cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulatory considerations for gene-therapy strategies and products

through the R & D companies, rather than through in-house research. More ideas originate in R&D companies, and if a particular research direction appears to be a cul-de-sac, it can be easily dropped by not renewing the agreement. If, on the other hand, the research looks promising, further agreements would be drawn up, or even purchase of the company would be considered. Sandoz, Merck, Parke-Davis (a division o f Warner-Lambert) and Green Cross Corporation have invested millions of dollars in GTI, Vical and Viagene, respectively, to develop clinical applications of gene therapy. Other drug-company giants are scouting for deals. It is hard to tell, at present, which company will be first to bring gene therapy to the market, and whether it will be a commercial success. GTI, the pioneer in the field, has been involved in more than a dozen clinical trials and has acquired much experience. However, the other companies that also have a strong scientific environment could become important competitors. Firms such as TargeTech or Vical, which are developing non-viral vectors, might be first to commercialize gene-therapy products, since gaining regulatory approval is likely to be easier. However, even when a gene-therapy protocol has been shown to be safe and effective, and has regulatory approval, commercial success will depend on the market size, and on the willingness of the company to meet the costs. Many governments are currently re-evaluating the cost of health-care systems and the problems of financing expensive new treatments. The costs o f gene therapy must, however, be compared with those for current treatments. A costly, but definitive cure for a disabling genetic disease may, in the long-run, be cheaper than lifelong palliative treatment the cost of current treatment for Gaucher's disease is estimated at US$450 000 annually. For some, even if not all, the diseases which are currently being targeted, gene therapy is likely to prove commercially as well as medically beneficial.
Review of Mixed-Integer Nonlinear and Generalized Disjunctive Programming Methods

This work presents a review of the main deterministic mixed-integer nonlinear programming (MINLP) solution methods for problems with convex and nonconvex functions. An overview for deriving MINLP formulations through generalized disjunctive programming (GDP), which is an alternative higher-level representation of MINLP problems, is also presented. A review of solution methods for GDP problems is provided. Some relevant applications of MINLP and GDP in process systems engineering are described in this work.
Red and blue shifts near compact objects

We show that radiation emitted from material falling toward a black hole or neutron star can be blue-shifted as well as red-shifted. Although the red shift can be arbitrarily large near a black hole, there is an upper limit for the blue shift of 1/2. Material incident toward the poles of a magnetic neutron star can simultaneously radiate red and blue-shifted lines. Near an oblique magnetic rotator, the red and blue shifts will show a sinusoidal variation. Such spectral variations are associated with SS 433.
Role of TET2 and ASXL1 Mutations in the Pathogenesis of Myeloproliferative Neoplasms

Since the discovery of activating mutations in JAK2 in patients with myeloproliferative neoplasms (MPNs) in 2005, gene discovery efforts have identified additional disease alleles, which can predate or occur subsequent to acquisition of JAK2/MPL mutations. In 2009, somatic copy number loss and mutations in the genes TET2 and ASXL1 were identified in MPN patients. Genetic analysis of MPN patient cohorts with adequate sample size and clear clinical annotation are needed to understand the importance of these mutations on MPN phenotype, risk of transformation to leukemia, response to therapy, and influence on overall survival.
An Examination of El Niño–La Niña-Related Precipitation and Temperature Anomalies across the Northern Plains

Abstract Monthly total precipitation and mean temperature data records extending from the late nineteenth century to 1990 were collected for 147 stations in South Dakota, North Dakota, and portions of adjacent states and provinces. This region, defined as the Northern Plains region (NPR), was examined for patterns associated with the warm phase (ENSO) and the cold phase (LNSO) of the Southern Oscillation to elucidate some of the debate concerning a signal in this area. Based on a correlation analysis, the NPR was treated as having one spatial degree of freedom. Using Monte Carlo simulations of the Student's t-test statistic, four seasons with significant changes in mean precipitation or temperature during either ENSO or LNSO were identified. A highly significant signal was evident during the ENSO April to October season for precipitation, where the mean precipitation increased 7.21 cm for the 23 events studied. Here 20 of these 23 ENSO events exhibited precipitation above the median value, and 14 of the 2...
The effects of extensive pitting on the mechanical properties of carbon nanotubes

As previously demonstrated, a single hole is sufficient to markedly reduce the fracture strength of a carbon nanotube (CNT). Herein we present calculations exploring the effects of multiple holes on the modulus, fracture strength, and fracture strain of CNTs. The modulus decreases sharply and approximately linearly as a function of the pitting density. A few holes cause a decrease in the failure strain but extensive pitting leads to higher failure strains. These results suggest that the unusually low modulus measurements and high failure strains reported in the experiments of Yu et al. [Science 287 (2000) 637] were a consequence of purification induced oxidative pitting.
Effective dyspnea management strategies identified by elders with end-stage chronic obstructive pulmonary disease.

