Basic and Clinical Aspects of the Medical Treatment of Cushings Disease

Under physiological conditions, the production of cortisol is tightly regulated by the so-called hypothalamuspituitary- adrenal (HPA) axis (Figure 1a). Adrenocorticotropin (ACTH) producing cells in the anterior pituitary lobe respond to the hypothalamic corticotropin-releasing hormone (CRH) by increasing the transcription of the pro-opiomelanocortin (POMC) gene. POMC is further processed by prohormone convertases that cleave the POMC molecule into various molecules, e.g. ACTH and α-melanocyte stimulating hormone ¹ ¯ ³. By binding to its receptor (the melanocortin type 2 receptor; MC2R), ACTH induces the expression of several steroidogenic enzymes in the zona fasciculata of the adrenal cortex that are required for the biosynthesis of cortisol, including CYP17A1 and CYP11B1 4. MC2R activation also triggers phosphorylation of the steroidogenic acute regulatory protein (STAR), which facilitates cholesterol transport over the mitochondrial inner membrane. Consequently, the production rate of cortisol will increase

Feasibility and reliability of PRISMA-Medical for specialty-based incident analysis

Aims and objectives: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. Methods: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t¿=¿3 months and t¿=¿12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised ¿ values for each level of classification. Results: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (¿ 0.70–0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (¿ 0.53–0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (¿ 0.40–0.47). Conclusion: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NIC

What Brown saw and you can too

A discussion is given of Robert Brown's original observations of particles ejected by pollen of the plant \textit{Clarkia pulchella} undergoing what is now called Brownian motion. We consider the nature of those particles, and how he misinterpreted the Airy disc of the smallest particles to be universal organic building blocks. Relevant qualitative and quantitative investigations with a modern microscope and with a "homemade" single lens microscope similar to Brown's, are presented.Comment: 14.1 pages, 11 figures, to be published in the American Journal of Physics. This differs from the previous version only in the web site referred to in reference 3. Today, this Brownian motion web site was launched, and http://physerver.hamilton.edu/Research/Brownian/index.html, is now correc

Reviewing recordings of neonatal resuscitation with parents

Background Recording of neonatal resuscitation, including video and respiratory parameters, was implemented for research and quality purposes at the neonatal intensive care unit (NICU) of the Leiden University Medical Center, and parents were offered to review the recording of their infant together with a neonatal care provider. We aimed to provide insight in parental experiences with reviewing the recording of the neonatal resuscitation of their premature infant. Methods This study combined participant observations during parental review of recordings with retrospective qualitative interviews with parents. Results Parental review of recordings of neonatal resuscitation was observed on 20 occasions, reviewing recordings of 31 children (12 singletons, 8 twins and 1 triplet), of whom 4 died during admission. Median (range) gestational age at birth was 27+5 (24+5-30+3) weeks. Subsequently, 25 parents (13 mothers and 12 fathers) were interviewed. Parents reported many positive experiences, with special emphasis on the value for getting hold of the start of their infant's life and coping with the trauma of neonatal resuscitation. Reviewing recordings of neonatal resuscitation frequently resulted in appreciation for the child, the father and the medical team. Timing and set-up of the review contributed to positive experiences. Parents considered screenshots/copies of the recording of the resuscitation of their infant as valuable keepsakes of their NICU story and reported that having the screenshots/video comforted them, especially when their child died during admission. Conclusion Parents consider reviewing recordings of neonatal resuscitation as valuable. These positive parental experiences could allay concerns about sharing recordings of neonatal resuscitation with parents.Developmen

On the Quantitative Impact of the Schechter-Valle Theorem

We evaluate the Schechter-Valle (Black Box) theorem quantitatively by considering the most general Lorentz invariant Lagrangian consisting of point-like operators for neutrinoless double beta decay. It is well known that the Black Box operators induce Majorana neutrino masses at four-loop level. This warrants the statement that an observation of neutrinoless double beta decay guarantees the Majorana nature of neutrinos. We calculate these radiatively generated masses and find that they are many orders of magnitude smaller than the observed neutrino masses and splittings. Thus, some lepton number violating New Physics (which may at tree-level not be related to neutrino masses) may induce Black Box operators which can explain an observed rate of neutrinoless double beta decay. Although these operators guarantee finite Majorana neutrino masses, the smallness of the Black Box contributions implies that other neutrino mass terms (Dirac or Majorana) must exist. If neutrino masses have a significant Majorana contribution then this will become the dominant part of the Black Box operator. However, neutrinos might also be predominantly Dirac particles, while other lepton number violating New Physics dominates neutrinoless double beta decay. Translating an observed rate of neutrinoless double beta decay into neutrino masses would then be completely misleading. Although the principal statement of the Schechter-Valle theorem remains valid, we conclude that the Black Box diagram itself generates radiatively only mass terms which are many orders of magnitude too small to explain neutrino masses. Therefore, other operators must give the leading contributions to neutrino masses, which could be of Dirac or Majorana nature.Comment: 18 pages, 4 figures; v2: minor corrections, reference added, matches journal version; v3: typo corrected, physics result and conclusions unchange