Feasibility study of ultrasound-guided resection of tongue cancer with immediate specimen examination to improve margin control - Comparison with conventional treatment

Objectives: Squamous cell carcinoma of the tongue (SCCT) is preferably treated by surgery. Free resection margins (> 5 mm) provide local control and disease-free survival. However, close (1-5 mm) and positive margins (< 1 mm) are frequently encountered. We present our first experience of in-vivo ultrasound (US) guided SCCT resections followed by ex-vivo US control on the resection specimen to obtain free margins. We compare the results with those from a hisorical cohort of 91 conventionally treated SCCT patients. Materials and methods: Ten patients with SCCT were included in a consecutive US-cohort. We aimed for a 5-10 mm margin during surgery, while we visualized the resection plane on US. Ex-vivo US measurements on the resection specimen determined whether there was any need for an immediate re-resection. US measurements were then compared with histopathology. Histopathological margins were compared with a consecutive cohort of 91 patients who had undergone conventional surgery for a SCCT. Results: In the US cohort, 70% of the margins were free. In the conventional cohort, this figure was 17% (P = 0.005). US predicted minimal histopathological margin distance with a mean +/- SD error of 1.9 +/- 1.8 mm. The mean +/- SD of the histopathological overall submucosal/deep margin distance was 7.9 +/- 2.1 mm in the US cohort and 7.0 +/- 2.2 mm in the conventional cohort (P = 0.188). Ex-vivo examination through use of US indicated an immediate re-resection, which prevented local adjuvant treatment. Conclusion: Use of US-guided SCCT resection is feasible and improves margin control

REVISITING ANNA MOSCOWITZ\u27S KROSS\u27S CRITIQUE OF NEW YORK CITY\u27S WOMEN\u27S COURT: THE CONTINUED PROBLEM OF SOLVING THE PROBLEM OF PROSTITUTION WITH SPECIALIZED CRIMINAL COURTS

This article explores New York City\u27s non-traditional, judicially based response to prostitution. This article first recounts the history of New York City’s Women’s Court. It then examines the work of the Midtown Community Court, the “problem-solving court” established in 1993 to address criminal issues, like prostitution, in Midtown Manhattan. It also discusses the renewed concerns about sex work in New York and describe the movement, propelled by modern reformers, to address prostitution through specialty courts. It then contrasts the shared features and attributes of the Women’s Court and Midtown Court models. Finally, the article urges modern reformers to step back from the problem-solving court movement and their call for the creation of more such specialized criminal courts

Recent Recombination Events in the Core Genome Are Associated with Adaptive Evolution in Enterococcus faecium

Peer reviewe

mlplasmids : a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species

Assembly of bacterial short-read whole-genome sequencing data frequently results in hundreds of contigs for which the origin, plasmid or chromosome, is unclear. Complete genomes resolved by long-read sequencing can be used to generate and label short-read contigs. These were used to train several popular machine learning methods to classify the origin of contigs from Enterococcus faecium, Klebsiella pneumoniae and Escherichia colt using pentamer frequencies. We selected support-vector machine (SVM) models as the best classifier for all three bacterial species (Fl-score E. faecium=0.92, F1-score K. pneumoniae=0.90, F1-score E. coli=0.76), which outperformed other existing plasmid prediction tools using a benchmarking set of isolates. We demonstrated the scalability of our models by accurately predicting the plasmidome of a large collection of 1644 E. faecium isolates and illustrate its applicability by predicting the location of antibiotic-resistance genes in all three species. The SVM classifiers are publicly available as an R package and graphical-user interface called 'mlplasmids'. We anticipate that this tool may significantly facilitate research on the dissemination of plasmids encoding antibiotic resistance and/or contributing to host adaptation.Peer reviewe

Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals

Abstract Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance

gplas : a comprehensive tool for plasmid analysis using short-read graphs

aSummary: Plasmids can horizontally transmit genetic traits, enabling rapid bacterial adaptation to new environments and hosts. Short-read whole-genome sequencing data are often applied to large-scale bacterial comparative genomics projects but the reconstruction of plasmids from these data is facing severe limitations, such as the inability to distinguish plasmids from each other in a bacterial genome. We developed gplas, a new approach to reliably separate plasmid contigs into discrete components using sequence composition, coverage, assembly graph information and network partitioning based on a pruned network of plasmid unitigs. Gplas facilitates the analysis of large numbers of bacterial isolates and allows a detailed analysis of plasmid epidemiology based solely on short-read sequence data.Peer reviewe

Численный анализ распространения и усиления волн цунами на северо-западном шельфе Черного моря

Выполнен численный анализ распространения длинных волн в северо-западной части Черного моря. Рассмотрено 10 возможных зон сейсмической генерации цунами. Расчеты выполнены на сетке с шагом 500 м. Показано, что положение очага цунами существенно влияет на распределение высот волн вдоль побережья. Как правило, наиболее интенсивные волны формируются у ближайшего участка берега. Землетрясения в Южнобережной сейсмической зоне не могут привести к цунамиопасности в западной части моря. Только сильные землетрясения в северо-западной части способны вызывать заметные колебания уровня Черного моря. Период цунами в районе Одессы составляет около 1 ч и зависит от магнитуды землетрясения, в районе Севастополя он в 2 – 3 раза меньше. В большинстве пунктов побережья экстремальные подъемы и понижения уровня моря не превышают по абсолютной величине начального смещения поверхности моря в очаге цунами. Для отдельных участков побережья Румынии и западного побережья Крыма наблюдается некоторое усиление волн, излученных из зон генерации, расположенных в более глубоководной части исследуемого района. С ростом магнитуды землетрясения усиление волн у берега становится более значительным.Виконаний чисельний аналіз розповсюдження довгих хвиль у північно-західній частині Чорного моря. Розглянуто 10 можливих зон сейсмічної генерації цунамі. Розрахунки виконані на сітці з кроком 500 м. Показано, що положення осередку цунамі суттєво впливає на розподіл висот хвиль уздовж побережжя. Як правило, найінтенсивніші хвилі формуються близько найближчої ділянки берега. Землетруси в південнобережній сейсмічній зоні не можуть призвести до цунамонебезпеки в західній частині моря. Лише сильні землетруси в північнозахідній частині здатні викликати помітні коливання рівня Чорного моря. Період цунамі в районі Одеси складає близько 1 години і залежить від магнітуди землетрусу, в районі Севастополя він в 2 – 3 рази менший. У більшості пунктів побережжя екстремальні підйоми і пониження рівня моря не перевищують за абсолютною величиною початкового зсуву поверхні моря в осередку цунамі. Для окремих ділянок побережжя Румунії і західного побережжя Криму спостерігається деяке посилення хвиль, які випромінюють із зон генерації, розташованих в більш глибоководній частині досліджуваного району. Із зростанням магнітуди землетрусу посилення хвиль біля берега стає значнішим.Numerical analysis of long wave propagation in the Black Sea northwestern part is carried out. Ten possible zones of tsunami seismic generation are considered. The calculation are performed on the grid with a step 500 m. It is shown that location of tsunami source effects essentially the distribution of waves’ heights along the coast. As a rule, the most intensive waves are formed in the part closest to the coast. Earthquakes in the South coast seismic zone can not result in tsunami threat in the western part of the sea. Only strong earthquakes in the Black Sea northwestern part can generate noticeable sea level oscillations. Tsunami period near Odessa is about one hour and it depends on the earthquake magnitude. In the Sevastopol region it is 2 – 3 times lower. In the majority of coastal points extreme rises and falls of the sea level do not exceed the absolute value of the initial sea surface elevation in the tsunami source. Some intensification of the waves generated in deeper regions of the area under study is possible in certain parts of the Romanian coast and the Crimean western coast. The wave intensification near the coast grows with the increase of the earthquake magnitude

The impact of host metapopulation structure on the population genetics of colonizing bacteria

Many key bacterial pathogens are frequently carried asymptomatically, and the emergence and spread of these opportunistic pathogens can be driven, or mitigated, via demographic changes within the host population. These inter-host transmission dynamics combine with basic evolutionary parameters such as rates of mutation and recombination, population size and selection, to shape the genetic diversity within bacterial populations. Whilst many studies have focused on how molecular processes underpin bacterial population structure, the impact of host migration and the connectivity of the local populations has received far less attention. A stochastic neutral model incorporating heightened local transmission has been previously shown to fit closely with genetic data for several bacterial species. However, this model did not incorporate transmission limiting population stratification, nor the possibility of migration of strains between subpopulations, which we address here by presenting an extended model. We study the consequences of migration in terms of shared genetic variation and show by simulation that the previously used summary statistic, the allelic mismatch distribution, can be insensitive to even large changes in microepidemic and migration rates. Using likelihood-free inference with genotype network topological summaries we fit a simpler model to commensal and hospital samples from the common nosocomial pathogens Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium. Only the hospital data for E. faecium display clearly marked deviations from the model predictions which may be attributable to its adaptation to the hospital environment

Enterococcus faecium genome dynamics during long-term asymptomatic patient gut colonization

Enterococcus faecium is a gut commensal of humans and animals. In addition, it has recently emerged as an important nosocomial pathogen through the acquisition of genetic elements that confer resistance to antibiotics and virulence. We performed a whole-genome sequencing-based study on 96 multidrug-resistant E. faecium strains that asymptomatically colonized five patients with the aim of describing the genome dynamics of this species. The patients were hospitalized on multiple occasions and isolates were collected over periods ranging from 15 months to 6.5 years. Ninety-five of the sequenced isolates belonged to E. faecium clade A1, which was previously determined to be responsible for the vast majority of clinical infections. The clade A1 strains clustered into six clonal groups of highly similar isolates, three of which consisted entirely of isolates from a single patient. We also found evidence of concurrent colonization of patients by multiple distinct lineages and transfer of strains between patients during hospitalization. We estimated the evolutionary rate of two clonal groups that each colonized single patients at 12.6 and 25.2 single-nucleotide polymorphisms (SNPs)/genome/year. A detailed analysis of the accessory genome of one of the clonal groups revealed considerable variation due to gene gain and loss events, including the chromosomal acquisition of a 37 kbp prophage and the loss of an element containing carbohydrate metabolism-related genes. We determined the presence and location of 12 different insertion sequence (IS) elements, with ISEfa5 showing a unique pattern of location in 24 of the 25 isolates, suggesting widespread ISEfa5 excision and insertion into the genome during gut colonization. Our findings show that the E. faecium genome is highly dynamic during asymptomatic colonization of the human gut. We observed considerable genomic flexibility due to frequent horizontal gene transfer and recombination, which can contribute to the generation of genetic diversity within the species and, ultimately, can contribute to its success as a nosocomial pathogen