Abstract The study's purpose was to identify dyspnea management strategies (DMS) perceived most effective by elders with end-stage chronic obstructive pulmonary disease (COPD). The mixed-method design also incorporated triangulation to compare results between qualitative and quantitative data. Specific DMS were selected and percentage effectiveness was rated. Four strategy categories emerged as most useful: changing activity, relaxation, inhaled medication use, and breathing pattern alteration. Gender differences in preferred DMS were revealed. All participants ( N = 30) preferred to use multiple strategies for effective dyspnea management; therefore, health care providers should consider employing individualized combinations of DMS when assisting elders with end-stage COPD during acute exacerbations of dyspnea.
Communication lower bounds and optimal algorithms for numerical linear algebra

The traditional metric for the efficiency of a numerical algorithm has been the number of arithmetic operations it performs. Technological trends have long been reducing the time to perform an arithmetic operation, so it is no longer the bottleneck in many algorithms; rather, communication, or moving data, is the bottleneck. This motivates us to seek algorithms that move as little data as possible, either between levels of a memory hierarchy or between parallel processors over a network. In this paper we summarize recent progress in three aspects of this problem. First we describe lower bounds on communication. Some of these generalize known lower bounds for dense classical (O(n3)) matrix multiplication to all direct methods of linear algebra, to sequential and parallel algorithms, and to dense and sparse matrices. We also present lower bounds for Strassen-like algorithms, and for iterative methods, in particular Krylov subspace methods applied to sparse matrices. Second, we compare these lower bounds to widely used versions of these algorithms, and note that these widely used algorithms usually communicate asymptotically more than is necessary. Third, we identify or invent new algorithms for most linear algebra problems that do attain these lower bounds, and demonstrate large speed-ups in theory and practice.
The dilemma of high‐risk deceased donor livers: Who should get them?

Key Points 1. The insufficient supply of deceased donor livers for transplantation has motivated the expansion of acceptance criteria; such organs are captured by the terms marginal and expanded criteria livers. 2. This context of aggressive liver utilization motivated the derivation of the donor risk index, a quantitative, objective, and continuous metric of liver quality based on factors known or knowable at the time of an organ offer. 3. Recommendations from traditional wisdom to pair high-risk livers with healthy candidates are strongly reflected in current practice. 4. Although deceased donor quality worsens posttransplant outcomes, it does not synergize negatively with increased recipient disease severity. 5. Calculations of survival benefit support the preferential transplantation of high-risk livers into sick candidates rather than healthy ones. 6. Those making individual decisions regarding transplant opportunities should consider donor and organ specifics, recipient characteristics, anticipated transplant circumstances, center expertise, and the dynamics of local organ availability in addition to data and analyses based on national registries. Liver Transpl 16:S60-S64, 2010. © 2010 AASLD.
Stochastic earthquake response of secondary systems in base‐isolated structures

This paper studies the stochastic responses of secondary systems in base-isolated shear beam structures. A number of base isolation systems such as the laminated rubber bearing (LRB), the resilient-friction base isolator (R-FBI) with or without sliding upper plate, and the EDF system are considered. The stochastic models for the El Centro 1940 and the Mexico City 1985 earthquakes which preserve the non-stationary evolutions of amplitude and frequency content of ground accelerations are used as earthquake excitations. The technique of equivalent linearization is utilized and the mean-square response statistics of secondary systems and primary structure are evaluated. The accuracy of the linearization scheme is verified by comparison with the Monte Carlo simulation results. Statistically estimated peak responses of the secondary system are evaluated and the results are compared with the response spectra for actual earthquake accelerograms. It is shown that the use of base isolation systems, generally, provides considerable protection for structural contents. In particular, the LRB system is remarkably effective in reducing responses of secondary systems. Results for the Mexico City earthquake show that the base-isolated structures are sensitive to long period ground excitations.
Hierarchical Control of Anaerobic Gene Expression in Escherichia coli K-12: the Nitrate-Responsive NarX-NarL Regulatory System Represses Synthesis of the Fumarate-Responsive DcuS-DcuR Regulatory System

Hierarchical control ensures that facultative bacteria preferentially use the available respiratory electron acceptor with the most positive standard redox potential. Thus, nitrate is used before other electron acceptors such as fumarate for anaerobic respiration. Nitrate regulation is mediated by the NarX-NarL two-component system, which activates the transcription of operons encoding nitrate respiration enzymes and represses the transcription of operons for other anaerobic respiratory enzymes, including enzymes involved in fumarate respiration. These are fumarate reductase (encoded by the frdABCD operon), fumarase B, which generates fumarate from malate, and the DcuB permease for fumarate, malate, and aspartate. The transcription of the corresponding structural genes is activated by the DcuS-DcuR two-component system in response to fumarate or its dicarboxylate precursors. We report results from preliminary transcription microarray experiments that revealed two previously unknown members of the NarL regulon: the aspA gene encoding aspartate-ammonia lyase, which generates fumarate; and the dcuSR operon encoding the dicarboxylate-responsive regulatory system. We measured beta-galactosidase expression from monocopy aspA-lacZ, frdA-lacZ, and dcuS-lacZ operon fusions in response to added nitrate and fumarate and with respect to the dcuR and narL genotypes. Nitrate, acting through the NarX-NarL regulatory system, repressed the transcription of all three operons. Only frdA-lacZ expression, however, was responsive to added fumarate or a dcuR(+) genotype. Phospho-NarL protein protected operator sites in the aspA and dcuS promoter regions from DNase I cleavage in vitro. The overall results are consistent with the hypothesis that nitrate represses frdA operon transcription not only directly, by repressing frdA promoter activity, but also indirectly, by repressing dcuS promoter activity.
Mineral emittance spectra: Clustering and classification using self-organizing maps

