Natural orifice surgery: initial clinical experience

Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience. Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance. Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred. The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access

Continental-scale bias-corrected climate and hydrological projections for Australia

The Australian Bureau of Meteorology has developed a national hydrological projections (NHP) service for Australia. The NHP aimed to provide nationally consistent hydrological projections across jurisdictional boundaries to support planning of water-dependent industries. NHP is complementary to those previously produced by federal and state governments, universities, and other organisations for limited geographical domains. The projections comprise an ensemble of application-ready bias-corrected climate model data, derived hydrological projections at daily temporal and 0.05° × 0.05° spatial resolution for the period 1960–2099, and two emission scenarios (Representative Concentration Pathway (RCP) 4.5 and RCP8.5). The spatial resolution of the projections matches that of gridded historical reference data used to perform the bias correction and the Bureau of Meteorology's operational gridded hydrological model. Three bias correction techniques were applied to four CMIP5 global climate models (GCMs), and one method was applied to a regional climate model (RCM) forced by the same four GCMs, resulting in a 16-member ensemble of bias-corrected GCM data for each emission scenario. The bias correction was applied to fields of precipitation, minimum and maximum temperature, downwelling shortwave radiation, and surface winds. These variables are required inputs to the Bureau of Meteorology's landscape water balance hydrological model (AWRA-L), which was forced using the bias-corrected GCM and RCM data to produce a 16-member ensemble of hydrological output. The hydrological output variables include root zone soil moisture (moisture in the top 1 m soil layer), potential evapotranspiration, and runoff. Here we present an overview of the production of the hydrological projections, including GCM selection, bias correction methods and their evaluation, technical aspects of their implementation, and examples of analysis performed to construct the NHP service. The data are publicly available on the National Computing Infrastructure (https://doi.org/10.25914/6130680dc5a51, Bureau of Meteorology, 2021), and a user interface is accessible at https://awo.bom.gov.au/products/projection/ (last access: 24 November 2023).</p

A high-throughput screening of a chemical compound library in ovarian cancer stem cells

This work was performed under the frame of COST Action collaboration (COST Action CM1106). The generous contribution of AIRC (The Italian Association for Cancer Research) IG14536 to G.D. is gratefully acknowledged. A.H. acknowledges support from the János Bolyai fellowship of the Hungarian Academy of Sciences.Background: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and to the development of drug resistance after a first platinum-based regimen. The presence of a specific population of “cancer stem cells” could be responsible of the relapse of the tumor, and of the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. Method: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. Results and conclusion: Interestingly there were compounds active only on stem cells, only on differentiated cells and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.PostprintPeer reviewe

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules