bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B
Authors: Handen Benjamin L. , Cohen Ann D. , Channamalappa Umapathy , Bulova Peter , Cannon Sheila A. , Cohen William I. , Mathis Chester A. , Price Julie C. , Klunk William E.
Published: October 2012

Down syndrome (DS) is one of the most common causes of intellectual disability. Although DS accounts for only 15% of all individuals with intellectual disabilities, adults with DS account for approximately 60% of individuals with intellectual disabilities and Alzheimer's disease. This is thought to be because of overproduction of the β‐amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. Pittsburgh compound B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age‐dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS‐1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer's disease also show preclinical amyloid deposition. This report describes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with objective cutoffs for amyloid positivity in older non‐DS cognitively normal control subjects, only two of the seven DS subjects (age: 38 and 44 years) showed increased PiB retention. The remaining five subjects aged between 20 and 35 years showed no detectable increase in PiB retention. Interestingly, the two subjects who showed elevated PiB retention showed a striatal‐predominant pattern similar to that previously reported for PS‐1 mutation carriers. These results demonstrate the feasibility of conducting PiB positron emission tomography scanning in this special population, and suggest a link between Aβ overproduction and early striatal deposition of fibrillar Aβ.
Current knowledge and future directions about the disclosure of dementia: A systematic review of the first decade of the 21st century
Authors: Werner Perla , Karnieli‐Miller Orit , Eidelman Shmuel
Published: October 2012

Background

The disclosure of Alzheimer's disease presents a great challenge because it entails emotionally charged communication about a life‐threatening, incurable, and stigmatized disease. Although a broad consensus has evolved regarding the potential benefits of early disclosure of the diagnosis, little is known about how these recommendations are actually implemented, and there is limited published research about the process issues of the disclosure.

Purpose

(1) To systematically obtain and evaluate the relevant literature on disclosing a diagnosis of dementia, with special attention to process issues, and (2) to summarize current research findings and draw conclusions for future research and clinical care in this area.

Methods

A systematic review of the literature on disclosure of dementia during the first decade of the 21st century was conducted.

Results

From 265 articles retrieved, 47 were included in the review. Although the studies published in the first years of the decade were concerned with assessing attitudes and preferences of those involved in the process of disclosing the diagnosis, those of the last years have focused more on communication and other process issues.

Conclusions

A conceptual development over time in the area is observed in which in the first years, thought processes begin as an ethical debate among clinicians and researchers about the topic of “truth telling” and dementia, continue as a search of the opinions of those involved in the process of disclosure about truth telling, and evolve (observed more recently) into an examination of how this truth telling is delivered.
Isolated left ventricular non‐compaction cardiomyopathy associated with polymorphous ventricular tachycardia mimicking torsades de pointes
Authors: Dickinson Oana , Zakharova Marina , Detloff Barry L. , Chen Lin Y. , Benditt David G. , Francis Gary S. , Sakaguchi Scott
Published: October 2012

Left ventricular non‐compaction (LVNC) cardiomyopathy is a rare congenital disorder, classified by the American Heart Association as a primary genetic cardiomyopathy and characterized by multiple trabeculations within the left ventricle. LVNC cardiomyopathy has been associated with 3 major clinical manifestations: heart failure, atrial and ventricular arrhythmias and thromboembolic events, including stroke. In this case report, we describe a female patient with apparently isolated LVNC in whom pause‐dependent polymorphic ventricular tachycardia suggesting torsades de pointes occurred in the presence of a normal QT interval.
Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): Randomized, Controlled Trial of Ibuprofen Versus Placebo for Prevention of Altitude Illness
Authors: Gertsch Jeffrey H. , Corbett Bryan , Holck Peter S. , Mulcahy Allison , Watts Melanie , Stillwagon Nathan Thomas , Casto Amanda Morgan , Abramson Charles Hessel , Vaughan Charles Peter Aloysius , Macguire Christopher , Farzan Neda Nicole , Vo Baotran Nguyen , Norvelle Rebecca Jean , May Kerstin , Holly Jessica Elizabeth , Irons Hillary , Stutz Aaron Michael , Chapagain Pradip , Yadav Siddhartha , Pun Matiram , Farrar Jeremy , Basnyat Buddha
Published: October 2012

Objective

To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH).

Methods

Double-blind, randomized, placebo-controlled trial.

Results

Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity).

Conclusions

Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.
‘A Most Protean Disease’: Aligning Medical Knowledge of Modern Influenza, 1890–1914
Authors: Bresalier Michael
Published: October 2012

This article reconstructs the process of defining influenza as an infectious disease in the contexts of British medicine between 1890 and 1914. It shows how professional agreement on its nature and identity involved aligning different forms of knowledge produced in the field (public health), in the clinic (metropolitan hospitals) and in the laboratory (bacteriology). Two factors were crucial to this process: increasing trust in bacteriology and the organisation of large-scale collective investigations into influenza by Britain’s central public authority, the Medical Department of the Local Government Board. These investigations integrated epidemiological, clinical and bacteriological evidence into a new definition of influenza as a specific infection, in which a germ –Bacillus influenzae– was determined as playing a necessary but not sufficient role in its aetiology, transmission and pathogenesis. In defining ‘modern influenza’, bacteriological concepts and techniques were adapted toandselectively incorporated into existing clinical, pathological and epidemiological approaches. Mutual alignment thus was crucial to its construction and, more generally, to shaping developing relationships between laboratory, clinical and public health medicine in turn-of-the-century Britain. While these relationships were marked by tension and conflict, they were also characterised by important patterns of convergence, in which the problems, interests and practices of public health professionals, clinicians and laboratory pathologists were made increasingly commensurable. Rather than retrospectively judge the late nineteenth-century definition of influenza as being based on the wrong microbe, this article argues for the need to examine how it was established through a particular alignment of medical knowledge, which then underpinned medical approaches to the disease up to and beyond the devastating 1918–19 pandemic.
How Words and Money Cultivate a Personal Vote: The Effect of Legislator Credit Claiming on Constituent Credit Allocation
Authors: GRIMMER JUSTIN , MESSING SOLOMON , WESTWOOD SEAN J.
Published: October 2012

Particularistic spending, a large literature argues, builds support for incumbents. This literature equates money spent in the district with the credit constituents allocate. Yet, constituents lack the necessary information and motivation to allocate credit in this way. We use extensive observational and experimental evidence to show how legislators’ credit claiming messages—and not just money spent in the district—affect how constituents allocate credit. Legislators use credit claiming messages to influence the expenditures they receive credit for and to affect how closely they are associated with spending in the district. Constituents are responsive to credit claiming messages—they build more support than other nonpartisan messages. But contrary to expectations from other studies, constituents are more responsive to the total number of messages sent rather than the amount claimed. Our results have broad implications for political representation, the personal vote, and the study of U.S. Congressional elections.
Recovery of probioticLactobacillus rhamnosusGG in tonsil tissue after oral administration: randomised, placebo-controlled, double-blind clinical trial
Authors: Kumpu Minna , Swanljung Elisa , Tynkkynen Soile , Hatakka Katja , Kekkonen Riina A. , Järvenpää Salme , Korpela Riitta , Pitkäranta Anne
Published: October 2012

The present randomised, double-blind, placebo-controlled study was conducted to determine whether consumption of probioticLactobacillus rhamnosusGG (GG) would lead to the recovery of GG in tonsil tissue. After 3 weeks' daily consumption of GG as a single strain (n20), GG as a part of a multispecies combination (n17) or placebo (n20), tonsil tissue samples were collected from fifty-seven young adults during tonsillectomy due to chronic or recurrent tonsillitis. Strain-specific real-time PCR was used to detect GG in the tonsil tissue. GG was recovered in the tonsil sample of 40 % of the subjects in the GG group, 41 % in the multispecies group and 30 % in the placebo group (Pvalue between groups 0·79). In all subjects with positive recovery of GG in the tonsil tissue, GG was also recovered in the faecal sample taken at the start of the intervention and at the time of the tissue sample collection, which indicates more persistent adherence of the probiotic. To conclude, GG can be recovered from tonsil tissue after oral administration as a single-strain probiotic or as a part of a multispecies probiotic combination. The present results suggest that individual variation exists in the ability of GG to adhere to tonsil tissue. Persistence of GG appears to be high in tonsil tissue as well, in addition to persistence in faecal samples, which has been demonstrated previously. Further clinical trials are warranted to evaluate whether probiotic adherence in the tonsil tissue could have a role in respiratory symptom prevalence.
A pair of characteristic subgroups for pushing-up. II
Authors: Glauberman George
Published: October 2012

Many problems about local analysis in a finite group G reduce to a special case in which G has a large normal p-subgroup satisfying several restrictions. In 1983, R. Niles and G. Glauberman showed that every finite p-group S of nilpotence class at least 4 must have two characteristic subgroups S1 and S2 such that, whenever S is a Sylow p-subgroup of a group G as above, S1 or S2 is normal in G. In this paper, we prove a similar theorem with a more explicit choice of S1 and S2.
Diet of the queen angelfish Holacanthus ciliaris (Pomacanthidae) in São Pedro e São Paulo Archipelago, Brazil
Authors: Reis Fernanda , Moraes Fernando , Batista Daniela , Villaça Roberto , Aguiar Aline , Muricy Guilherme
Published: October 2012

