cssi/SciSciGPT-SciSciNet huggingface dataset:
Measuring Appropriate Antimicrobial Use: Attempts at Opening the Black Box

Indiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice >70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing.
The significance of folklore for vaccine policy: discarding the deficit model

AbstractThis paper addresses the relevance of medical folklore for vaccine policy intended to increase vaccination uptake. There are two primary claims of this paper: First, that dominant approaches to increasing US vaccination uptake have largely been based on deficient understandings of the root causes of anti-vaccination behavior; and second, that superior approaches to evidence-based policy must enlarge the scope of that evidence base to include crucial findings on belief formation, technical, and risk communication, and the folklore of vaccination. The failure to attend to this evidence results in interventions that are disconnected from the factors actually driving vaccination refusal. The paper describes the deficiencies in dominant approaches, and based on its analysis of the root causes of anti-vaccination behavior recommends superior evidence-based policies that emphasize upstream structural determinants of health behaviors.
IPM for Food and Environmental Security in the Tropics

The global population, by 2050, is estimated to reach nine billion people. Studies show that during the years 2000–2010, worldwide crop production increased at a rate of 23 % while the number of harvested acres increased at only 9 %. In order for supply to meet the growing demand, farmers need to maximize their yield. In fact, crop yields have fallen in many areas because of declining investments in research and infrastructure, as well as increasing water scarcity, land degradation, climate change and biotic stresses (insect pests, weeds, pathogens and vertebrates).
Bacteriology of Electrically Stimulated and Unstimulated Rabbit, Pork, Lamb and Beef Carcasses.

Electrical stimulation of rabbit muscles caused a reduction in count of Pseudomonas putrefaciens and of a Lactobacillus sp. when inoculated muscles were held for 45 min after electrical stimulation. Little if any change in count was detected on rabbit muscles immediately after electrical stimulation and after 20 min of storage. Electrical stimulation (ES) of pork carcasses did not affect the aerobic plate count (APC) of the skin surface. APC of cutaneous trunci from electrically stimulated sides of beef and lamb carcasses were similar to those of muscles from unstimulated sides or carcasses. APC of ground beef and blade steaks fabricated pre-rigor from electrically stimulated sides were often numerically lower after 3 days of storage than those of corresponding samples from unstimulated sides. Differences in APC between conventional and ES samples of ground beef prepared from vacuum packaged top round were significant (P < 0.05) after 6 days of storage. However, none of the other differences in count were...
Combined Drugs and Procedure Trials

Combined drug and device trials are efficient methods in evaluating the clinical efficacy and safety profile of a device or a procedure in patients. The design of such trials is complex and different from the usual randomized controlled trials. Often, the challenge lies in designing the control arm and blinding methods. The sham procedure which is comparable to a placebo drug is sometimes used in the control arm, but there have been ethical questions raised with regard to this strategy, as well as logistical issues. In this chapter, we will discuss fundamentals of trial design, case studies evaluating a combined drug and device trial, challenges associated with such designs, and strategies in limiting biases.
Use Case Diagrams

As you are developing your learning environment, one of the questions that you should ask yourself is “How can I determine what functionality the environment will have?” That is, how will the environment function in response to demands placed upon it? For example, if you are developing an environment that teaches how to play baseball you may wonder what to display to a user who wants to learn about pitching. A series of pictures detailing how to hold the ball for a specific type of pitch? An animation? A series of anecdotal information about how famous major league pitchers held the ball? A combination of all of these? To produce any of these what must happen internally within the environment? How can this be visualized?
In Memoriam: Chet Bowers

I first encountered Chet Bowers in the middle of the 1980s, at an informal debate with Paulo Freire. As a confirmed Freiran, I wondered who this cantankerous pedant was, daring to challenge the gos...
Nanoscale Carbon Modified α-MnO2 Nanowires: Highly Active and Stable Oxygen Reduction Electrocatalysts with Low Carbon Content

Carbon-coated α-MnO2 nanowires (C-MnO2 NWs) were prepared from α-MnO2 NWs by a two-step sucrose coating and pyrolysis method. This method resulted in the formation of a thin, porous, low mass-percentage amorphous carbon coating (<5 nm, ≤1.2 wt % C) on the nanowire with an increase in single-nanowire electronic conductivity of roughly 5 orders of magnitude (α-MnO2, 3.2 × 10–6 S cm–1; C-MnO2, 0.52 S cm–1) and an increase in surface Mn3+ (average oxidation state: α-MnO2, 3.88; C-MnO2, 3.66) while suppressing a phase change to Mn3O4 at high temperature. The enhanced physical and electronic properties of the C-MnO2 NWs—enriched surface Mn3+ and high conductivity—are manifested in the electrocatalytic activity toward the oxygen reduction reaction (ORR), where a 13-fold increase in specific activity (α-MnO2, 0.13 A m–2; C-MnO2, 1.70 A m–2) and 6-fold decrease in charge transfer resistance (α-MnO2, 6.2 kΩ; C-MnO2, 0.9 kΩ) were observed relative to the precursor α-MnO2 NWs. The C-MnO2 NWs, composed of ∼99 wt % MnO...
The role of dopant charge state on defect chemistry and grain growth of doped UO2

Abstract Additives are widely used to control the microstructure of materials via their effect on defect chemistry during sintering. As the primary nuclear fuel, the properties of UO2 are crucial for safe and efficient reactor operation. UO2 has been manipulated by fuel vendors through doping to enhance grain size to provide improved fission gas retention and plasticity. In this work the common phenomenon that governs the effect of Mg, Ti, V, Cr, Mn, and Fe doping of UO2 for enhanced grain growth is revealed, elucidating experimental observations. A combined density functional theory and empirical potential description of defect free energy is used to calculate the doped UO2 defect concentrations as a function of temperature. At high (sintering) temperatures all dopants studied transition to a positively charged interstitial defect. Furthermore, a number of dopants (Ti, V, Cr, and Mn) do so in sufficiently high concentrations to greatly increase the negatively charged uranium vacancy concentration. High uranium vacancy concentrations can enhance grain growth and fission gas diffusion. Mg and Fe also enhance uranium vacancy concentrations but to a lesser extent, while Al has no impact. The enhanced uranium vacancy concentrations, associated with solution of dopants interstitially, is proposed as the mechanism responsible for the enlarged grains seen experimentally in (Ti/V/Cr/Mg)-doped systems. Mn- and V-doped UO2 have been predicted to have higher uranium vacancy concentrations than the more widely used Cr-doped UO2, leading to higher grain growth and fission gas diffusivity.
Alginic Acid-Aided Dispersion of Carbon Nanotubes, Graphene, and Boron Nitride Nanomaterials for Microbial Toxicity Testing

Robust evaluation of potential environmental and health risks of carbonaceous and boron nitride nanomaterials (NMs) is imperative. However, significant agglomeration of pristine carbonaceous and boron nitride NMs due to strong van der Waals forces renders them not suitable for direct toxicity testing in aqueous media. Here, the natural polysaccharide alginic acid (AA) was used as a nontoxic, environmentally relevant dispersant with defined composition to disperse seven types of carbonaceous and boron nitride NMs, including multiwall carbon nanotubes, graphene, boron nitride nanotubes, and hexagonal boron nitride flakes, with various physicochemical characteristics. AA's biocompatibility was confirmed by examining AA effects on viability and growth of two model microorganisms (the protozoan Tetrahymena thermophila and the bacterium Pseudomonas aeruginosa). Using 400 mg·L-1 AA, comparably stable NM (200 mg·L-1) stock dispersions were obtained by 30-min probe ultrasonication. AA non-covalently interacted with NM surfaces and improved the dispersibility of NMs in water. The dispersion stability varied with NM morphology and size rather than chemistry. The optimized dispersion protocol established here can facilitate preparing homogeneous NM dispersions for reliable exposures during microbial toxicity testing, contributing to improved reproducibility of toxicity results.
Ubiquitin-Proteasome System and Plasticity

Regulated proteolysis of substrates that are marked with ubiquitin for degradation by a complex called the proteasome plays an important role in altering synaptic strength. Linkage of ubiquitin to substrates is highly specific and occurs through finely controlled steps. The ubiquitin–proteasome pathway is known to degrade several proteins critical for synaptic plasticity. Also, some of the components of the pathway play a role in inducing changes in synapses that underlie some forms of memory. This article describes workings of the ubiquitin–proteasome pathway and how this pathway contributes to synaptic plasticity.
Competing Discourses of Scientific Identity among Postdoctoral Scholars in the Biomedical Sciences.

In interviews, postdocs from biomedical fields used two primary discourses to describe their scientific identities: bench scientist and principal investigator. These discourses support generating p...
Implications of medical screenings of patients arriving for dental treatment: the results of a comprehensive laboratory screening.

Background The authors conducted medical laboratory screenings in a dental setting to determine the relationships between the laboratory test results and self-reported medical health findings.
Aspects of a Categorial Theory of Binding

A great deal of attention has been devoted in recent discussions to the complementary (or nearly complementary) distribution of reflexive and non-reflexive pronouns within certain ‘local’ domains in languages like English. As is well known, within such domains, non-reflexive pronouns must in some sense not corefer with one another, while reflexives have to have an antecedent. This phenomenon has been called ‘opacity’ and in what follows we shall refer to it with the term ‘anaphoric opacity’ (A-opacity for short) to distinguish it from what logicians call opacity. A-opacity is interesting not only in its own right, but also because of the role it plays in determining what kind of structural considerations are relevant in characterizing admissible types of binding in natural language.
Tolerance, Regulation and Rescue: Dishonoured Women and Abandoned Children in Italy, 1300–1800. By Brian Pullan. (Manchester, UK: Manchester University Press, 2016. Pp. viii, 240. $110.00.)

