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The greatest impact on the burden of CNS infections resulted from preventive measures, mainly vaccination programs, that have decreased the incidence of many CNS infections significantly. Here, we highlight the main cornerstones of vaccination programs on bacterial and viral CNS infections and point at future chances of upcoming vaccines. Vaccination programs have significantly decreased the number of cases due to Haemophilus influenzae type B and Neisseria meningitidis. For pneumococcal meningitis, new vaccines that prevent neuroinvasive serotypes have the potential to decrease numbers in the future. Whereas a vaccine is available for tick-borne encephalitis, prevention of neuroborreliosis is limited to contact precautions. However, vaccination rates against tick-borne encephalitis remain too low in many countries. Another neurotropic virus that can be prevented effectively by vaccination is varicella zoster virus (VZV). Interestingly, vaccination against VZV also seems to reduce the risk of dementia as recently shown. While vaccination is important in general, patients with immunosuppression benefit most from vaccinations. Finally, recent measles outbreaks impressively underline the efficacy of vaccination programs and demonstrate what can happens if vaccination rates decrease. Vaccination programs have shown to be effective in reducing the burden of CNS infections. As vaccination rates are generally still too low and as new vaccines are coming up, it is obvious that the potential of vaccines to prevent CNS infections is not maxed out yet.
Organic NE213 liquid scintillator neutron detectors are commonly used at accelerator facilities for neutron beam diagnostics. In recent years, they have also been installed at nuclear fusion facilities to measure the neutron energy spectra from Deuterium (D) and Deuterium-Tritium plasmas, e.g., at the ASDEX Upgrade (Garching, Germany) and at the Joint European Torus (JET, Culham, UK). The NE213 equivalent scintillating material (now BC501A) of the detector is sensitive to neutron and gamma radiation, so pulse discrimination techniques are applied in order to obtain the measured neutron pulse height spectrum (PHS). If the neutron detector is stable, controlled, and well-characterized (i.e., its response function to incoming neutrons of known energy is determined with high accuracy), it can be used as a neutron spectrometer. The measured PHS can then be analyzed using standard techniques such as unfolding to determine the incoming neutron energy spectrum. This article focuses on the unfolding of neutron data measured in D plasma experiments at JET by a compact broadband neutron spectrometer using the maximum entropy unfolding code MAXED. A general method for optimizing MAXED input parameters is described and applied to the measured PHS to diagnose the effects of the auxiliary heating of JET D plasma on the neutron energy spectra.
Reliable neutron dosimetry requires knowledge of the neutron spectrum. We discuss the problem of analyzing data from a multisphere neutron spectrometer to infer the energy spectrum of the incident neutrons and describe the code MAXED, a computer program developed to apply the maximum entropy principle to this problem. The code and documentation are available from the authors upon request.
About 900 astronomers gathered 2 weeks ago near the birthplace of Eastman Kodak Co. to share their latest pictures of the sky at the American Astronomical Society's 196th Meeting. Notable findings pointed to a cold origin for comet Hale-Bopp, a nasty environment for extrasolar planets, and a maximum size for the biggest structures in the universe.
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Both laboratory and field respirometry are rapidly growing techniques to determine animal performance thresholds. However, replicating protocols to estimate maximum metabolic rate (MMR) between species, populations, and individuals can be difficult, especially in the field. We therefore evaluated seven different exercise treatments-four laboratory methods involving a swim tunnel (critical swim speed [Ucrit], Ucrit postswim fatigue, maximum swim speed [Umax], and Umax postswim fatigue) and three field-based chasing methods (3-min chase with 1-min air exposure, 3-min chase with no air exposure, and chase to exhaustion)-in adult coho salmon (Oncorhynchus kisutch) as a case study to determine best general practices for measuring and quantifying MMR in fish. We found that all seven methods were highly comparable and that chase treatments represent a valuable field alternative to swim tunnels. Moreover, we caution that the type of test and duration of measurement windows used to calculate MMR can have significant effects on estimates of MMR and statistical power for each approach.
A 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation and exclusion of infection, he underwent successful orthotopic liver transplantation. After histologic examination of the explanted liver, he subsequently admitted to 5 months of daily use of a detoxifying supplement known as MaxOne (®), containing D-ribose- L-cysteine, consistent with a drug-induced acute-on-chronic liver failure. The use of complementary and alternative medicines and its potential for causing drug-induced liver injury and acute-on chronic liver failure requires a high index of suspicion and increased awareness among health care providers.
The phagocytic clearance of host cells is important for eliminating dying cells and for the therapeutic clearance of antibody-targeted cells. As ubiquitous, motile and highly phagocytic immune cells, macrophages are principal players in the phagocytic removal of host cells throughout the body. In recent years, great strides have been made in identifying the molecular mechanisms that control the recognition and phagocytosis of cells by macrophages. However, much less is known about the physical and metabolic constraints that govern the amount of cellular material macrophages can ingest and how these limitations affect the overall efficiency of host cell clearance in health and disease. In this review we will discuss, in the contexts of apoptotic cells and antibody-targeted malignant cells, how physical and metabolic factors associated with the internalization of host cells are relayed to the phagocytic machinery and how these signals can impact the overall efficiency of cell clearance. We also discuss how this information can be leveraged to increase cell clearance for beneficial therapeutic outcomes.