Holacanthus ciliaris is an important benthic-feeding reef fish but the relationship between the composition of its diet and prey availability is still unknown. Here we determined the quantitative composition of the gut contents of H. ciliaris in São Pedro e São Paulo Archipelago, Brazil (SPSPA), and compared it to the abundance of benthic organisms in the area. Holacanthus ciliaris has a relatively diversified diet with more than 30 prey species in SPSPA, especially sponges (13 spp., average 68% of gut contents total weight), algae (12 spp., 25%) and bryozoans (3 spp., 5%). In contrast, the benthic community is composed mainly of algae (average 81% of total cover) and followed by sponges (13%), bryozoans (5%), cnidarians (0.5%), polychaetes (0.5%) and tunicates (0.5%). The most common species were the algae Caulerpella ambigua and Caulerpa racemosa var. peltata; the bryozoan Margaretta buski; and the sponges Scopalina ruetzleri, Chondrosia collectrix and Clathria calla. The Manly resource selection function showed that H. ciliaris preferred the sponges Geodia neptuni, Erylus latens, Clathria calla and Asteropus niger, among others, and avoided common species such as the sponges Scopalina ruetzleri, Dysidea etheria and Hemimycale insularis and the algae Caulerpella ambigua, Bryopsis plumosa and Neomeris annulata. Kendall's rank correlation index showed no significant correlation between prey abundance in the field and in the diet of H. ciliaris, which seems to actively choose relatively rare and less defended prey.
Benthic foraminifera assemblages in turtle congregation sites along the north-east coast of India
Authors: Bhattacharjee Dola , Choudhury B.C. , Sivakumar K. , Sharma Charu , John Sajan , Behera Satyaranjan , Behera Subrata , Bhadury Punyasloke
Published: October 2012

Near-shore recent benthic foraminifera from three ecologically important (Olive Ridley turtle congregation sites) but vulnerable sites encompassing 23 sampling stations (12 in Rushikulya, 5 in Devi and 6 in Gahirmatha) along coastal Orissa, north-west Bay of Bengal (BoB) in India were studied for the first time for their composition, distribution and assemblage patterns. Thirty-nine species of benthic foraminifers (from 6 orders and 23 families) were identified of which all 39 were present in Rushikulya, 22 in Devi and 12 in Gahirmatha with abundance ranging from 35–2620 individuals/10 cm3 in the sediments. The communities across the sites were dominated by eurytopic rotalids followed by miliolids and textularids. Benthic foraminifer assemblages were found to be dominated by Ammonia species complex (up to 38% in Rushikulya, 64% in Devi and 22% in Gahirmatha). Agglutinated foraminifers were infrequent in the sediments (7 species in Rushikulya, 4 species in Devi and 3 in Gahirmatha) on the other hand, being dominated by Quinqueloculina agglutinans in Rushikulya and Trochammina macrescens and Ammobaculites agglutinans in Devi and Gahirmatha. The substrates along the study sites were found mostly to be sand dominated and in some of the stations sediment composition influenced the foraminifer distribution pattern. The present findings on the assemblage patterns of benthic foraminifers from three coastal settings in Orissa along the BoB are comparable with previous reports from other sandy coastal ecosystems in the world. Overall these data provide valuable insights into the distribution and assemblage patterns of benthic foraminifers from the BoB coastal regions.
Religious Orientations in the Lives of Indian Entrepreneurs: Three Case Studies
Authors: BAKUNINA ALINA
Published: October 2012

This paper aims to demonstrate how ‘the religious’ is conceptualized and practiced among urban Indian entrepreneurs. It investigates a continuum of religious sentiment and practice, including non-religious elements, rather than a fixed repertoire of belief and ritual. These religious orientations range from the incorporation of certain Hindu religious practices into the business setting to a denial of any substantive role religion may play in the lives of entrepreneurs and the imbuing of religious dispositions with secular meaning. I argue in this paper that the religious and quasi religious practices of India's new social and economic elite are geared primarily towards the enhancement of their ‘flexible’ lifestyles. The study also makes a claim that modern urban Hinduism accommodates hybrid secular-sacred religious beliefs and practices.
Is genomics bad for you?
Authors: Dickins Benjamin J. A.
Published: October 2012

The plasticity of the genome complicates genetic causation but should be investigated from a functional perspective. Specific adaptive hypotheses are referenced in the target article, but it is also necessary to explain how the integrity of the genome is maintained despite processes that tend towards its diversification and degradation. These include the accumulation of deleterious changes and intragenomic conflict.
Biology trumps statistics in the postgenomic era
Authors: Glatt Charles E.
Published: October 2012