Early modern societies were deeply concerned with prostitution and extramarital sexual relations, which threatened marriage, family honor, and social order. The prevalence of child abandonment and ...
Dose Adjustments for Accuracy: Ultralow Dose Radiation 3D CBCT for Dental and Orthodontic Application

Cone beam computed tomography (CBCT) is increasingly popular when gathering initial patient imaging records for diagnosis and treatment planning. Although traditional two-dimensional panoramic or cephalometric radiographs can provide sufficient information to perform treatment in most cases, clinicians have become aware of the distortion inherent with these radiographs that can affect angular and linear measurements and, more importantly, tooth location and tooth-bone-jaw relationships.
The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 3, 1984–2008

The dramatic changes in drug metabolism research in the last 25 years are well documented in the publications of the American Society for Pharmacology and Experimental Therapeutics (ASPET). New analytical tools combined with modern molecular biological techniques have provided unprecedented access to the workings of the cell. A field that concentrated on only a handful of primary enzymes now has a list of hundreds in its purview. Genetic variation, environmental impact, and molecular diversity have all come under study in attempts to follow the fate of drugs and chemicals. Examples from ASPET journals will be used to illustrate the dramatic advancements in the field.
Pediatric tropical medicine: The neglected diseases of children

New information released by the Infectious Diseases Society of America (IDSA) and the National Resident Matching Program shows continued declines in interest in pediatric infectious diseases as a career, highlighting that we risk losing a generation of trained experts in pediatric infectious and tropical diseases. The loss paradoxically coincides with updated estimates revealing the disproportionate global health impact of tropical infectious diseases on children. Our objective is to highlight several ominous trends, including our findings that (1) the pediatric tropical disease burdens are huge and do not appear to be declining and (2) fewer trainees are entering the field. Included here are are some key suggestions to address these concerns.
Ultrasound-guided Radiofrequency Lesioning of the Articular Branches of the Femoral Nerve for the Treatment of Chronic Post-arthroplasty Hip Pain.

Background Total hip arthroplasty (THA) is a common surgical treatment for several conditions of the hip. While the majority of patients obtain satisfactory results, many develop chronic post-arthroplasty hip pain that can be difficult to treat. Objective We evaluate the effectiveness of cooled (60°C) radiofrequency lesioning of the articular branches of the femoral nerve (ABFN) as a minimally invasive treatment for patients suffering from chronic post-arthroplasty hip pain. This treatment has never been described previously in this population. Study design Case report. Setting Center for Pain Medicine, Massachusetts General Hospital, Harvard Medical School. Method A 59-year-old woman with long-standing osteoarthritis of the right hip who underwent primary total hip arthroplasty and presented with chronic post-arthroplasty hip pain Intervention: Cooled (60°C) radiofrequency lesioning of the ABFN under ultrasound guidance Outcome Measure: Functional ability and numeric rating scale (NRS) scores at rest and with activity. Results Prior to intervention, the patient reported severe disruption in daily activities, sleep, and relationships; NRS scores at rest and with activity were 4/10 and 10/10, respectively. At 4 weeks following intervention, the patient reported significant improvement in functional ability and NRS scores decreased to 1/10 and 2/10, respectively. At 6 months, the patient's NRS scores at rest and with activity were 0/10 and 1/10, respectively. At 24-month follow-up, the patient continued to endorse significant pain relief with NRS scores at rest and with activity of 0 - 1/10 and 1 - 2/10, respectively. There were no side effects or complications including motor weakness, sensory loss, and neuralgias. Limitations Although the patient obtained good results from the intervention, the description of the study is from a single case report. Further study is necessary to investigate the widespread use of this technique and its outcomes. Conclusions Cooled (60°C) radiofrequency lesioning of the ABFN under ultrasound guidance is both an effective and minimally invasive intervention for chronic post-arthroplasty hip pain. Key words: Radiofrequency lesioning, articular branches, femoral nerve, post-arthoplasty, total hip arthoplasty, hip pain, chronic pain.
Great Oxidation and Lomagundi events linked by deep cycling and enhanced degassing of carbon

For approximately the first 2 billion years of the Earth’s history, atmospheric oxygen levels were extremely low. It was not until at least half a billion years after the evolution of oxygenic photosynthesis, perhaps as early as 3 billion years ago, that oxygen rose to appreciable levels during the Great Oxidation Event. Shortly after, marine carbonates underwent a large positive spike in carbon isotope ratios known as the Lomagundi event. The mechanisms responsible for the Great Oxidation and Lomagundi events remain debated. Using a carbon–oxygen box model that tracks the Earth’s surface and interior carbon fluxes and reservoirs, while also tracking carbon isotopes and atmospheric oxygen levels, we demonstrate that about 2.5 billion years ago a tectonic transition that resulted in increased volcanic CO2 emissions could have led to increased deposition of both carbonates and organic carbon (organic C) via enhanced weathering and nutrient delivery to oceans. Increased burial of carbonates and organic C would have allowed the accumulation of atmospheric oxygen while also increasing the delivery of carbon to subduction zones. Coupled with preferential release of carbonates at arc volcanoes and deep recycling of organic C to ocean island volcanoes, we find that such a tectonic transition can simultaneously explain the Great Oxidation and Lomagundi events without any change in the fraction of carbon buried as organic C relative to carbonate, which is often invoked to explain carbon isotope excursions. Carbon cycling in the mantle may be a common mechanism that links the Great Oxidation Event and the subsequent Lomagundi increase in carbon isotope values, according to a box model that accounts for carbon and oxygen fluxes and reservoirs.
Refactoring courseware to engage undergraduates in computational thinking across boundaries