Remote sensing of terrestial and planetary surfaces in the infrared for the purpose of identifying minerals and their distribution is an ongoing activity. The huge amount of spectral data currently available and expected from future space missions presents a challenge to the scientist determine to extract useful scientific information from this data. Automated methods to facilitate this process are clearly needed to complete these investigations in a timely manner. Organizing this data into meaningful chunks is a crucial first step of this analysis that can be be addressed with clustering techniques. We have developed an automated clustering and classification scheme based on Kohonen Self-Organizing maps (SOM). The SOM is a type of unsupervised neural network widely used to cluster data and identify anomalies. A modification of the Davies-Bouldin (DB) cluster validation index which incorporates the measurement uncertainties of the SOM training data is used to determine the optimal number of clusters. This scheme was trained and tested with the mineral spectral libraries prepared at Arizona State University (ASU) and John Hopkins University (JHU) whose samples have been hierarchically labeled with Class, Subclass and Group names. These names are used to measure the spectral purity of the derived clusters and the accuracy of classification. We describe in detail the SOM scheme itself, the performance measures, and testing procedure. The test results demonstrate that the SOM can be a useful component in autonomous systems designed to identify minerals from reflectance or emissivity measurements in the thermal infrared.
Voronoi diagram for multiply-connected polygonal domains 11: implementation and application

Voronoi diagrams have many novel applications in computer-aided design. In this paper, an implementation of a Voronoi diagram algorithm described in a companion paper by Srinivasan and Nackman is presented. This Voronoi diagram is then used for an application in which equivalent resistance networks are derived from a boundary representation of a two-dimensional VLSI geometry.
Chest pain in the emergency department: role of cardiac imaging

Millions of patients with acute chest pain, or other symptoms suggestive of acute coronary syndrome (ACS), are evaluated daily in emergency departments (EDs) around the world. These patients comprise a broad spectrum of cardiac risk. At one end of the spectrum are patients with abnormal ECG and thus definite ACS who require immediate invasive diagnostic procedures and possibly coronary intervention. At the other end of the spectrum are patients with atypical and non-cardiac chest discomfort and normal ECG who can be sent home safely. In between these two extremes are numerous patients with atypical presentation of ischaemic chest pain and normal or non-diagnostic ECG who might have ACS. Cardiac imaging may play an important role in triaging and directing clinical management of these patients. Until the institution of ED based chest pain centres (CPCs) in the USA, about two thirds of these patients with acute chest pain and normal or non-diagnostic ECG usually were admitted to the hospital for further evaluation, whereas the remaining one third of the patients was sent home. Of those admitted, as much as one half of patients are labelled with the vague admission diagnosis of “chest pain” or “rule-out-infarction” (fig 1). In the latter group of patients, complete diagnostic work-up typically confirms a cardiac cause for the symptoms in only about 10%. Thus, about 90% of these hospitalisations were in retrospect unnecessary.1 On the other hand, some studies have indicated that of the patients sent home, about 2–4% had unrecognised acute myocardial infarctions (MIs). Missed MI is a major cause for legal action against ED physicians in the USA. Figure 1 Admission diagnoses of 764 patients who presented with acute chest pain in the emergency department before the institution of a dedicated chest pain centre. More than half of the patients were identified as having unspecified …
Modular transformation methods for generalized Petri nets and their application to automated manufacturing systems

The authors present transformation methods for generalized Petri nets by introducing and using the concept of a live and bounded circuit (LB-circuit), based on fusing common paths. An LB-circuit is a generalized version of a simple elementary circuit. The authors briefly review generalized Petri nets, including their formal definitions and properties, and define an arc ratio, a remainder, and an LB-circuit. A partially overlapping relation is introduced. Using these concepts, four lemmas and three theorems which are the theoretical background for the transformation methods are presented. Reduction methods are described with examples. Synthesis methods are illustrated for a simple automated manufacturing system, a machining/assembly process with three robots and two workstations. >
Posterior lumbar interbody fusion with metal cages: Current techniques

Posterior lumbar interbody fusion (PLIF) is a technically rigorous surgical fusion procedure. The procedure has had a resurgence in application and acceptance due to recent technological advances in cage design. We review the history of this procedure, indications, and patient evaluation. We also describe the surgical technique of freestanding PLIF and a new technique utilizing a single cage with pedicle screw supplementation.
Wave techniques for noise modeling and measurement

The noise wave approach is applied to analysis, modeling, and measurement applications. Methods are presented for the calculation of component and network noise wave correlation matrices. Embedding calculations, relations to two-port figures-of-merit, and transformations to traditional representations are discussed. Simple expressions are derived for MESFET and HEMT noise wave parameters based on a linear equivalent circuit. A noise wave measurement technique is presented and experimentally compared with the conventional method. >
Educational expertise: the concept of ‘mind frames’ as an integrative model for professionalisation in teaching

Professionalisation in teaching has been the topic of extensive research in recent years, following in general two different approaches: the ‘competence-based approach’ and the ‘critical reflection approach’. With large-scale comparative studies such as PISA, TIMMS and PIRLS at the beginning of the 21st century, the former approach came to dominate the field and—especially in Germany—a specific model of professionalisation advanced to the status of a paradigm. However, this model does not seem unproblematic when one considers its roots. In this article I begin by inquiring into the concept and methodology behind the status quo in order to reveal its limitations. As a means of developing this concept further, I then introduce a model of educational expertise that takes as its theoretical foundation the didactic triangle, which has a rigid systematic structure for critical and reflective thinking about teaching and is backed up by empirical findings. At the core of this model of educational expertise are mi...
Metastatic carcinoma to percutaneous endoscopic gastrostomy tube sites. A report of five cases.

Objective: To characterize the clinicopathologic features of metastatic carcinomas at percutaneous endoscopic gastrostomy (PEG) tube sites. Methods: We reviewed the metastatic malignancies at PEG tube sites (2002–2011). Results: Five patients were identified, each with primary head and neck keratinizing squamous cell carcinoma. The metastases had a mean size of 6.08 cm (95% confidence interval [CI], 3.75–8.41). The time from PEG tube placement to metastasis diagnosis was 9.8 months (95% CI, 6.59–13.01). The survival times from PEG tube placement and from metastasis diagnosis were 23.5 (95% CI, 7.65–39.35) and 13.7 (95% CI, 0–31.08) months, respectively. Compared with a meta-analysis of the largest case series, our male patients were significantly older (mean, 73 years; 95% CI, 62.2–83.9 vs mean 59 years, 95% CI, 56.0–62.0) but had similar survival times. Conclusions: Despite their older ages, our male patients had similar survival times to those reported previously. Larger series are needed to confirm our findings and explore the causes.
The Consequences of Damaged Mitochondrial DNA

The highly conserved mitochondrial DNA (mtDNA) is particularly susceptible to mutations due to its close proximity to respiratory chain, inheritance at birth, lack of histones in structure, as well as ineffective repair mechanisms. Oxidative stress-induced mtDNA damage and mutations are most profound since the mitochondria are constantly exposed to reactive oxygen species generated by electron transport chain. Dysfunctional mitochondria which are commonly observed in aging or diseases, can exacerbate oxidative stress thereby contributing to disease development. MtDNA encompasses essential genes that encode ribosomal RNAs, transfer RNAs, and several respiratory protein complexes. Thus, mutation in mtDNA impairs mitochondrial functions and results in cellular alterations such as disrupted protein synthesis and decreased ATP bioenergetics. The accumulation of mutated mtDNA throughout lifetime and the subsequent mitochondrial dysfunction are implicated in neurodegeneration and multiple mtDNA-related diseases including myoclonic epilepsy with ragged red fibers (MERRF), Leigh syndrome (LS), and Leber’s hereditary optic neuropathy (LHON). Although the management of these mitochondrial diseases remains challenging, the prevention of maternal transmission of mtDNA mutations can be an essential approach. Despite the negative effects caused by mtDNA damage, high mtDNA mutation rates contribute to the genetic polymorphism in the population, which is likely related to human evolution and migration. In this chapter, we will focus on discussing the structure and function of mtDNA, potential sources leading to mtDNA defect, common mtDNA-related diseases, as well as potential treatment for mtDNA damage.
Are Surgical and Anesthesia Medical Missions in Low- and Middle-Income Countries Helping or Hurting? The Evolving Fields of Global Anesthesia and Global Surgery

In the geopolitical wake of colonialism and World Ward II, globalization has increasingly provided opportunities for physicians and surgeons to care for patients beyond their country's borders. Motivated by humanitarianism, this care is typically provided to those in low and middle-income countries (LMICs) in the form of short-term medical and surgical missions. As the field of global health evolves to include surgical and anaesthesia care as vital components in healthcare system development in LMICs, so should our models of care evolve--to employ best practices and utilize evidence to inform our approach. In these complex social and cultural settings, it is incumbent upon those of us who engage in these endeavours to examine our efforts and realize that our good intentions are sometimes accompanied by unintentional harm.
A Dedicated Orthopaedic Trauma Operating Room Improves Efficiency at a Pediatric Center.

