An overview and update on soft tissue lesions of the head and neck

Soft tissue lesions of the head and neck encompass a broad range of pathological entities associated with different prognoses and requiring different treatments. All pathologists will encounter a wide range of soft tissue tumours in whatever specialist area they practice. Getting the diagnosis ‘right the first time’ is critical for patients to be offered optimal treatment. Molecular testing can help reach the correct diagnoses and this arena is developing fast. However, pathologists should not rely unquestioningly on special tests, whether it is immunohistochemistry or whole genome sequencing as no test is entirely specific or sensitive. Pathologists should provide a diagnosis in the context of all tests including the histology along with medical imaging and the patient's symptoms, signs and family history. This article reviews key clinical, pathological and histologic features of tumours most commonly presenting in the head and neck region, including those most recently described

The pseudo-reachability problem for diagonalisable linear dynamical systems

We study fundamental reachability problems on pseudo-orbits of linear dynamical systems. Pseudo-orbits can be viewed as a model of computation with limited precision and pseudo-reachability can be thought of as a robust version of classical reachability. Using an approach based on o-minimality of Rexp we prove decidability of the discrete-time pseudo-reachability problem with arbitrary semialgebraic targets for diagonalisable linear dynamical systems. We also show that our method can be used to reduce the continuous-time pseudo-reachability problem to the (classical) time-bounded reachability problem, which is known to be conditionally decidable

TIRSPEC : TIFR Near Infrared Spectrometer and Imager

We describe the TIFR Near Infrared Spectrometer and Imager (TIRSPEC) designed and built in collaboration with M/s. Mauna Kea Infrared LLC, Hawaii, USA, now in operation on the side port of the 2-m Himalayan Chandra Telescope (HCT), Hanle (Ladakh), India at an altitude of 4500 meters above mean sea level. The TIRSPEC provides for various modes of operation which include photometry with broad and narrow band filters, spectrometry in single order mode with long slits of 300" length and different widths, with order sorter filters in the Y, J, H and K bands and a grism as the dispersing element as well as a cross dispersed mode to give a coverage of 1.0 to 2.5 microns at a resolving power R of ~1200. The TIRSPEC uses a Teledyne 1024 x 1024 pixel Hawaii-1 PACE array detector with a cutoff wavelength of 2.5 microns and on HCT, provides a field of view of 307" x 307" with a plate scale of 0.3"/pixel. The TIRSPEC was successfully commissioned in June 2013 and the subsequent characterization and astronomical observations are presented here. The TIRSPEC has been made available to the worldwide astronomical community for science observations from May 2014.Comment: 20 pages, 21 figures, 2 tables. Accepted for publication in Journal of Astronomical Instrumentatio

Structure and Evolution of Streptomyces Interaction Networks in Soil and In Silico

Soil grains harbor an astonishing diversity of Streptomyces strains producing diverse secondary metabolites. However, it is not understood how this genotypic and chemical diversity is ecologically maintained. While secondary metabolites are known to mediate signaling and warfare among strains, no systematic measurement of the resulting interaction networks has been available. We developed a high-throughput platform to measure all pairwise interactions among 64 Streptomyces strains isolated from several individual grains of soil. We acquired more than 10,000 time-lapse movies of colony development of each isolate on media containing compounds produced by each of the other isolates. We observed a rich set of such sender-receiver interactions, including inhibition and promotion of growth and aerial mycelium formation. The probability that two random isolates interact is balanced; it is neither close to zero nor one. The interactions are not random: the distribution of the number of interactions per sender is bimodal and there is enrichment for reciprocity—if strain A inhibits or promotes B, it is likely that B also inhibits or promotes A. Such reciprocity is further enriched in strains derived from the same soil grain, suggesting that it may be a property of coexisting communities. Interactions appear to evolve rapidly: isolates with identical 16S rRNA sequences can have very different interaction patterns. A simple eco-evolutionary model of bacteria interacting through antibiotic production shows how fast evolution of production and resistance can lead to the observed statistical properties of the network. In the model, communities are evolutionarily unstable—they are constantly being invaded by strains with new sets of interactions. This combination of experimental and theoretical observations suggests that diverse Streptomyces communities do not represent a stable ecological state but an intrinsically dynamic eco-evolutionary phenomenon

A Differential Drug Screen for Compounds That Select Against Antibiotic Resistance

Antibiotics increase the frequency of resistant bacteria by providing them a competitive advantage over sensitive strains. Here, we develop a versatile assay for differential chemical inhibition of competing microbial strains, and use it to identify compounds that preferentially inhibit tetracycline-resistant relative to sensitive bacteria, thus “inverting” selection for resistance. Our assay distinguishes compounds selecting directly against specific resistance mechanisms and compounds whose selection against resistance is based on their physiological interaction with tetracycline and is more general with respect to resistance mechanism. A pilot screen indicates that both types of selection-inverting compounds are secreted by soil microbes, suggesting that nature has evolved a repertoire of chemicals that counteracts antibiotic resistance. Finally, we show that our assay can more generally permit simple, direct screening for drugs based on their differential activity against different strains or targets

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Pyrosequencing of Antibiotic-Contaminated River Sediments Reveals High Levels of Resistance and Gene Transfer Elements

The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance