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Abstract Background The aim of this study was to evaluate how anaesthesiologists manage a “cannot intubate, can ventilate” (CI) and “cannot intubate, cannot ventilate” (CICV) scenarios, and how following simulation training will affect their guideline adherence, skills and decision-making immediately after training and 6 months later. Methods A prospective controlled study was conducted from July to December 2022. Anaesthesiologists who applied for the continuous medical education course “Difficult Airway Management” were involved in the study. Each volunteer participated in two simulation scenarios (CI, CICV) with structural debriefing after each scenario. After the first simulation round, volunteers were trained in difficult airway management according to DAS guidelines, using the same equipment as during the simulation. The participants repeated the simulation scenarios the day after the training and six months later. The primary and secondary endpoints were compared between three rounds: initial simulation (Group 1), immediately after training (Group 2), and six months after training (Group 3). Results A total of 24 anaesthesiologists consented to participate in the study and completed the initial survey form. During the first session, 83.3% of participants had at least one major deviation from the DAS protocol. During the first CICV scenario, 79% of participants made at least one deviation from the DAS protocol. The second time after simulation training, significantly better results were achieved: the number of anaesthesiologists, who attempted more than 3 laryngoscopies decreased (OR = 7 [1.8–26.8], p = 0.006 right after training and OR = 3.9 [1.06–14.4], p = 0.035 6 month later); the number, who skipped the supralaryngeal device attempt, call for help and failure to initiate surgical airway also decreased. Simulation training also significantly decreases the time to call for help, cricothyroidotomy initiation time, and mean desaturation time and increases the odds ratio of successful cricothyroidotomy (OR 0.02 [0.003–0.14], p

Abstract Background Release from prison is characterized by discontinuity of healthcare services and results in poor health outcomes, including an increase in mortality. Institutions capable of addressing this gap in care seldom collaborate in comprehensive, data-driven transition of care planning. This study harnesses information from a data exchange between correctional facilities and community-based healthcare agencies in Colorado to model a care continuum after release from prison. Methods We merged records from Denver Health (DH), an urban safety-net healthcare system, and the Colorado Department of Corrections (CDOC), for people released from January 1 to June 30, 2021. The study population was either (a) released to the Denver metro area (Denver and its five neighboring counties), or (b) assigned to the DH Regional Accountable Entity, or (c) assigned to the DH medical home based on Colorado Department of Healthcare Policy and Financing attribution methods. Outcomes explored were outpatient, acute care, and inpatient utilization in the first 180 days after release. We used Pearson’s chi-squared tests or Fisher exact for univariate comparisons and logistic regression for multivariable analysis. Results The care continuum describes the healthcare utilization at DH by people released from CDOC. From January 1, 2021, to June 30, 2021, 3242 people were released from CDOC and 2848 were included in the data exchange. 905 individuals of the 2848 were released to the Denver metro area or attributed to DH. In the study population of 905, 78.1% had a chronic medical or psychological condition. Within 180 days of release, 31.1% utilized any health service, 24.5% utilized at least one outpatient service, and 17.1% utilized outpatient services two or more times. 10.1% utilized outpatient services within the first 30 days of release. Conclusions This care continuum highlights drop offs in accessing healthcare. It can be used by governmental, correctional, community-based, and healthcare agencies to design and evaluate interventions aimed at improving the health of a population at considerable risk for poor health outcomes and death.

Despite energy-related financial concerns and the growing demand for sustainability, many energy efficiency measures are not being implemented in industrial practice. There are a number of reasons for this, including a lack of knowledge about energy efficiency potentials and the assessment of energy savings as well as the high workloads of employees. This article describes the systematic development of an expert system, which offers a chance to overcome these obstacles and contribute significantly to increasing the energy efficiency of production machines. The system employs data-driven regression models to identify inefficient parameter settings, calculate achievable energy savings, and prioritize actions based on a fuzzy rule base. Proposed measures are first applied to an analytical real-time simulation model of a production machine to verify that the constraints required for the specified product quality are met. This provides the machine operator with the expert means to apply proposed energy efficiency measures to the physical entity. We demonstrate the development and application of the system for a throughput parts-cleaning machine in the metalworking industry.

The ongoing challenge to ensure a sustainable and affordable energy supply forces industrial companies to transform their energy system. This transformation usually leads to an increase in topological complexity, which in turn results in increased operational complexity. Existing approaches from the field of supervisory and optimal control are capable of mastering complex operational problems. However, due to the complex and non-transparent implementation, there is still no industrial penetration, which hinders the necessary transformation of energy systems. This work aims at establishing trust in these control approaches and presents a procedure model for the systematic development of application-oriented operating strategies for industrial energy heating systems. It combines research approaches from the fields of sequencing control and approximate MPC to extract rule-based operating strategies, which are inherently easy to understand and implementable. By splitting the procedure model into five phases, expert knowledge can be integrated in a targeted manner. The procedure model is validated by the exemplary application to an industrial heating supply system. As part of an optimization study, the operating strategy developed is compared with both an MPC strategy and a baseline strategy. While the conventional MPC approach represents the upper limit of optimality, the operating strategy developed is able to achieve comparable results. Compared to the baseline strategy, a relative reduction in operating costs of 5.4% to 37.0% is achieved.

Background. A survey was conducted among anesthesiologists in 38 Ukrainian hospitals to evaluate the current incidence and treatment quality of the local anesthetic systemic toxicity (LAST). With the growing preference for regional anesthetic techniques, implementation of measures for timely detection and treatment of LAST is becoming a priority for many surgical hospitals. This study aims to provide primary country-wide epidemiological data to guide further safety improvement in Ukraine. It should be noted, that the survey was performed before the beginning of the full-scale Russian invasion of Ukraine. The resulting surge in the incidence of limb injury has resulted in an unprecedented scale of application of regional anesthesia, including out-of-hospital cases with very limited monitoring, which will no doubt generate great amount of new data on the subject. We hope that our current analysis may be used as a reference point for the future research on this subject. Material and methods. A link to the survey was distributed via e-mail to the members of the Association of Anesthesiologists of Ukraine. Data submission was anonymous. Statistical analysis was performed using Microsoft Excel. Descriptive statistics are provided. Results. Responses were submitted by 186 anesthesiologists from 38 Ukrainian cities. Among them, 65.9% practice in public hospitals, 25.4% - in private hospitals, 8.7% - in university hospitals. Majority of respondents (60.3%) reported performing over 100 regional anesthetic procedures per year. Peripheral nerve blocks were routinely performed in the hospitals of 76.9% of respondents. 42.4% are using peripheral nerve blocks or more times per week, 24.4% perform this amount monthly, 21.7% - yearly, with 11.5% not utilizing peripheral nerve blocks at all. Ultrasound guidance was commonly used by 64.1% of anesthesiologists, 60.3% reported relying on landmark techniques often and 38.5% are routinely using a neuromuscular electrical stimulator. LAST cases were previously encountered by 37.2% of respondents. However, only 37% have reported having a LAST protocol in their hospital and 42.3% did not have a lipid emulsion available. Regarding patient education, in 62.8% of cases the patients were specifically warned about the possible complications of regional anesthesia prior to procedures, where it was performed. When the local anesthetic related adverse events did occur, they were recorded in the patient’s card in 27.2% of cases; the chief of anesthesiology department was informed in 36.9%, while in 35.9% the event was not reported in any way. Conclusions. The practice of regional anesthesia is becoming more widespread in Ukraine, but the minimal measures required to provide patient safety during such procedures are still not being employed in many hospitals.

Abstract Kyphoscoliotic Ehlers–Danlos syndrome (kEDS) is a rare genetic disorder combining congenital hypotonia, congenital/early onset and progressive kyphoscoliosis, and generalized joint hypermobility. Vascular fragility is another characteristic of the disease rarely described. We report a severe case of kEDS‐PLOD1 with several vascular complications leading to difficulties in disease management.

