Recommendations on treatment for IPF

Patient management in Idiopathic Pulmonary Fibrosis (IPF) is largely based on societal guidelines and recommendations. A recent update by the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Association (ALAT) provided updated guidance on the diagnosis and management of IPF, along with recommendations on pharmacologic and non-pharmacologic approaches to patient management. The treatment guidance is based on GRADE criteria, which rates the quality of evidence according to previously published methodology. Here we discuss how to interpret the recent guideline updates and the implications of this guidance for clinical practice. In addition we discuss the assessment and recommendations for a number of pharmacological agents that have been the focus of clinical trials over the past years. Although no single pharmacological agent was recommended by the guidelines committee, we discuss how since then, more recent data have resulted in the approval of pirfenidone in Europe, and preliminary negative findings regarding the safety of a triple therapy regimen consisting of prednisone, azathioprine and N-acetylcysteine have raised the question of whether it is no longer a treatment option. As clinicians, we must interpret the available guidance and recommendations as we consider each individual patient and as we discuss the available clinical data and the patient’s own preferences in our approach to the management of this disease.     

A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis

IntroductionThere is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH (SSc-PAH) with the commonly used European Society of Cardiology/European Respiratory Society (ESC/ERS 2009) guidelines.MethodsWe included 73 consecutive SSc patients with suspected PAH undergoing right heart catheterization (RHC). The three screening models were applied to each patient. For each model, contingency table analysis was used to determine sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for PAH. These properties were also evaluated in an ‘alternate scenario analysis’ in which the prevalence of PAH was set at 10%.ResultsRHC revealed PAH in 27 (36.9%) patients. DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of only 91%, missing one case of PAH; these guidelines could not be applied to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%.ConclusionsIn this cohort, the DETECT and ASIG algorithms out-perform the ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0517-5) contains supplementary material, which is available to authorized users.     

热带季节雨林优势树种叶片和冠层尺度二氧化碳交换特征

采用叶室法和涡度相关法分析了西双版纳热带季节雨林优势树种绒毛番龙眼和大叶白颜树冠层及其叶片在不同季节的CO₂交换量,并拟合得到主要特征值.结果表明：以叶室法测得的两树种冠层最大净光合速率(P_{max A})为雨季>雨季末>雾凉季>干热季,叶片暗呼吸速率(R_d)为雨季>雨季末>干热季>雾凉季;以涡度相关法得到的两树种冠层最大净光合速率(P_{max B})为雨季>雨季末>雾凉季>干热季,而冠层呼吸速率(R_e)则是雨季>干热季>雾凉季>雨季末.两种方法得到的不同季节植物冠层最大净光合速率相差0.9～2.0 μmol·m^-2·s^-1.     

The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF) - practical implications

Idiopathic pulmonary fibrosis (IPF), the most prevalent idiopathic interstitial pneumonia, is associated with a poor prognosis. An accurate diagnosis of IPF is essential for optimal management. The recent ATS/ERS/JRS/ALAT recommendations on the diagnosis and management of IPF were developed from a systematic review of the published literature. High-resolution computed tomography (HRCT) scanning has a central role in the IPF diagnostic pathway with formal designation of criteria for an HRCT pattern of UIP. In the correct clinical context, a UIP pattern on HRCT is indicative of a definite diagnosis of IPF without the need for a surgical lung biopsy. However, although the 2011 ATS/ERS/JRS/ALAT statement is a major advance, the application of guideline recommendations by clinicians has identified limitations that need to be addressed in future statements. Key problems include: 1) the lack of management recommendations for the highly prevalent clinical scenarios of probable and possible IPF; 2) the ongoing confusion about the diagnostic role of bronchoalveolar lavage (reflecting ambiguity in the current recommendation); 3) HRCT misdiagnosis by less experienced radiologists, increasingly recognised as a major problem; and 4) the lack of integration of clinical data, including the treated course of disease, in the designation of the diagnostic likelihood of IPF.     

ETB receptor polymorphism is associated with airway obstruction

Background

Cardiopulmonary exercise testing (CPET) has become an important modality for the evaluation and management of patients with a diverse array of medical problems. However, interpreting these tests is often difficult and time consuming, requiring significant expertise.

Methods

We created a computer software program (XINT) that assists in CPET interpretation. The program uses an integrative approach as recommended in the Official Statement of the American Thoracic Society/American College of Chest Physicians (ATS/ACCP) on Cardiopulmonary Exercise Testing. In this paper we discuss the principles behind the software. We also provide the detailed logic in an accompanying file (Additional File 1). The actual program and the open source code are also available free over the Internet at http://www.xint.org. For convenience, the required download files can also be accessed from this article.

