Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Exploring Web-Based University Policy Statements on Plagiarism by Research-Intensive Higher Education Institutions

Plagiarism may distress universities in the US, but there is little agreement as to exactly what constitutes plagiarism. While there is ample research on plagiarism, there is scant literature on the content of university policies regarding it. Using a systematic sample, we qualitatively analyzed 20 Carnegie-classified universities that are “Very High in Research.” This included 15 public state universities and five high-profile private universities. We uncovered highly varied and even contradictory policies at these institutions. Notable policy variations existed for verbatim plagiarism, intentional plagiarism and unauthorized student collaboration at the studied institutions. We conclude by advising that the American Association of University Professors (AAUP), the American Association of Colleges and Universities (AACU) and others confer and come to accord on the disposition of these issues

Healthcare professionals' intentions to use wiki-based reminders to promote best practices in trauma care: a survey protocol

<p>Abstract</p> <p>Background</p> <p>Healthcare professionals are increasingly using wikis as collaborative tools to create, synthesize, share, and disseminate knowledge in healthcare. Because wikis depend on collaborators to keep content up-to-date, healthcare professionals who use wikis must adopt behaviors that foster this collaboration. This protocol describes the methods we will use to develop and test the metrological qualities of a questionnaire that will assess healthcare professionals' intentions and the determinants of those intentions to use wiki-based reminders that promote best practices in trauma care.</p> <p>Methods</p> <p>Using the Theory of Planned Behavior, we will conduct semi-structured interviews of healthcare professionals to identify salient beliefs that may affect their future use of wikis. These beliefs will inform our questionnaire on intended behavior. A test-retest of the survey will verify the questionnaire's stability over time. We will interview 50 healthcare professionals (25 physicians and 25 allied health professionals) working in the emergency departments of three trauma centers in Quebec, Canada. We will analyze the content of the interviews and construct and pilot a questionnaire. We will then test the revised questionnaire with 30 healthcare professionals (15 physicians and 15 allied health professionals) and retest it two weeks later. We will assess the internal consistency of the questionnaire constructs using Cronbach's alpha coefficients and determine their stability with the intra-class correlation (ICC).</p> <p>Discussion</p> <p>To our knowledge, this study will be the first to develop and test a theory-based survey that measures healthcare professionals' intentions to use a wiki-based intervention. This study will identify professionals' salient beliefs qualitatively and will quantify the psychometric capacities of the questionnaire based on those beliefs.</p

Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

BackgroundCabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs), which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein.Methodology/Principal FindingsTo determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS) previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2.Conclusions/SignificanceOur results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the existence of similarities and differences in both aspects of Cbt function between the insect and the vertebrate TIEG proteins

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

Oxygen carrying capacity of salvaged blood in patients undergoing off-pump coronary artery bypass grafting surgery : a prospective observational study

BACKGROUND: Intraoperative cell salvage (ICS), hereby referred to ‘mechanical red cell salvage’, has been widely used and proven to be an effective way to reduce or avoid the need for allogeneic red blood cells (RBCs)transfusion and its associated complications in surgeries involving major blood loss. However, little is known about the influence of this technique on the functional state of salvaged RBCs. Furthermore, there are no articles that describe the change of free hemoglobin (fHb) in salvage blood during storage, which is a key index of the quality control of salvaged blood. Therefore, in this study, the influence of ICS on the function of salvaged RBCs and the changes of salvaged RBCs during storage were studied with respect to the presence of oxyhemoglobin affinity (recorded as a P(50) value) and the level of 2, 3-diphosphoglycerate (2, 3-DPG) and fHb by comparing salvaged RBCs with self-venous RBCs and 2-week-old packed RBCs. METHODS: Fifteen patients undergoing off-pump coronary artery bypass grafting (OPCAB) surgery were enrolled. Blood was collected and processed using a Dideco Electa device. The level of P(50), 2, 3-DPG and fHB from salvaged RBCs, venous RBCs and 2-week-old packed RBCs was measured. We also measured the changes of these indicators among salvaged RBCs at 4 h (storage at 21–24 °C) and at 24 h (storage at 1–6 °C). RESULTS: The P(50) value of salvaged RBCs at 0 h (28.77 ± 0.27 mmHg) was significantly higher than the value of venous RBCs (27.07 ± 0.23 mmHg, p = 0.000) and the value of the 2-week-old packed RBCs (16.26 ± 0.62 mmHg, p = 0.000). P(50) value did not change obviously at 4 h (p = 0.121) and 24 h (p = 0.384) compared with the value at 0 h. The 2, 3-DPG value of salvaged RBCs at 0 h (17.94 ± 6.91 μmol/g Hb) was significantly higher than the value of venous RBCs (12.73 ± 6.52 mmHg, p = 0.007) and the value of the 2-week-old packed RBCs (2.62 ± 3.13 mmHg, p = 0.000). The level of 2, 3-DPG slightly decreased at 4 h (p = 0.380) and 24 h (p = 0.425) compared with the value at 0 h. Percentage of hemolysis of the salvaged blood at 0 h(0.51 ± 0.27 %) was significantly higher than the level of venous blood (0.07 ± 0.05 %, p = 0.000) and the value of 2-week-old packed RBCs (0.07 ± 0.05 %, p = 0.000), and reached 1.11 ± 0.42 % at 4 h (p = 0.002) and 1.83 ± 0.77 % at 24 h (p = 0.000). CONCLUSIONS: The oxygen transport function of salvaged RBCs at 0 h was not influenced by the cell salvage process and was better than that of the venous RBCs and 2-week-old packed RBCs. At the end of storage, the oxygen transport function of salvaged RBCs did not change obviously, but percentage of hemolysis significantly increased

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research