Charney discusses the growing realization in the postgenomic era that genomic biology deviates from Mendelian assumptions at the heart of genetic heritability and association studies. Given the complexity of genomic biology, how are we to identify meaningful genetic factors that contribute to behavioral? One response is to make genetic variants the focus of biological rather than statistical analyses of behavior.
A call for an expanded synthesis of developmental and evolutionary paradigms
Authors: Lewis Andrew J.
Published: October 2012

Charney's target article continues a critique of genetic blueprint models of development that suggests reconsideration of concepts of adaptation, inheritance, and environment, which can be well illustrated in current research on infant attachment. The concepts of development and adaptation are so heavily based on the model of genetics and inheritance forged in the modern synthesis that they will require reconsideration to accommodate epigenetic inheritance.
Estimating the actual subject-specific genetic correlations in behavior genetics
Authors: Molenaar Peter C. M.
Published: October 2012

Generalization of the standard behavior longitudinal genetic factor model for the analysis of interindividual phenotypic variation to a genetic state space model for the analysis of intraindividual variation enables the possibility to estimate subject-specific heritabilities.
Gene-independent heritability of behavioural traits: Don't we also need to rethink the “environment”?
Authors: Müller Christian P. , Lenz Bernd , Kornhuber Johannes
Published: October 2012

Behavioural phenotypes have been explained by genetic and environmental factors (E) and their interaction. Here we suggest a rethinking of the E factor. Passively incurred environmental influences (Epass) and actively copied information and behaviour (Eact) may be distinguished at shared and non-shared level. We argue that Eact underlies mutation and selection and is the base of gene-independent heritability.
Parental brain and socioeconomic epigenetic effects in human development
Authors: Swain James E. , Perkins Suzanne C. , Dayton Carolyn J. , Finegood Eric D. , Ho S. Shaun
Published: October 2012

Critically significant parental effects in behavioral genetics may be partly understood as a consequence of maternal brain structure and function of caregiving systems recently studied in humans as well as rodents. Key parental brain areas regulate emotions, motivation/reward, and decision making, as well as more complex social-cognitive circuits. Additional key environmental factors must include socioeconomic status and paternal brain physiology. These have implications for developmental and evolutionary biology as well as public policy.
Affirmation of a developmental systems approach to genetics
Authors: Halpern Carolyn Tucker
Published: October 2012

More than 40 years ago, Gilbert Gottlieb and like-minded scholars argued for the philosophical necessity of approaching genetic contributions to development through a multilevel, bidirectional systems perspective. Charney's target article builds on this heritage in significant ways, offering more recent examples of the interactions of biology and context, as well as the diversity of developmental mechanisms, and reaffirming a way forward for genetic research.
Is behavioral genetics ‘too-big-to-know’ science?
Authors: Battaglia Marco
Published: October 2012

Several new molecular findings and concepts furnish evidence in support of gene–environment interdependence, challenging some of the current tenets and basic statistics of behavioral genetics. I, however, argue that (1) some of the expectations evoked by “neogenomics” are contradicted by findings; and (2) while epigenetic and gene expression effects are complex, they can to some extent be incorporated into “classical” behavioral genetics modeling.
Assumptions in studies of heritability and genotype–phenotype association
Authors: Miller Michael B. , DeYoung Colin G. , McGue Matt
Published: October 2012

Charney's dismissal of well-established methods in behavioral genetic research is misguided. He claims that studies of heritability and genetic association depend for their validity on six assumptions, but he cites no sources to support this claim. We explain why none of the six assumptions is strictly necessary for the utility of either method of genetic analysis.
Benchmarking Routine Psychological Services: A Discussion of Challenges and Methods
Authors: Delgadillo Jaime , McMillan Dean , Leach Chris , Lucock Mike , Gilbody Simon , Wood Nick
Published: October 2012

Background: Policy developments in recent years have led to important changes in the level of access to evidence-based psychological treatments. Several methods have been used to investigate the effectiveness of these treatments in routine care, with different approaches to outcome definition and data analysis. Aims: To present a review of challenges and methods for the evaluation of evidence-based treatments delivered in routine mental healthcare. This is followed by a case example of a benchmarking method applied in primary care. Method: High, average and poor performance benchmarks were calculated through a meta-analysis of published data from services working under the Improving Access to Psychological Therapies (IAPT) Programme in England. Pre-post treatment effect sizes (ES) and confidence intervals were estimated to illustrate a benchmarking method enabling services to evaluate routine clinical outcomes. Results: High, average and poor performance ES for routine IAPT services were estimated to be 0.91, 0.73 and 0.46 for depression (using PHQ-9) and 1.02, 0.78 and 0.52 for anxiety (using GAD-7). Data from one specific IAPT service exemplify how to evaluate and contextualize routine clinical performance against these benchmarks. Conclusions: The main contribution of this report is to summarize key recommendations for the selection of an adequate set of psychometric measures, the operational definition of outcomes, and the statistical evaluation of clinical performance. A benchmarking method is also presented, which may enable a robust evaluation of clinical performance against national benchmarks. Some limitations concerned significant heterogeneity among data sources, and wide variations in ES and data completeness.
Polymorphisms in genes within the IGF-axis influence antenatal and postnatal growth
Authors: Parmar P. G. , Marsh J. A. , Rob Taal H. , Kowgier M. , Uitterlinden A. G. , Rivadeneira F. , Briollais L. , Newnham J. P. , Hofman A. , Lye S. J. , Steegers E. A. P. , van Duijn C. M. , Palmer L. J. , Jaddoe V. W. V. , Pennell C. E.
Published: October 2012

Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n= 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1–17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n= 2642). Of the SNPs within the IGF-axis genes, 40% (n= 58) were associated with measures of antenatal growth (P⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%;n= 34) and IGF-2R (13%;n= 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n= 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n= 31) and 9% in IGF-2R (n= 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.
Experimental evaluation of common spacecraft data analysis techniques for reconnection region analysis in a laboratory plasma
Authors: Yoo Jongsoo , Yamada Masaaki
Published: October 2012

A laboratory plasma is utilized to assess the effectiveness of several prominent spacecraft data analysis techniques. These include minimum variance analysis on the magnetic field (MVAB) and various boundary‐crossing time analyses (BCTA) such as the constant velocity approach (CVA), constant thickness approach (CTA), and minimum thickness variance (MTV). Magnetic field data from measurement points that resemble the formation of multispacecraft flying though a reconnecting current sheet is used to check MVAB and BCTA to deduce a proper normal vector. Results from each method are compared to the values measured by 2‐D magnetic probe arrays. We examine discharges with a two‐dimensional (2‐D) X‐line structure as well as cases in which a flux rope forms within the layer. All discharges are in a two‐fluid regime in which electrons are magnetized but ions are not. We conclude that CVA with four sample measurement points forming a tetrahedron generates a reasonable unit normal vector
, relative velocity along the normal vector Vn, and current sheet thickness δCS for all of the tested cases. Unlike CVA, both CTA and MTV sometimes generate Vn and δCS that are different from the measured values, which indicates that CTA and MTV are sensitive to changes in the current sheet thickness. CTA is, however, successful at estimating
. MVAB, on the other hand, often fails to predict a proper normal direction. This is because the reconnecting neutral sheet fundamentally contains 2‐D or 3‐D structures. MVAB, however, does determine the direction along the reconnecting magnetic field that is close to the real magnetic geometry. Based on these observations, we suggest a hybrid procedure for determining a local coordinate system for data from four spacecraft passing through a reconnecting current sheet.
Spatially heterogeneous diapycnal mixing in the abyssal ocean: A comparison of two parameterizations to observations
Authors: Decloedt Thomas , Luther Douglas S.
Published: October 2012

The spatial distributions of the diapycnal diffusivity predicted by two abyssal mixing schemes are compared to each other and to observational estimates based on microstructure surveys and large‐scale hydrographic inversions. The parameterizations considered are the tidal mixing scheme by Jayne, St. Laurent and co‐authors (JSL01) and the Roughness Diffusivity Model (RDM) by Decloedt and Luther. Comparison to microstructure surveys shows that both parameterizations are conservative in estimating the vertical extent to which bottom‐intensified mixing penetrates into the stratified water column. In particular, the JSL01 exponential vertical structure function with fixed scale height decays to background values much nearer topography than observed. JSL01 and RDM yield dramatically different horizontal spatial distributions of diapycnal diffusivity, which would lead to quite different circulations in OGCMs, yet they produce similar basin‐averaged diffusivity profiles. Both parameterizations are shown to yield smaller basin‐mean diffusivity profiles than hydrographic inverse estimates for the major ocean basins, by factors ranging from 3 up to over an order of magnitude. The canonical 10−4 m2 s−1abyssal diffusivity is reached by the parameterizations only at depths below 3 km. Power consumption by diapycnal mixing below 1 km of depth, between roughly 32°S and 48°N, for the RDM and JSL01 parameterizations is 0.40 TW & 0.28 TW, respectively. The results presented here suggest that present‐day mixing parameterizations significantly underestimate abyssal mixing. In conjunction with other recently published studies, a plausible interpretation is that parameterizing the dissipation of bottom‐generated internal waves is not sufficient to approximate the global spatial distribution of diapycnal mixing in the abyssal ocean.
Critical assessment of surface incident solar radiation observations collected by SURFRAD, USCRN and AmeriFlux networks from 1995 to 2011
Authors: Wang Kaicun , Augustine John , Dickinson Robert E.
Published: October 2012