Results

To test the clinical usefulness of XINT, we present the computer generated interpretations of the case studies discussed in the ATS/ACCP document in another accompanying file (Additional File 2). We believe the interpretations are consistent with the document's criteria and the interpretations given by the expert panel.

Conclusion

Computers have become an integral part of modern life. Peer-reviewed scientific journals are now able to present not just medical concepts and experimental studies, but actual functioning medical interpretive software. This has enormous potential to improve medical diagnoses and patient care. We believe XINT is such a program that will give clinically useful interpretations when used by the medical community at large.     

Bacteriological quality of runoff water from pastureland.

Runoff from a cow-calf pasture in eastern Nebraska was monitored for total coliforms (TC), fecal coliforms (FC), and fecal streptococci (FS) during 1976, 1977, and 1978. Bacteriological counts in runoff from both grazed and ungrazed areas generally exceeded recommended water quality standards. The FC group was the best indicator group of the impact of grazing. Rainfall runoff from the grazed area contained 5 to 10 times more FC than runoff from the fenced, ungrazed area. There was little difference in TC counts between the two areas, but FS counts were higher in runoff from the ungrazed area and reflected the contributions from wildlife. Recommended bacteriological water quality standards, developed for point source inputs, may be inappropriate for characterizing nonpoint source pollution from pasture runoff. The FC/FS ratio in pasture runoff was useful in identifying the relative contributions of cattle and wildlife. Ratios below 0.05 were indicative of wildlife sources and ratios above 0.1 were characteristic of grazing cattle. Occasions when the FC/FS ratio of diluted cattle waste exceeded one resulted from differential aftergrowth and die-off between FC and FS. The FC/FS ratio and percentage of Streptococcus bovis in pasture runoff are useful indicators for evaluating the effectiveness of livestock management practices for minimizing bacterial contamination of surface water. The importance of choice of medium for the enumeration of FS in runoff derived from cattle wastes is discussed.     

Bacteriological Quality of Runoff Water from Pastureland

Runoff from a cow-calf pasture in eastern Nebraska was monitored for total coliforms (TC), fecal coliforms (FC), and fecal streptococci (FS) during 1976, 1977, and 1978. Bacteriological counts in runoff from both grazed and ungrazed areas generally exceeded recommended water quality standards. The FC group was the best indicator group of the impact of grazing. Rainfall runoff from the grazed area contained 5 to 10 times more FC than runoff from the fenced, ungrazed area. There was little difference in TC counts between the two areas, but FS counts were higher in runoff from the ungrazed area and reflected the contributions from wildlife. Recommended bacteriological water quality standards, developed for point source inputs, may be inappropriate for characterizing nonpoint source pollution from pasture runoff. The FC/FS ratio in pasture runoff was useful in identifying the relative contributions of cattle and wildlife. Ratios below 0.05 were indicative of wildlife sources and ratios above 0.1 were characteristic of grazing cattle. Occasions when the FC/FS ratio of diluted cattle waste exceeded one resulted from differential aftergrowth and die-off between FC and FS. The FC/FS ratio and percentage of Streptococcus bovis in pasture runoff are useful indicators for evaluating the effectiveness of livestock management practices for minimizing bacterial contamination of surface water. The importance of choice of medium for the enumeration of FS in runoff derived from cattle wastes is discussed.     

Multiple foundation species shape benthic habitat islands

Pattern generation by foundation species (FS) is a primary structuring agent in marine and terrestrial communities. Prior research, focused on single-species or guild-dominated habitats, stressed the role of facilitation in maintaining community structure. However, many habitats are developed by multiple FS from different guilds. Competition between these FS may provide an additional agent potentially responsible for spatial and temporal patterns. In the White Sea, epibenthic patches formed by barnacles (Balanus crenatus) and solitary ascidians (mainly Styela spp. and Molgula spp.) on small stones and empty bivalve shells (mainly Serripes groenlandicus) produce microhabitats for different sessile taxa. We hypothesized that: (1) several FS would provide habitats for most of other species in the community; (2) different FS promote different assemblages of sessile organisms; (3) the interplay of facilitation and competition best explains observed patterns of abundance and demography in FS; and (4) these interactions shape the whole community, increasing the diversity compared to less heterogeneous patches constituted by single FS. We examined 459 patches and the results generally supported this hypothesis. The number of FS in a patch positively affected species diversity. Most sessile species (72% of individuals) resided on barnacles, ascidians and red algae, except barnacles that dominated the primary substrate. The size structure of barnacles (live individuals and empty shells) and ascidians were interrelated, suggesting long-term patch dynamics whereby ascidians regularly replace barnacles. Following this replacement, we expect consequent changes to the entire dependent assemblage. Evidence for these changes exists in the spatial pattern: most sessile and motile taxa demonstrated significant associations with either FS. Our results indicate that the small-scale patterns observed in patches formed by multiple FS are primarily generated by facilitation of dependent taxa by FS, and facilitation and competition between different FS. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Dedicated to E. A. Ninbourg, our late tutor.     

