Assessment of Inter-Laboratory Differences in SARS-CoV-2 Consensus Genome Assemblies between Public Health Laboratories in Australia

Whole-genome sequencing of viral isolates is critical for informing transmission patterns and for the ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences in consensus genome assemblies of 72 matched SARS-CoV-2-positive specimens sequenced at different laboratories in Sydney, Australia. Raw sequence data were assembled using two different bioinformatics pipelines in parallel, and resulting consensus genomes were compared to detect laboratory-specific differences. Matched genome sequences were predominantly concordant, with a median pairwise identity of 99.997%. Identified differences were predominantly driven by ambiguous site content. Ignoring these produced differences in only 2.3% (5/216) of pairwise comparisons, each differing by a single nucleotide. Matched samples were assigned the same Pango lineage in 98.2% (212/216) of pairwise comparisons, and were mostly assigned to the same phylogenetic clade. However, epidemiological inference based only on single nucleotide variant distances may lead to significant differences in the number of defined clusters if variant allele frequency thresholds for consensus genome generation differ between laboratories. These results underscore the need for a unified, best-practices approach to bioinformatics between laboratories working on a common outbreak problem.     

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II–IV Epithelial Ovary,Fallopian Tube,or Primary Peritoneal Carcinoma: A Practice Guideline

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.     

Rheumatoid arthritis in a United States Public Health Service Hospital in Oklahoma. Serologic manifestations in rheumatoid arthritis vary among tribal groups

Objective. To study the serologic manifestations of rheumatoid arthritis (RA) at a United States Public Health Service Hospital that serves numerous tribes in Oklahoma. Methods. Forty-five patients with RA were identified, and serologic studies for antinuclear antibody (ANA), rheumatoid factor, and antibodies to extractable nuclear antigens were performed. Extraarticular manifestions of RA were also evaluated. Results. Twelve of the 45 patients with RA were Kiowa. These patients were significantly more likely to have a positive ANA (75%) than the other patients with RA (28%). In addition, anti-Ro was significantly more common among Kiowa (33%) than among members of other tribes (3%). There was no difference in the extraarticular manifestions of the Kiowa compared with the other Native American tribes. Conclusion. RA can be distinctly characterized by serology among groups of American Indians living in the same geographic area.     

自发性脑出血治疗指南美国心脏协会/美国卒中协会对医疗卫生专业人员发布的指南

目的 本指南旨在为急性自发性脑出血的诊断和治疗提供最新的综合性推荐意见.方法 通过Medline进行规范的文献检索,利用证据表合并资料.撰写委员会成员通过远程电信会议讨论根据资料得出的推荐意见.采用美国心脏协会卒中委员会的证据分级方案对推荐意见进行分级.由6位同行评议专家以及卒中委员会科学声明监督委员会和卒中委员会领导委员会成员对指南 的草案进行发表前审阅.预期本指南在3年内完全更新.结果 本文为脑出血患者的医疗诊治提供了循证指南.重点包括诊断、止血、血压管理、院内管理和护理、预防内科合并症、外科治疗、转归预测、康复、预防复发以及将来需要考虑的问题.结论 脑出血是一种严重的疾病,早期积极救治可影响其转归.本指南为脑出血患者的目标导向治疗提供了一个框架.     

Treatment of frostbite with the calmodulin antagonists thioridazine and trifluoperazine

1. Thioridazine and trifluoperazine, which have been previously found in this laboratory to be the most effective calmodulin antagonists in treatment of burns, are shown here to be also effective in the treatment of frostbite. 2. Electron microscopic studies have revealed a complete reversal of both the vascular and skin tissue damage induced by frostbite. 3. The reversal of the vascular damage was also demonstrated by the ability of these compounds to abolish the increase in hemoglobin content in the skin. 4. The reversal of the skin tissue damage was also revealed by the ability of these compounds to raise the decreased ATP level and the reduced activities of 6-phosphogluconate dehydrogenase and mitochondrial and soluble hexokinase in skin, induced by frostbite, to normal control levels.     

Postextrasystolic U Wave Augmentation, a New Marker of Increased Arrhythmic Risk in Patients Without the Long QT Syndrome

Objectives. We attempted to determine the correlation between the presence of postextrasystolic changes in the STU segment and a history of sustained ventricular arrhythmias.

