bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes, behavior, and behavior genetics
Authors: Charney Evan
Published: December 2016

According to the ‘first law’ of behavior genetics, ‘All human behavioral traits are heritable.’ Accepting the validity of this first law and employing statistical methods, researchers within psychology, sociology, political science, economics, and business claim to have demonstrated that all the behaviors studied by their disciplines are heritable—no matter how culturally specific these behaviors appear to be. Further, in many cases they claim to have identified specific genes that play a role in those behaviors. The validity of behavior genetics as a discipline depends upon the validity of the research methods used to justify such claims. It also depends, foundationally, upon certain key assumptions concerning the relationship between genotype (one's specific DNA sequences) and phenotype (any and all observable traits or characteristics). In this article, I examine—and find serious flaws with—both the methodologies of behavior genetics and the underlying assumptions concerning the genotype–phenotype relationship. WIREs Cogn Sci 2017, 8:e1405. doi: 10.1002/wcs.1405

This article is categorized under:

Cognitive Biology > Genes and Environment

Neuroscience > Genes, Molecules, and Cells
Neuroembryology
Authors: Darnell Diana , Gilbert Scott F.
Published: December 2016

How is it that some cells become neurons? And how is it that neurons become organized in the spinal cord and brain to allow us to walk and talk, to see, recall events in our lives, feel pain, keep our balance, and think? The cells that are specified to form the brain and spinal cord are originally located on the outside surface of the embryo. They loop inward to form the neural tube in a process called neurulation. Structures that are nearby send signals to the posterior neural tube to form and pattern the spinal cord so that the dorsal side receives sensory input and the ventral side sends motor signals from neurons to muscles. In the brain, stem cells near the center of the neural tube migrate out to form a mantel zone, and a set of dividing cells from the mantle zone migrate further to produce a second set of neurons at the outer surface of the brain. These neurons will form the cerebral cortex, which contains six discrete layers. Each layer has different connections and different functions. WIREs Dev Biol 2017, 6:e215. doi: 10.1002/wdev.215

This article is categorized under:

Early Embryonic Development > Gastrulation and Neurulation

Early Embryonic Development > Development to the Basic Body Plan
Association Between BMI and Recurrence of Primary Spontaneous Pneumothorax
Authors: Tan Juntao , Yang Yang , Zhong Jianhong , Zuo Chuantian , Tang Huamin , Zhao Huimin , Zeng Guang , Zhang Jianfeng , Guo Jianji , Yang Nuo
Published: December 2016

Background

Whether body mass index (BMI) is a significant risk factor for recurrence of primary spontaneous pneumothorax (PSP) remains controversial. The purpose of this study was to examine whether BMI and other factors are linked to risk of PSP recurrence.

Methods

A consecutive cohort of 273 patients was retrospectively evaluated. Patients were divided into those who experienced recurrence (n = 81) and those who did not (n = 192), as well as into those who had low BMI (n = 75) and those who had normal or elevated BMI (n = 198). The two pairs of groups were compared in terms of baseline data, and Cox proportional hazards modeling was used to identify predictors of PSP recurrence.

Results

Rates of recurrence among all 273 patients were 20.9% at 1 year, 23.8% at 2 years, and 28.7% at 5 years. Univariate analysis identified the following significant predictors of PSP recurrence: height, weight, BMI, size of pneumothorax, and treatment modality. Multivariate analyses identified several risk factors for PSP recurrence: low BMI, pneumothorax size ≥50%, and non‐surgical treatment. Kaplan–Meier survival analysis indicated that patients with low BMI showed significantly lower recurrence‐free survival than patients with normal or elevated BMI (P < 0.001).

Conclusions

Low BMI, pneumothorax size ≥50%, and non‐surgical treatment were risk factors for PSP recurrence in our cohort. Low BMI may be a clinically useful predictor of PSP recurrence.
Surgical reconstruction for fibular hemimelia
Authors: Paley Dror
Published: December 2016

Fibular hemimelia presents with foot deformity and leg length discrepancy. Previous classifications have focused on the degree of fibular deficiency rather than the type of foot deformity. Published methods of surgical reconstruction have often failed due to residual or recurrent foot deformity. The purpose of this report is to introduce new classification and reconstruction methods. The Paley SHORDT procedure is used to stabilize the ankle when there is a hypoplastic distal fibula with a dynamic valgus deformity. It involves shortening and realignment of the distal tibia relative to the fibula. In contrast, the Paley SUPERankle procedure is used when there is a fixed equinovalgus foot deformity. The SUPERankle uses a supramalleolar shortening-realignment osteotomy and/or subtalar osteotomies with anlage resection. Due to the bony instead of soft tissue correction of deformity, residual or recurrent deformity is prevented. Weakening of gastro-soleus and peroneal muscles is avoided by shortening of the tibia instead of tendon lengthening. The limitation of ankle motion is related to ankle dysplasia rather than surgery or lengthening. A plantigrade-stable foot and ankle leads to an excellent functional result comparable or better than a Syme's amputation with prosthetic fitting. Serial lengthening procedures combined with the SHORDT or SUPERankle reconstruction lead to limb length equalization with a plantigrade, painless, functional foot.
Advances in endovascular therapy for ischemic cerebrovascular diseases
Authors: Lu Jun , Wang Daming
Published: December 2016

Endovascular therapy for ischemic cerebrovascular diseases has developed rapidly in recent years. The latest clinical trials of acute ischemic stroke have shown promising results with the continued advancement of concepts, techniques, and materials. Mechanical thrombectomy is recommended in the treatment of acute ischemic stroke caused by large vessel occlusion of the anterior circulation, according to the guidelines updated in Europe, USA, and China. The long‐term therapeutic efficacy of endovascular stenting for carotid artery stenosis has also been proved noninferior to that of carotid endarterectomy. However, the latest clinical trials have shown that the efficacy of stenting for intracranial artery and vertebral artery stenosis is inferior to that of medical treatment alone, which needs urgent attention through further development and studies.
Standards for Clinical Trials in Male and Female Sexual Dysfunction: II. Patient-Reported Outcome Measures
Authors: Fisher William A. , Gruenwald Ilan , Jannini Emmanuele A. , Lev-Sagie Ahinoam , Lowenstein Lior , Pyke Robert E. , Reisman Yakov , Revicki Dennis A. , Rubio-Aurioles Eusebio
Published: December 2016

The second article in this series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, focuses on measurement of patient-reported outcomes (PROs). Together with the design of appropriate phase I to phase IV clinical trials, the development, validation, choice, and implementation of valid PRO measurements—the focus of the present article—form the foundation of research on treatments for male and female sexual dysfunctions. PRO measurements are assessments of any aspect of a patient's health status that come directly from the patient (ie, without the interpretation of the patient's responses by a physician or anyone else). PROs are essential for assessing male and female sexual dysfunction and treatment response, including symptom frequency and severity, personal distress, satisfaction, and other measurements of sexual and general health-related quality of life. Although there are some relatively objective measurements of sexual dysfunction (ie, intravaginal ejaculatory latency time, frequency of sexual activity, etc), these measurements do not comprehensively assess the occurrence and extent of sexual dysfunction or treatment on the patient's symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient's perspective.
Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design
Authors: Fisher William A. , Gruenwald Ilan , Jannini Emmanuele A. , Lev-Sagie Ahinoam , Lowenstein Lior , Pyke Robert E. , Reisman Yakov , Revicki Dennis A. , Rubio-Aurioles Eusebio
Published: December 2016

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical trial design for women.
The Influence of Test Positions on Clinical Assessment for Scapular Dyskinesis
Authors: Deng Simin , Chen Kang , Ma Yanhong , Chen Juan , Huang Mi
Published: December 2016

Background

Appropriate evaluation of scapular dyskinesis is essential for therapeutic strategies. Although the current visual‐based assessment is rapid and practical, the reliability of this method is unsatisfactory. It is necessary to adequately understand the conditions of assessment to maximize the benefit of therapeutic interventions.

Objective

To explore the influence of different test positions on clinical assessment for scapular dyskinesis.

Design

Observational study.

Setting

University rehabilitation department.

Patients

A total of 102 subjects diagnosed with unilateral shoulder disorder were recruited from among rehabilitation outpatients from November 2015 to February 2016.

Methods

Two experienced raters categorized the subjects' scapular movement pattern according to Kibler et al classification by the vision‐palpation method at 4 test positions (at rest, and the end range of elevation in the sagittal, scapular, and coronal planes).

Main Outcome Measurements

The overall prevalence of scapular dyskinesis, the distribution of types, and the reproducibility of types at the 4 test positions were analyzed.