There is a growing need to develop courses that demonstrate the articulations between computer science and an array of computing-dependent fields. This hands-on workshop will introduce participants to a model for students and faculty to collaborate across disciplines and with a community organization to develop computational solutions to address complex real-world problems. The strength of this model lies in leveraging existing courses and courseware rather developing new ones. Participants will learn how to develop at their own institutions, similar collaborations that involve computer science, a computing-dependent discipline and a community partner. We will provide access to materials that participants can adapt for their own courses to redesign existing courseware: best practices; pitfalls to be avoided and how to deal with them; instructional materials developed for the courses used in our project; assessment and evaluation instruments developed for the courses used in our project; instructions on adapting the assessment and evaluation instruments for other courses; instructions, documentation, and configuration scripts for using the technology needed for such collaborations. The presenters will share experiences and lead a brainstorming session to design strategies for dealing with challenges and for gaining institutional support for such collaborations. Participants are encouraged to bring their laptops to work on, but this is not required.
Association of Neighborhood Measures of Social Determinants of Health With Breast, Cervical, and Colorectal Cancer Screening Rates in the US Midwest.

Importance Despite advances in cancer treatment and cancer-related outcomes, disparities in cancer mortality remain. Lower rates of cancer prevention screening and consequent delays in diagnosis may exacerbate these disparities. Better understanding of the association between area-level social determinants of health and cancer screening may be helpful to increase screening rates. Objective To examine the association between area deprivation, rurality, and screening for breast, cervical, and colorectal cancer in patients from an integrated health care delivery system in 3 US Midwest states (Minnesota, Iowa, and Wisconsin). Design, Setting, and Participants In this cross-sectional study of adults receiving primary care at 75 primary care practices in Minnesota, Iowa, and Wisconsin, rates of recommended breast, cervical, and colorectal cancer screening completion were ascertained using electronic health records between July 1, 2016, and June 30, 2017. The area deprivation index (ADI) is a composite measure of social determinants of health composed of 17 US Census indicators and was calculated for all census block groups in Minnesota, Iowa, and Wisconsin (11 230 census block groups). Rurality was defined at the zip code level. Using multivariable logistic regression, this study examined the association between the ADI, rurality, and completion of cancer screening after adjusting for age, Charlson Comorbidity Index, race, and sex (for colorectal cancer only). Main Outcomes and Measures Completion of recommended breast, cervical, and colorectal cancer screening. Results The study cohorts were composed of 78 302 patients eligible for breast cancer screening (mean [SD] age, 61.8 [7.1] years), 126 731 patients eligible for cervical cancer screening (mean [SD] age, 42.6 [13.2] years), and 145 550 patients eligible for colorectal cancer screening (mean [SD] age, 62.4 [7.0] years; 52.9% [77 048 of 145 550] female). The odds of completing recommended screening were decreased for individuals living in the most deprived (highest ADI) census block group quintile compared with the least deprived (lowest ADI) quintile: the odds ratios were 0.51 (95% CI, 0.46-0.57) for breast cancer, 0.58 (95% CI, 0.54-0.62) for cervical cancer, and 0.57 (95% CI, 0.53-0.61) for colorectal cancer. Individuals living in rural areas compared with urban areas also had lower rates of cancer screening: the odds ratios were 0.76 (95% CI, 0.72-0.79) for breast cancer, 0.81 (95% CI, 0.79-0.83) for cervical cancer, and 0.93 (95% CI, 0.91-0.96) for colorectal cancer. Conclusions and Relevance Individuals living in areas of greater deprivation and rurality had lower rates of recommended cancer screening, signaling the need for effective intervention strategies that may include improved community partnerships and patient engagement to enhance access to screening in highest-risk populations.
Nanoparticle albumin-bound paclitaxel with cetuximab and carboplatin as first-line therapy for recurrent or metastatic head and neck cancer: A single-arm, multicenter, phase 2 trial.

