Contrasts in China and Soviet reform: sub-national and national causes

Why did reform in China and the former Soviet Union produce drastically different outcomes? Why did some provinces in China embrace faster economic reform than others? This article argues that the state sector and reform initiatives in the sub-national units, reform strategies, entrenchment and maturation of central planning, the size of the defence industry, policy choice and the historical context help explain the differences in Soviet and Chinese reform courses and outcomes. A predominant state sector in the former Soviet republics had stifled local reform initiatives. Gorbachev resorted to democratisation in order to unbolt the gate for popular support for marketisation, yet resulting in the breakup of the Soviet Union and destabilising the economy. In China, some provinces had sizable non-state sectors and were inclined to push forth marketization. Reform resulted in expanding non-state sectors, generating high growth and encouraging the regime to maintain its monopoly of power. China’s reform also benefited from a yet-to-be-entrenched and rudimentary central planning, a small defence sector, popular backlash against past policies, and reformist pragmatic strategy

Clinical patterns in asthma based on proximal and distal airway nitric oxide categories

<p>Abstract</p> <p>Background</p> <p>The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'aw_NO(nl/s), maximum airway flux] and distal contributions [CA_NO(ppb), distal airway/alveolar NO concentration]. We hypothesized that J'aw_NOand CA_NOare selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.</p> <p>Methods</p> <p>In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'aw_NOand CA_NO.</p> <p>Results</p> <p>J'aw_NOwas not correlated with CA_NO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'aw_NO(≥ 1.5 nl/s) and CA_NO(≥ 2.3 ppb): Type I (normal J'aw_NOand CA_NO), Type II (elevated J'aw_NOand normal CA_NO), Type III (elevated J'aw_NOand CA_NO) and Type IV (normal J'aw_NOand elevated CA_NO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'aw_NO, but was not related to CA_NO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA_NO(III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.</p> <p>Conclusions</p> <p>J'aw_NOand CA_NOreveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CA_NOwere related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.</p

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion

<i>De Novo</i> and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects

Congenital heart disease (CHD) has a complex genetic etiology, and recent studies suggest that high penetrance de novo mutations may account for only a small fraction of disease. In a multi-institutional cohort surveyed by exome sequencing, combining analysis of 987 individuals (discovery cohort of 59 affected trios and 59 control trios, and a replication cohort of 100 affected singletons and 533 unaffected singletons) we observe variation at novel and known loci related to a specific cardiac malformation the atrioventricular septal defect (AVSD). In a primary analysis, by combining developmental coexpression networks with inheritance modeling, we identify a de novo mutation in the DNA binding domain of NR1D2 (p.R175W). We show that p.R175W changes the transcriptional activity of Nr1d2 using an in vitro transactivation model in HUVEC cells. Finally, we demonstrate previously unrecognized cardiovascular malformations in the Nr1d2tm1-Dgen knockout mouse. In secondary analyses we map genetic variation to protein-interaction networks suggesting a role for two collagen genes in AVSD, which we corroborate by burden testing in a second replication cohort of 100 AVSDs and 533 controls (p = 8.37e-08). Finally, we apply a rare-disease inheritance model to identify variation in genes previously associated with CHD (ZFPM2, NSD1, NOTCH1, VCAN, and MYH6), cardiac malformations in mouse models (ADAM17, CHRD, IFT140, PTPRJ, RYR1 and ATE1), and hypomorphic alleles of genes causing syndromic CHD (EHMT1, SRCAP, BBS2, NOTCH2, and KMT2D) in 14 of 59 trios, greatly exceeding variation in control trios without CHD (p = 9.60e-06). In total, 32% of trios carried at least one putatively disease-associated variant across 19 loci,suggesting that inherited and de novo variation across a heterogeneous group of loci may contribute to disease risk

Pulmonary responses of asthmatic and normal subjects to different temperature and humidity conditions in an environmental chamber