Background: Dedicated orthopaedic trauma operating rooms have improved operating room efficiency, physician schedules, and patient outcomes in adult populations. The purpose of this study was to determine if a dedicated orthopaedic trauma operating room was associated with improved patient flow and cost savings at a level-I pediatric trauma center. Methods: A retrospective analysis was performed for two 3-year intervals before and after implementation of a weekday, unbooked operating room reserved for orthopaedic trauma cases. Index procedures for 5 common fractures were investigated, including supracondylar humeral fractures, both bone forearm fractures, lateral condylar fractures, tibial fractures, and femoral fractures. To provide a control group to account for potential extrinsic changes in hospital efficiency, laparoscopic appendectomies were also analyzed. For each procedure, efficiency parameters and surgical complications, defined as unplanned reoperations, were compared between time periods. The mean cost reduction per patient was calculated on the basis of the mean daily cost of an inpatient hospital bed. Results: Of 1,469 orthopaedic procedures analyzed, 719 cases occurred before the implementation of the dedicated orthopaedic trauma operating room, and 750 cases were performed after the implementation. The frequency of after-hours procedures (5 p.m. to 7 a.m.) was reduced by 48% (p < 0.001). The mean wait time for the operating room decreased among supracondylar humeral fractures, lateral condylar fractures, and tibial fractures, whereas no significant decrease (p = 0.302) occurred among 2,076 laparoscopic appendectomy cases. The mean duration of the surgical procedure and the mean time in the operating room were not significantly affected. Across all orthopaedic procedures, the mean duration of inpatient hospitalization decreased by 5.6 hours (p < 0.001), but no significant difference occurred among appendectomies. Decreased length of stay resulted in a mean cost reduction of $1,251 per patient. Supracondylar humeral fracture cases performed after implementation of the dedicated orthopaedic trauma operating room had fewer surgical complications (p = 0.018). No difference in complication rate was detected among the other orthopaedic procedures. Conclusions: A dedicated orthopaedic trauma operating room in a pediatric trauma center was associated with fewer after-hours procedures, decreased wait time to the surgical procedure, reduced length of hospitalization, and decreased cost.
My worst faults and misdeeds: Self-criticism and self-enhancement can co-exist*

AbstractThree studies explored whether self-enhancement is precluded when people recognize or even exaggerate their worst faults and behaviors. Even when acknowledging their faults, participants minimized the extent to which their bad characteristics reflected what kind of people they were, predicted that they would improve more in the future than would others with the same faults, claimed that others have done worse things to them than they have to others, and indicated that others are more likely to repeat the same bad behaviors in the future than themselves. Observers who read actors’ descriptions of their own misdeeds and those of others also saw the things that were done to actors as worse than the things actors had done.
Radionuclide Imaging of Medullary Carcinoma

Medullary thyroid cancer (MTC) has a favorable prognosis if locally confined at diagnosis. Its 10-yr survival rate decreases dramatically if distant metastases are present. Early recognition of residual/metastatic disease allows surgical excision of the tumor, which can be curative. If surgical excision cannot be done, chemotherapy and externalbeam radiation have limited therapeutic success. The initial diagnostic evaluation should include neck ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI). Nuclear medicine studies have an important role for the early localization of metastatic disease when it is suspected based on persistently elevated calcitonin or carcinoembryonic antigen (CEA) plasma levels following the initial surgery. For the evaluation of metastatic disease, nuclear medicine studies are used in conjunction with US, CT, and MRI, particularly if the extent and location of metastatic foci are still inconclusive.
NEUTRAL MECHANICAL ALIGNMENT: STICKIN' WITH THE ONE THAT BRUNG YA – AFFIRMS

Abstract Restoring the overall mechanical alignment to neutral has been the gold standard in total knee arthroplasty since the 1970s. Recently, there has been renewed interest in alternative alignment goals that place implants in a more “physiologic” position with the hope of improving clinical outcomes. However, placing components outside of the classic “safe zone” of ± 3° is controversial, as studies have shown increased risk of mechanical failure, especially in obese patient populations. This paper will outline mechanical and kinematic alignment and present the evidence for why mechanical alignment is still the gold standard in total knee arthroplasty.
Psychological Correlates and Explanations of Alcohol Use and Abuse

There are a number of psychological correlates and explanations for the excessive consumption of alcohol. The selection of topics covered in this chapter represents the major psychological approaches used to explain excessive alcohol use, namely, the psychodynamic, disease, and behavioral/social learning models. Research on the psychological aspects of alcohol consumption is relatively new. An attempt has been made to present the basic ideas of each of the models along with research evidence and methodological issues pertaining to their evaluation. Each of the models presented has contributed to our continuing attempts to understand the complex mechanisms and issues involved in excessive alcohol use. As our theoretical and methodological sophistication increases, further refinement of each of these approaches seems likely. For the present, they represent laudable initial efforts to develop psychological frameworks within which one can study and treat problem drinking.
The Most Visited Sites of Certain Lévy Processes

