cssi/SciSciGPT-SciSciNet huggingface dataset:
Improving understanding in the research informed consent process: a systematic review of 54 interventions tested in randomized control trials.

Obtaining informed consent is a cornerstone of biomedical research, yet participants comprehension of presented information is often low. The most effective interventions to improve understanding rates have not been identified. To systematically analyze the random controlled trials testing interventions to research informed consent process. The primary outcome of interest was quantitative rates of participant understanding; secondary outcomes were rates of information retention, satisfaction, and accrual. Interventional categories included multimedia, enhanced consent documents, extended discussions, test/feedback quizzes, and miscellaneous methods. The search spanned from database inception through September 2010. It was run on Ovid MEDLINE, Ovid EMBASE, Ovid CINAHL, Ovid PsycInfo and Cochrane CENTRAL, ISI Web of Science and Scopus. Five reviewers working independently and in duplicate screened full abstract text to determine eligibility. We included only RCTs. 39 out of 1523 articles fulfilled review criteria (2.6%), with a total of 54 interventions. A data extraction form was created in Distiller, an online reference management system, through an iterative process. One author collected data on study design, population, demographics, intervention, and analytical technique. Meta-analysis was possible on 22 interventions: multimedia, enhanced form, and extended discussion categories; all 54 interventions were assessed by review. Meta-analysis of multimedia approaches was associated with a non-significant increase in understanding scores (SMD 0.30, 95% CI, -0.23 to 0.84); enhanced consent form, with significant increase (SMD 1.73, 95% CI, 0.99 to 2.47); and extended discussion, with significant increase (SMD 0.53, 95% CI, 0.21 to 0.84). By review, 31% of multimedia interventions showed significant improvement in understanding; 41% for enhanced consent form; 50% for extended discussion; 33% for test/feedback; and 29% for miscellaneous.Multiple sources of variation existed between included studies: control processes, the presence of a human proctor, real vs. simulated protocol, and assessment formats. Enhanced consent forms and extended discussions were most effective in improving participant understanding. Interventions of all categories had no negative impact on participant satisfaction or study accrual. Identification of best practices for studies of informed consent interventions would aid future systematic comparisons.
Clinical review of the 'Snodgrass' hypospadias repair.

Background: Snodgrass first described the tubularized, incised plate (TIP) urethroplasty for distal hypospadias repair in 1994 based on the concept of hingeing the incised urethral plate. The use of this technique allows a vertically orientated glanular meatus to be produced. A retrospective review of patients who had this procedure for the primary repair of distal hypospadias at New Children’s Hospital was performed to objectively assess the cosmetic and functional outcomes of this technique. Methods: All patients having a TIP urethroplasty for the primary repair of distal hypospadias between 1996 and 1998 were requested to attend for review in an independent clinic. The parents were interviewed and the patient was examined to determine meatal location, meatal size, glanular configuration, urinary stream, straightness of erections, cosmesis, and the presence or absence of cutaneous sinus tracts or a urethral fistula. Results: Sixty patients were identified. Forty-nine were reviewed in person, 10 were reviewed by telephone and one could not be traced. The median age at surgery was 13 months (range: 6–144 months), with a median follow up of 27 months (range: 2–33 months). A glanular meatus was achieved in 57 patients (97%) and a conical glanular configuration was achieved in 58 patients (98%). The urinary stream and erections were straight in 54 (89%) and 58 patients (98%), respectively. Suture sinus tracts were present in 14 (24%) patients. Six patients (10%) developed a urethral fistula and three (5%) developed meatal stenosis. A good or satisfactory final cosmetic and functional result was achieved in 58 patients (98%). Conclusions: The results of TIP urethroplasty are satisfactory at New Children’s Hospital with the benefit of a cosmetic final outcome similar to a circumcised penis.
BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3

Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways. Cullins are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex. The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins. F-box proteins bind Skp1 through the F-box motif, and substrates by means of carboxy-terminal protein interaction domains. Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide.
High speed travelling wave carrier depletion silicon Mach-Zehnder modulator

We present the first demonstration of a travelling wave carrier depletion Mach-Zehnder modulator impedance matched to 50 Ω. This device has a bandwidth of 24 GHz and a halfwave voltage length product of 0.7 V-cm, placing it among the best in its class.
Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis

Transient attacks of weakness in hypokalaemic periodic paralysis are caused by reduced fibre excitability from paradoxical depolarization of the resting potential in low potassium. Mutations of calcium channel and sodium channel genes have been identified as the underlying molecular defects that cause instability of the resting potential. Despite these scientific advances, therapeutic options remain limited. In a mouse model of hypokalaemic periodic paralysis from a sodium channel mutation (NaV1.4-R669H), we recently showed that inhibition of chloride influx with bumetanide reduced the susceptibility to attacks of weakness, in vitro. The R528H mutation in the calcium channel gene (CACNA1S encoding CaV1.1) is the most common cause of hypokalaemic periodic paralysis. We developed a CaV1.1-R528H knock-in mouse model of hypokalaemic periodic paralysis and show herein that bumetanide protects against both muscle weakness from low K+ challenge in vitro and loss of muscle excitability in vivo from a glucose plus insulin infusion. This work demonstrates the critical role of the chloride gradient in modulating the susceptibility to ictal weakness and establishes bumetanide as a potential therapy for hypokalaemic periodic paralysis arising from either NaV1.4 or CaV1.1 mutations.
Physician specialty and variation in carotid revascularization technique selected for Medicare patients

Objective Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA) for select patients with carotid atherosclerosis. We hypothesized that the choice of CAS vs CEA varies as a function of treating physician specialty, which would result in regional variation in the relative use of these treatment types. Methods We used Medicare claims (2002-2010) to calculate annual rates of CAS and CEA and examined changes by procedure type over time. To assess regional preferences surrounding CAS, we calculated the proportion of revascularizations by CAS, across hospital referral regions, defined according to the Dartmouth Atlas of Healthcare . We then examined relationships between patient factors, physician specialty, and regional use of CAS. Results The annual number of all carotid revascularization procedures decreased by 30% from 2002 to 2010 (3.2 to 2.3 per 1000; P = .005). Whereas rates of CEA declined by 35% during these 8 years (3.0 to 1.9 per 1000; P P = .014). Variation in utilization of carotid revascularization varied across the Unites States, with some regions performing as few as 0.7 carotid procedure per 1000 beneficiaries (Honolulu, Hawaii) and others performing nearly 8 times as many (5.3 per 1000 in Houma, La). Variation in procedure type (CEA vs CAS) was evident as well, as the proportion of carotid revascularization procedures that were constituted by CAS varied from 0% (Casper, Wyo, and Meridian, Miss) to 53% (Bend, Ore). The majority of CAS procedures were performed by cardiologists (49% of all CAS cases), who doubled their rates of CAS during the study period from 0.07 per 1000 in 2002 to 0.15 per 1000 in 2010. Conclusions Variation in rates of carotid revascularization exists. Whereas rates of carotid revascularization have declined by more than 30% in recent years, utilization of CAS has increased. The proportion of all carotid revascularization procedures performed as CAS varies markedly by geographic region, and regions with the highest proportion of cardiologists perform the most CAS procedures. Evidence-based guidelines for carotid revascularization will require a multidisciplinary approach to ensure uniform adoption across specialties that care for patients with carotid artery disease.
Angler Activist: Kenneth Reid, the Izaak Walton League, and the Crusade for Federal Water Pollution Control

The Commonwealth of Pennsylvania is not generally associated with environmental activism, but the state has actually made enormous contribu tions to the structure of American environmental policy and attitudes. In the 1930s and 1940s, national debates over the role of the United States govern ment in water quality issues focused on Pennsylvania problems. Pennsylvania native Kenneth Reid, the vigorous leader of the Izaak Walton League of America, advocated a shift from local to national pollution authority?a shift that has sparked debate across the country for the balance of the century. The Izaak Walton League, a national sportsman's club with many Penn sylvania chapters, alerted its members and the public to the destructive power of water pollution and agitated for solutions. Reid served as the organization's voice, promoting national pollution control. As editor and foremost writer for the League and other conservationist publications, Reid generated broad and influential grassroots support for federal authority and pollution abatement programs. In addition to his writing, Reid served on state water pollution boards, organized national pollution conferences, was among the first to use radio for resource issue discussions, and clashed with the country's highest political leadership over policy. Although he is not recognized as a prominent environmental activist?his declining health and death in 1956 prevented him from assuming the role of an environmental elder statesman during the 1960s and 1970s?Reid is nonetheless a person worthy of recognition in Penn sylvania as well as in the nation's conservation history. Kenneth Alexander Reid encountered the destructiveness of stream pol lution early in life. Born in 1895 at Connellsville, Reid grew up fishing along the Youghiogheny River and its tributaries. He witnessed first-hand the de struction of several area streams, especially on the Indian Creek drainage where acidic water from local coal mines ruined one of the state's most pristine recre ation areas. After graduating from Yale (1917) and serving in the army air corps as a gunnery pilot, Reid operated an auto-supply business in Fort Worth,
Measuring Functional Change in Children With Acquired Brain Injury (ABI): Comparison of Generic and ABI-Specific Scales Using the Pediatric Evaluation of Disability Inventory (PEDI)

