Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Office otology follow-up

The validation of otological care in the previous quarter century has been based, by and large, on short-term follow-up information. The rapid variation in procedures introduced during this period indicates that there may be need for further consideration. Analyses based on relatively short duration have led the "acceptance" of a variety of diagnostic and treatment methods which have proven disappointing in some cases. To help avoid this invalid "acceptance," a review of patients with significant follow-up may result in a more critical evaluation of future procedural changes. This presentation will be in four parts: 1. History of the office structure. 2. Discussion of five long-term patients that illustrates and supports certain otological concepts. 3. A review of surgical care for chronic suppurative otitis media in 1968. 4. A review of patients treated for serous otitis media with myringotomy and tubal insertion in 1968.     

Sodium nitroprusside: pharmacology, toxicology and therapeutics

Sodium nitroprusside is a potent, effective, and readily reversible direct vasodilating agent. It is broken down by hemoglobin into cyanide, which is in part detoxified by liver and kidney to thiocyanate. Some cyanide, especially in nitroprusside- "resistant" individuals who need large amounts of the drug, appears to remain free to cause cyanide poisoning. Patients requiring inordinate amounts probably should not continue to receive the drug, although maximum dosage limits for long-term therapy are not established. Blood thiocyanate levels do not indicate the extent to which free cyanide is limiting oxygen utilization in essential tissue, nor do blood cyanide levels. Metabolic acidosis, elevated lactate levels, elevated lactate/pyruvate ratios, and elevated mixed venous blood oxygen content are at present the best indications of the presence of cyanide poisoning during nitroprusside administration. Nitroprusside appears useful for induction of hypotension during surgery, and for treatment of hypertensive emergencies from all causes, although continuance for more than a few days is probably unwise. The reductions of cardiac afterload and ventricular filling pressure by nitroprusside appear useful in treatment of severe myocardial failure or infarction, but studies of myocardial cyanide toxicity are needed before complete acceptance of this therapy is warranted. Initial dose rates between 0.5 and 1.5 mug/kg/min are recommended only as starting points for very careful titration. Total projected intra-operative dosage should be calculated as quickly as possible and should not exceed 3-3.5 mg/kg. It is hoped that future studies will reveal the maximum dose of nitroprusside that can safely be metabolized in a 24-hour period, and may indicate that cofactors of rhodanase such as thiosulfate, or cobalamins such as hydroxocobalamin, can be administered with nitroprusside to prevent cyanide poisoning.     

Gastric pacing improves emptying and symptoms in patients with gastroparesis

BACKGROUND & AIMS: No effective treatment is available for patients with gastroparesis refractory to standard medical therapy. The aim of this study was to investigate the effects of gastric pacing on gastric electrical activity, gastric emptying, and symptoms in patients with gastroparesis. METHODS: Nine patients with gastroparesis participated in this study. Four pairs of cardiac pacing wires were implanted on the serosa of the stomach. The protocol consisted of two portions: a temporary inpatient study period and an outpatient study for a period of 1 month or more. RESULTS: Gastric pacing entrained the gastric slow wave in all subjects and converted tachygastria in 2 patients into regular 3-cpm slow waves. Gastric emptying was significantly improved after the outpatient treatment with gastric pacing. The gastric retention at 2 hours was reduced from 77.0% +/- 3.3% to 56.6% +/- 8.6% (P < 0.05). Symptoms of gastroparesis were substantially reduced at the end of the outpatient treatment (1.51 +/- 0.46 vs. 2.84 +/- 0.61; P < 0.04). Eight of 9 patients no longer relied on jejunostomy tube feeding, and no adverse events were noted related to the pacing unit. CONCLUSIONS: Gastric pacing seems to be able to improve symptoms of gastroparesis and to accelerate gastric emptying in patients with gastroparesis. More controlled studies are necessary to further investigate the role of gastric pacing in clinical practice.     

Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.     