Abstract Background FLNA Loss-of-Function (LoF) causes periventricular nodular heterotopia type 1 (PVNH1), an acknowledged cause of seizures of various types. Neurological symptoms are inconstant, and cardiovascular (CV) defects or connective tissue disorders (CTD) have regularly been associated. We aimed at refining the description of CV and CTD features in patients with FLNA LoF and depicting the multisystemic nature of this condition. Methods We retrospectively evaluated FLNA variants and clinical presentations in FLNA LoF patient with at least one CV or CTD feature, from three cohorts: ten patients from the French Reference Center for Rare Vascular Diseases, 23 patients from the national reference diagnostic lab for filaminopathies-A, and 59 patients from literature review. Results Half of patients did not present neurological symptoms. Most patients presented a syndromic association combining CV and CTD features. CV anomalies, mostly aortic aneurysm and/or dilation were present in 75% of patients. CTD features were present in 75%. Variants analysis demonstrated an enrichment of coding variants in the CH1 domain of FLNA protein. Conclusion In FLNA LoF patients, the absence of seizures should not be overlooked. When considering a diagnosis of PVNH1, the assessment for CV and CTD anomalies is of major interest as they represent interlinked features. We recommend systematic study of FLNA within CTD genes panels, regardless of the presence of neurological symptoms.

BackgroundVascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to pathogenic variants in COL3A1 leading to medium-size-artery (MSA) dissection, aneurysm, rupture. Aortic lesions are rarer and less investigated. The objective was to describe the distribution of MSA and aortic lesions and the type of COL3A1 variants in a multicentric cohort of 330 adult vEDS patients.MethodsAt the time of the study, 87% were alive, 60.3% were index cases, and 60.0% were women. COL3A1 variants were identified using NGS and/or Sanger sequencing and classified according to functional consequences: 80.6% leading to dominant-negative (DN) and 19.4% leading to haploinsufficiency (HI). Imaging was systematically performed during the initial workup. Carotid mechanics were assessed by echo tracking in a subgroup of patients.ResultsArterial lesions were reported in 82.4% of the patients (N = 272): 83.5% had MSA lesions alone, 3.3% had aortic lesions alone, and 13.2% both. DN variants were associated with a higher prevalence of arterial lesions (P < 0.044), especially in supra-aortic trunks and renal arteries. The prevalence of aortic lesions in HI patients with arterial lesions was higher than that in patients with DN (P 0.027), but not anymore when adjusted for age (P < 0.559). Carotid Young’s modulus was lower in patients with DN, in association with the higher incidence of MSA lesions in this group.ConclusionThe prevalence of aortic lesions is not influenced by the COL3A1 genotype when adjusted for age. Patients with DN variant vEDS have a higher frequency of MSA lesions, especially in supra-aortic trunks associated with lower carotid stiffness. These results support optimized care and follow-up for these vulnerable patients.

Abstract Background Major depressive disorder (MDD) is associated with decreased patient well-being and symptoms that can cause substantial impairments in patient functioning and even lead to suicide. Worldwide, MDD currently causes the second-most years lived with disability and is predicted to become the leading cause of disability by 2030. Utility values, capturing patient quality of life, are required in economic evaluations for new treatments undergoing reimbursement submissions. We aimed to identify health state utility values (HSUVs) and disutilities in MDD for use in future economic evaluations of pharmacological treatments. Methods Embase, PubMed, Econlit, and Cochrane databases, plus gray literature, were searched from January 1998 to December 21, 2018, with no language or geographical restrictions, for relevant studies that reported HSUVs and disutilities for patients with MDD receiving pharmacological interventions. Results 443 studies were identified; 79 met the inclusion criteria. We focused on a subgroup of 28 articles that reported primary utility data from 16 unique studies of MDD treated with pharmacological interventions. HSUVs were elicited using EQ-5D (13/16, 81%; EQ-5D-3L: 11/16, 69%; EQ-5D-3L or EQ-5D-5L not specified: 2/16), EQ-VAS (5/16, 31%), and standard gamble (1/16, 6%). Most studies reported baseline HSUVs defined by study entry criteria. HSUVs for a first or recurrent major depressive episode (MDE) ranged from 0.33 to 0.544 and expanded from 0.2 to 0.61 for patients with and without painful physical symptoms, respectively. HSUVs for an MDE with inadequate treatment response ranged from 0.337 to 0.449. Three studies reported HSUVs defined by MADRS or HAMD-17 clinical thresholds. There was a large amount of heterogeneity in patient characteristics between the studies. One study reported disutility estimates associated with treatment side effects. Conclusions Published HSUVs in MDD, elicited using methods accepted by health technology assessment bodies, are available for future economic evaluations. However, the evidence base is limited, and it is important to select appropriate HSUVs for the intervention being evaluated and that align with clinical health state definitions used within an economic model. Future studies are recommended to elicit HSUVs for new treatments and their side effects and add to the existing evidence where data are lacking.