Results

The overall prevalence of scapular dyskinesis was 90.08%, and the highest frequency was found at the resting position. Type III was the most common type in our sample. In reproducibility analysis, 21.57% of subjects presented with the same type at any position, and 75.49% of subjects presented with 2 types.

Conclusions

Scapular dyskinesis in individuals with shoulder disorder showed a high prevalence, especially at the resting position. More than 1 type of scapular pattern would be present if assessed at different positions. This study indicates that test positions can affect the results of scapular dyskinesis assessment, and that the resting position should primarily be applied.

Level of Evidence

III
The generation of gravity–capillary solitary waves by a pressure source moving at a trans-critical speed
Authors: Masnadi Naeem , Duncan James H.
Published: December 2016

The unsteady response of a water free surface to a localized pressure source moving at constant speed $U$ in the range $0.95c_{min}\lesssim U\leqslant 1.02c_{min}$, where $c_{min}$ is the minimum phase speed of linear gravity–capillary waves in deep water, is investigated through experiments and numerical simulations. This unsteady response state, which consists of a V-shaped pattern behind the source, and features periodic shedding of pairs of depressions from the tips of the V, was first observed qualitatively by Diorio et al. (Phys. Rev. Lett., vol. 103, 2009, 214502) and called state III. In the present investigation, cinematic shadowgraph and refraction-based techniques are utilized to measure the temporal evolution of the free-surface deformation pattern downstream of the source as it moves along a towing tank, while numerical simulations of the model equation described by Cho et al. (J. Fluid Mech., vol. 672, 2011, pp. 288–306) are used to extend the experimental results over longer times than are possible in the experiments. From the experiments, it is found that the speed–amplitude characteristics and the shape of the depressions are nearly the same as those of the freely propagating gravity–capillary lumps of inviscid potential theory. The decay rate of the depressions is measured from their height–time characteristics, which are well fitted by an exponential decay law with an order one decay constant. It is found that the shedding period of the depression pairs decreases with increasing source strength and speed. As the source speed approaches $c_{min}$, this period tends to approximately 1 s for all source magnitudes. At the low-speed boundary of state III, a new response with unsteady asymmetric shedding of depressions is found. This response is also predicted by the model equation.
Rayleigh–Taylor mixing between density stratified layers
Authors: Williams R. J. R.
Published: December 2016

We have performed numerical calculations of fluid mixing driven by Rayleigh–Taylor instability for density profiles based on the stratified density experiments of Lawrie & Dalziel (J. Fluid Mech., vol. 688, 2011, pp. 507–527) and Davies Wykes & Dalziel (J. Fluid Mech., vol. 756, 2014, pp. 1027–1057). We find that the late-time mixing profiles are similar to their experimental results for similar initial conditions; we consider a range of additional initial conditions to investigate the robustness of the results. A model for the late-time structure of the mixing layer, based on the maximization of configurational entropy, is compared with the results of the numerical calculations, and shows good agreement.
THE STRENGTH OF THE TREE THEOREM FOR PAIRS IN REVERSE MATHEMATICS
Authors: PATEY LUDOVIC
Published: December 2016

No natural principle is currently known to be strictly between the arithmetic comprehension axiom (ACA0) and Ramsey’s theorem for pairs ($RT_2^2$) in reverse mathematics. The tree theorem for pairs ($TT_2^2$) is however a good candidate. The tree theorem states that for every finite coloring over tuples of comparable nodes in the full binary tree, there is a monochromatic subtree isomorphic to the full tree. The principle $TT_2^2$ is known to lie between ACA0 and $RT_2^2$ over RCA0, but its exact strength remains open. In this paper, we prove that $RT_2^2$ together with weak König’s lemma (WKL0) does not imply $TT_2^2$, thereby answering a question of Montálban. This separation is a case in point of the method of Lerman, Solomon and Towsner for designing a computability-theoretic property which discriminates between two statements in reverse mathematics. We therefore put the emphasis on the different steps leading to this separation in order to serve as a tutorial for separating principles in reverse mathematics.
CLASS FORCING, THE FORCING THEOREM AND BOOLEAN COMPLETIONS
Authors: HOLY PETER , KRAPF REGULA , LÜCKE PHILIPP , NJEGOMIR ANA , SCHLICHT PHILIPP
Published: December 2016

The forcing theorem is the most fundamental result about set forcing, stating that the forcing relation for any set forcing is definable and that the truth lemma holds, that is everything that holds in a generic extension is forced by a condition in the relevant generic filter. We show that both the definability (and, in fact, even the amenability) of the forcing relation and the truth lemma can fail for class forcing.

