Dynamic changes during the treatment of pancreatic cancer

This manuscript follows a single patient with pancreatic adenocarcinoma for a five year period, detailing the clinical record, pathology, the dynamic evolution of molecular and cellular alterations as well as the responses to treatments with chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from biopsies and blood identified a dynamic set of changes in allelic imbalances and copy number variations in response to therapies. Organoid cultures established from biopsies over time were employed for extensive drug testing to determine if this approach was feasible for treatments. When an unusual drug response was detected, an extensive RNA sequencing analysis was employed to establish novel mechanisms of action of this drug. Organoid cell cultures were employed to identify possible antigens associated with the tumor and the patient\u27s T-cells were expanded against one of these antigens. Similar and identical T-cell receptor sequences were observed in the initial biopsy and the expanded T-cell population. Immunotherapy treatment failed to shrink the tumor, which had undergone an epithelial to mesenchymal transition prior to therapy. A warm autopsy of the metastatic lung tumor permitted an extensive analysis of tumor heterogeneity over five years of treatment and surgery. This detailed analysis of the clinical descriptions, imaging, pathology, molecular and cellular evolution of the tumors, treatments, and responses to chemotherapy, targeted therapies, and immunotherapies, as well as attempts at the development of personalized medical treatments for a single patient should provide a valuable guide to future directions in cancer treatment

Obesity and kidney stone disease. A systematic review

INTRODUCTION: Currently, abdominal obesity has reached an epidemic stage and obesity represents an important challenge for worldwide health authorities. Epidemiologic studies have demonstrated that the stone risk incidence increases with Body Mass Index, through multiple pathways. Metabolic syndrome and diabetes are associated with an increased renal stones disease incidence. The aim of this systematic review was to investigate the prevalence, morbidity, risk factors involved in the association between obesity and urolithiasis. EVIDENCE ACQUISITION: The search involved finding relevant studies from MEDLINE, EMBASE, Ovid, the Cochrane Central Register of Controlled Trials, CINAHL, Google Scholar, and individual urological journals between January 2001 and May 2017. The inclusion criteria were for studies written in the English language, reporting on the association between obesity and urinary stones. EVIDENCE SYNTHESIS: The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are observed frequently in these patients. Insulin resistance is thought to alter the renal acid-base metabolism, resulting in a lower urine pH, and increasing the risk of uric acid stone disease. Obesity is also associated with excess nutritional intake of lithogenic substances and with an increase in urinary tract infection incidence. Recent studies highlighted that renal stone disease increases the risk of myocardial infarction, progression of chronic kidney disease, and diabetes. Contemporary, bariatric surgery has been shown to be associated with hyperoxaluria and oxalate nephropathy. Certainly, the many health risks of obesity, including nephrolithiasis, will add more burden on urologists and nephrologists. CONCLUSIONS: Obesity related nephrolithiasis seems to necessitate weight loss as primary treatment, but the recognition of the associated complications is necessary to prevent induction of new and equally severe medical problems. The optimal approach to obesity control that minimizes stone risk needs to be determined in order to manage obesity-induced renal stones disease

Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease

Background: Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. Methods: We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm3/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. Results: The age-corrected bilateral annualized atrophy rate (%/year) were: -. 1.6 (0.6) for CTRL, -. 2.2 (1.0) for MCI-. nc, -. 3.2 (1.2) for MCI-. co and -. 4.0 (1.5) for AD. Combined (. v, Λ) discrimination ability gave an Area under the ROC curve (. auc). =. 0.93 for CTRL vs AD and auc=. 0.88 for CTRL vs MCI-. co. Conclusions: Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information

Combined laparoscopic pyelolithotomy and endoscopic pyelolithotripsy for staghorn calculi. Long-term follow-up results from a case series

Purpose: Staghorn renal stones are a challenging field in urology. Due to their high recurrence rates, particularly those associated with an infective process, a complete removal is the ultimate goal in their management. We report our experience with a combined approach of laparoscopic pyelolithotomy and endoscopic pyelolithotripsy, the stone clearance rate, and long-term, follow-up outcomes. Methods: From June 2012 to October 2014, nine adult patients with large staghorn renal calculi (mean size, 7.2 cm; range, 6.2–9.0 cm) underwent a combined laparoscopic and endoscopic approach. The technique comprised laparoscopic pyelolithotomy and holmium-YAG laser stone fragmentation with the use of a flexible cystoscope introduced through a 12 mm trocar. Results: The average operative time was 140 min (range, 90–190 min). The mean estimated hemoglobin loss was 0.6 mmol/l (range 0.5–0.7 mmol/l). None of the patients required an open- surgery conversion. The mean hospital stay was 4 days (range, 2–6 days). A computed tomography urogram control at 6 months of follow up did not show any stone recurrence. Conclusions: Laparoscopic pyelolithotomy combined with endoscopic pyelolithotripsy could be a therapeutic option in cases where mini-invasive procedures, that is, extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy (PCNL) have failed. This technique has a high stone-clearance rate (75–100%) comparable with open surgery and PCNL. However, it could be technically demanding and should be performed by skilled laparoscopy surgeons

Photonics based perfect secrecy cryptography : toward fully classical implementations

Funding: A.D.F. acknowledges support from UK EPSRC (EP/L017008/1).Developing an unbreakable cryptography is a longstanding question and a global challenge in the internet era. Photonics technologies are at the frontline of research, aiming at providing the ultimate system capable of ending the cybercrime industry by changing the way information is treated and protected now and in the long run. Such perspective discusses some of the current challenges as well as opportunities that classical and quantum systems open in the field of cryptography as both a science and an engineering.PostprintPeer reviewe

Study of cosmogenic activation above ground for the DarkSide-20k experiment

The activation of materials due to exposure to cosmic rays may become an important background source for experiments investigating rare event phenomena. DarkSide-20k, currently under construction at the Laboratori Nazionali del Gran Sasso, is a direct detection experiment for galactic dark matter particles, using a two-phase liquid-argon Time Projection Chamber (TPC) filled with 49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Despite the outstanding capability of discriminating γ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; text-wrap: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3e�/β role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; text-wrap: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3e� background in argon TPCs, this background must be considered because of induced dead time or accidental coincidences mimicking dark-matter signals and it is relevant for low-threshold electron-counting measurements. Here, the cosmogenic activity of relevant long-lived radioisotopes induced in the experiment has been estimated to set requirements and procedures during preparation of the experiment and to check that it is not dominant over primordial radioactivity; particular attention has been paid to the activation of the 120 t of UAr used in DarkSide-20k. Expected exposures above ground and production rates, either measured or calculated, have been considered in detail. From the simulated counting rates in the detector due to cosmogenic isotopes, it is concluded that activation in copper and stainless steel is not problematic. The activity of 39Ar induced during extraction, purification and transport on surface is evaluated to be 2.8% of the activity measured in UAr by DarkSide-50 experiment, which used the same underground source, and thus considered acceptable. Other isotopes in the UAr such as 37Ar and 3H are shown not to be relevant due to short half-life and assumed purification methods