Background. Postextrasystolic U wave augmentation (a marked increment in U wave amplitude after premature ventricular complexes [PVCs]) is an adverse prognostic sign in the “pause-dependent long QT syndrome.” However, the prevalence of postextrasystolic changes in patients without the long QT syndrome is unknown.

Methods. We compared the configuration of the STU segment of the postextrasystolic beat (the sinus beat after a PVC) with the STU configuration during sinus rhythm in three patient groups: 1) 41 patients with spontaneous ventricular tachycardia/fibrillation (VT/VF) (VT/VF group), 2) 63 patients with heart disease and high grade ventricular arrhythmias (control group), and 3) 29 patients with high grade ventricular arrhythmias but no heart disease (reference group).

Results. Postextrasystolic T wave changes did not correlate with a history of ventricular tachyarrhythmias. However, postextrasystolic U wave changes were more common among the patients with VT/VF than among control subjects (39% vs. 8.7%, p < 0.001). By logistic multiple regression analysis, a low left ventricular ejection fraction (p < 0.001) and postextrasystolic U wave changes (p < 0.005) were independent predictors of ventricular tachyarrhythmias.

Conclusions. Postextrasystolic T wave changes are common and lack predictive value. Postextrasystolic U wave changes may be a specific marker of a tendency to the development of spontaneous ventricular arrhythmias. Prospective studies should be performed to confirm this association.

(J Am Coll Cardiol 1996;28:1746–52)>     

局限性胸膜纤维瘤的影像表现

目的：探讨胸膜局限性纤维瘤的影像特点,以提高对它的认识。方法：回顾性分析了2002年～2008年经穿刺及手术病理证实的12例局限性纤维瘤的影像表现。结果：12例均为单发性病灶,右侧7例,左侧5例。其中最小1例直径约3cm,3～10cm的4例,10～15cm的3例,4例大于15cm。12例X线平片均见病灶密度均匀,边界清楚,无肋骨及椎体的骨质破坏征象。CT平扫见病灶与胸壁紧密相连。较小病灶密度均匀,境界清楚,大病灶内可见斑点状低密度坏死区,但其边界光滑,相邻组织受压移位。CT平扫中12例病灶的CT值平均为33.4±5.7HU,而周边肌肉的CT值平均为52.9±6.2 HU,经两样本均数的t检验,P=0.0367（P〈0.05）。3例增强扫描见病灶中等度强化,坏死区不强化。2例行MRI检查,T1WI见病灶呈类似肌肉的稍低信号,T2WI为与肌肉相似的等信号,坏死区为高信号。结论：局限性纤维瘤具有相对特征性的影像表现,CT、MRI均可显示其病变的范围及其性质。     

白细胞介素6、信号传导和转录活化因子3和血管内皮生长因子在人脑胶质瘤中的表达及相关性研究

目的研究人脑不同级别胶质瘤中白细胞介素（IL）-6，信号传导和转录活化因子3（STAT3）和血管内皮生长因子（VEGF）的表达，探讨IL-6、STAT3和VEGF与肿瘤病理级别和侵袭性的关系。方法采用免疫组织化学法，检测70例人脑胶质瘤，10例脑膜瘤和5例正常脑组织中IL-6、STAT3和VEGF的表达。结果胶质瘤中IL-6、STAT3和VEGF的表达水平在高级别组（Ⅲ、Ⅳ级）明显高于低级别组（Ⅰ、Ⅱ级），两组间差异有统计学意义（P〈0．01），STAT3的表达与IL-6和VEGF的表达均呈正相关（P〈0．01）。结论IL-6、STAT3和VEGF的表达与胶质瘤的恶性程度有密切关系；且三者协同在胶质瘤发生、发展过程中起重要作用。三者的相关性证实VEGF基因由STAT3蛋白调节，而STAT3又由IL-6刺激活化。     

Gastrointestinal Anastomosis with the Nickel-Titanium Double Ring

We used a dog model to test the safety and effectiveness of sutureless gastrointestinal anastomoses (n= 23) (end-to-end, end-to-side, or side-to-side) with the nickel-titanium double ring with temperature-dependent shape memory. Results were compared to conventional hand-sutured anastomoses (n= 5). Examination performed after 2 weeks' follow-up showed no leaks and no difference in return of bowel function between the experimental groups and the control group. Microscopic studies showed a complete epithelial lining and perfectly functioning anastomoses. We conclude that the nickel-titanium double-ring device may have an important place in the armamentarium of the gastrointestinal surgeon.     

Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies

This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.