In addition to these negative results, we show that the forcing theorem is equivalent to the existence of a (certain kind of) Boolean completion, and we introduce a weak combinatorial property (approachability by projections) that implies the forcing theorem to hold. Finally, we show that unlike for set forcing, Boolean completions need not be unique for class forcing.
DESCRIPTIONS AND CARDINALS BELOW
Authors: JACKSON STEVE , KHAFIZOV FARID T.
Published: December 2016

Assuming AD, we show that all of the ordinals below $\delta _5^1$ represented by descriptions (c.f. [2], but also defined below) are cardinals. Using this analysis we also get a simple representation for the cardinal structure below $\delta _5^1$. As an application, we compute the cofinalitites of all cardinals below $\delta _5^1$.
Politicians, Bureaucrats, and Development: Evidence from India
Authors: GULZAR SAAD , PASQUALE BENJAMIN J.
Published: December 2016

When do politicians prompt bureaucrats to provide effective services? Leveraging the uneven overlap of jurisdictions in India, we compare bureaucrats supervised by a single political principal with those supervised by multiple politicians. With an original dataset of nearly half a million villages, we find that implementation of India’sNational Rural Employment Guarantee Scheme, the largest employment program in the world, is substantially better where bureaucrats answer to a single politician. Regression discontinuity estimates help increase confidence that this result is causal. Our findings suggest that politicians face strong incentives to motivate bureaucrats as long as they internalize the benefits from doing so. In contrast to a large literature on the deleterious effects of political interventions, our results show that political influence may be more favorable to development than is commonly assumed.
The Labour Recruitment of Local Inhabitants as Rōmusha in Japanese-Occupied South East Asia
Authors: Melber Takuma
Published: December 2016

During World War II, Japan, as occupying power, mobilized thousands of labourers in South East Asia. While the history of Allied prisoners of war (POWs) deployed as forced labourers on the Burma-Siam “Death Railway” is well known, the coercive labour recruitment of local inhabitants as so-called rōmusha has, until today, remained an almost completely untold story. This article introduces rōmusha, with a particular focus on the Burma-Siam Railway, and presents the methods used by the occupying powers to recruit local inhabitants in Java, Malaya, and Singapore, initially as volunteers, and increasingly using force. We look, too, at the tactics and strategies of avoidance the locals were able to deploy. The article offers insights into the poor working conditions on the railway, discusses the body count, and gives an idea of the huge impact of the forced labour recruitment not only in economic terms, but also in terms of the effect it had on the social structure at both the micro and macro levels.
Dynamics of Continuity and Change: Shifts in Labour Relations in the Potosí Mines (1680–1812)
Authors: Barragán Romano Rossana
Published: December 2016

Labour relations in the silver mines of Potosí are almost synonymous with the mita, a system of unfree work that lasted from the end of the sixteenth century until the beginning of the nineteenth century. However, behind this continuity there were important changes, but also other forms of work, both free and self-employed. The analysis here is focused on how the “polity” contributed to shape labour relations, especially from the end of the seventeenth century and throughout the eighteenth century. This article scrutinizes the labour policies of the Spanish monarchy on the one hand, which favoured certain economic sectors and regions to ensure revenue, and on the other the initiatives both of mine entrepreneurs and workers – unfree, free, and self-employed – who all contributed to changing the system of labour.
From Possibility to Properties? Or from Properties to Possibility?
Authors: Allen Sophie R.
Published: December 2016

This paper contrasts two metaphysical accounts of modality and properties: Modal Realism which treats possible entities as primitive; and Strong Dispositionalism in which metaphysical possibility and necessity are determined by actually existing dispositions or powers. I argue that Strong Dispositionalism loses its initial advantages of simplicity and parsimony over Modal Realism as it is extended and amended to account for metaphysical rather than just causal necessity. Furthermore, to avoid objections to its material and formal adequacy, Strong Dispositionalism requires a richer fundamental ontology which it cannot explicate without appealing either to possible worlds or to an account of counterfactual truth conditions, both of which Strong Dispositionalism was intended to replace.
ON CONSISTENCY OF LS ESTIMATORS IN THE ERRORS-IN-VARIABLE REGRESSION MODEL
Authors: Wang Xuejun , Xi Mengmei , Wang Hongxia , Hu Shuhe
Published: December 2016