Background and Purpose. The Pediatric Evaluation of Disability Inventory (PEDI) subscales are hierarchic in nature, with item placements within each subscale reflecting the general order of skill attainment in children without disabilities. The purpose of this study was to determine whether a hierarchical subscale developed in this study for children with acquired brain injuries (ABIs) corresponds to the generic PEDI subscales, and, if not, whether condition-specific (ABI-specific) PEDI subscales are more sensitive for measuring change. Subjects. Eighty-seven children and adolescents (mean age=9.2 years, SD=5.2, range=1–20) with ABI during inpatient rehabilitation admissions were included. Methods. Data were collected by retrospective chart review. Rasch one-parameter analyses were conducted to construct the ABI-specific PEDI scale focusing on the Mobility and Self-care domains (content areas) only. Each domain consists of a Functional Skills subscale and a Caregiver Assistance subscale. Thus, in all, 4 scales were constructed within the ABI-specific PEDI scale. Differences in item hierarchies and sensitivity between generic and ABI-specific PEDI subscales for each domain were then examined. Results. Both generic and ABI-specific PEDI scales were sensitive for measuring functional changes during inpatient rehabilitation hospitalization. Even though the generic and ABI-specific item hierarchies differed substantially, only one of the 4 ABI-specific PEDI subscales (Caregiver Assistance Self-care subscale) was more sensitive for measuring change than the generic PEDI scale. Discussion and Conclusion. The ABI-specific scales added relatively little improvement in sensitivity compared with the generic PEDI scales of the Mobility and Self-care domains. Thus, for group analyses, the authors recommend use of the generic PEDI subscales for children with ABI. Future work with ABI-specific subscales may improve the physical therapist's ability to describe an individual's pattern of functional recovery.
c-ets-2 and the mitogenic signal pathway.

The feature that defines a cancer cell is its ability to propagate under conditions that typically inhibit the growth of the normal cell. In cells where the genetic constitution remains unaltered, restraints on growth are imposed by regulatory activities that take place at the cell surface. These activities, which may be due to either cell contact or a decrease in the production and availability of growth factors, are communicated through the cytoplasm to the nucleus, thus regulating the synthesis of messenger RNAs essential for the unique proteins needed to initiate subsequent DNA synthesis and mitosis. Cells can be relieved of this barrier to mitosis by cell dispersal or addition of growth factors; this molecular environmental change is similarly recognized at the surface of the cell, and is transmitted through the cytoplasm to the nucleus. This signal transduction process activates the transcription and synthesis of specific proteins and other macromolecules that trigger the mitotic process. The process and events leading to cell division are called here the “mitogenic signal pathway”.
Evolutionary Implications of Genic Variation among Insular Populations of Peromyscus maniculatus and Peromyscus oreas

A survey of electrophoretic variation in proteins encoded by 24 gene loci revealed differences in allele frequencies (principally at ADH, ES-1, and GOT-1) between two karyotypically characterized species of deer mice ( Peromyscus maniculatus and P. oreas ) from Vancouver Island and smaller islands in the Queen Charlotte Strait and Strait of Georgia. The large number of alleles common to the two taxa and the absence of fixed allelic differences are consistent with a hypothesis of recent common ancestry. In addition, random variance in allele frequencies among small-island populations of both species is indicative of interspecific divergence accelerated by stochastic processes. Nevertheless, genetic consequences of geographic isolation (low genic variability and high interpopulational differentiation) are more pronounced in P. oreas than in P. maniculatus , and this is attributed to differences in potential for gene flow. Patterns of geographic variation evident in morphological analyses, summarized in the recognition of P. maniculatus austerus and three subspecies of P. oreas ( P. o. oreas, P. o. interdictus , and P. o. isolatus ) from Pacific regions of British Columbia and Washington, may stem from genetic factors related to peripheral isolation of P. oreas from P. maniculatus and interspecific differences in dispersal abilities.
Caveolin-3 Mutations in Rippling Muscle Disease

