbean, and white European ethnic origin. Vision, open-field autorefraction (without cycloplegia), and ocular biometry were measured in each eye. Myopia was defined as spherical equivalent refraction of -0.50 D with unaided vision of 20/30 or worse (in one or both eyes). Ethnic differences in the prevalence of myopia were examined by using logistic regression, and multiple linear regression was used for ethnic differences in ocular biometry. All models were adjusted for age, sex, and clustering within school. Data were available for 1179 children. The prevalence of myopia was 25.2%, 10.0%, and 3.4%, respectively, in the South Asian, black African Caribbean, and white European children. Adjusted odds ratios (ORs) of myopia compared with the white European children were 8.9 (95% confidence interval [CI] 4.0 to 19.4) in the South Asian and 3.2 (95% CI, 1.4 to 7.2) in black African Caribbean children. Ethnic differences in the prevalence of myopia were largely accounted for by ethnic differences in axial length. The South Asian and black African Caribbean children had longer axial lengths (0.44 mm; 95% CI, 0.30 to 0.57 mm and 0.30 mm; 95% CI, 0.16 to 0.44 mm, respectively). Among British children exposed to the same schooling environment, the South Asians had the highest prevalence of myopia, followed by the black African Caribbeans compared with the white Europeans. A quarter of British South Asian children were myopic, which is strongly related to increased axial length.


Investigating food insecurity measurement globally to inform practice locally: a rapid evidence review.
The objective of this review was to examine the methods used to measure food insecurity (FI) globally, to inform considerations relating to adopting a novel, or reviewing an existing, FI measurement approach in developed countries. Considerations for measurement are examined with particular applicability to the United Kingdom (UK) which has recently announced adoption of the US Household Food Security Survey Module (HFSSM) as an indicator to facilitate annual FI monitoring. This study uses a Rapid Evidence Assessment (REA) methodological approach to systematically review the literature on FI measurement and considers: geographical jurisdiction, methodological approach, sampling strategy, FI indicator(s) used, and implications for measurement. Results found that the majority of papers reviewed emanate from North America with the US Household Food Security Scale Module (HFSSM) and its various adapted forms being the most commonly reported indicator. FI is becoming a key concern within developed countries with a range of indicators being used to report on the severity of the issue. This paper provides a contribution to knowledge by: (i) identifying various approaches to FI measurement and commonalities of existing measurement approaches; (ii) providing a summation of the methodologies and findings of studies relating to FI measurement, and associated implications for measurement, (iii) providing a justification evidenced by the literature for the adoption of the HFSSM in the UK; and (iv) assessing the methodological usefulness of a REA review. Understanding the components of robust FI indicators and their effectiveness can help inform existing and novel measurement approaches to ensure that data collected on FI are meaningful and thereby useful to inform future policy work in this area.


Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism.
Global agricultural emissions of the greenhouse gas nitrous oxide (N2O) have increased by around 20% over the last 100 y, but regulation of these emissions and their impact on bacterial cellular metabolism are poorly understood. Denitrifying bacteria convert nitrate in soils to inert di-nitrogen gas (N2) via N2O and the biochemistry of this process has been studied extensively in Paracoccus denitrificans. Here we demonstrate that expression of the gene encoding the nitrous oxide reductase (NosZ), which converts N2O to N2, is regulated in response to the extracellular copper concentration. We show that elevated levels of N2O released as a consequence of decreased cellular NosZ activity lead to the bacterium switching from vitamin B12-dependent to vitamin B12-independent biosynthetic pathways, through the transcriptional modulation of genes controlled by vitamin B12 riboswitches. This inhibitory effect of N2O can be rescued by addition of exogenous vitamin B12.


Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease--study protocol for a randomised controlled trial [ISRCTN11611768].
Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation. We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12-15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out. Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice.


High-resolution fMRI reveals match enhancement and attentional modulation in the human medial temporal lobe.
A primary function of the medial temporal lobe (MTL) is to signal prior encounter with behaviorally relevant stimuli. MTL match enhancement--increased activation when viewing previously encountered stimuli--has been observed for goal-relevant stimuli in nonhuman primates during delayed-match-to-sample tasks and in humans during more complex relational memory tasks. Match enhancement may alternatively reflect (a) an attentional response to familiar relative to novel stimuli or (b) the retrieval of contextual details surrounding the past encounter with familiar stimuli. To gain leverage on the functional significance of match enhancement in the hippocampus, high-resolution fMRI of human MTL was conducted while participants attended, ignored, or passively viewed face and scene stimuli in the context of a modified delayed-match-to-sample task. On each "attended" trial, two goal-relevant stimuli were encountered before a probe that either matched or mismatched one of the attended stimuli, enabling examination of the consequences of encountering one of the goal-relevant stimuli as a match probe on later memory for the other (nonprobed) goal-relevant stimulus. fMRI revealed that the hippocampus was insensitive to the attentional manipulation, whereas parahippocampal cortex was modulated by scene-directed attention, and perirhinal cortex showed more subtle and general effects of attention. By contrast, all hippocampal subfields demonstrated match enhancement to the probe, and a postscan test revealed more accurate recognition memory for the nonprobed goal-relevant stimulus on match relative to mismatch trials. These data suggest that match enhancement in human hippocampus reflects retrieval of other goal-relevant contextual details surrounding a stimulus's prior encounter.