Surface incident solar radiation (Rs) drives weather and climate changes. Observations of Rs have been widely used as reference data to evaluate climate model simulations and satellite retrievals. However, few have studied uncertainties of Rs observations, especially long term. This paper compares Rs from 1995 to 2011 at collocated sites collected by the Surface Radiation Budget Network (SURFRAD), the U.S. Climate Reference Network (USCRN) and the AmeriFlux network. SURFRAD stations have measured separately the diffuse and direct components of Rs as well as Rs by a pyranometer, while Rs was measured by a pyranometer or a net radiometer at the USCRN and AmeriFlux sites. Rs can be calculated by summing the diffuse and direction radiation measurements. Rs measured by the summation technique was compared those measured by a pyranometer or a net radiometer at collocated sites. Agreement among these four independent Rs measurements is good with correlation coefficients higher than 0.98 and an average error (one standard deviation) of about 4% at both hourly and monthly time scales. Rs has a large spatial variability at the hourly time scale, even exceeding 100 W m−2 in ∼6 km. This spatial variability is substantially reduced at the monthly time scale. The two independent measurement systems at the SURFRAD sites agree rather well in annual variability of Rs with an average relative standard deviation error of 34%. The errors are 71% and 85% for the USCRN and AmeriFlux sites. Evidently, caution should be taken when using the Rs data collected at the USCRN and AmeriFlux sites to study annual variability of Rs.
Growth of Screen‐Detected Abdominal Aortic Aneurysms in Men: A Bayesian Analysis
Authors: Sherer EA , Bies RR , Clancy P , Norman PE , Golledge J
Published: October 2012

There is considerable interindividual variability in the growth of abdominal aortic aneurysms (AAAs), but an individual's growth observations, risk factors, and biomarkers could potentially be used to tailor surveillance. To assess the potential for tailoring surveillance, this study determined the accuracy of individualized predictions of AAA size at the next surveillance observation. A hierarchical Bayesian model was fitted to a total of 1,732 serial ultrasound measurements from 299 men in whom ultrasound screening identified an AAA. The data were best described by a nonlinear model with a constant first derivative of the AAA growth rate with size. The area under the receiver operating characteristic (ROC) curves for predicting whether an AAA was ≥40 or ≥50 mm at the next observation were 0.922 and 0.979, respectively, and the median root mean squared error was 2.52 mm. These values were nearly identical for models with or without plasma D‐dimer effects.

CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e12; doi:10.1038/psp.2012.13; advance online publication 24 October 2012
Temperature-dependence of the DnaA–DNA interaction and its effect on the autoregulation of dnaA expression
Authors: Saggioro Chiara , Olliver Anne , Sclavi Bianca
Published: October 2012

The DnaA protein is a key factor for the regulation of the timing and synchrony of initiation of bacterial DNA replication. The transcription of the dnaA gene in Escherichia coli is regulated by two promoters, dnaAP1 and dnaAP2. The region between these two promoters contains several DnaA-binding sites that have been shown to play an important role in the negative auto-regulation of dnaA expression. The results obtained in the present study using an in vitro and in vivo quantitative analysis of the effect of mutations to the high-affinity DnaA sites reveal an additional effect of positive autoregulation. We investigated the role of transcription autoregulation in the change of dnaA expression as a function of temperature. While negative auto-regulation is lost at dnaAP1, the effects of both positive and negative autoregulation are maintained at the dnaAP2 promoter upon lowering the growth temperature. These observations can be explained by the results obtained in vitro showing a difference in the temperature-dependence of DnaA–ATP binding to its high- and low-affinity sites, resulting in a decrease in DnaA–ATP oligomerization at lower temperatures. The results of the present study underline the importance of the role for autoregulation of gene expression in the cellular adaptation to different growth temperatures.
Myeloperoxidase-derived oxidants modify apolipoprotein A-I and generate dysfunctional high-density lipoproteins: comparison of hypothiocyanous acid (HOSCN) with hypochlorous acid (HOCl)
Authors: Hadfield Katrina A. , Pattison David I. , Brown Bronwyn E. , Hou Liming , Rye Kerry-Anne , Davies Michael J. , Hawkins Clare L.
Published: October 2012