Abstract Tuning deformation mechanisms is imperative to overcome the well-known strength-ductility paradigm. Twinning-induced plasticity (TWIP), transformation-induced plasticity (TRIP) and precipitate hardening have been investigated separately and have been altered to achieve exceptional strength or ductility in several alloy systems. In this study, we use a novel solid-state alloying method—friction stir alloying (FSA)—to tune the microstructure, and a composition of a TWIP high-entropy alloy by adding Ti, and thus activating site-specific deformation mechanisms that occur concomitantly in a single alloy. During the FSA process, grains of the as-cast face-centered cubic matrix were refined by high-temperature severe plastic deformation and, subsequently, a new alloy composition was obtained by dissolving Ti into the matrix. After annealing the FSA specimen at 900 °C, hard Ni–Ti rich precipitates formed to strengthen the alloy. An additional result was a Ni-depleted region in the vicinity of newly-formed precipitates. The reduction in Ni locally reduced the stacking fault energy, thus inducing TRIP-based deformation while the remaining matrix still deformed as a result of TWIP. Our current approach presents a novel microstructural architecture to design alloys, an approach that combines and optimizes local compositions such that multiple deformation mechanisms can be activated to enhance engineering properties.

Boiling conjugate heat transfer is an active field of research encountered in several industries, including metallurgy, power generation and electronics. This paper presents a computational fluid dynamics approach capable of accurately modelling the heat transfer and flow phenomena during immersion quenching: a process in which a hot solid is immersed into a liquid, leading to sudden boiling at the solid–liquid interface. The adopted methodology allows us to couple solid and fluid regions with very different physics, using partitioned coupling. The energy equation describes the solid, while the Eulerian two-fluid modelling approach governs the fluid’s behaviour. We focus on a film boiling heat transfer regime, yet also consider natural convection, nucleate and transition boiling. A detailed overview of the methodology is given, including an analytical description of the conjugate heat transfer between all three phases. The latter leads to the derivation of a fluid temperature and Biot number, considering both fluid phases. These are then employed to assess the solver’s behaviour. In comparison with previous research, additional heat transfer regimes, extra interfacial forces and separate energy equations for each fluid phase, including phase change at their interface, are employed. Finally, the validation of the computational approach is conducted against published experimental and numerical results.