Pseudomonas signal molecule 3-oxo-C12-homoserine lactone interferes with binding of rosiglitazone to human PPARgamma.
Peroxisome proliferator activated receptor (PPARgamma) has been suggested as a target for anti-inflammatory therapy in chronic lung disease, including infection with Pseudomonas aeruginosa. However, the P. aeruginosa signal molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) has been reported to inhibit function of PPARs in mammalian cells. This suggests that binding of 3-oxo-C12-HSL to PPARs could increase inflammation during P. aeruginosa infection, particularly if it could compete for binding with other PPAR ligands. We investigated the ability of 3-oxo-C12-HSL to bind to a PPARgamma ligand binding domain (LBD) construct, and to compete for binding with the highly active synthetic PPARgamma agonist rosiglitazone. We demonstrate that 3-oxo-C12-HSL binds effectively to the PPARgamma ligand binding domain, and that concentrations of 3-oxo-C12-HSL as low as 1 nM can effectively interfere with the binding of rosiglitazone to the PPARgamma ligand binding domain. Because 3-oxo-C12 HSL has been demonstrated in lungs during P. aeruginosa infection, blockade of PPARgamma-dependent signaling by 3-oxo-C12-HSL produced by the infecting P. aeruginosa could exacerbate infection-associated inflammation, and potentially impair the action of PPAR-activating therapy. Thus the proposed use of PPARgamma agonists as anti-inflammatory therapy in lung P. aeruginosa infection may depend on their ability to counteract the effects of 3-oxo-C12-HSL.


Adrenaline-induced hypertension in rats.
1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated controls rats. 2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of controls rats. 3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation. 4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 microgram (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in controls rats. 5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on transmission by acting on prejunctional beta-adrenoceptors.


Determination of non-market values to inform conservation strategies for the threatened Alistana-Sanabresa cattle breed.
Livestock breed-related public good functions are often used to justify support for endangered breed conservation despite the fact that little is known about such non-market values. We show how stated preference techniques can be used to assess the non-market values that people place on livestock breeds. Through the application of a case study choice experiment survey in Zamora province, Spain, the total economic value (TEV) of the threatened Alistana-Sanabresa (AS) cattle breed was investigated. An analysis of the relative importance of the non-market components of its TEV and an assessment of the socio-economic variables that influence people's valuation of such components is used to inform conservation strategy design. Overall, the findings reveal that the AS breed had significant non-market values associated with it and that the value that respondents placed on each specific public good function also varied significantly. Functions related with indirect use cultural and existence values were much more highly valued than landscape maintenance values. These high cultural and existence values (totalling over 80% of TEV) suggest that an AS in situ conservation strategy will be required to secure such values. As part of such a strategy, incentive mechanisms will be needed to permit farmers to capture some of these public good values and thus be able to afford to maintain breed population numbers at socially desirable levels. One such mechanism could be related to the development of breed-related agritourism initiatives, with a view to enhancing private good values and providing an important addition to continued direct support. Where linked with cultural dimensions, niche product market development, including through improving AS breed-related product quality and brand recognition may also have a role to play as part of such an overall conservation and use strategy. We conclude that livestock breed conservation strategies with the highest potential to maximise societal welfare would be those that secure the breed-related functions that people value most, with appropriate in situ conservation interventions and strategies being identified accordingly.


CD8+ TIL recruitment may revert the association of MAGE A3 with aggressive features in thyroid tumors.
We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker. We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8) were evaluated using immunohistochemistry and compared with clinical pathological features. The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P < 0.0001), also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P = 0.0206) and in patients with stage II disease (P = 0.0107). MAGE A3+ tumors were more likely to present CD8+ TIL (P = 0.0346), and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease. We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.


The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B'-LTR for driving gene expression.
The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized. Here, by characterizing the sequences and functions of LTRs from endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core promoter and NF-κB element are associated with varied LTR capacity for driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B'-LTR for driving viral gene transcription upon stimulation is associated with an increased level of viral reactivation. Moreover, we demonstrated that the introduction of CRISPR/dead Cas9 targeting Sp1 or NF-κB element suppressed viral gene expression. Taken together, our study characterized LTRs from endemic HIV-1 subtypes in China and suggests a potential target for the suppression of viral gene expression and a novel strategy that facilitates the accomplishment of a functional cure.


Three-dimensional characterization of optical coherence tomography point spread functions with a nanoparticle-embedded phantom.
We present a novel (to our knowledge) approach for measurement of the three-dimensional point spread function (PSF) of optical coherence tomography (OCT) systems using a nanoparticle-embedded phantom (NEP), toward development of standardized test methods for biophotonic imaging. The NEP comprises highly reflective plasmonic nanoparticles, homogeneously distributed in a transparent silicone matrix. OCT image volumes were analyzed to characterize PSFs in axial and lateral directions at a variety of locations in the NEP. Results indicate submicrometer agreement with conventional approaches to measure dimensions of the PSF. The NEP offers a robust approach for validating and comparing imaging performance of OCT devices.