Two unrelated patients with novel homozygous missense mutations (L86P and A92T) in caveolin-3 gene (CAV3), presenting with a severe form of rippling muscle disease (RMD), are reported from the University of Bonn, and other centers in Germany.
Measurement of ϕ3 with Dalitz Plot Analysis of B+→D(∗)K(∗)+ Decay

Results from the Belle and BaBar experiments on measurement of the weak angle ϕ 3 using a Dalitz plot analysis of the K S 0 π + π − decay of the neutral D meson from the B ± → D ( ∗ ) K ( ∗ ) ± process are presented. The method employs the interference between D 0 and D ¯ 0 to extract the angle ϕ 3 , strong phase δ and the ratio r of suppressed and allowed amplitudes.
Damage Assessment of the Annual White Grub, Cyclocephala lurida (Coleoptera: Scarabaeidae), in Com and Soybean

Relative damage to com and soybean seedlings caused by feeding larvae of Cyclocephala lunda Bland was assessed with plants grown in a greenhouse. Single com or soybean plants were grown for 27 d under three densities of larvae (three, six, or nine per plant) and an uninfested check. Soybean seedling emergence, dry root weights, total dry weights, or leaf areas were not different among any of the treatments. Com seedling emergence, dry root weights, total dry weights, or leaf areas were not different among any larval densities except for 1 yr when nine larvae per plant resulted in smaller plants relative to the uninfested plants. This density, however, is several times larger than any that have been observed under field conditions. Results of this 2-yr study strongly suggest that a soil insecticide would not be necessary to protect seedling com or soybean plants from damage by this insect.
A Nutrition Algorithm Incorporating Early Initiation of Nutrition With Higher Feeding Rates, Percentage of Gastric Residual Volume, Small-Bowel Feedings, and Compensatory Nighttime Feeds Leads to Reduced Energy Deficit in Critically Ill Patients

Background/Objective. A discrepancy often emerges between nutritional goals and actual delivery. This study assesses the relationship between energy balance and length of stay (LOS) in surgical intensive care unit (SICU) patients. SICU patients are frequently catabolic and at risk of underfeeding. We set forth to identify if a nutritional algorithm will improve energy delivery and outcomes. Methods. A prospective observational study conducted in surgical critical care patients was performed. After implementation of a nutrition algorithm; demographic data, initiation of feeding, acquiring caloric goal, caloric deficit, LOS, and mortality were recorded. Cumulative energy balance was calculated as energy delivery minus daily target. Data are presented as mean ± standard deviation. Results. In all, 100 patients aged 66 ± 17 years (45% female and 55% male) admitted to the SICU were evaluated. All were nutritionally compromised, with 72% being NPO (nothing by mouth), 9% orally fed, and 9% enterally fed. SICU LO...
Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.
Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201 , RIM101 , and SP1 . Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. IMPORTANCE Cryptococcus neoformans causes fatal meningitis in immunocompromised individuals, mainly HIV positive, killing over 600,000 each year. A unique feature of this yeast, which makes it particularly virulent, is its polysaccharide capsule; this structure impedes host efforts to combat infection. Capsule size and structure respond to environmental conditions, such as those encountered in an infected host. We have combined computational and experimental tools to elucidate capsule regulation, which we show primarily occurs at the transcriptional level. We also demonstrate that loss of a novel transcription factor alters virulence factor expression and host cell interactions, changing the lethal condition from meningitis to pneumonia with an exacerbated host response. We further demonstrate the relevant targets of regulation and kinetically map key regulatory and host interactions. Our work elucidates mechanisms of capsule regulation, provides methods and resources to the research community, and demonstrates an altered pathogenic outcome that resembles some human conditions.
Unstained cell counts as a method of evaluating cancerocidal agents.