Let X be a symmetric Levy process with $$Ee^{i\lambda X_t } = e^{ - t\psi (\lambda )}$$ Let $$\phi (x) = \frac{2}{\pi }\int_0^\infty {\frac{{1 - \cos \lambda x}}{{\psi (\lambda )}}} d\lambda $$ Assume that • ψ(λ) is regularly varying at zero with index 1<α≤2 and (1/ψ(λ)) I [λ≥1]∈L 1(R). • φ(x) is increasing on [0, ∞)Let L x t denote the local time of X at x up to time t. Following The most visited sites of symmetric stable processes, by Bass, Eisenbaum, and Shi, let V(t) be such that L V(t) t =sup x∈R L x t . We call V(t) the most visited site of X up to time t. We show that under the above conditions on X,V(t) is transient. In particular, for all γ>9 $$\mathop {\lim }\limits_{t \to \infty } \frac{{\left| {V(t)} \right|}}{{\phi ^{ - 1} \left( {\frac{{t\psi ^{ - 1} (1/t)}}{{(\log t)^\gamma }}} \right)}} = \infty {\text{ a}}{\text{.s}}{\text{.}}$$ This result is obtained for symmetric stable processes in the above reference. We use their approach and many of their methods.
Property Modeling across Transition Temperatures in PMC's: Part III. Bending Fatigue

Parts I [1] and II [2] of the present paper introduced systematic models for the computation of thermal effects on strength and stiffness of unidirectional polymer matrix composites (PMC's) as well as the life prediction of these materials in end-loaded bending at elevated temperatures. The last step of this study was the possibility of introducing such models in durability codes such as MRLife [3]. A recent method was developed for the experimental characterization of end-loaded bending fatigue behavior of composites at elevated temperatures. The literature dealing with the durability of composite materials in bending focuses mainly on 3 and 4 point bending [4–6]. A limited set of data as well as the basis for theoretical modeling for fatigue end-loaded bending is available in the literature [7]. However, the life prediction scheme required elevated temperature experiments. New experiments in fatigue bending were performed in order to complete the available data. Microscopic observations revealed new information for the understanding of the damage process of unidirectional AS4/PPS composites in end-loaded fatigue bending. Finally, the models developed in Parts I and II were integrated into the MRLife integral enabling the life prediction of unidirectional PMC's under combined mechanical and thermal loads from room temperature experimental data.
Tax Avoidance and Asymmetric Cost Behavior

This study examines the relationship between tax avoidance and asymmetric cost behavior. This relationship arises due to direct economic benefits of cash savings from tax avoidance. On one hand, ca...
Simulation training in palliative care: state of the art and future directions

Background The growing need for palliative care (PC) among patients with serious illness is outstripped by the short supply of PC specialists. This mismatch calls for competency of all health care providers in primary PC, including patient-centered communication, management of pain and other symptoms, and interprofessional teamwork. Simulation-based medical education (SBME) has emerged as a promising modality to teach key skills and close the educational gap. This paper describes the current state of SBME in training of PC skills. Methods We conducted a systematic review of the literature reporting on simulation experiences addressing PC skills for clinical learners in medicine and nursing. We collected data on learner characteristics, the method and content of the simulation, and outcome assessments. Results In a total of 78 studies, 76% involved learners from medicine and 38% involved learners from nursing, while social work (6%) and spiritual care (3%) learners were significantly underrepresented. Only 16% of studies involved collaboration between participants at different training levels. The standardized patient encounter was the most popular simulation method, accounting for 68% of all studies. Eliciting treatment preferences (50%), delivering bad news (41%), and providing empathic communication (40%) were the most commonly addressed skills, while symptom management was only addressed in 13% of studies. The most common method of simulation evaluation was subjective participant feedback (62%). Only 4% of studies examined patient outcomes. In 22% of studies, simulation outcomes were not measured at all. Discussion We describe the current state of SBME in PC education, highlighting advances over recent decades and identifying gaps and opportunities for future directions. We recommend designing SBME for a broader range of learners and for interprofessional skill building. We advocate for expansion of skill content, especially symptom management education. Finally, evaluation of SBME in PC training should be more rigorous with a shift to include more patient outcomes.
Sociodemographic and Psychosocial Predictors of VIP Attendance in Smart Beginnings Through 6 Months: Effectively Targeting At-Risk Mothers in Early Visits.

Past research on predictors of participation in early childhood parenting programs suggest that families experiencing higher levels of sociodemographic adversity (e.g., younger maternal age, single parenthood, lower income or education) are less likely to participate in parenting programs. This is significant, as it may indicate that those most in need of additional support are the least likely to receive it. Data from a randomized control trial (RCT) of Smart Beginnings, an integrated, tiered model for school readiness, were used to explore predictors of attendance in Video Interaction Project (VIP) through 6 months. VIP is a primary preventive intervention delivered in tandem with pediatric well-child visits, aimed at reducing income-based disparities in early child development through promotion of responsive parent-child interactions. Using Poisson distribution models (N = 403; treatment arm, n = 201), we find that demographic, socioeconomic status (SES), and psychosocial variables are associated with program attendance but not always in the expected direction. While analyses show that first-time mothers have higher levels of program attendance as expected, we find that less-educated mothers and those with lower parenting self-efficacy have higher levels of attendance as well. The latter findings may imply that the VIP intervention is, by some indicators, effectively targeting families who are more challenging to engage and retain. Implications for pediatric-based interventions with population-level accessibility are discussed.
An Assessment of the Vulnerability of Illinois' Rarest Plant Species to Climate Change

Illinois is home to approximately 2,107 native plant species of which about 16% are listed as threatened or endangered (T & E). In addition to the common threats associated with the decline of these species, climate change is a rapidly emerging threat. Climate predictions for Illinois have estimated that summer temperatures will resemble present-day summers in Texas by mid- to late-century, while precipitation patterns are less predictable. Using NatureServe's Climate Change Vulnerability Index (CCVI) tool we evaluated the climate change vulnerability for all 331 of Illinois T & E plant species. Overall, we found that over 80% are vulnerable to climate change. Barriers to migration are a leading factor associated with vulnerability in Illinois, where 97% of listed species are affected by anthropogenic barriers and 24% are affected by natural barriers. The sensitivity of species to changes in temperature, precipitation, and hydrology are also associated with vulnerability. The CCVI score was associated with most of the dozen or so other factors incorporated in the tool, though to a lesser degree. This study provides insights into the most vulnerable plant species in Illinois and provides much needed information to land managers, policy makers, and researchers. By highlighting which T & E species are most vulnerable to climate change, and what factors are most responsible for their vulnerability, this work will aid in prioritizing limited resources and developing adaptation strategies for them.
An Acidic Environment Induces APOL1-Associated Mitochondrial Fragmentation

BACKGROUND Apolipoprotein L1 gene (APOL1) G1 and G2 kidney-risk variants (KRVs) cause CKD in African Americans, inducing mitochondrial dysfunction. Modifying factors are required, because a minority of individuals with APOL1 high-risk genotypes develop nephropathy. Given that APOL1 function is pH-sensitive and the pH of the kidney interstitium is <7, we hypothesized the acidic kidney interstitium may facilitate APOL1 KRV-induced mitochondrial dysfunction. METHODS Human embryonic kidney (HEK293) cells conditionally expressing empty vector (EV), APOL1-reference G0, and G1 or G2 KRVs were incubated in media pH 6.8 or 7.4 for 4, 6, or 8 h. Genotype-specific pH effects on mitochondrial length (µm) were assessed using confocal microscopy in live cells and Fiji derivative of ImageJ software with MiNA plug-in. Lower mitochondrial length indicated fragmentation and early dysfunction. RESULTS After 6 h doxycycline (Dox) induction in pH 6.8 media, G2-expressing cells had shorter mitochondria (6.54 ± 0.40) than cells expressing EV (7.65 ± 0.72, p = 0.02) or G0 (7.46 ± 0.31, p = 0.003). After 8 h Dox induction in pH 6.8 media, both G1- (6.21 ± 0.26) and G2-expressing cells had shorter mitochondria (6.46 ± 0.34) than cells expressing EV (7.13 ± 0.32, p = 0.002 and p = 0.008, respectively) or G0 (7.22 ± 0.45, p = 0.003 and p = 0.01, respectively). Mitochondrial length in cells incubated in pH 7.4 media were comparable after 8 h Dox induction regardless of genotype. APOL1 mRNA expression and cell viability were comparable regardless of pH or genotype after 8 h Dox induction. CONCLUSION Acidic pH facilitates early mitochondrial dysfunction induced by APOL1 G1 and G2 KRVs in HEK293 cells. We propose that the acidic kidney interstitium may play a role in APOL1-mediated mitochondrial pathophysiology and nephropathy.
Interactive FORTRAN IV computer programs for the thermodynamic and transport properties of selected cryogens (fluids pack)

The thermodynamic and transport properties of selected cryogens had programmed into a series of computer routines. Input variables are any two of P, rho or T in the single phase regions and either P or T for the saturated liquid or vapor state. The output is pressure, density, temperature, entropy, enthalpy for all of the fluids and in most cases specific heat capacity and speed of sound. Viscosity and thermal conductivity are also given for most of the fluids. The programs are designed for access by remote terminal; however, they have been written in a modular form to allow the user to select either specific fluids or specific properties for particular needs. The program includes properties for hydrogen, helium, neon, nitrogen, oxygen, argon, and methane. The programs include properties for gaseous and liquid states usually from the triple point to some upper limit of pressure and temperature which varies from fluid to fluid.
Psychological Reactivity to Daily Family Experiences During Adolescence: Individual Differences and Developmental Stability.