Determining the possible adverse health effects of air pollutants can be complicated by differences in the environmental conditions of temperature and humidity. To evaluate the potentially confounding effects of differences in temperature and humidity, we exposed 8 normal male subjects and 8 male subjects with asthma to the extremes in temperature and humidity that could be maintained in an environmental chamber. We performed serial pulmonary function tests for these subjects before and during 6 hr exposure periods on 5 separate occasions: cold, dry (10°C, 10% relative humidity); cold, humid (10°C, 50% relative humidity); normal ambient (22°C, 40% relative humidity); hot, dry (37°C, 15% relative humidity); and hot, humid (37°C, 60% relative humidity). The exposure period included a 12 min exercise on a cycle ergometer. We found no significant change in spirometry, airways resistance, or diffusing capacity for either group of subjects at rest alone over the 6 hr period of exposure for any exposure condition. However, there were changes in spirometry and airways resistance as a result of the 12 min period of exercise. The subjects with asthma had significant decreases in forced expiratory volume in 1 sec (FEV1) (20–21%) and increases in specific airways resistance when exercising in conditions of cold and dry, cold and humid, and hot and dry. The normal subjects had an average increase in FEV 1 of approximately 6% when exercising in the hot and humid conditions. We found significant correlations for the changes in FEV 1 with the water content of the exposure conditions for both groups of subjects. We also found that the work performance (expressed as the external work performed divided by the oxygen consumed) was decreased for the subjects in both groups at the conditions of the higher temperature (37°C) compared with the lower temperature (10°C). These results confirm that controlling for the conditions of temperature and humidity is essential in chamber studies, field studies, or epidemiologic evaluations determining the adverse effect of an air pollutant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41344/1/408_2004_Article_BF00164755.pd

Failure to apply standard limit-of-detection or limit-of-quantitation criteria to specialized pro-resolving mediator analysis incorrectly characterizes their presence in biological samples

Specialized pro-resolving mediators (SPM) derived from oxygenation of long chain polyunsaturated fatty acids (PUFA) were originally described by Serhan and colleagues and have been proposed as mediators of inflammation resolution. Families of SPM described in the literature include lipoxins, resolvins, maresins, protectins and their peptide conjugates. Gomez and co-authors reported that levels of plasma SPM from patients with early rheumatoid arthritis predict response to biologic therapy after 6 months. SPM were measured in this study using liquid chromatography tandem mass spectrometry (LC-MS/MS). On reviewing the methods, supplementary analytical data, and the online peer review file, we note serious concerns, regarding both analytical methods and experimental conclusions. Application of this flawed methodology to SPM analysis brings into question the very occurrence of many of these lipids in biological samples, their proposed impact on inflammatory processes, and claims of their utility as biomarkers

Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency

Rationale: NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective: We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15. Methods and Results: We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions: These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function

Compliance with herpes zoster vaccination in young and adult individuals in two regions of Italy

Background: The purpose of this work was to explore the knowledge and acceptance of Varicella Zoster Virus (VZV)- Herpes Zoster (HZ) vaccination in the general Italian population, where the HZ vaccine has not yet been distributed, using a prevalence study of subjects from two regions in Italy. Methods: A group of 3,173 individuals were interviewed using a questionnaire. The youngest age group (≤ 20 year) was composed of students interviewed at university. The middle age group (21-40 years) and the older age group (≥ 41 years) were interviewed by general practitioners in their office. Results: In both regions, the majority of subjects had been infected with varicella, and only 165 (5.2%) subjects reported receiving the VZV vaccination. Regarding HZ, 2,749 (86.6%) individuals stated that they knew of the virus and 2,233 (70%) were willing to be vaccinated against HZ. The majority of people willing to be vaccinated were in the middle and older age groups (36.6% and 44.7%, respectively). Conclusion: Compliance versus vaccination results were satisfactory and probably, with the upcoming availability of the HZ vaccine in Italy, adults will be favourably disposed towards vaccination