Abstract The in vitro method of unstained cell counts is proposed as a means of screening the cytocidal and the cancerocidal activity of reagents. This procedure was tested by determining the cytocidal action of 4 reagents against the cells of Walker tumor 256 and against rat thymocytes. The reagents in varying amounts were incubated with the tumor and normal cells at 37 °C. for twenty-two hours. The number of viable cells was then determined by adding a safranine solution and counting the unstained cells. The reagents tested were moccasin venom, nitrogen mustard, adrenal cortex extract, and radioactive gold. All of the reagents had the same or a lesser toxic action on the tumor than the normal cells. According to the method of unstained cell counts, none of the reagents had apparently any specific cancerocidal activity. The findings were further controlled by inoculating the incubated mixtures of reagent and tumor cell suspensions into susceptible animals and observing the number of takes and the latent periods of the tumors. The findings obtained by unstained cell counts and by rat inoculations were in good agreement on the toxicity of three of the reagents to the tumor cells. Radioactive gold had, however, a low toxicity according to the method of unstained cell counts, but the reagent did prevent the growth of the tumor cells on inoculation into rats. Apparently Au 198 was antimitotic but not cytocidal. The unstained cell counts seemed to be a simple in vitro procedure for obtaining data on the relative cytocidal action of agents to normal and tumor cells.
Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases.

Cytochromes P450 (CYPs) are a large group of hemeproteins located on mitochondrial membranes or the endoplasmic reticulum. They play a crucial role in the metabolism of endogenous and exogenous molecules. The activity of CYP is associated with a number of factors including redox potential, protein conformation, the accessibility of the active site by substrates, and others. This activity may be potentially modulated by a variety of small molecules. Extensive experimental data collected over the past decade point at the active role of natural polyphenols in modulating the catalytic activity of CYP. Polyphenols are widespread micronutrients present in human diets of plant origin and in medicinal herbs. These compounds may alter the activity of CYP either via direct interactions with the enzymes or by affecting CYP gene expression. The polyphenol–CYP interactions may significantly alter the pharmacokinetics of drugs and thus influence the effectiveness of chemical therapies used in the treatment of different...
The Hippocratic surgical instrumentarium: A study in nomenclature.

Precisely what surgical tools were available to Greek surgeons in the fifth and fourth centuries BCE? In the absence of material survivals we must depend mainly on descriptions of instruments and their use in the Hippocratic Corpus to answer this question. We can also speculate on why so few Hippocratic instruments come down to us in contrast to the relative abundance of survivals from the Roman Empire. Key Words: Hippocratic surgery - instruments
Rheology of cubic particles in a concentrated colloidal dispersion suspending medium

The flow behavior of mixtures of micron-sized cubic particles suspended in a concentrated colloidal dispersion is investigated across a broad range of cubic particle concentrations. In the semi-dilute regime, the qualitative shape of the dynamic moduli and flow curves reflect those of the underlying colloidal dispersion medium. These curves are superimposed with the underlying colloidal dispersion using shift factors that are found to be larger than those obtained in a recent study of suspensions of non-colloidal spherical particles in the same colloidal dispersion medium. At higher concentrations of cubic particles, deviations from this shifting procedure are apparent. Scaling calculations suggest depletion interactions are responsible for the increase in the low shear viscosity and confinement of the underlying colloidal dispersion can be expected to enhance the shear thickening behavior at high shear stresses. The results of this study provide guidance for formulating suspensions through control of particle shape and mixture concentration. © 2016 American Institute of Chemical Engineers AIChE J, 63: 1091–1101, 2017
Transferability Analysis of Heterogeneous Overdispersion Parameter Negative Binomial Crash Models

This paper presents a detailed analysis of the temporal transferability of heterogeneous overdispersion parameter negative binomial models for crash severity types in California. The Furnival–Wilson leaps and bounds algorithm was used to identify optimal safety performance function specifications. The overdispersion parameter was allowed to vary across roadway segments as a function of roadway geometrics. Sixty models were developed for five major severity outcomes for homogeneous roadway segments for each of the periods 2005 to 2010, 2011 to 2012, and 2005 to 2012. Model transferability tests were conducted with likelihood ratio tests, and it was determined that temporal transferability rates (from the 2005–2010 period to the 2011–2012 period) were poor. The findings indicate the potential time instability of safety performance function parameters. The analysis found a higher rate of transferability for rural safety performance functions compared with urban safety performance functions. The rate of trans...
Cultural Distress: An Emerging Paradigm:

Although cultural competence in practice is a common goal within the health care professions, little is known about the consequences of a lack of such competence in health and healing. We propose a novel theoretical framework of cultural distress to describe patient experiences of and reactions to care that does not incorporate attention to cultural needs. Use of the cultural distress model to guide research offers an innovative framework by which researchers may identify potential interventions such that patients never reach a level of cultural distress.
Challenges and Innovations in Phase I Dose-Finding Designs for Molecularly Targeted Agents and Cancer Immunotherapies