Barriers to and facilitators of walking and bicycling to school: formative results from the non-motorized travel study.
Barriers to and facilitators of walking and bicycling to school were explored through 12 focus groups made up of fourth- and fifth-grade students and their parents who lived near their respective schools. The barriers and facilitators reported by parents and children generally fell into one of three categories: intrapersonal and interpersonal characteristics of parents and children, environmental characteristics of the neighborhood, and environmental and policy characteristics of the school. Findings indicate that a supportive environment is a necessary but insufficient condition to increase walking and biking to school. Initiatives to increase active school travel may need to include multiple levels of intervention to be effective.


Beyond Black and White: Conceptualizing and essentializing Black-White identity.
Psychological research suggests that Black-White individuals are often conceptualized as Black and White, and that essentialist beliefs about race are negatively associated with conceptualizing Black-White individuals as such. The present research examined what people think it means to be Black and White (e.g., a mixture of Black and White vs. completely Black and completely White) and whether essentialism is indeed negatively associated with such concepts. We used multiple methodologies (e.g., surveys, open-ended explanations, experimental manipulations) to examine how Black, White, and Black-White perceivers conceptualized Black-White individuals (Studies 1-3) and the extent to which essentialist beliefs, both dispositional (Studies 2-3) and experimentally induced (Study 4), predicted those concepts. We find that U.S. Black-White individuals most often conceptualized "Black and White" to mean a mixture of Black and White (Study 1), as did U.S. White individuals and U.S. Black individuals (Studies 2 and 3), and that racial essentialism-both dispositional (Studies 2 and 3) and experimentally manipulated (Study 4)-was positively associated with this conception. Our data shed new light on the complexity of race concepts and essentialism and advance the psychological understanding of Black-White identity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Variable responses of the depth of tree nitrogen uptake to pruning and competition.
Trees in cropped fields may improve nitrogen (N) use efficiency by intercepting leached N, but crop yield will be reduced if the trees compete strongly with crops for N. Ideal trees for intercropping will take up N from deeper soil layers not accessed by the crop species. Spatiotemporal aspects of tree nitrogen capture niches were investigated within a hedgerow intercropping system by placing 15N at three depths and monitoring 15N uptake by trees pruned either 25 or 4 days before application of 15N. Trees with contrasting rooting patterns (Gliricidia sepium L. and Peltophorum dasyrrachis (Miq.) Kurz) were grown in mixed hedgerows and intercropped with maize (Zea mays L.). Neither species showed significant N uptake during the 5-14 days after pruning, even though some shoot regrowth occurred during this time. Mean topsoil (0-5 cm depth) root length density of G. sepium was 520% greater than that of P. dasyrrachis, whereas total root length (0-100 cm depth) of G. sepium was only 450% greater. On average, G. sepium recovered 15 times as much 15N as P. dasyrrachis, following application of 15N at 5 cm depth, but the two species recovered a similar amount following application at 80 cm depth, suggesting that P. dasyrrachis had better niche complementarity with shallow rooting crops. However, both species showed strong plasticity in vertical N uptake pattern in response to competition from establishing maize plants. The species differed in their response: N uptake activity by G. sepium shifted down the soil profile in response to increasing competition from a growing maize crop (uptake from 80 cm depth changed from 4 to 9% of uptake from 5 cm depth), whereas N uptake by P. dasyrrachis became relatively shallow (uptake from 80 cm depth changed from 305 to 25% of uptake from 5 cm depth). Niche avoidance and increased competitiveness within the topsoil represent alternative responses to competition. The response displayed may be related to soil fertility in the species' natural habitats.


Impact of weather on COVID-19 pandemic in Turkey.
The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (°C), dew point (°C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.


Spectral power and functional connectivity changes during mindfulness meditation with eyes open: A magnetoencephalography (MEG) study in long-term meditators.
Whilst a number of previous studies have been conducted in order to investigate functional brain changes associated with eyes-closed meditation techniques, there is a relative scarcity in the literature with regards to changes occurring during eyes-open meditation. The current project used magnetoencephalography (MEG) to investigate differences in spectral power and functional connectivity between 11 long-term mindfulness meditators (LTMMs) with >5 years of experience and 12 meditation-naïve control participants both during baseline eyes-open rest and eyes-open open-monitoring (OM) mindfulness meditation. During resting with eyes-open, prior to meditating, greater mean alpha power was observed for LTMMs in comparison to controls. However, during the course of OM meditation, a significantly greater increase in theta power was observed over a broad fronto-centro-parietal region for control participants in comparison to LTMMs. In contrast, whole-head mean connectivity was found to be significantly greater for long-term meditators in comparison to controls in the theta band both during rest as well as during meditation. Additionally, mean connectivity was significantly lower for long-term meditators in the low gamma band during rest and significantly lower in both low and high gamma bands during meditation; and the variance of low-gamma connectivity scores for long-term meditators was significantly decreased compared to the control group. The current study provides important new information as to the trait functional changes in brain activity associated with long-term mindfulness meditation, as well as the state changes specifically associated with eyes-open open monitoring meditation techniques.