Under some mild conditions, the strong consistency and complete consistency of the LS estimators in the errors-in-variable regression model with weakly negative dependent errors are obtained, which generalize the corresponding ones for negatively associated random variables. In addition, the simulation study shows that the biases of our method are small, and our method performs well.
Laboratory surveillance of arboviral infections in a southern France region colonized byAedes albopictus
Authors: CADOT L. , SEGONDY M. , FOULONGNE V.
Published: December 2016

The establishment ofAedes albopictusin southern France, a recognized competent vector for several arboviruses, represents a new threat for the local transmission and spread of what were until recently considered as tropical diseases. A preparedness and response plan, based on vigilance of both clinicians and laboratories, has introduced significant changes in guidelines and behaviour regarding patients’ care specifically during the activity period of mosquitoes. In the present study, we report the results of a 1-year activity in arboviral infection diagnosis. A total of 141 patients were included in this retrospective study. The number of suspected imported and autochthonous cases was 69 and 72, respectively. A diagnosis of arboviral infection was confirmed for 15 (21·7%) suspected imported cases, with identification of 13 dengue viruses, one chikungunya virus and one Zika virus. No autochthonous cases were detected. This report illustrates the increase in requests for arboviral infection diagnosis and confirms the challenge with identifying autochthonous arboviral infection cases in many unspecific febrile syndromes.
Mapping the Demos: The Scientisation of the Political, Electoral Research and Dutch Political Parties, c. 1900–1980
Authors: DE JONG WIM , KAAL HARM
Published: December 2016

The ‘scientisation of the political’, understood as the increasing influence of social science within twentieth century (party) politics, provides insight into politicians’ conceptions of political representation and the shifts in those conceptions over time. Social science based knowledge exerted a profound effect on how parties approached political identity formation and on their perceptions of the electorate. Based on a Dutch case study, this article tracks the impact of electoral geography and mass psychology and, from the 1940s onwards, electoral research and polling data on party strategies, showing the important role played by party political think tanks which acted as hubs of social-scientific knowledge. Comparisons with British and West German political parties reveal the complex reception and negotiation of social scientific insights regarding the nature and behaviour of the electorate, as well as the persistence of ingrained stereotypes.
The cumulative effect of frailty and cognition on mortality – results of a prospective cohort study
Authors: St. John Philip D. , Tyas Suzanne L. , Griffith Lauren E. , Menec Verena
Published: December 2016

Background:

Both physical frailty and cognitive impairment predict death, but the joint effect of these two factors is uncertain. The objectives are to determine if the Mini-mental state examination (MMSE) and the Frailty Index (FI) predict death over a five-year interval after accounting for the effect of the other; and if there is an interaction in this effect.

Methods:

An analysis of an existing prospective cohort study of 1,751 community living older adults followed over a five-year time frame. Age, gender, and education were self-reported. The predictor variables were the FI – a measure of frailty based on the “Accumulation of Deficits” model of frailty; and the MMSE. Cox proportional hazards models were constructed for the outcome of time to death.

Results:

The unadjusted Hazard Ratio (HR) (95% CI) for mortality was 2.17 (1.69, 2.80) for those who were only cognitively impaired, 2.02 (1.53, 2.68) for those who were only frail, and 3.57 (2.75, 4.62) for those who were both frail and cognitively impaired with the reference group of those who were neither frail nor cognitively impaired. Adjusted for age, gender, and education, the HR (95% CI) was 1.49 (1.13. 1.95) for those who were only cognitively impaired, 1.81 (1.35, 2.41) for those who were only frail, and 2.28 (1.69, 3.09) for those who were both frail and cognitively impaired.

Conclusions:

Both frailty and cognitive impairment are predictors of mortality and the effect is cumulative. There was no interaction in this effect.
Prediction of Free and Cued Selective Reminding Test Performance Using Volumetric and Amyloid-Based Biomarkers of Alzheimer’s Disease
Authors: Quenon Lisa , Dricot Laurence , Woodard John L. , Hanseeuw Bernard , Gilis Nathalie , Lhommel Renaud , Ivanoiu Adrian
Published: December 2016