Therapeutic antibodies must have “drug-like” properties. These include high affinity and specificity for the intended target, biological activity, and additional characteristics now known as “developability properties”: long-term stability and resistance to aggregation when in solution, thermodynamic stability to prevent unfolding, high expression yields to facilitate manufacturing, low self-interaction, among others. Sequence-based liabilities may affect one or more of these characteristics. Improving the stability and developability of a lead antibody is typically achieved by modifying its sequence, a time-consuming process that often results in reduced affinity. Here we present a new antibody library format that yields high-affinity binders with drug-like developability properties directly from initial selections, reducing the need for further engineering or affinity maturation. The innovative semi-synthetic design involves grafting natural complementarity-determining regions (CDRs) from human antibodies into scaffolds based on well-behaved clinical antibodies. HCDR3s were amplified directly from B cells, while the remaining CDRs, from which all sequence liabilities had been purged, were replicated from a large next-generation sequencing dataset. By combining two in vitro display techniques, phage and yeast display, we were able to routinely recover a large number of unique, highly developable antibodies against clinically relevant targets with affinities in the subnanomolar to low nanomolar range. We anticipate that the designs and approaches presented here will accelerate the drug development process by reducing the failure rate of leads due to poor antibody affinities and developability.Abbreviations: AC-SINS: affinity-capture self-interaction nanoparticle spectroscopy; CDR: complementarity-determining region; CQA: critical quality attribute; ELISA: enzyme-linked immunoassay; FACS: fluorescence-activated cell sorting; Fv: fragment variable; GM-CSF: granulocyte-macrophage colony-stimulating factor; HCDR3: heavy chain CDR3; IFN2a: interferon α-2; IL6: interleukin-6; MACS: magnetic-activated cell sorting; NGS: next generation sequencing; PCR: polymerase chain reaction; SEC: size-exclusion chromatography; SPR: surface plasmon resonance; TGFβ-R2: transforming growth factor β-R2; VH: variable heavy; VK: variable kappa; VL: variable light; Vl: variable lambda;

INTRODUCTION:Schizophrenia is a condition that places a significant burden on individuals with the condition, their family, and society. A large proportion of those treated for schizophrenia do not experience treatment response and are referred to as having "treatment-resistant schizophrenia" (TRS). Expert opinion has long held that the prevalence of TRS among individuals with schizophrenia is 30%, but the basis of this estimate is unclear. This article presents a model developed for estimating the prevalence of TRS in the United States 2014. METHODS:An incidence-prevalence-mortality model was developed to estimate the prevalence of TRS in the United States. The model was populated with data from public health agencies and published literature. Prevalence in 2014 was modelled using a Markov cohort simulation for each birth cohort between 1930 to 2014. RESULTS:Using different scenarios for baseline incidence, relative risks of mortality, it was estimated that approximately 22% of individuals with schizophrenia would be considered treatment-resistant in 2014. DISCUSSION:The results suggests that prevalence of TRS may be somewhat lower than the 30% often reported, however this is highly dependent on the definition of treatment resistance. Methods such as this may help answer epidemiological and health policy questions as well as test the influence of key underlying assumptions.

Abstract Background Vascular Ehlers-Danlos syndrome (vEDS) is a rare condition characterized by connective tissue fragility. Direct spontaneous carotid-cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted this study to understand the possible mechanisms of occurrence of sCCF in this subset of patients. Methods We conducted a retrospective analysis of a monocentric vEDS cohort along with a literature review regarding sCCF in this condition. Results Of 133 patients regularly followed in our centre between 2000 and 2017, 13 (9.8%) had a diagnosis of direct sCCF (92.3% female, median age 33.0 years, interquartile range (IQR) [26.0–39.5]). There were 7 Glycine missense and 6 splice-site variants but no variant leading to haploinsufficiency. The literature search identified 97 vEDS patients with direct sCCF (79.4% female, 7.2% sex not reported, median age 31.0 years, IQR [24.0–39.0]). Increased carotid circumferential wall stress, higher carotid distensibility and lower carotid intima-media thickness could contribute to a higher risk for direct sCCF in vEDS. There is no predictive factor for the occurrence of sCCF apart from female sex in vEDS. Conclusions In vEDS, anatomical and pathophysiological features of the intra-cavernous internal carotid artery make it prone to shunting in the cavernous sinus, due either to a spontaneous rupture or to a spontaneous dissection with pseudoaneurysm formation. Direct sCCF in seemingly healthy young individuals should be highly suggestive of vEDS and prompt further investigation.

Mental Abacus (MA) is a popular arithmetic technique in which students learn to solve math problems by visualizing a physical abacus structure. Prior studies conducted in Asia have found that MA can lead to exceptional mathematics achievement in highly motivated individuals, and that extensive training over multiple years can also benefit students in standard classroom settings. Here we explored the benefits of shorter-term MA training to typical students in a US school. Specifically, we tested whether MA (1) improves arithmetic performance relative to a standard math curriculum, and (2) leads to changes in spatial working memory, as claimed by several recent reports. To address these questions, we conducted a one-year, classroom-randomized trial of MA instruction. We found that first-graders students struggled to achieve abacus expertise over the course of the year, while second-graders were more successful. Neither age group showed a significant advantage in cognitive abilities or mathematical computation relative to controls, although older children showed some hints of an advantage in learning place-value concepts. Overall, our results suggest caution in the adoption of MA as a short-term educational intervention.

Este trabalho apresenta a aplicação de ferramentas da qualidade na busca de melhoria contínua e redução de erros na área de soldagem para manufatura de torres eólicas, que apresentava alto índice de retrabalhos. Assim o projeto de melhoria contínua foi dividido em: pré-Kaisen, onde foram levantadas, abordadas e discutidas todas as falhas e possíveis causas de erros, através da formação de equipes, utilização de ferramentas de apontamento como Pareto e diagrama de Ishikawa e Brainstorming; na etapa Kaisen, as causas foram abordadas e solucionadas, com as propostas das equipes formadas no pré-Kaisen, utilizando técnicas de Brainstorming e 5W2H. Ao final das aplicações e correções de problemas estruturais e organizacionais, foi reduzido em quatro meses o índice de retrabalho, provocados por má qualidade de solda, de 73,00 para 18,70%, mostrando a eficácia das ferramentas de qualidade e diminuindo o custo de produção do produto.

Some internal medicine residency program directors have expressed concerns that their third-year residents may have been subjected to inappropriate communication during the 2016 fellowship recruitment season. The authors sought to study applicants’ interpersonal communication experiences with fellowship programs. Many respondents indicated that they had been asked questions that would constitute violations of the National Residency Matching Program (NRMP) Communications Code of Conduct agreement, including how they plan to rank specific programs. Moreover, female respondents were more likely to have been asked questions during interview experiences about other programs to which they applied, and about their family plans. Post-interview communication policies were not made clear to most applicants. These results suggest ongoing challenges for the internal medicine community to improve communication with applicants and uniform compliance with the NRMP communications code of conduct during the fellowship recruitment process.

The re-kindled fascination in machine learning (ML), observed over the last few decades, has also percolated into natural sciences and engineering. ML algorithms are now used in scientific computing, as well as in data-mining and processing. In this paper, we provide a review of the state-of-the-art in ML for computational science and engineering. We discuss ways of using ML to speed up or improve the quality of simulation techniques such as computational fluid dynamics, molecular dynamics, and structural analysis. We explore the ability of ML to produce computationally efficient surrogate models of physical applications that circumvent the need for the more expensive simulation techniques entirely. We also discuss how ML can be used to process large amounts of data, using as examples many different scientific fields, such as engineering, medicine, astronomy and computing. Finally, we review how ML has been used to create more realistic and responsive virtual reality applications.

Background: Fibromuscular dysplasia (FMD) is a rare idiopathic, non-atherosclerotic non-inflammatory vascular disease. This work represents the first study of the pathophysiology of FMD. We investigated the relationships between circulating biomarkers and the non-invasive vascular parameters. Methods: We included 50 patients with FMD, 50 essential hypertensive patients (HT) and 50 healthy subjects (NT) matched for age, sex, ethnicity and blood pressure. We determined circulating levels of total microparticles (MPs) (annexinV+MPs), endothelial MPs (CD144+MPs, CD62E+MPs and CD31+CD41-MPs) and SMC-MPs by flow cytometry analysis. We measured forearm endothelial function by post-ischemic flow dependent vasodilation. Shear stress was estimated using the formula of Weaver (1–3). Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity. Triple signal score was assessed from 15-MHz echotracking system. Results: There are no significant differences between rates of total MPs, endothelial MPs (CD144+MPs, CD62E+MPs and CD31+CD41-MPs) and SMC-MPs between 3 groups (with p-value 0.38 0.52 0.65 0.17 and 0.25 respectively). Endothelial MPs were not correlated with the endothelial dysfunction, nor with the shear stress, whether in FMD, NT or HT. We observed a strong negative correlation between aortic stiffness and nitroglycerin-mediated dilation in the group NT, HT and whole population (r= −0.43, p= 0.001 r= −0.29, p= 0.03 r = −0.35, p

