Surgery during holiday periods and prognosis in oesophageal cancer: a population-based nationwide Swedish cohort study

OBJECTIVE: Previous studies indicate an increased short-term and long-term mortality from major cancer surgery performed towards the end of the working week or during the weekend. We hypothesised that the prognosis after major cancer surgery is also negatively influenced by surgery conducted during holiday periods. SETTING: Population-based nationwide Swedish cohort study. PARTICIPANTS: Patients undergoing oesophagectomy for oesophageal cancer between 1987 and 2010. Among 1820 included patients, 206 (11.3%) and 373 (20.5%) patients were operated on during narrow and wide holiday periods, respectively. INTERVENTIONS: Narrow (7 weeks) and wide (14 weeks) Swedish holiday periods. PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day all-cause, 5-year all-cause and 5-year disease-specific mortality. RESULTS: Narrow holiday period did not increase all-cause 90-day (HR=0.84, 95% CI 0.53 to 1.33), all-cause 5-year (HR=1.01, 95% CI 0.85 to 1.21) or disease-specific 5-year mortality (HR=1.04, 95% CI 0.87 to 1.26). Similarly, wide holiday period did not increase the risk of 90-day (HR=0.79, 95% CI 0.55 to 1.13), all-cause 5-year (HR=0.96, 95% CI 0.84 to 1.1) or disease-specific 5-year mortality (HR=1.03, 95% CI 0.89 to 1.19). CONCLUSIONS: No measurable effects of holiday periods on short-term or longer term mortality following surgery for oesophageal cancer were observed in this population-based study, indicating that an adequate surgical experience was maintained during holiday periods

Downstream water-level feedback control

Presented at the 2002 USCID/EWRI conference, Energy, climate, environment and water - issues and opportunities for irrigation and drainage on July 9-12 in San Luis Obispo, California.Includes bibliographical references.Over the last 40 years researchers have made various efforts to develop automatic feedback controllers for irrigation canals. However, most of this work has concentrated on feedback controllers for single, in-line canals with no branches. In practice it would be desirable to automate an entire canal network and not just one of the branches. Because the branches in a network are hydraulically coupled with each other, a branching canal network cannot be controlled by designing separate controllers for each branch and then letting them run simultaneously. Changing the gate position in one pool on one branch can affect the water levels in pools on other branches. Because of this effect, the controllers designed for each of the in-line branches of the network will interfere with each other and potentially create instabilities in the branching canal network. Thus, the controller must be designed for the network as a whole and the branching flow dynamics must be explicitly taken into account during the controller design process. This paper presents preliminary simulation results on three different downstream feedback controllers on a branching canal network. The first controller is a series of Proportional-Integral (PI) controllers, one per pool. The second is a fully centralized PI controller. The third controller uses Model Predictive Control (MPC) to determine the appropriate control actions

Epigenetics and cell death: DNA hypermethylation in programmed retinal cell death.

BackgroundVertebrate genomes undergo epigenetic reprogramming during development and disease. Emerging evidence suggests that DNA methylation plays a key role in cell fate determination in the retina. Despite extensive studies of the programmed cell death that occurs during retinal development and degeneration, little is known about how DNA methylation might regulate neuronal cell death in the retina.MethodsThe developing chicken retina and the rd1 and rhodopsin-GFP mouse models of retinal degeneration were used to investigate programmed cell death during retinal development and degeneration. Changes in DNA methylation were determined by immunohistochemistry using antibodies against 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC).ResultsPunctate patterns of hypermethylation paralleled patterns of caspase3-dependent apoptotic cell death previously reported to occur during development in the chicken retina. Degenerating rd1 mouse retinas, at time points corresponding to the peak of rod cell death, showed elevated signals for 5mC and 5hmC in photoreceptors throughout the retina, with the most intense staining observed in the peripheral retina. Hypermethylation of photoreceptors in rd1 mice was associated with TUNEL and PAR staining and appeared to be cCaspase3-independent. After peak rod degeneration, during the period of cone death, occasional hypermethylation was observed in the outer nuclear layer.ConclusionThe finding that cell-specific increases of 5mC and 5hmC immunostaining are associated with the death of retinal neurons during both development and degeneration suggests that changes in DNA methylation may play a role in modulating gene expression during the process of retinal degeneration. During retinal development, hypermethylation of retinal neurons associates with classical caspase-dependent apoptosis as well as caspase-3 independent cell death, while hypermethylation in the rd1 mouse photoreceptors is primarily associated with caspase-3 independent programmed cell death. These findings suggest a previously unrecognized role for epigenetic mechanisms in the onset and/or progression of programed cell death in the retina

Cornea organoids from human induced pluripotent stem cells.