Phase I oncology trials are designed to identify a safe dose with an acceptable toxicity profile. In traditional phase I dose-finding design, the dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. The recent development of molecularly targeted agents and cancer immunotherapies call for new innovations in phase I designs, because of prolonged treatment cycles often involved. Various phase I designs using toxicity and efficacy endpoints from multiple treatment cycles have been developed for these new treatment agents. Here, we will review the novel endpoints and designs for the phase I oncology clinical trials.
Relapsing Clostridium difficile colitis

78 The above image was captured during a sigmoidoscopy of an 82-year-old woman who was complaining of yellowish, watery diarrhea and left lower quadrant pain. Her past medical history included congestive heart failure, diabetes, and chronic renal insufficiency. Two weeks previous, she was discharged from a local hospital where she had been treated with antibiotics for pneumonia. During that hospital course, she acquired Clostridium difficile colitis, and was treated with metronidazole. Upon discharge, she remained on oral metronidazole and completed a 14day regimen of the medication. The patient had resolution of her symptoms, however, within a week of completing her treatment the diarrhea had returned. Of note on physical examination was a moderately tender lower abdomen, more so on the left side. Her oral temperature was 100.8, and her white blood cell count was 19.1. Stool cytotoxin assays for Clostridium difficile were positive. On sigmoidoscopy, biopsies of the above lesions (refer to illustration) were obtained and the histological findings were consistent with pseudomembranous colitis. The patient was again treated with oral metronidazole, 500 mg TID for fourteen days. She was provided with complete resolution of her symptoms. Infection with Clostridium difficile can manifest in a number of ways. Depending upon the condition of the host, it can be as benign as an asymptomatic carrier state or as severe as toxic megacolon requiring colectomy. These two conditions represent the extremes of the clinical spectrum. The typical presentation is that of watery diarrhea, lower abdominal pain and lowgrade fevers starting either during or shortly after Relapsing Clostridium Difficile Colitis A CASE REPORT
Reconstruction of a 3D Virtual Colon Structure and Camera Motion for Screening Colonoscopy

Background/PurposeOptical colonoscopy is the gold standard for detection and prevention of Colorectal cancer. However, any lesion outside the field of view of the camera during colonoscopy is missed, and can develop from a polyp into a cancer or from a small cancer into a large, metastatic cancer. Hence, viewing the colon mucosa as much as possible is desirable. The ultimate goal is to use the reconstruction results to mark the area likely unobserved during colonoscopy where polyps may be hidden.Materials and Methods:This paper presents a novel method for reconstructing (i) a 3D virtual colon structure from a sequence of 2D colonoscopic images and (ii) the endoscope camera navigation path. Unlike existing work that focus on reconstruction of accurate colon surface for a computer-aided surgery, this work focuses on estimating the alignment of the colon haustral folds, thickness and protrusion of the folds, and the camera path for computer-aided screening colonoscopy to inspect as much as possible of the colon mucosa.Results:On endoscopy video of a synthetic colon model, we achieved at least 73% and 90% accuracy in estimating the directions of camera translation and rotation motions, respectively. The average percentage of the depth error is about 10% (8.5/85.8) of the average depth of all the folds seen in all the image sequences. The average percentage of the circumference error is about 10% (17/178.2) of the average circumference of all the folds seen in all the image sequences. The results are promising and give further insight to address this challenging problem.Conclusions:We present the work on reconstruction of a colon structure and endoscope motion from a colonoscopic image sequence for screening colonoscopy. We overcame several challenges such as the scale difference of consecutive reconstructed models, estimating closed fold contours from tracked fold edges, and registering the models. As future work, we will investigate a multi-frame registration approach to further reduce the depth and circumference estimation errors by registering nearby frames that are more similar in fold shape together.
Reversible Tuning of the Surface Plasmon Resonance of Indium Tin Oxide Nanocrystals by Gas-Phase Oxidation and Reduction

Heavily doped oxide nanocrystals exhibit a tunable localized surface plasmon resonance (LSPR) in the infrared, a property that is promising for applications in photonics, spectroscopy, and photochemistry. Nanocrystal carrier density and, thus, spectral response are adjustable via chemical reaction; however, the fundamental processes that govern this behavior are poorly understood. Here, we study the time dependence of the LSPR supported by indium tin oxide (ITO) nanocrystals during O2 and N2 annealing with in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). We show that the LSPR red-shifts upon oxidation in O2 and blue-shifts to its original position upon reduction in N2. A reaction–diffusion model allows us to rationalize the underlying physicochemical processes and quantitatively connect nanocrystal redox chemistry, solid-state diffusion, carrier density, and the LSPR.
Immediate postpartum use of long-acting reversible contraceptives in low- and middle-income countries.