Inverse material identification in coupled acoustic-structure interaction using a modified error in constitutive equation functional

This work focuses on the identification of heterogeneous linear elastic moduli in the context of frequency-domain, coupled acoustic-structure interaction (ASI), using either solid displacement or fluid pressure measurement data. The approach postulates the inverse problem as an optimization problem where the solution is obtained by minimizing a modified error in constitutive equation (MECE) functional. The latter measures the discrepancy in the constitutive equations that connect kinematically admissible strains and dynamically admissible stresses, while incorporating the measurement data as additional quadratic error terms. We demonstrate two strategies for selecting the MECE weighting coefficient to produce regularized solutions to the ill-posed identification problem: 1) the discrepancy principle of Morozov, and 2) an error-balance approach that selects the weight parameter as the minimizer of another functional involving the ECE and the data misfit. Numerical results demonstrate that the proposed methodology can successfully recover elastic parameters in 2D and 3D ASI systems from response measurements taken in either the solid or fluid subdomains. Furthermore, both regularization strategies are shown to produce accurate reconstructions when the measurement data is polluted with noise. The discrepancy principle is shown to produce nearly optimal solutions, while the error-balance approach, although not optimal, remains effective and does not need a priori information on the noise level.     

Contactless Spin Switch Sensing by Chemo-Electric Gating of Graphene

Direct electrical probing of molecular materials is often impaired by their insulating nature. Here, graphene is interfaced with single crystals of a molecular spin crossover complex, [Fe(bapbpy)(NCS)₂], to electrically detect phase transitions in the molecular crystal through the variation of graphene resistance. Contactless sensing is achieved by separating the crystal from graphene with an insulating polymer spacer. Next to mechanical effects, which influence the conductivity of the graphene sheet but can be minimized by using a thicker spacer, a Dirac point shift in graphene is observed experimentally upon spin crossover. As confirmed by computational modeling, this Dirac point shift is due to the phase-dependent electrostatic potential generated by the crystal inside the graphene sheet. This effect, named as chemo-electric gating, suggests that molecular materials may serve as substrates for designing graphene-based electronic devices. Chemo-electric gating, thus, opens up new possibilities to electrically probe chemical and physical processes in molecular materials in a contactless fashion, from a large distance, which can enhance their use in technological applications, for example, as sensors.     

Oxidation Resistance of Thermal Barrier Coatings Based on Hollow Alumina Particles

Thermal barrier coatings were synthesized in a single step process from a slurry containing Al microspheres onto different Ni-based superalloys. Upon growth of the coating a top coat of hollow alumina spheres linked to an aluminium diffused coating through an alumina TGO formed. The isothermal and cyclic oxidation tests at different temperatures (900 till 1100 °C) up to 1000 h or 1500 cycles revealed progressive growth of different thermal oxides depending on the substrate composition. Faster degradation of the coatings occurred in the titanium-rich substrates (e.g. IN-738LC and PWA1483) compared to the titanium-poor ones (CM-247LC and René N5). By comparing with conventional low activity aluminide coatings, it appeared that the incorporation of alloying elements (notably Ti and Ta) to the diffused layers upon the high activity slurry coating process is responsible for such fastest degradation.     

EAPB0503, an Imidazoquinoxaline Derivative Modulates SENP3/ARF Mediated SUMOylation,and Induces NPM1c Degradation in NPM1 Mutant AML

Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML.     

A slip model for micro/nano gas flows induced by body forces

A slip model for gas flows in micro/nano-channels induced by external body forces is derived based on Maxwell’s collision theory between gas molecules and the wall. The model modifies the relationship between slip velocity and velocity gradient at the walls by introducing a new parameter in addition to the classic Tangential Momentum Accommodation Coefficient. Three-dimensional Molecular Dynamics simulations of helium gas flows under uniform body force field between copper flat walls with different channel height are used to validate the model and to determine this new parameter.