Abstract Objectives Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum). Materials and methods Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS). Results Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1–7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7–23). The median OS was 17.8 months (95% CI, 8.5–21.7) for all patients, and 19.8 months (95% CI, 10.9–22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6–23.3) for HPV-unrelated HNSCC. Conclusion Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.
Effectiveness of Electroacupuncture or Auricular Acupuncture vs Usual Care for Chronic Musculoskeletal Pain Among Cancer Survivors: The PEACE Randomized Clinical Trial

Importance The opioid crisis creates challenges for cancer pain management. Acupuncture confers clinical benefits for chronic nonmalignant pain, but its effectiveness in cancer survivors remains uncertain. Objective To determine the effectiveness of electroacupuncture or auricular acupuncture for chronic musculoskeletal pain in cancer survivors. Design, Setting, and Participants The Personalized Electroacupuncture vs Auricular Acupuncture Comparative Effectiveness (PEACE) trial is a randomized clinical trial that was conducted from March 2017 to October 2019 (follow-up completed April 2020) across an urban academic cancer center and 5 suburban sites in New York and New Jersey. Study statisticians were blinded to treatment assignments. The 360 adults included in the study had a prior cancer diagnosis but no current evidence of disease, reported musculoskeletal pain for at least 3 months, and self-reported pain intensity on the Brief Pain Inventory (BPI) ranging from 0 (no pain) to 10 (worst pain imaginable). Interventions Patients were randomized 2:2:1 to electroacupuncture (n = 145), auricular acupuncture (n = 143), or usual care (n = 72). Intervention groups received 10 weekly sessions of electroacupuncture or auricular acupuncture. Ten acupuncture sessions were offered to the usual care group from weeks 12 through 24. Main Outcomes and Measures The primary outcome was change in average pain severity score on the BPI from baseline to week 12. Using a gatekeeping multiple-comparison procedure, electroacupuncture and auricular acupuncture were compared with usual care using a linear mixed model. Noninferiority of auricular acupuncture to electroacupuncture was tested if both interventions were superior to usual care. Results Among 360 cancer survivors (mean [SD] age, 62.1 [12.7] years; mean [SD] baseline BPI score, 5.2 [1.7] points; 251 [69.7%] women; and 88 [24.4%] non-White), 340 (94.4%) completed the primary end point. Compared with usual care, electroacupuncture reduced pain severity by 1.9 points (97.5% CI, 1.4-2.4 points;P Conclusions and Relevance In this randomized clinical trial among cancer survivors with chronic musculoskeletal pain, electroacupuncture and auricular acupuncture produced greater pain reduction than usual care. However, auricular acupuncture did not demonstrate noninferiority to electroacupuncture, and patients receiving it had more adverse events. Trial Registration ClinicalTrials.gov Identifier:NCT02979574
The semicircular law of free probability as noncommutative multivariable operator theory

In this paper, we study semicircular elements induced by connected finite directed graphs. It is shown that if the graph groupoid $$\mathbb {G}$$ of a given graph G contains at least one loop finite path, then it induces a semicircular element under suitable representations of $$\mathbb {G}$$ . As application, if a graph G is fractal (or, satisfies the fractal property) in a certain sense, then it automatically generates infinitely many semicircular elements.
Halving the cost of quantum multiplexed rotations.

We improve the number of $T$ gates needed for a $b$-bit approximation of a multiplexed quantum gate with $c$ controls applying $n$ single-qubit arbitrary phase rotations from $4n b+\mathcal{O}(\sqrt{cn b})$ to $2n b+\mathcal{O}(\sqrt{cn b})$, and reduce the number of qubits needed by up to a factor of two. This generic quantum circuit primitive is found in many quantum algorithms, and our results roughly halve the cost of state-of-art electronic structure simulations based on qubitization of double-factorized or tensor-hypercontracted representations. We achieve this by extending recent ideas on stochastic compilation of quantum circuits to classical data and discuss space-time trade-offs and concentration of measure in its implementation.
The plaque-forming-cell (PFC) response of human blood lymphocytes. II. PFC response by mixtures of allogeneic lymphocytes cultured with formalin-treated staphylococci.

Abstract Formalin-treated Staphylococci (FSA) induce anti-SRBC PFC in cultures of human lymphocytes. Regulation of the PFC response induced by FSA in cultures containing lymphocytes from two allogeneic donors was studied. The PFC response observed in such cocultures could not be predicted from the responses of lymphocytes from the two donors cultured individually. The PFC response of approximately one half the cocultures was less than expected. The remaining cocultures generated more PFC than expected. The depression or augmentation in the PFC response which was observed in cocultures was reproducible when lymphocytes from the same pair of donors were cocultured. Cocultures containing lymphocytes from identical twins generated the expected PFC response. The data suggest that suppressor or helper activity may be generated during a “two-way” allogeneic mixed lymphocyte reaction (MLR). Much less deviation from the expected PFC response was observed during a “one-way” MLR. Anti-Ia antiserum treatment of either donor's lymphocyte population tended to eliminate the deviation from the expected PFC response in coculture. The data suggest that a feedback loop, involving cells from both donors, may be operating in the “two-way” MLR, which leads to the generation of suppressor or helper activity.
Comorbidity Assessment in Skin Cancer Patients: A Pilot Study Comparing Medical Interview with a Patient-Reported Questionnaire

