Concurrent isolation of hepatic stem cells and hepatocytes from the human liver

Hepatocytes differentiated from induced pluripotent stem cells or stem cells have the potential to be representative in vitro models of the human liver for research as well as early safety assessment programs. However, up until now, there has been no definitive proof that differentiated hepatocytes recapitulate the phenotype and functional characteristics of primary hepatocytes from the same individual. Thus, a method for the concurrent isolation of hepatocytes and hepatic stem cells is presented here to provide the cells necessary for the evaluation of the required benchmarking. The method presented here generated high-quality hepatocytes with a purity of 94 ± 1% and a high percentage viability of 79 ± 2%. Furthermore, the hepatic stem cells isolated were found to be actively proliferating and have a purity of 98 ± 1%. Thus, these isolated cells can be used as a powerful tool for the validation of differentiated hepatocyte in vitro models

Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. Main body: We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. Conclusions: This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment

GNOSIS: the first instrument to use fibre Bragg gratings for OH suppression

GNOSIS is a prototype astrophotonic instrument that utilizes OH suppression fibres consisting of fibre Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47-1.7 microns. GNOSIS was commissioned at the 3.9-meter Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibres, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput and excellent suppression of the skylines by the OH suppression fibres, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS and IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise-dominated. OH suppression fibres could potentially impact ground-based astronomy at the level of adaptive optics or greater. However, until a clear reduction in the interline background and the corresponding increasing in sensitivity is demonstrated optimized OH suppression fibres paired with a fibre-fed spectrograph will at least provide a real benefits at low resolving powers.Comment: 15 pages, 13 figures, accepted to A

GNOSIS: The first instrument to use fiber bragg gratings for OH suppression

The near-infrared is an important part of the spectrum in astronomy, especially in cosmology because the light from objects in the early universe is redshifted to these wavelengths. However, deep near-infrared observations are extremely difficult to makeThe GNOSIS team acknowledges funding by ARC LIEF grant LE100100164. C.Q.T. gratefully acknowledges support by the National Science Foundation Graduate Research Fellowship under grant No. DGE-1035963

Three Lyman-alpha Emitters at z approx 6: Early GMOS/Gemini Data from the GLARE Project

We report spectroscopic detection of three z~6 Lyman-alpha emitting galaxies, in the vicinity of the Hubble Ultra Deep Field, from the early data of the Gemini Lyman-$\alpha$ at Reionisation Era (GLARE) project. Two objects, GLARE#3001 (z =5.79) and GLARE#3011 (z =5.94), are new detections and are fainter in $z'$ (z'_{AB} =26.37 and 27.15) than any Lyman break galaxy previously detected in Lyman-alpha. A third object, GLARE#1042 (z =5.83) has previously been detected in line emission from the ground; we report here a new spectroscopic continuum detection. Gemini/GMOS-S spectra of these objects, obtained using nod & shuffle, are presented together with a discussion of their photometric properties. All three objects were selected for spectroscopy via the i-drop Lyman Break technique, the two new detections from the GOODS v1.0 imaging data. The red i'-z' colors and high equivalent widths of these objects suggest a high-confidence z>5 Lyman-alpha identification of the emission lines. This brings the total number of known z>5 galaxies within 9 arcmin of the Hubble Ultra Deep Field to four, of which three are at the same redshift (z=5.8 within 2000 km/s suggesting the existence of a large-scale structure at this redshift.Comment: 5 pages, 2 figures. Revised to match accepted versio

Supportive interventions to improve physiological and psychological health outcomes among patients undergoing cystectomy: A systematic review

Background Our understanding of effective perioperative supportive interventions for patients undergoing cystectomy procedures and how these may affect short and long-term health outcomes is limited. Methods Randomised controlled trials involving any non-surgical, perioperative interventions designed to support or improve the patient experience for patients undergoing cystectomy procedures were reviewed. Comparison groups included those exposed to usual clinical care or standard procedure. Studies were excluded if they involved surgical procedure only, involved bowel preparation only or involved an alternative therapy such as aromatherapy. Any short and long-term outcomes reflecting the patient experience or related urological health outcomes were considered. Results 19 articles (representing 15 individual studies) were included for review. Heterogeneity in interventions and outcomes across studies meant meta-analyses were not possible. Participants were all patients with bladder cancer and interventions were delivered over different stages of the perioperative period. The overall quality of evidence and reporting was low and outcomes were predominantly measured in the short-term. However, the findings show potential for exercise therapy, pharmaceuticals, ERAS protocols, psychological/educational programmes, chewing gum and nutrition to benefit a broad range of physiological and psychological health outcomes. Conclusions Supportive interventions to date have taken many different forms with a range of potentially meaningful physiological and psychological health outcomes for cystectomy patients. Questions remain as to what magnitude of short-term health improvements would lead to clinically relevant changes in the overall patient experience of surgery and long-term recovery

Dietary carbohydrate restriction as the first approach in diabetes management:Critical review and evidence base

AbstractThe inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed

Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.

Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies

Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus

BACKGROUND: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. METHODS: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. RESULTS: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 ± 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. CONCLUSIONS: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival

Comparative indoor and outdoor stability measurements of polymer based solar cells

We report comparative indoor and outdoor stability testing of organic solar cells based on a blend between a donor-acceptor polyfluorene copolymer and a fullerene derivative. The outdoor testing was conducted for a period over 12,000 hours in Sheffield, England, with a Ts80 lifetime determined in excess of 10,000 hours (420 days). Indoor lifetime testing was performed on solar cells using a solar simulator under a constant irradiance of 1000 W/m(2) for more than 650 hours. We show that under the conditions explored here, device degradation under the two sets of conditions is approximately dependent on the absorbed optical energy dose