Objectives:Relatively few studies have investigated relationships between performance on clinical memory measures and indexes of underlying neuropathology related to Alzheimer’s disease (AD). This study investigated predictive relationships between Free and Cued Selective Reminding Test (FCSRT) cue efficiency (CE) and free-recall (FR) measures and brain amyloid levels, hippocampal volume (HV), and regional cortical thickness.Methods:Thirty-one older controls without memory complaints and 60 patients presenting memory complaints underwent the FCSRT, amyloid imaging using [F18]-flutemetamol positron emission tomography, and surface-based morphometry (SBM) using brain magnetic resonance imaging. Three groups were considered: patients with high (Aβ+P) and low (Aβ− P) amyloid load and controls with low amyloid load (Aβ− C).Results:Aβ+P showed lower CE than both Aβ− groups, but the Aβ− groups did not differ significantly. In contrast, FR discriminated all groups. SBM analyses revealed that CE indexes were correlated with the cortical thickness of a wider set of left-lateralized temporal and parietal regions than FR. Regression analyses demonstrated that amyloid load and left HV independently predicted FCSRT scores. Moreover, CE indexes were predicted by the cortical thickness of some regions involved in early AD, such as the entorhinal cortex.Conclusions:Compared to FR measures, CE indexes appear to be more specific for differentiating persons on the basis of amyloid load. Both CE and FR performance were predicted independently by brain amyloid load and reduced left HV. However, CE performance was also predicted by the cortical thickness of regions known to be atrophic early in AD. (JINS, 2016,22, 991–1004)
Intraindividual Cognitive Variability in Middle Age Predicts Cognitive Impairment 8–10 Years Later: Results from the Wisconsin Registry for Alzheimer’s Prevention
Authors: Koscik Rebecca L. , Berman Sara E. , Clark Lindsay R. , Mueller Kimberly D. , Okonkwo Ozioma C. , Gleason Carey E. , Hermann Bruce P. , Sager Mark A. , Johnson Sterling C.
Published: December 2016

Objectives: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. Methods: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer’s Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer’s disease). The primary outcome was Wave 4 cognitive status (“cognitively normal” vs. “impaired”) determined by consensus conference; “impaired” included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: “6 Factor IICV” and “4 Test IICV”. Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. Results: Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. Conclusions: While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016–1025)
More than two-thirds of dietary iodine in children in northern Ghana is obtained from bouillon cubes containing iodized salt
Authors: Abizari Abdul-Razak , Dold Susanne , Kupka Roland , Zimmermann Michael B
Published: December 2016

Objective

Bouillon cubes are widely consumed by poor households in sub-Saharan Africa. Because their main ingredient is salt, bouillon cubes could be a good source of iodine if iodized salt is used in their production and if their consumption by target groups is high. Our objective was to measure the iodine content of bouillon cubes, estimate their daily intake in school-aged children and evaluate their potential contribution to iodine intakes.

Design

In a cross-sectional study, we measured urinary iodine concentrations (UIC) and estimated total daily iodine intakes. We administered a questionnaire on usage of bouillon cubes. We measured the iodine content of bouillon cubes, household salt, drinking-water and milk products.

Setting

Primary schools in northern Ghana.

Subjects

Schoolchildren aged 6–13 years.

Results

Among school-aged children (n250), median (interquartile range) UIC and estimated iodine intake were 242 (163–365) µg/l and 129 (85–221) µg/d, indicating adequate iodine status. Median household salt iodine concentration (n100) was only 2·0 (0·83–7·4) µg/g; 72 % of samples contained <5 µg iodine/g. Iodine concentrations in drinking-water and milk-based drinks were negligible. Median iodine content of bouillon cubes was 31·8 (26·8–43·7) µg/g, with large differences between brands. Estimated median per capita consumption of bouillon cubes was 2·4 (1·5–3·3) g/d and median iodine intake from bouillon cubes was 88 (51–110) µg/d.

Conclusions

Despite low household coverage with iodized salt, iodine nutrition in school-aged children is adequate and an estimated two-thirds of their dietary iodine is obtained from bouillon cubes.
ON THE -ADIC COHOMOLOGY OF SOME -ADICALLY UNIFORMIZED SHIMURA VARIETIES
Authors: Shen Xu
Published: December 2016

We determine the Galois representations inside the$\ell$-adic cohomology of some unitary Shimura varieties at split places where they admit uniformization by finite products of Drinfeld upper half spaces. Our main results confirm Langlands–Kottwitz’s description of the cohomology of Shimura varieties in new cases.
Journal of Geophysical Research: Planets Celebrates 25 Years
Authors: Wendel JoAnna
Published: December 2016

Two editors look at the past, present, and future of the American Geophysical Union's planetary science journal.
STAT6 deficiency ameliorates Graves’ disease severity by suppressing thyroid epithelial cell hyperplasia
Authors: Jiang Xuechao , Zha Bingbing , Liu Xiaoming , Liu Ronghua , Liu Jun , Huang Enyu , Qian Tingting , Liu Jiajing , Wang Zhiming , Zhang Dan , Wang Luman , Chu Yiwei
Published: December 2016

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves’ disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves’ disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.
Combined nifuroxazide and SAT05f therapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation
Authors: Jia Huijie , Zhao Tiesuo , Ji Yinghua , Jia Xiaolong , Ren Wenjing , Li Chen , Li Minming , Xiao Yali , Wang Hui , Xu Kailin
Published: December 2016

Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy. The results showed combined therapy significantly decreased the severity of aGvHD and prolonged the survival rate. Furthermore, after treatment, the activation of CD4+ effect T cells was reduced, whereas Treg cells was increased, and the cytokine release was inhibited. In conclusion, combined therapy of nifuroxazide with SAT05f may be potential for the prevention or treatment of aGvHD, providing theoretic and experimental basis.
Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis
Authors: Meng Xiao-Ming , Wang Shuang , Huang Xiao-Ru , Yang Chen , Xiao Jun , Zhang Yang , To Ka-Fai , Nikolic-Paterson David J , Lan Hui-Yao
Published: December 2016

Myofibroblasts play a central role in renal fibrosis although the origin of these cells remains controversial. We recently reported that bone marrow-derived macrophages can give rise to myofibroblasts through macrophage to myofibroblast transition (MMT). However, several important issues remain to be addressed, including whether MMT occurs in human kidney disease and verification of the MMT process through lineage tracing. Biopsies from a cohort of 58 patients with various forms of kidney disease were examined for MMT cells that co-express macrophage (CD68) and myofibroblast (α-smooth muscle actin, α-SMA) markers. MMT cells were evident in active fibrotic lesions, but were largely absent in acute inflammatory or sclerotic lesions, suggesting that MMT cells contribute to progressive renal fibrosis. Fate-mapping studies in LysMCreTomato mice identified substantial numbers of Tomato+ myeloid cells with F4/80+ macrophage phenotype expressing α-SMA and collagen I in the unilateral ureteral obstructive model of renal fibrosis, providing direct evidence for the MMT process during the development of renal fibrosis. In addition, MMT cells had a predominant M2 phenotype in both human and mouse renal fibrosis. Finally, selective depletion of myeloid cells via diphtheria toxin in LysMCreiDTR mice largely abolished macrophage infiltration and MMT cells in the obstructed kidney and substantially reduced accumulation of α-SMA+ myofibroblasts and collagen deposition, revealing a pathogenic role for inflammatory macrophages in MMT and tissue fibrosis. In conclusion, these findings provide substantial new data to support the postulate that macrophages can directly transdifferentiate into collagen-producing myofibroblasts in human and experimental kidney disease.
Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis
Authors: Chen Xi , Cao Xinwei , Sun Xiaohua , Lei Rong , Chen Pengfei , Zhao Yongxu , Jiang Yuhang , Yin Jie , Chen Ran , Ye Deji , Wang Qi , Liu Zhanjie , Liu Sanhong , Cheng Chunyan , Mao Jie , Hou Yingyong , Wang Mingliang , Siebenlist Ulrich , Eugene Chin Y , Wang Ying , Cao Liu , Hu Guohong , Zhang Xiaoren
Published: December 2016

Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFβ signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFβ treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.
Biomimetic Sniffing Improves the Detection Performance of a 3D Printed Nose of a Dog and a Commercial Trace Vapor Detector
Authors: Staymates Matthew E. , MacCrehan William A. , Staymates Jessica L. , Kunz Roderick R. , Mendum Thomas , Ong Ta-Hsuan , Geurtsen Geoffrey , Gillen Greg J. , Craven Brent A.
Published: December 2016

Unlike current chemical trace detection technology, dogs actively sniff to acquire an odor sample. Flow visualization experiments with an anatomically-similar 3D printed dog’s nose revealed the external aerodynamics during canine sniffing, where ventral-laterally expired air jets entrain odorant-laden air toward the nose, thereby extending the “aerodynamic reach” for inspiration of otherwise inaccessible odors. Chemical sampling and detection experiments quantified two modes of operation with the artificial nose-active sniffing and continuous inspiration-and demonstrated an increase in odorant detection by a factor of up to 18 for active sniffing. A 16-fold improvement in detection was demonstrated with a commercially-available explosives detector by applying this bio-inspired design principle and making the device “sniff” like a dog. These lessons learned from the dog may benefit the next-generation of vapor samplers for explosives, narcotics, pathogens, or even cancer, and could inform future bio-inspired designs for optimized sampling of odor plumes.
Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia
Authors: Guo Jiahua , Yong Yonghong , Aa Jiye , Cao Bei , Sun Runbin , Yu Xiaoyi , Huang Jingqiu , Yang Na , Yan Lulu , Li Xinxin , Cao Jing , Aa Nan , Yang Zhijian , Kong Xiangqing , Wang Liansheng , Zhu Xuanxuan , Ma Xiaohui , Guo Zhixin , Zhou Shuiping , Sun He , Wang Guangji
Published: December 2016

The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.
Association between preterm brain injury and exposure to chorioamnionitis during fetal life
Authors: Anblagan Devasuda , Pataky Rozalia , Evans Margaret J. , Telford Emma J. , Serag Ahmed , Sparrow Sarah , Piyasena Chinthika , Semple Scott I. , Wilkinson Alastair Graham , Bastin Mark E. , Boardman James P.
Published: December 2016

Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain. Histologic chorioamnionitis (HCA) reflects intrauterine inflammation, can trigger a fetal inflammatory response, and is closely associated with premature birth. In a cohort of 90 preterm infants with detailed placental histology and neonatal brain magnetic resonance imaging (MRI) data at term equivalent age, we used Tract-based Spatial Statistics (TBSS) to perform voxel-wise statistical comparison of fractional anisotropy (FA) data and computational morphometry analysis to compute the volumes of whole brain, tissue compartments and cerebrospinal fluid, to test the hypothesis that HCA is an independent antenatal risk factor for preterm brain injury. Twenty-six (29%) infants had HCA and this was associated with decreased FA in the genu, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, limbs of the internal capsule, external capsule and cerebellum (p < 0.05, corrected), independent of degree of prematurity, bronchopulmonary dysplasia and postnatal sepsis. This suggests that diffuse white matter injury begins in utero for a significant proportion of preterm infants, which focuses attention on the development of methods for detecting fetuses and placentas at risk as a means of reducing preterm brain injury.
Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping
Authors: Müller Vilhelm , Rajer Fredrika , Frykholm Karolin , Nyberg Lena K. , Quaderi Saair , Fritzsche Joachim , Kristiansson Erik , Ambjörnsson Tobias , Sandegren Linus , Westerlund Fredrik
Published: December 2016

Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples.
Biochemical and Structural Analysis of a Novel Esterase from Caulobacter crescentus related to Penicillin-Binding Protein (PBP)
Authors: Ryu Bum Han , Ngo Tri Duc , Yoo Wanki , Lee Sojeong , Kim Boo-Young , Lee Euijoo , Kim Kyeong Kyu , Kim T. Doohun
Published: December 2016

Considering that the prevalence of antibiotic-resistant pathogenic bacteria is largely increasing, a thorough understanding of penicillin-binding proteins (PBPs) is of great importance and crucial significance because this enzyme family is a main target of β-lactam-based antibiotics. In this work, combining biochemical and structural analysis, we present new findings that provide novel insights into PBPs. Here, a novel PBP homologue (CcEstA) from Caulobacter crescentus CB15 was characterized using native-PAGE, mass spectrometry, gel filtration, CD spectroscopy, fluorescence, reaction kinetics, and enzyme assays toward various substrates including nitrocefin. Furthermore, the crystal structure of CcEstA was determined at a 1.9 Å resolution. Structural analyses showed that CcEstA has two domains: a large α/β domain and a small α-helix domain. A nucleophilic serine (Ser68) residue is located in a hydrophobic groove between the two domains along with other catalytic residues (Lys71 and Try157). Two large flexible loops (UL and LL) of CcEstA are proposed to be involved in the binding of incoming substrates. In conclusion, CcEstA could be described as a paralog of the group that contains PBPs and β-lactamases. Therefore, this study could provide new structural and functional insights into the understanding this protein family.