Oxidative modification of HDLs (high-density lipoproteins) by MPO (myeloperoxidase) compromises its anti-atherogenic properties, which may contribute to the development of atherosclerosis. Although it has been established that HOCl (hypochlorous acid) produced by MPO targets apoA-I (apolipoprotein A-I), the major apolipoprotein of HDLs, the role of the other major oxidant generated by MPO, HOSCN (hypothiocyanous acid), in the generation of dysfunctional HDLs has not been examined. In the present study, we characterize the structural and functional modifications of lipid-free apoA-I and rHDL (reconstituted discoidal HDL) containing apoA-I complexed with phospholipid, induced by HOSCN and its decomposition product, OCN− (cyanate). Treatment of apoA-I with HOSCN resulted in the oxidation of tryptophan residues, whereas OCN− induced carbamylation of lysine residues to yield homocitrulline. Tryptophan residues were more readily oxidized on apoA-I contained in rHDLs. Exposure of lipid-free apoA-I to HOSCN and OCN− significantly reduced the extent of cholesterol efflux from cholesterol-loaded macrophages when compared with unmodified apoA-I. In contrast, HOSCN did not affect the anti-inflammatory properties of rHDL. The ability of HOSCN to impair apoA-I-mediated cholesterol efflux may contribute to the development of atherosclerosis, particularly in smokers who have high plasma levels of SCN− (thiocyanate).
Surface Composition of Mixtures of Ethylammonium Nitrate, Ethanolammonium Nitrate, and Water
Authors: Wakeham Deborah , Eschebach Daniel , Webber Grant B. , Atkin Rob , Warr Gregory G.
Published: October 2012

Surface tensiometry of binary mixtures of ethylammonium nitrate (EAN), ethanolammonium nitrate (EtAN), and water reveals distinctive amphiphilic character for the ethylammonium cation, but not for ethanolammonium. Results also show that the surface film incorporates nitrate counterions, and that electrostatic and H-bonding interactions, rather than alkyl chain packing, determines the saturated adsorbed film structure and limiting molecular area.
The contribution of Primary Health Care Research, Evaluation and Development-supported research to primary health care policy and practice
Authors: Brown Lynsey J. , McIntyre Ellen L.
Published: October 2012

The importance of primary health care (PHC) research is well understood yet conducting this research can be challenging. Barriers include a lack of funding, support and opportunity. In 2000 the Australian government introduced the Primary Health Care Research, Evaluation and Development (PHCRED) Strategy to address the gap in high-quality research. One component of the strategy, the Research Capacity Building Initiative, provided funding to university departments of general practice and rural health, allowing them to expand their pool of researchers and produce more research relevant to policy and practice. This study investigates the impact of phase two of the PHCRED Strategy by analysing peer-reviewed publications from PHCRED-supported departments. Research output was recorded from 2006 to 2010 incorporating 661 publications in 212 journals. Rural departments often had fewer resources than urban departments yet demonstrated steady research contributions focusing on issues relevant to their community. Since its inception the PHCRED Strategy has enabled development of research capacity and contributed to the body of PHC knowledge. While PHC is a diverse field, reflected in the publications produced, the themes underlying much of this work were representative of current health reform and the priority areas and building blocks of the National PHC Strategy.
Intrinsic reaction-cycle time scale of Na+,K+-ATPase manifests itself in the lipid–protein interactions of nonequilibrium membranes
Authors: Bouvrais Hélène , Cornelius Flemming , Ipsen John H. , Mouritsen Ole G.
Published: October 2012

Interaction between integral membrane proteins and the lipid-bilayer component of biological membranes is expected to mutually influence the proteins and the membrane. We present quantitative evidence of a manifestation of the lipid–protein interactions in liposomal membranes, reconstituted with actively pumping Na+,K+-ATPase, in terms of nonequilibrium shape fluctuations that contain a relaxation time, τ, which is robust and independent of the specific fluctuation modes of the membrane. In the case of pumping Na+-ions, analysis of the flicker-noise temporal correlation spectrum of the liposomes leads to τ ≃ 0.5 s, comparing favorably with an intrinsic reaction-cycle time of about 0.4 s from enzymology.
Fibroblast growth factor 10
gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium
Authors: Watanabe Yusuke , Zaffran Stéphane , Kuroiwa Atsushi , Higuchi Hiroaki , Ogura Toshihiko , Harvey Richard P. , Kelly Robert G. , Buckingham Margaret
Published: October 2012

During cardiogenesis,
Fibroblast Growth Factor
(
Fgf10
) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these cardiac progenitor cells that form the arterial pole of the heart. We have identified a 1.7-kb region in the first intron of
Fgf10
that is necessary and sufficient to direct transgene expression in this cardiac context. The 1.7-kb sequence is directly controlled by T-box transcription factor 1 (Tbx1) in anterior second heart field cells that contribute to the outflow tract. It also responds to both NK2 transcription factor related, locus 5 (Nkx2-5) and ISL1 transcription factor, LIM/homeodomain (Islet1), acting through overlapping sites. Mutation of these sites reduces transgene expression in the anterior second heart field where the
Fgf10
regulatory element is activated by Islet1 via direct binding in vivo. Analysis of the response to
Nkx2-5
loss- and
Isl1
gain-of-function genetic backgrounds indicates that the observed up-regulation of its activity in
Nkx2-5
mutant hearts, reflecting that of
Fgf10
, is due to the absence of Nkx2-5 repression and to up-regulation of
Isl1
, normally repressed in the myocardium by Nkx2-5. ChIP experiments show strong binding of Nkx2-5 in differentiated myocardium. Molecular and genetic analysis of the
Fgf10
cardiac element therefore reveals how key cardiac transcription factors orchestrate gene expression in the anterior second heart field and how genes, such as
Fgf10
, normally expressed in the progenitor cell population, are repressed when these cells enter the heart and differentiate into myocardium. Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue.
N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods
Authors: Yu Xinzi , Zech Tobias , McDonald Laura , Gonzalez Esther Garcia , Li Ang , Macpherson Iain , Schwarz Juliane P. , Spence Heather , Futó Kinga , Timpson Paul , Nixon Colin , Ma Yafeng , Anton Ines M. , Visegrády Balázs , Insall Robert H. , Oien Karin , Blyth Karen , Norman Jim C. , Machesky Laura M.
Published: October 2012

Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated in breast cancer, and has a pivotal role in mediating the assembly of elongated pseudopodia that are instrumental in matrix degradation. Although a role for N-WASP in invadopodia was known, we now show how N-WASP regulates invasive protrusion in 3D matrices. In actively invading cells, N-WASP promoted trafficking of MT1-MMP into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane. Upon MT1-MMP’s arrival at the plasma membrane in pseudopodia, N-WASP stabilized MT1-MMP via direct tethering of its cytoplasmic tail to F-actin. Thus, N-WASP is crucial for extension of invasive pseudopods into which MT1-MMP traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion.
Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling
Authors: Jayasena Chathurani S. , Bronner Marianne E.
Published: October 2012

Cranial neural crest cells form much of the facial skeleton, and abnormalities in their development lead to severe birth defects. In a novel zebrafish protein trap screen, we identified an RNA-binding protein, Rbms3, that is transiently expressed in the cytoplasm of condensing neural crest cells within the pharyngeal arches. Morphants for rbms3 displayed reduced proliferation of prechondrogenic crest and significantly altered expression for chondrogenic/osteogenic lineage markers. This phenotype strongly resembles cartilage/crest defects observed in Tgf-βr2:Wnt1-Cre mutants, which suggests a possible link with TGF-β signaling. Consistent with this are the findings that: (a) Rbms3 stabilized a reporter transcript with smad2 3′ untranslated region, (b) RNA immunoprecipitation with full-length Rbms3 showed enrichment for smad2/3, and (c) pSmad2 levels were reduced in rbms3 morphants. Overall, these results suggest that Rbms3 posttranscriptionally regulates one of the major pathways that promotes chondrogenesis, the transforming growth factor β receptor (TGF-βr) pathway.
Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation
Authors: Sumigray Kaelyn D. , Foote Henry P. , Lechler Terry
Published: October 2012

During differentiation, many cells reorganize their microtubule cytoskeleton into noncentrosomal arrays. Although these microtubules are likely organized to meet the physiological roles of their tissues, their functions in most cell types remain unexplored. In the epidermis, differentiation induces the reorganization of microtubules to cell–cell junctions in a desmosome-dependent manner. Here, we recapitulate the reorganization of microtubules in cultured epidermal cells. Using this reorganization assay, we show that cortical microtubules recruit myosin II to the cell cortex in order to engage adherens junctions, resulting in an increase in mechanical integrity of the cell sheets. Cortical microtubules and engaged adherens junctions, in turn, increase tight junction function. In vivo, disruption of microtubules or loss of myosin IIA and B resulted in loss of tight junction–mediated barrier activity. We propose that noncentrosomal microtubules act through myosin II recruitment to potentiate cell adhesion in the differentiating epidermis, thus forming a robust mechanical and chemical barrier against the external environment.
Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation
Authors: Joshi Bharat , Bastiani Michele , Strugnell Scott S. , Boscher Cecile , Parton Robert G. , Nabi Ivan R.
Published: October 2012

Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In this paper, we show that Cav1 tyrosine phosphorylation induces caveola biogenesis via actin-dependent mechanotransduction and inactivation of the Egr1 (early growth response-1) transcription factor, relieving inhibition of endogenous Cav1 and cavin-1 genes. Cav1 phosphorylation reduces Egr1 binding to Cav1 and cavin-1 promoters and stimulates their activity. In MDA-231 breast carcinoma cells that express elevated levels of Cav1 and caveolae, Egr1 regulated Cav1, and cavin-1 promoter activity was dependent on actin, Cav1, Src, and Rho-associated kinase as well as downstream protein kinase C (PKC) signaling. pCav1 is therefore a mechanotransducer that acts via PKC to relieve Egr1 transcriptional inhibition of Cav1 and cavin-1, defining a novel feedback regulatory loop to regulate caveola biogenesis.