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The maximum effective dose (MaxED) is an important quantity for therapeutic drugs. The MaxED for therapeutic drugs is defined as the dose above which no improvement in efficacy is obtained. In this article, we propose two experimental designs and analytic methods (one single-stage design and one two-stage design) to select the MaxED among several fixed doses and to compare the therapeutic effect of the selected MaxED with a control. The selection of MaxED is based on the isotonic regression under the restriction of monotonicity. In the single-stage design, both the selection of the MaxED and assessing its efficacy are carried out at the end of experiment. In the two-stage design, the selection of the MaxED and assessment of its efficacy are carried out at the interim analysis (first stage), the experiment in the second stage is carried out only at the selected MaxED and control if the first-stage test is not significant. Thus, the two-stage design enables selection of the MaxED at an earlier stage and stopping the trial earlier if the treatment effect at MaxED is extreme. Williams' test (1972) is applied to test whether the selected MaxED is significantly different from control for the single-stage design and the first-stage test of the two-stage design. The sample size calculation for each design is provided. Extensive simulations are carried out to illustrate the performances of the proposed methods.
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Since work-hour restrictions were instituted in 2003, sustainably complying with duty-hour regulations remains a challenge for general surgery residency programs across the nation. To determine whether industry-based process improvement techniques could be leveraged to increase compliance with work-hour restrictions within a general surgery residency. This quality improvement project using Lean methodology was conducted from October to November of the 2021 to 2022 academic year. The setting was a university-based general surgery residency program in southern California with rotations across 5 regional hospitals. The program trains 7 categorical general surgery residents per postgraduate year (PGY) and offers an optional 1 to 3 years for research and career development. Programmatic structures were examined, current and target states were analyzed, opportunities for improvement were identified, root-cause analyses were conducted, and targeted interventions were developed. Resident time logs and annual Accreditation Council for Graduate Medical Education resident and faculty surveys were reviewed from academic years 2019/2020 to 2022/2023. Attending faculty were surveyed on resident preparedness using a 5-point Likert scale. Differences between means and proportions were calculated with corresponding 95% CIs. The web-based survey responses of 29 residents (residents per PGY, 7 [PGY1], 14 [PGY2/3], 8 [PGY4/5]; 17 female [54.7%]) were included in this study. Root causes included maxed baseline schedules, late in shift work, culture, service variability, clinical volume, and inefficient workflows. Fifteen multifactorial interventions impacting call and weekend scheduling, work practices and efficiencies, intern and service orientations, and faculty and cultural expectations were implemented. The mean number of residents per block who logged more than 80 hours per week decreased by 3.6 violations per block (95% CI, 2.98-4.22), from 4.4 (12.4%) to 0.8 (2.2%) for a difference of 10.2% (95% CI, 8.4%-16.2%). On the annual resident survey, perceived compliance with 80 hours was 72%, 83%, 83%, and 88%, respectively, over the following study periods: 2019 to 2020, 2020 to 2021, 2021 to 2022, and 2022 to 2023. Faculty perception of resident preparedness for the case increased from a mean (SD) of 2.6 (0.8) to 3.0 (0.5), with a difference of 0.47 (95% CI, -0.52 to 0.68). There were no statistically significant differences in technical skill, clinical judgment, sense of responsibility, efficiency, or sense of well-being. Results of this quality improvement study suggest that through Lean methodology, surgical residency programs can improve working environments. This novel approach can increase compliance with resident work hours by engaging front line trainees in the process.
Painless acute pancreatitis (PAP) is a slowly progressive disease that involves inflammation, scarring, and thickening of pancreatic cells, which can happen due to either alcohol, idiopathic, or genetic. Clinicians usually miss PAP due to lack of pain and additional symptoms of hypotension and fever can lead to an infectious work-up instead. In this case report, we discuss the importance of the rapid discovery of this condition to prevent devastating complications like diabetes, necrotizing pancreatitis, or even death. A 47-years old male with past medical history of hypotension and alcohol abuse presented for loss of consciousness. Patient was found with pinpoint pupils, hypoglycemia, and hypotensive. He received Narcan, dextrose, and IV fluids and became responsive. In the emergency department, the patient was hypotensive and the physical exam was only significant for diaphoresis. Patient denied abdominal or radiating pain. Labs significant for elevated lipase, metabolic acidosis, and hyponatremia with imaging positive for AP without chronic inflammation. Based on imaging, lipase and absence of pain, PAP was diagnosed. Patient had multiple episodes of hypoglycemia and remained hypotensive requiring pressor support and intubation. After intubation, he had pulseless electrical activity cardiac arrest. Return of spontaneous circulation achieved but the patient had worsening acidosis, acute kidney injury, liver injury, and bandemia. Empiric antibiotics started, dexamethasone, and maxed on five pressors and transferred to the medical intensive care unit for management of severe AP (SAP). This case report featured PAP without chronic inflammation which is an even rarer disease than PAP which progressed to SAP.