Computational Fluid Dynamics (CFD) has numerous applications in the field of energy research, in modelling the basic physics of combustion, multiphase flow and heat transfer; and in the simulation of mechanical devices such as turbines, wind wave and tidal devices, and other devices for energy generation. With the constant increase in available computing power, the fidelity and accuracy of CFD simulations have constantly improved, and the technique is now an integral part of research and development. In the past few years, the development of multiscale methods has emerged as a topic of intensive research. The variable scales may be associated with scales of turbulence, or other physical processes which operate across a range of different scales, and often lead to spatial and temporal scales crossing the boundaries of continuum and molecular mechanics. In this paper, we present a short review of multiscale CFD frameworks with potential applications to energy problems.

An oil and gas separator is a device used in the petroleum industry to separate a fluid mixture into its gaseous and liquid phases. A computational fluid dynamics (CFD) study aiming to identify key design features for optimising the performance of the device, is presented. A multiphase turbulent model is employed to simulate the flow through the separator and identify flow patterns that can impinge on or improve its performance. To verify our assumptions, we consider three different geometries. Recommendations for the design of more cost- and energy-effective separators, are provided. The results are also relevant to broader oil and gas industry applications, as well as applications involving stratified flows through channels.

SUMMARY Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.

This paper concerns a computational study of the process of removing water from an aircraft’s fuel tank by pumping nitrogen enriched air (NEA) from the bottom of the tank. This is an important procedure for the smooth, efficient, and safe operation of the aircraft’s engine. Due to the low partial pressure of water in the pumped NEA, it absorbs water from the fuel. The water-laden bubbles enter the ullage, the empty space above the fuel, and escape into the environment. The effects of the number of NEA inlets and the NEA mass flow rate on the timescale of the NEA pumping were investigated using Computational Fluid Dynamics. The results reveal that the absorption of water by the NEA bubbles is low and is not affected by the number of the inlets used. Yet, the water content in the fuel decreases fast during the procedure, which is the desired outcome. We show that this is due to the relatively dry NEA entering the ullage and displacing the moist air, thus reducing the partial pressure of water at the fuel/ullage interface. This shift from equilibrium conditions forces water to evaporate from the fuel’s entire surface. Furthermore, the amount of water migrating from the fuel directly into the ullage is significantly greater than that absorbed by the rising bubbles. In turn, the rate of decrease of the water content in the ullage is determined by the total NEA mass flow rate and this is the dominant contributor to the draining time, with the number of NEA nozzles playing a minor role. We confirmed this by pumping NEA directly into the ullage, where we observe a significant decrease of water even when the NEA is not pumped through the fuel. We also show that doubling the mass flow rate halves the draining time. When considering the capability of most modern aircraft to pump NEA through the fuel as part of their inerting system, the proposed method for removing water is particularly attractive, requiring very little (if at all) design modification.

A 69 year old male developed rapid deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 µmol/L (5.5 mg/dl) on presentation. Anti-MPO was positive (titer>8 units, normal

Objectives: To assess the reliability and validity of faculty evaluations of medicine residents. Methods: We conducted a retrospective study (2004–2012) involving 228 internal medicine residency graduates at the Medical College of Wisconsin who were evaluated by 334 attendings. Measures included evaluations of residents by attendings, based on six competencies and interns and residents’ performance on the American Board of Internal Medicine certification exam and annual in-service training examination. All residents had at least one in-service training examination result and 80% allowed the American Board of Internal Medicine to release their scores. Results: Attending evaluations had good consistency (Cronbach’s α = 0.96). There was poor construct validity with modest inter-rater reliability and evidence that attendings were rating residents on a single factor rather than the six competencies intended to be measured. There was poor predictive validity as attending ratings correlated weakly with performance on the in-service training examination or American Board of Internal Medicine certification exam. Conclusion: We conclude that attending evaluations are poor measures for assessing progress toward competency. It may be time to move beyond evaluations that rely on global, end-of-rotation appraisals.

Abstract Introduction This resource contains a focused, 2.5 hour interactive session explicitly designed to orient new housestaff to the six ACGME General Competencies, and address key topics related to risk management and do-not-resuscitate (DNR) orders. Methods Trained facilitators (residency program directors, associate program directors, or faculty) guide discussions in small, six-person groups within their own classroom of housestaff. In the small groups, housestaff read a scenario about an intern who must respond in a difficult situation. They then answer questions about the scenario including what they should do if they were the intern, what resources are available, and how and where the ACGME General Competencies appear in this situation. After small groups discuss a scenario, facilitators led a discussion with the large group (whole classroom) about the answers to the scenario questions. Results Three data sets highlight the success of this program. Results of a multiple-choice pre- and posttest requiring residents to identify the ACGME competencies associated with 20 statements revealed that housestaff arrived with a general understanding of the competencies and that this session enhances that comprehension. Mean percentages for the housestaff scores changed from 76% to 81% (p < .001) following the session. Results from the housestaff evaluation of the session revealed that they enjoyed the case-based discussions, citing the opportunities to interact in small groups, discuss relevant and interesting scenarios, and learning the ACGME General Competencies. Faculty facilitators evaluated the sessions highly and volunteered to serve as facilitators the following year. Discussion The strength of this overall approach is that the length of the session may be reduced or lengthened dependent on the degree to which objectives have been achieved, and facilitators can change the content or characters in the scenarios to enable the discussion to continue in a related direction. Also, housestaff may want to contribute their own experiences to the discussions, especially new fellows. It was decided not to separate the groups by level of experience, as the fellows would likely add more to the discussions when discussing the scenarios with new residents. In some cases, fellows were able to say, “This actually happened to me and here's what I did …” providing valuable insight for the new residents in their group.

Abstract Background Histophilus somni, a gram-negative coccobacillus, is an obligate inhabitant of bovine and ovine mucosal surfaces, and an opportunistic pathogen responsible for respiratory disease and other systemic infections in cattle and sheep. Capsules are important virulence factors for many pathogenic bacteria, but a capsule has not been identified on H. somni. However, H. somni does form a biofilm in vitro and in vivo, and the biofilm matrix of most bacteria consists of a polysaccharide. Results Following incubation of H. somni under growth-restricting stress conditions, such as during anaerobiosis, stationary phase, or in hypertonic salt, a polysaccharide could be isolated from washed cells or culture supernatant. The polysaccharide was present in large amounts in broth culture sediment after H. somni was grown under low oxygen tension for 4-5 days (conditions favorable to biofilm formation), but not from planktonic cells during log phase growth. Immuno-transmission electron microscopy showed that the polysaccharide was not closely associated with the cell surface, and was of heterogeneous high molecular size by gel electrophoresis, indicating it was an exopolysaccharide (EPS). The EPS was a branched mannose polymer containing some galactose, as determined by structural analysis. The mannose-specific Moringa M lectin and antibodies to the EPS bound to the biofilm matrix, demonstrating that the EPS was a component of the biofilm. The addition of N-acetylneuraminic acid to the growth medium resulted in sialylation of the EPS, and increased biofilm formation. Real-time quantitative reverse transcription-polymerase chain reaction analyses indicated that genes previously identified in a putative polysaccharide locus were upregulated when the bacteria were grown under conditions favorable to a biofilm, compared to planktonic cells. Conclusions H. somni is capable of producing a branching, mannose-galactose EPS polymer under growth conditions favorable to the biofilm phase of growth, and the EPS is a component of the biofilm matrix. The EPS can be sialylated in strains with sialyltransferase activity, resulting in enhanced density of the biofilm, and suggesting that EPS and biofilm formation may be important to persistence in the bovine host. The EPS may be critical to virulence if the biofilm state is required for H. somni to persist in systemic sites.