The current study examined adolescent psychological reactivity to daily family experiences, an important feature of emotion regulation that could have significant implications for psychopathology. A total of 428 Mexican-heritage adolescents (Mage = 15.02 years, range: 13-18 years) completed daily diary checklists for 14 days and again 1 year later. Results revealed that adolescents' family experiences were associated with negative mood, positive mood, and role fulfillment on a daily basis. Only role fulfillment reactivity was stable across 1 year, suggesting instability in individual differences in positive and negative mood reactivity. Sex moderated the relation between positive and negative mood reactivity during the second year of study, with males exhibiting broad psychological reactivity to daily family experiences. However, females who experienced higher negative mood reactivity exhibited less positive mood reactivity. Implications for possible sex differences in depression risk during the high school years are discussed.
E-Governance as an Anti-Corruption StrategyIn India: Successes, Scope and Challenges

The new government in India under the leadership of Prime Minister Narendra Modi has sought to pursue e-Governance as a part of its bigger strategy to improve governance and reduce corruption in the country. There is empirical evidence supporting the efficacy of e-Governance as a tool to reduce corruption. This goal of adopting e-Governance is not a new phenomenon in India as an elaborate National e-Governance Plan (NeGP) was adopted way back in 2006. In spite of being an early starter, India has made little progress in this area. There have been several e-Governance projects in the past, which have been initiated by governments at state/ local levels. However, these projects met with limited success due to the lack of adequate digital infrastructure, lack of long-term planning, lack of continuity due to changing leadership and others. The current initiatives are under a comprehensive plan and motivated leadership, which were lacking in the previous ad-hoc attempts. Yet, there are several challenges faced by the Government of India in implementing e-Governance to reduce corruption. This policy paper aims to assess the scope of recent e- Governance schemes of the Modi government to reduce corruption and make policy recommendations on increasing their efficacy.
Recurrent tension pneumopericardium in a term neonate on high-frequency ventilation: Early recognition and percutaneous management

Background: Air leak syndrome (ALS) can be seen in sick neonates on positive pressure ventilation. Tension pneumopericardium is uncommon, but life-threatening if not promptly identified and treated. Needle decompression can be life-saving. Recurrent tension pneumopericardium is difficult to treat and ideally indicates the placement of a pericardial drain under fluoroscopic guidance. We describe an alternative technique of percutaneous drain placement using intrapericardial saline infusion when the transport of the neonate to a catherization laboratory was not feasible. Clinical Description: A neonate with hyaline membrane disease and persistent pulmonary hypertension of new-born on high-frequency mechanical ventilation developed recurrent tension pneumopericardium that caused hemodynamic compromise. Management: Emergency needle decompression was performed twice. Further recurrence necessitated pericardial drain placement under echocardiographic guidance. Rapid exit of air from the pericardial cavity made advancement of the guidewire challenging. A small amount of sterile saline was injected in the pericardial space to assist advancement following which placement of the pericardial drain was successful. Subsequently, the neonate had an uneventful course and was discharged after 3 weeks. Conclusion: Prompt recognition and management of ALS can be life-saving. Urgent needle decompression and pericardial drain placement can be performed under fluoroscopic (ideally) or echocardiographic guidance by trained personnel. Instillation of saline in the pericardial space may assist with pericardial drain placement.
Luck and Risk

We speak of risk of capture in warfare or crime, of losing in games or fighting, of accident in transport, and so on. Risk is always a matter of potential loss or negativity. To be sure there is also the risk of “losing out”—in not realizing a positivity of some sort—but this too is in the end a sort of negativity.
High Rainfall May Induce Fungal Attack of Hemlock Woolly Adelgid (Hemiptera: Adelgidae) Leading to Regional Decline.

Hemlock woolly adelgid (HWA; Adelges tsugae Annand (Hemiptera: Adelgidae)) is the cause of widespread mortality of Carolina and eastern hemlock (Tsuga caroliniana Engelmann and T. canadensis (L.) Carriere) throughout the eastern United States (U.S.). Since its arrival in the northeastern U.S., HWA has steadily invaded and established throughout eastern hemlock stands. However, in 2018, anecdotal evidence suggested a sharp, widespread HWA decline in the northeastern U.S. following above-average summer and autumn rainfall. To quantify this decline in HWA density and investigate its cause, we surveyed HWA density in hemlock stands from northern Massachusetts to southern Connecticut and analyzed HWA density and summer mortality in Pennsylvania. As native fungal entomopathogens are known to infect HWA in the northeastern U.S. and rainfall facilitates propagation and spread of fungi, we hypothesized high rainfall facilitates fungal infection of aestivating nymphs, leading to a decline in HWA density. We tested this hypothesis by applying a rain-simulation treatment to hemlock branches with existing HWA infestations in western MA. Our results indicate a regional-scale decline and subsequent rebound in HWA density that correlates with 2018 rainfall at each site. Experimental rain treatments resulted in higher proportions of aestivating nymphs with signs of mortality compared to controls. In conjunction with no evidence of increased mortality from extreme winter or summer temperatures, our results demonstrate an indirect relationship between high rainfall and regional HWA decline. This knowledge may lead to better prediction of HWA population dynamics.