Background. Comorbidities are conditions that occur simultaneously but independently of another disorder. Among skin cancer patients, comorbidities are common and may influence management. Objective. We compared comorbidity assessment by traditional medical interview (MI) and by standardized patient-reported questionnaire based on the Adult Comorbidity Evaluation-27 (ACE-27). Methods. Between September 2011 and October 2013, skin cancer patients underwent prospective comorbidity assessment by a Mohs surgeon (MI) and a radiation oncologist (using a standardized patient-reported questionnaire based on the ACE-27, the PRACE-27). Comorbidities were identified and graded according to the ACE-27 and compared for agreement. Results. Forty-four patients were evaluated. MI and PRACE-27 identified comorbidities in 79.5% and 88.6% (p = 0.12) of patients, respectively. Among 27 comorbid ailments, the MI identified 9.9% as being present, while the PRACE-27 identified 12.5%. When there were discordant observations, PRACE-27 was more likely than MI to identify the comorbidity (OR = 5.4, 95% CI = 2.4–14.4, p < 0.001). Overall comorbidity scores were moderate or severe in 43.2% (MI) versus 59.1% (PRACE-27) (p = 0.016). Limitations. Small sample size from a single institution. Conclusion. Comorbidities are common in skin cancer patients, and a standardized questionnaire may better identify and grade them. More accurate comorbidity assessments may help guide skin cancer management.
Synthesis and Characterization of Metallo-Organic Conducting Materials With Tetraazannulenes

Intensive research activities in university, industrial and national research laboratories on mixed valence organic and metallo organic compounds have led to insights into the chemical and structural features which determine such physical properties as magnetic behavior and electrical conductivities.1 The aim of the research Is the production of new materials with properties which may be exploited in technological applications, with the expected dividends being the discovery of new phenomena, the invention of new experimental methods, and the development of new theoretical models. The recent observation2 of superconductivity in bis(tetra- methyltetraselenafulvalene)hexafluorophosphate, (TMTSF)2PF6, provides an excellent example of the successes which may be expected as this research area is expanded and developed.
Modification of the human fetal phagocytic response by promethazine hydrochloride

Abstract Anti-Rh (D) antibody has been demonstrated to be nonhemolytic to Rh-positive red blood cells. However, fetal macrophages in vitro have been shown to bind Rh-positive red blood cells which are coated with this antibody. Promethazine hydrochloride inhibits the ability of fetal macrophages to bind Rh-positive red blood cells in vitro. These data suggest macrophage-mediated red blood cell destruction in erythroblastosis fetalis and offer one explanation for the success of promethazine hydrochloride in ameliorating the effects of this disease.
Overuse of Cardiovascular Services Evidence, Causes, and Opportunities for Reform

Cardiovascular disease is the leading cause of death in the United States and constitutes 17% of overall national health expenditures,1 with noninvasive testing contributing much of the cost growth in recent years.2,3 Cardiovascular medicine has long been at the forefront of evidence-based practice, with arguably the longest-standing and most comprehensive array of efforts to measure risk factors and outcomes, to analyze the clinical effectiveness and cost-effectiveness of treatment options, and to formulate practice recommendations.4,5 Professional societies for cardiovascular medicine have established health policy statements,6 national databases on quality,7 clinical guidelines,8 and appropriate use criteria9 (AUC) for high-cost cardiovascular services (Table 1). More recently, the profession has taken steps to right-size cardiovascular services by defining the problem of overuse and underuse and working to shape clinical and policy interventions that improve quality and access and reduce unnecessary cost.10 For example, the American College of Cardiology Wisconsin and Florida chapters recently received a $15.8 million Centers for Medicare & Medicaid Innovation grant to pilot a comprehensive cardiovascular program to improve quality and to reduce cost of cardiovascular care through better data transparency, patient engagement, and shared decision making (SDM). View this table: Table 1. Summary of Initiatives to Identify and Reduce Overuse in Cardiovascular Medicine Despite efforts to improve the value of cardiovascular care, there is a concern that significant overuse of cardiovascular services persists in the United States. The published evidence of overuse is necessarily incomplete for 2 key reasons. First, for many tests and treatments, there is a lack of agreement on the basic definition of overuse. The Institute of Medicine originally defined overuse as occurring when “a health care service is provided under circumstances in which its potential for harm exceeds the possible benefit”.11 Others have since expanded the notion of …
Restitution of frog gastric mucosa in vitro: effect of basic fibroblast growth factor.

Abstract Background: Rapid re-epithelialization after superficial gastric mucosal injury is caused by migration of persisting viable epithelial cells. Basic fibroblast growth factor (bFGF) has been reported to enhance the healing of experimental duodenal ulcer, but its mode of action is unclear. The present experiments examine whether an effect of bFGF on restitution might contribute to such healing. Methods: Paired halves of bullfrog fundic gastric mucosa in Ussing chambers were injured by luminal exposure to 1 mol/L NaCl for 10 minutes. Results: Luminal protamine or suramin, both known to interfere with endogenous bFGF, significantly inhibited electrophysiological recovery at neutral luminal pH (pH L ). Luminal sucrose octasulfate, which prevents acid degradation of bFGF, and an exogenous, acid-resistant form of bFGF allowed electrophysiological recovery at a pH L of 3.0 that completely prevented restitution in control tissues. Electrophysiological recovery correlated well with morphological restitution. The presence of endogenous bFGF in normal and restituting bullfrog mucosa was confirmed by positive staining with a monoclonal antibody. Conclusions: It is concluded that rapid epithelial repair after surface injury is at least in part mediated by bFGF.
Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems.