The cornea is the transparent outermost surface of the eye, consisting of a stratified epithelium, a collagenous stroma and an innermost single-cell layered endothelium and providing 2/3 of the refractive power of the eye. Multiple diseases of the cornea arise from genetic defects where the ultimate phenotype can be influenced by cross talk between the cell types and the extracellular matrix. Cell culture modeling of diseases can benefit from cornea organoids that include multiple corneal cell types and extracellular matrices. Here we present human iPS cell-derived organoids through sequential rounds of differentiation programs. These organoids share features of the developing cornea, harboring three distinct cell types with expression of key epithelial, stromal and endothelial cell markers. Cornea organoid cultures provide a powerful 3D model system for investigating corneal developmental processes and their disruptions in diseased conditions

The relation between sea ice thickness and freeboard in the Arctic

Retrieval of Arctic sea ice thickness from CryoSat-2 radar altimeter freeboard data requires observational data to verify the relation between these two variables. In this study in-situ ice and snow data from 689 observation sites, obtained during the Sever expeditions in the 1980s, have been used to establish an empirical relation between thickness and freeboard of FY ice in late winter. Estimates of mean and variability of snow depth, snow density and ice density were produced on the basis of many field observations. These estimates have been used in the hydrostatic equilibrium equation to retrieve ice thickness as a function of ice freeboard, snow depth and snow/ice density. The accuracy of the ice thickness retrieval has been calculated from the estimated variability in ice and snow parameters and error of ice freeboard measurements. It is found that uncertainties of ice density and freeboard are the major sources of error in ice thickness calculation. For FY ice, retrieval of ≈ 1.0 m (2.0 m) thickness has an uncertainty of 46% (37%), and for MY ice, retrieval of 2.4 m (3.0 m) thickness has an uncertainty of 20% (18%), assuming that the freeboard error is ± 0.03 m for both ice types. For MY ice the main uncertainty is ice density error, since the freeboard error is relatively smaller than that for FY ice. If the freeboard error can be reduced to 0.01 m by averaging measurements from CryoSat-2, the error in thickness retrieval is reduced to about 32% for a 1.0 m thick FY floe and to about 18% for a 2.4 m thick MY floe. The remaining error is dominated by uncertainty in ice density. Provision of improved ice density data is therefore important for accurate retrieval of ice thickness from CryoSat-2 data

Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field

<p>Abstract</p> <p>Background</p> <p>The use of Specific Pathogen Free (SPF) eggs in combination with RCAS retrovirus, a member of the Avian Sarcoma-Leukosis Virus (ASLV) family, is of standard practice to study gene function and development. SPF eggs are certified free of infection by specific pathogen viruses of either exogenous or endogenous origin, including those belonging to the ASLV family. Based on this, SPF embryos are considered to be free of ASLV viral protein expression, and consequently in developmental research studies RCAS infected cells are routinely identified by immunohistochemistry against the ASLV viral proteins p19 and p27. Contrary to this generally accepted notion, observations in our laboratory suggested that certified SPF chicken embryos may endogenously express ASLV viral proteins p19 and p27. Since these observations may have significant implications for the developmental research field we further investigated this possibility.</p> <p>Results</p> <p>We demonstrate that certified SPF chicken embryos have transcriptionally active endogenous ASLV loci (<it>ev loci</it>) capable of expressing ASLV viral proteins, such as p19 and p27, even when those <it>loci </it>are not capable of producing viral particles. We also show that the extent of viral protein expression in embryonic tissues varies not only among flocks but also between embryos of the same flock. In addition, our genetic screening revealed significant heterogeneity in <it>ev loci </it>composition even among embryos of the same flock.</p> <p>Conclusions</p> <p>These observations have critical implications for the developmental biology research field, since they strongly suggest that the current standard methodology used in experimental studies using the chick embryo and RCAS vectors may lead to inaccurate interpretation of results. Retrospectively, our observations suggest that studies in which infected cells have been identified simply by pan-ASLV viral protein expression may need to be considered with caution. For future studies, they point to a need for careful selection and screening of the chick SPF lines to be used in combination with RCAS constructs, as well as the methodology utilized for qualitative analysis of experimental results. A series of practical guidelines to ensure research quality animals and accuracy of the interpretation of results is recommended and discussed.</p

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro

Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation.

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and 7 days on antibiotics, >3 but 30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 106/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 106/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P 500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care