Multilevel examination of minor salivary gland biopsy for Sjögren's syndrome significantly improves diagnostic performance of AECG classification criteria

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjögren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-μm intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American–European Consensus Group (AECG) criteria set for Sjögren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS ≥ 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2.     

Reduced Motor Cortex Deactivation in Individuals Who Suffer from Writer's Cramp

This study investigated the neuromagnetic activities of self-paced finger lifting task and electrical median nerve stimulation in ten writer''s cramp patients and fourteen control subjects. The event-related de/synchronizations (ERD/ERS) of beta-band activity levels were evaluated and the somatosensory cortical activity levels were analyzed using equivalent-current dipole modeling. No significant difference between the patients and control subjects was found in the electrical stimulation-induced beta ERS and electrical evoked somatosensory cortical responses. Movement-related beta ERD did not differ between controls and patients. Notably, the amplitude of the beta ERS after termination of finger movement was significantly lower in the patients than in the control subjects. The reduced movement-related beta ERS might reflect an impairment of motor cortex deactivation. In conclusion, a motor dependent dysregulation of the sensorimotor network seems to be involved in the functional impairment of patients with writer''s cramp.     

AMarge

AMarge is a web tool for the automatic quality assessment of Affymetrix GeneChip data. It is essential to have a trustworthy set of chips in order to derive gene expression data for phenotypic analysis, and AMarge provides a complete and rigorous web-accessible tool to fulfill this need. The quality assessment steps include image plots of weights derived from a robust linear model fit of the data, a 3'/5' RNA digestion plot, and Affymetrix Microarray Suite version 5.0 (MAS 5.0) quality standard procedures. Furthermore, robust multi-array average expression values are generated in order to have a start-up expression set for the subsequent analysis. The results of the complete analysis are summarised and returned as an HTML report. AVAILABILITY: The AMarge web interface is accessible at http://nin.crg.es/cgi-binf/AMargeWeb.cgi. A mirror server is also available at http://bioinformatics.istge.it/AMarge-bin/AMargeWeb.cgi. The software implementing all these methods is part of the Bioconductor project (http://www.bioconductor.org).     

Diatom Model Affinity (DMA), a New Index for Water Quality Assessment

A new index, diatom model affinity (DMA) was erected as a reference-based community metric, derived from generic and species composition. DMA provides an assessment of water quality by the calculation of percent similarity to a model community, which can be viewed as a reference standard. High similarity to the model indicates communities that are minimally disturbed, while lower similarity suggests water quality problems. The index is similar to that developed for macroinvertebrate communities by Novak & Bode (1992, Journal of the North American Benthological Society 11: 80-85). The index correlated well with environmental factors operating on hierarchical scales. Compared to other commonly used diatom indices, DMA-based community assessments demonstrated high correspondence to patterns derived from multivariate statistics.     

Diversity,equity, and inclusion in the melanoma research community

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant reports of inequity in opportunity, discrimination, and sexual harassment demonstrate there is much work remaining to ensure all scientists in our community experience an academic workplace culture built on mutual respect, fair access, inclusion, and equitable opportunity.     

不同施肥处理对玉米-小麦轮作土壤微生物群落功能多样性的影响

土壤微生物多样性能反应土壤的肥力,不同的施肥措施对土壤微生物的种群和功能多样性也会产生重要的影响。以山东德州连续两年小麦季和玉米季收获后土壤为研究对象,利用Biolog技术研究了6种不同施肥处理对土壤微生物群落功能多样性的影响。结果表明:其中各个施肥处理的平均颜色变化率(average well color development,AWCD)差异显著,常规氮磷钾肥+全量秸秆还田+秸秆腐熟剂(FS)处理代谢活性最高;物种丰富度指数(H)和均匀度指数(E)也表明各施肥方式均能够维持微生物种群的多样性,其中FS和30%猪粪+70%常规氮磷钾肥(OF)处理物种丰富度指数(H)和均匀度指数(E)最高;PCA及RDA分析显示,OF和FS处理微生物功能多样性相似,且其微生物功能多样性与有机质(Soil organic matter,SOM)、全氮(Total N,TN)、速效磷(Available P,AP)和速效钾(Available K,AK)密切相关。猪粪堆肥有机无机复合肥3 600 kg/hm2(OI2)处理与猪粪堆肥有机无机复合肥1 800 kg/hm2(OI1)处理相似,其功能多样性比常规施肥(CF)处理稍高。综上所述,OF处理和FS处理的土壤微生物群落功能多样性程度高于其他处理,说明秸秆还田+秸秆腐熟剂和有机肥部分替代氮磷钾肥能够显著提高土壤微生物功能多样性,有利于保护土壤微生态。     

Validation of the “World Health Organization Disability Assessment Schedule for Children,WHODAS-Child” in Rwanda

Overview

The World Health Organization Disability Assessment Schedule for children (WHODAS-Child) is a disability assessment instrument based on the WHO''s International Classification of Functioning, Disability and Health for children and youth. It is modified from the original adult version specifically for use with children. The aim of this study was to assess the WHODAS-Child structure and metric properties in a community sample of children with and without reported psychosocial problems in rural Rwanda.

Methods

The WHODAS-Child was first translated into Kinyarwanda through a detailed committee translation process and back-translation. Cognitive interviewing was used to assess the comprehension of the translated items. Test-retest reliability was assessed in a group of 64 children. The translated WHODAS-Child was then administered to a final sample of 367 children in southern Kayonza district in rural southeastern Rwanda within a larger psychosocial assessment battery. The latent structure was assessed through confirmatory factor analysis. Reliability was evaluated in terms of internal consistency (Cronbach''s alpha) and test-retest reliability (Pearson''s correlation coefficient). Construct validity was explored by examining convergence between WHODAS-Child scores and mental disorder status, and divergence of WHODAS-Child scores with protective factors and prosocial behaviors. Concordance between parent and child scores was also assessed.

Results

The six-factor structure of the WHODAS-Child was confirmed in a population sample of Rwandan children. Test-retest and inter-rater reliability were high (r = .83 and ICC = .88). WHODAS-Child scores were moderately positively correlated with presence of depression (r = .42, p<.001) and post-traumatic stress disorder (r = .31, p<.001) and moderately negatively correlated with prosocial behaviors (r = .47, p<.001). The Kinyarwanda version of the WHODAS-Child was found to be a reliable and acceptable self-report tool for assessment of functional impairment among children largely referred for psychosocial problems in the study district in rural Rwanda. Further research in low-resource settings and with more general populations is recommended.     

Purification and characterization of recombinant antistasin: a leech-derived inhibitor of coagulation factor Xa

Antistasin (ATS) is a selective, tight-binding inhibitor of blood coagulation Factor Xa originally isolated from the salivary glands of the Mexican leech Haementeria officinalis. In order to provide sufficient quantities of ATS to further investigate the role of Factor Xa in blood coagulation, a recombinant version of ATS has been produced in an insect baculovirus host-vector system. In this study, we describe the purification and in vitro and in vivo characterization of a single recombinant antistasin (rATS) isoform. The purified protein constitutes a minor isoform relative to the more abundant ATS isoforms present in leech salivary gland extracts. In vitro, rATS inhibits purified human Factor Xa stoichiometrically, prolongs plasma-based clotting assays at nanomolar concentrations, and like native ATS, is cleaved at a single position by Factor Xa during the course of inhibition. An initial evaluation of the in vivo efficacy of rATS was addressed utilizing a rhesus monkey model of mild disseminated intravascular coagulation. rATS was shown to fully suppress thromboplastin-induced fibrinopeptide A generation in a dose-dependent fashion. The availability of rATS should provide a valuable tool for the critical evaluation of the specific role played by Factor Xa in coagulation.     

A comparison between different models of the relation between recorded intradental nerve impulse activity and reported pain in man

In this study three different models of the relation between intradental nerve impulse activity (INA) and pain report, expressed by finger-span (FS), in man were investigated. The techniques were (i) a previously described mathematical model, (ii) the relation between the Areas of INA and FS and (iii) the relation between the Peaks of INA and FS. Their usefulness in 533 clinical experiments on 15 subjects were evaluated by means of a statistical analysis of the variability and accuracy of the models. It was shown that the mathematical model was the most accurate and stable method of the three different methods investigated. This was indicated by, among other things, a significantly smaller variability for the mathematical model within experimental sessions than between sessions. The two other methods were found to be of less scientific value since they had an undesired high variability within sessions, and also showed contradicting results during control conditions.     