Abstract Background and purpose CLR1404 is a phospholipid ether that exhibits selective uptake and retention in malignant tissues. Radiolabeled CLR1404 enables tumor-specific positron-emission tomography (PET) imaging ( 124 I) and targeted delivery of ionizing radiation ( 131 I). Here we describe the first preclinical studies of this diapeutic molecule in head and neck cancer (HNC) models. Material and methods Tumor-selective distribution of 124 I-CLR1404 and therapeutic efficacy of 131 I-CLR1404 were tested in HNC cell lines and patient-derived xenograft tumor models. Monte Carlo dose calculations and 124 I-CLR1404 PET/CT imaging were used to examine 131 I-CLR1404 dosimetry in preclinical HNC tumor models. Results HNC tumor xenograft studies including patient-derived xenografts demonstrate tumor-selective uptake and retention of 124 I-CLR1404 resulting in a model of highly conformal dose distribution for 131 I-CLR1404. We observe dose-dependent response to 131 I-CLR1404 with respect to HNC tumor xenograft growth inhibition and this effect is maintained together with external beam radiation. Conclusions We confirm the utility of CLR1404 for tumor imaging and treatment of HNC. This promising agent warrants further investigation in a developing phase I trial combining 131 I-CLR1404 with reduced-dose external beam radiation in patients with loco-regionally recurrent HNC.
Education for Deliberative Character: The Problem of Persistent Disagreement and Religious Individuals

As Amy Gutmann and Dennis Thompson’s Democracy and Disagreement underscores, value pluralism is endemic to democratic-decision making. Citizens’ persistent moral disagreement represents one of democracy’s thorniest problems: as a matter of stability, the democratic state needs a process by which to decide public policy issues across deep differences, but democracy’s commitment to individual liberty limits the means by which the state may manage citizens’ moral disagreement. To improve upon preference aggregation theories that may repeatedly marginalize dissenting minority viewpoints, proponents of deliberative democracy place ex ante constraints on the deliberative process to safeguard individual liberty. Yet, as Joshua Cohen notes, these preconditions for public deliberation in effect remove some issues from the deliberation table: “the richer the requirements for institutionalizing free public deliberation, the larger the range of issues that...form the background framework of public deliberation rather than its subject matter.” Taking Cohen’s observation as a starting point, I will focus on Gutmann and Thompson’s theory to consider the following question: if their ex ante constraints on deliberation move certain issues from the public agenda to the background, what impositions might follow for religious groups in this context if there is less open to public debate?
Regression of experimental oral carcinomas by local injection of β‐carotene and canthaxanthin

Regression of 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermoid carcinomas of hamster buccal pouch was accomplished by local injections of beta-carotene and canthaxanthin. One-hundred male hamsters (2-3 months old) were divided into five groups of 20 animals. All animals had the right buccal pouches painted three times weekly for 14 weeks with a 0.5% solution of DMBA in mineral oil, at which time all animals exhibited gross tumors of variable size and number. Group 1 animals were then injected locally into the right buccal pouch twice weekly for 4 weeks with 250 micrograms-carotene in 0.1 ml minimal essential medium (MEM) per injection. Group 2 animals were similarly injected with 250 micrograms canthaxanthin in 0.1 ml MEM. Group 3 animals were similarly injected with 250 micrograms 13-cis-retinoic acid in 0.1 ml MEM. Group 4 animals were injected only with MEM; Group 5 animals were untreated controls. Animals were killed in a carbon dioxide chamber, and buccal pouches were photographed. Tumors were counted and measured. Tumor burden in each group was compared, and statistical significance between groups was recorded. beta-Carotene was more effective than canthaxanthin in tumor regression. 13-cis-Retinoic acid had no effect in this system.
Anomaly and quantum corrections to solitons in two-dimensional theories with minimal supersymmetry

We reexamine the issue of the soliton mass in two-dimensional models with $\mathcal{N}=1$ supersymmetry. The superalgebra has a central extension, and at the classical level the soliton solution preserves 1/2 of supersymmetry which is equivalent to BPS saturation. We prove that the property of BPS saturation, i.e. the equality of the soliton mass to the central charge, remains intact at the quantum level in all orders of the weak coupling expansion. Our key finding is an anomaly in the expression for the central charge. The classical central charge, equal to the jump of the superpotential, is amended by an anomalous term proportional to the second derivative of the superpotential. The anomaly is established by various methods in explicit one-loop calculations. We argue that this one-loop result is not affected by higher orders. We discuss in detail how the impact of the boundary conditions can be untangled from the soliton mass calculation. In particular, the soliton profile and the energy distribution are found at one loop. A ``supersymmetry'' in the soliton mass calculations in the non-supersymmetric models is observed.
Behavioural considerations in veterinary practice

ABSTRACT:This article explores the importance of behavioural considerations in veterinary practice and identifies appropriate methods to find and employ a suitably qualified behaviourist. Following this it discusses the role of the behaviourist in practice and identifies easily implementable, small changes that can be made to increase behavioural awareness and explains the benefit of these in relation to the practice, owner and animal.
Requirements for bursting pacemaker potential activity in molluscan neurones.

