Polysialylated-neural cell adhesion molecule (PSA-NCAM) in the human trigeminal ganglion and brainstem at prenatal and adult ages

<p>Abstract</p> <p>Background</p> <p>The polysialylated neuronal cell adhesion molecule (PSA-NCAM) is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG) and brainstem neuronal populations at prenatal and adult age.</p> <p>Results</p> <p>Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age, the distribution pattern remains fairly steady, whereas the density of immunoreactive structures and the staining intensity may change and are usually higher in newborn than in adult specimens.</p> <p>Conclusion</p> <p>The results obtained show that, in man, the expression of PSA-NCAM in selective populations of central and peripheral neurons occurs not only during prenatal life, but also in adulthood. They support the concept of an involvement of this molecule in the structural and functional neural plasticity throughout life. In particular, the localization of PSA-NCAM in TG primary sensory neurons likely to be involved in the transmission of protopathic stimuli suggests the possible participation of this molecule in the processing of the relevant sensory neurotransmission.</p

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Dark, Beyond Deep: A Paradigm Shift to Cognitive AI with Humanlike Common Sense

Recent progress in deep learning is essentially based on a "big data for small tasks" paradigm, under which massive amounts of data are used to train a classifier for a single narrow task. In this paper, we call for a shift that flips this paradigm upside down. Specifically, we propose a "small data for big tasks" paradigm, wherein a single artificial intelligence (AI) system is challenged to develop "common sense", enabling it to solve a wide range of tasks with little training data. We illustrate the potential power of this new paradigm by reviewing models of common sense that synthesize recent breakthroughs in both machine and human vision. We identify functionality, physics, intent, causality, and utility (FPICU) as the five core domains of cognitive AI with humanlike common sense. When taken as a unified concept, FPICU is concerned with the questions of "why" and "how", beyond the dominant "what" and "where" framework for understanding vision. They are invisible in terms of pixels but nevertheless drive the creation, maintenance, and development of visual scenes. We therefore coin them the "dark matter" of vision. Just as our universe cannot be understood by merely studying observable matter, we argue that vision cannot be understood without studying FPICU. We demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense by showing how to observe and apply FPICU with little training data to solve a wide range of challenging tasks, including tool use, planning, utility inference, and social learning. In summary, we argue that the next generation of AI must embrace "dark" humanlike common sense for solving novel tasks.Comment: For high quality figures, please refer to http://wellyzhang.github.io/attach/dark.pd

[The determination of folate - an evaluation of recent literature with speciale emphasis on food.]

The literature from 1985 up to 1994 has been studied for folic acid in biological substrates and for the group of compounds similar to folic acid in respect of chemical structure and biological activities ("folates"). Emphasis in the evaluation was on nomenclature, occurrence, physiology, dietary recommendations and in particular on the determination of folates in food. Data on the determination of these compounds in food are collected in Table 1, in Table 2 for body fluids and in Table 3 for other matrices. It was found that determination of folates in food is still predominantly done by microbiology in combination with the test organism Lactobacillus casei. However, from collaborative studies it is evident that there is an urgent need to much further standardize this procedure than achieved sofar, to improve the comparability of laboratory results. In addition, the advice is to discontinue the use of the term "free" folate since this is deceptive and ambiguous. HPLC methods fit best to the present and future needs of the folate determination. However these procedures also require further optimalization towards a method in which, after actraction with optional hog kidney deconjugase, the extracts are cleaned (anion exchange) and enriched (affinity chromatography) and subsequently assayed for folates by HPLC in combination with fluorescence- and UV-detection in series. HIG

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In opdracht van de dienstleiding is in september 2002 voor de Commissie van Toezicht een bibliometrisch onderzoek uitgevoerd. Het betreft een kwantitatieve 'output'-meting van de wetenschappelijke productie van alle sectoren van het RIVM in de periode 1999-2001. Onder 'output' worden de RIVM-rapporten en openbare publicaties (artikelen, dissertaties, boeken en boekbijdragen) verstaan. Inzicht is gegeven in de productie per laboratorium, per sector en van heel het RIVM. Tevens zijn samenwerkingsverbanden, trendontwikkelingen in de periode 1999-2001 en 'impact factors' van de tijdschriften waarin gepubliceerd is, in beeld gebracht. Het onderzoek is vooral descriptief van aard en geeft inzicht in het publicatiegedrag van het RIVM. Voor een eventueel toekomstig bibliometrisch onderzoek worden enkele aanbevelingen gedaan