贵州省生态游憩空间时空演化特征及其驱动因素

生态游憩空间是生态文明建设和大众游憩权利普及的重要载体,是提升城乡居民生活质量和幸福感的重要场域。基于贵州省1982-2020年908处生态游憩空间样本数据,采用Google Earth批量获取生态游憩空间地理坐标,并使用ArcGIS 10.2对其进行空间数字化处理,采用热点分析工具识别其冷热点区的空间分布和演化特征,利用地理探测器测算主要驱动因子对生态游憩空间时空演化的解释力。研究发现：1）在时间演化上,生态游憩空间数量持续快速增长,面积全域扩展,数量由1982年的5处增加到2020年的908处,面积由0.05万km²演变为3.7万km²。2）在数量空间演化上,从极化分布转向均衡发展,分布方向始终呈东北-西南走向。3）在密度空间演化上,空间集聚随时序发生明显变化,贵阳市区始终是集聚高地,遵义市区最终成长为热点区。4）在驱动因素方面,自然环境要素对生态游憩空间时空演化具有基础约束效应,产业经济因素是其时空演化的内在驱动力,社会政策因素是其时空演化的外在推力。旅游收入占国内生产总值比重、建成区面积、相关政策和平均海拔是生态游憩空间数量时空演化的控制性驱动因子,而第三产业比重、农村居民可支配收入和固定资产投资是其密度时空演化的控制性驱动因子,生态游憩空间时空格局是多因素长期交互作用的结果。未来,贵州省生态游憩空间建设与发展应根据其分布特征及演化规律,通过科学规划、合理布局和城乡统筹发展,有序推进生态游憩空间的增量扩展和存量更新,有效破解生态游憩空间供给不平衡不充分的问题。同时,不断提升主导因子的驱动能力,促进城乡生态游憩空间供需协调耦合发展,逐步实现生态游憩空间的社会公平。     

青弋江流域大型底栖动物群落结构及水质评价

研究河流大型底栖动物群落结构特征及水环境质量对水生态的保护与修复具有重要意义。以青弋江流域为研究对象,于2020年9月进行了大型底栖动物及水体理化因子的调查,采用相对重要性指数、生物多样性指数及Jaccard相似性系数分析了大型底栖动物群落结构特征,运用丰度/生物量比较曲线法及冗余分析法探究了底栖动物群落受到的干扰程度及其主要影响环境因子,最后利用水生态环境质量综合指数对河流水质进行评价。研究结果表明：(1)共采集鉴定大型底栖动物61种,隶属于3门6纲17目,平均丰度为265.9个/m~2,平均生物量41.6 g/m~2。相对重要性指数分析显示,日本沼虾(Macrobrachium nipponensis)、中国圆田螺(Cipangopaludina chinensis)、羽摇蚊(Chironomus plumosus)及扁蜉(Ecdyrus)为群落中的主要优势种。(2)由群落相似性分析知,Jaccard相似性系数较低,调查点位之间存在较强的空间异质性。(3)冗余分析表明,电导率、氨氮浓度及流速是影响底栖动物群落结构的主要环境因子。(4)生物指数分析结果显示该流域水质为轻度污染或中度污...     

人动脉壁蛋白聚糖与血清脂蛋白形成的不溶性复合物

本文报道了人主动脉壁中正常及异常(脂纹,FS)区的三种蛋白聚糖(PG)即:硫酸软骨素PG(CSPG)、硫酸皮肤素—硫酸软骨素PG(DSCSPG)及硫酸乙酰肝素PG(HSPG)与血清极低密度脂蛋白(VLDL)及低密度脂蛋白(LDL)所形成的不溶性复合物。在30mmol/L Ca~(2+)对,三种PG都能与这两种脂蛋白形成不溶性复合物,随放置时间的增加,形成的复合物都发生解离,但其复合物形成的曲线及解离程度明显不同。DSCSPG与CSPG比较,前者与两种脂蛋白更易形成不溶性复合物且不易解离。HSPG与两种脂蛋白形成不溶性复合物所需时间远大于CSPG及DSCSPG。FS区及正常区三种PG形成复合物曲线类型相似,异常区CSPG、DSCSPG与VLDL形成的复合物量低于正常区的相应PG,而与VLDL则高于正常区的相应PG。异常区的HSPG与两种脂蛋白形成不溶性复合物的量均高于正常区。