THE mechanisms underlying endogenous rhythmical electrical activity of some molluscan neurones are not completely understood. Their membranes have several significant properties: (1) rapidly inactivating Na+ and Ca2+ conductances associated with spikes1–5; (2) voltage-dependent K+ conductances (GK) (delayed1,6 and anomalous rectification3,7); and (3) a negative slope region (NSR) in the steady-state, voltage clamp current–voltage (I–V) curve8,9. Although (1) is unnecessary for bursting pacemaker potentials (BPPs)4 the relationship of (2) and (3) to the generation of BPPs has not been elucidated completely. We present here evidence that the NSR of the I–V curve is due to a voltage-dependent Na+ conductance (GNa) which inactivates incompletely and that BPPs depend on this conductance coupled to cyclical changes in GK.
Some comments on the accuracy and the validity of a cue variable

Abstract The concepts of cue accuracy and cue validity are defined in the context of multiple-alternative tasks using the correlational model. The interdependence of cue validity (ϱXY) and cue inaccuracy (σD2) are illustrated and the importance of cue variance (σX2) is demonstrated. Conditions under which σD2 is at a minimum are indicated and possible tradeoff decisions between accuracy and validity are commented upon.
Extracellular SOD-Derived H2O2 Promotes VEGF Signaling in Caveolae/Lipid Rafts and Post-Ischemic Angiogenesis in Mice

Reactive oxygen species (ROS), in particular, H(2)O(2), is essential for full activation of VEGF receptor2 (VEGFR2) signaling involved in endothelial cell (EC) proliferation and migration. Extracellular superoxide dismutase (ecSOD) is a major secreted extracellular enzyme that catalyzes the dismutation of superoxide to H(2)O(2), and anchors to EC surface through heparin-binding domain (HBD). Mice lacking ecSOD show impaired postnatal angiogenesis. However, it is unknown whether ecSOD-derived H(2)O(2) regulates VEGF signaling. Here we show that gene transfer of ecSOD, but not ecSOD lacking HBD (ecSOD-DeltaHBD), increases H(2)O(2) levels in adductor muscle of mice, and promotes angiogenesis after hindlimb ischemia. Mice lacking ecSOD show reduction of H(2)O(2) in non-ischemic and ischemic limbs. In vitro, overexpression of ecSOD, but not ecSOD-DeltaHBD, in cultured medium in ECs enhances VEGF-induced tyrosine phosphorylation of VEGFR2 (VEGFR2-pY), which is prevented by short-term pretreatment with catalase that scavenges extracellular H(2)O(2). Either exogenous H(2)O(2) (<500 microM), which is diffusible, or nitric oxide donor has no effect on VEGF-induced VEGFR2-pY. These suggest that ecSOD binding to ECs via HBD is required for localized generation of extracellular H(2)O(2) to regulate VEGFR2-pY. Mechanistically, VEGF-induced VEGFR2-pY in caveolae/lipid rafts, but non-lipid rafts, is enhanced by ecSOD, which localizes at lipid rafts via HBD. One of the targets of ROS is protein tyrosine phosphatases (PTPs). ecSOD induces oxidation and inactivation of both PTP1B and DEP1, which negatively regulates VEGFR2-pY, in caveolae/lipid rafts, but not non-lipid rafts. Disruption of caveolae/lipid rafts, or PTPs inhibitor orthovanadate, or siRNAs for PTP1B and DEP1 enhances VEGF-induced VEGFR2-pY, which prevents ecSOD-induced effect. Functionally, ecSOD promotes VEGF-stimulated EC migration and proliferation. In summary, extracellular H(2)O(2) generated by ecSOD localized at caveolae/lipid rafts via HBD promotes VEGFR2 signaling via oxidative inactivation of PTPs in these microdomains. Thus, ecSOD is a potential therapeutic target for angiogenesis-dependent cardiovascular diseases.
The utilization of an iPad for increasing work-related behaviors in adults with disabilities

The purpose of this study was to investigate the effectiveness of an iPad to increase work related behaviors for one adult with disabilities in a vocational setting. A multiple baseline across behaviors single subject research design was used to determine if an iPad helped to increase independence in three identified behaviors, which included setting up a workstation for maximum efficiency, managing time accurately, and identifying faces and names of coworkers. Results indicate that the subject was able to use the iPad to achieve independence in the work setting, thus making him less reliant on site staff and his vocational trainer and making him potentially employable. The results of the study prove to be important because little research has been conducted on how technological devices such as the iPad can help individuals with disabilities in the vocational setting.