In cochlear implantation (CI), precise preoperative cochlear duct length (CDL) and angular insertion depth (AID) measurements are pivotal for individualized electrode carrier selection, since recipients benefit from sufficient cochlear coverage of the electrode carrier, enabling electric stimulation of all crucial frequency bands. Since the quality of temporal bone CT largely depends on acquisition and reconstruction settings and is limited by the technical capabilities of the CT scanner, this study aims to assess how radiation dose and reconstruction field-of-view (FOV) affect automatic cochlear morphometry and electrode contact determination in conventional multislice CT. Twenty fresh-frozen human petrous bone specimens were examined at three radiation dose levels (40, 20, and 10 mGy) using a multislice CT scanner. Each dataset was reconstructed with three different FOV settings (250, 125, and 50 mm). Preoperative CDL and AID measurements were performed with dedicated otological planning software. Maxed-out dose images (250 mGy) served as standard of reference for comparing the morphometric results. Regardless of the selected combination of dose level and FOV, significant CDL or AID measurement differences were neither ascertained among the individual groups, nor in comparison to the reference scans (all p ≥ 0.05). Likewise, the simulation of all stimulable frequency bandwidths showed no dependency on radiation dose or FOV settings (all p ≥ 0.05). The assessment of cochlear morphometry with conventional multislice CT imaging before CI surgery allowed a radiation dose reduction up to 75% without compromising the accuracy of software-based cochlear analysis. Notably, automatic CDL and AID measurements for surgical planning did not benefit from a smaller reconstruction FOV.
Fast neutrons are produced from cosmic ray interactions with matter posing particular dosimetric challenges for aviation and space exploration. Progress towards a compact detector system suitable for measurements of cosmic ray induced neutrons with energies up to 120 MeV is presented. The detector was comprised of a 6 mm × 6 mm × 120 mm prism of EJ-276 scintillator and a pair of MicroFC-60035 silicon photomultipliers, coupled with a digital data acquisition system. A comparison was made of pulse shape discrimination capabilities and light output resolution for single and dual silicon photomultiplier detector systems. The dual SiPM detector was characterised in mono-energetic fast neutron fields between 2.5-19.0 MeV. The simulation of detector response functions with Geant4 was explored, using measurements in mono-energetic fields to derive scaling and broadening parameters. Quasi-monoenergetic detector response functions were measured for neutrons with energies up to 16 MeV using Time-of-Flight techniques, and were used to demonstrate the spectroscopic capabilities of the prototype device through the unfolding of known neutron fields.
The n-lab is a fast neutron facility based in the Department of Physics, University of Cape Town, offering collimated neutron beams produced by an MP 320 deuterium-tritium sealed tube neutron generator, and a 220 GBq americium-beryllium radioisotopic source. Characterisations of the spatial and energy distributions of the fast neutron beams were performed using an EJ-301 organic liquid scintillator detector and digital data acquisition system. Neutron energy spectra were obtained through unfolding analyses with MAXED, and a Monte Carlo approach to the propagation of uncertainties was implemented. Measurements of fluence and neutron emission rates were determined through the neutron activation of copper foils and subsequently used to validate the scaling of the unfolded neutron energy spectra.
Parenteral nutrition (PN) is a standard of care for preterm infants in the first postnatal days. The European Society of Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has updated their guideline recommendations on PN in 2018. However, data on actual 2018 guideline adherence in clinical practice are sparse. In this retrospective study, conducted at the neonatal intensive care unit (NICU) of Ghent University Hospital, we analyzed the ESPGHAN 2018 PN guideline adherence and growth for 86 neonates admitted to the NICU. Analyses were stratified by birth weight (<1000 g, 1000 to <1500 g, ≥1500 g). We documented the provisions for enteral nutrition (EN) and PN, and we tested the combined EN and PN provisions for ESPGHAN 2018 adherence. The nutrition protocols showed a high adherence to PN guidelines in terms of carbohydrate provisions, yet lipid provisions for EN and PN often exceeded the recommended maximum of 4 g/kg/d; although, PN lipid intakes maxed out at 3.6 g/kg/d. Protein provisions tended to fall below the recommended minimum of 2.5 g/kg/d for preterm infants and 1.5 g/kg/d for term neonates. The energy provisions also tended to fall below the minimum recommendations, especially for neonates with a birth weight (BW) < 1000 g. Over a mean PN duration of 17.1 ± 11.4 d, the median weekly Fenton Z-scores changes for length, weight, and head circumference were positive for all BW groups. Future studies have to assess how protocols adapt to current guidelines, and how this affects short- and long-term growth across different BW groups. In conclusion, the reported findings provide real-world evidence regarding the effect of ESPGHAN 2018 PN guideline adherence, and they demonstrate how standardized neonatal PN solutions can safeguard stable growth during NICU stays.