Globally, data show that many women of reproductive age desire to use modern family planning methods. Many of these women do not have access to modern contraceptives, which is termed their ‘unmet need’ for contraception. In low- and middle-income countries where total fertility rates can be high and many women have undesired fertility, or wish to increase their inter-pregnancy intervals, access to modern contraceptives is often inadequate. The puerperium is a unique time for interventions to offer modern contraceptive methods. Having just given birth, women may desire contraceptives to prevent short-interval pregnancy, or further pregnancy, altogether. In high-, middle-, and low-income countries there has been an increased interest in the placement of long-acting reversible contraceptives at or immediately after delivery, regardless of delivery mode. These methods can provide women with highly effective contraception for years, can be manufactured at low cost, are generally well tolerated with a good safety profile, and do not require the user to remember to take them. Oral contraceptives and injectable medications require the patient to present to the clinic during a specific timeframe for follow-up care or a refill, and the clinic may not be proximate, affordable, or have the desired contraceptive in stock. This document will review the currently published literature on the use of immediate postpartum long-acting reversible contraceptives (placed within two days of delivery) in low- and middle-income countries to report on the prevalence of use and satisfaction rates, and note the lack of data on cost and economic implications. We will also explore data on how future maternal, neonatal, and infant outcomes may be influenced by increased peripartum long-term contraceptive use.
Mobile augmented reality for teaching structural analysis

Abstract Structural analysis is an introductory core course that is taught in every civil engineering program as well as in most architectural and construction engineering programs. Previous research unveils students' deficits in understanding the behavior of structural elements in a three-dimensional (3D) context due to the shortcomings of traditional lecturing approaches, which put too much emphasis on the analysis of individual structural members, thereby falling short in providing a solid, easy-to-follow, and holistic approach to analyzing complex structures with a large number of interconnected elements. In this paper, the authors introduce a new pedagogy for teaching structural analysis that incorporates mobile augmented reality (AR) and interactive 3D visualization technology. The goal of this study is to enhance the contents used in structural analysis textbooks and on worksheets by visualizing discrete structural members employing AR along with interactive 3D models in order to illustrate how the structures behave under different loading conditions. Students can interactively change the load and observe the reaction resulting from this change with the instant feedback provided by the AR interface. The feasibility of AR concepts and interaction metaphors, as well as the potential of using AR for teaching structural analysis are investigated, specifically by focusing on challenges regarding content integration and interaction. An AR application is designed and developed, and a pilot study is conducted in a junior level structural analysis class to assess the pedagogical impact and the design concepts employed by the AR tool. Control and test groups are deployed, and students’ performance is measured using pre- and post-tests. The results of the pilot study indicate that the utilized AR design concepts have potential to contribute to students’ learning by providing interactive and 3D visualization features, which support constructive engagement and retention of information in students.
Can clients of economically dependent auditors benefit from voluntary audit firm rotation? An experiment with lenders

Abstract This study utilizes a nationwide random selection of 111 lenders in a 2 × 2 between-subjects experiment to determine whether the level of an auditor's economic dependence on a client and type of auditor rotation affect lenders’ independence and reliability perceptions and decisions to lend money to a potential borrower. Previous literature shows that financial statement users use client importance as a measure of audit quality when revenue streams are not equal across clients. This can negatively affect perceptions of independence and financial statement reliability. As United States regulators look for ways to improve audit quality under the current partner rotation mandate, this study explores whether an audited entity that voluntarily adopts a policy of firm rotation can mitigate the negative effects of the auditor's dependence on the client. Findings suggest that lenders view clients of economically dependent auditors (CEDA) as less independent from its auditor and perceive its financials as less reliable than clients without a dependent auditor (non-CEDA). Lenders are less likely to grant a loan to CEDA. However, under firm rotation, there is not only an increase in lenders’ perceptions of reliability of CEDA financials, but also no difference in perceptions of reliability of CEDA and non-CEDA financials.
What Determines User-Generated Content Creation of College Football? A Big-Data Analysis of Structural Influences

The question of how and why users engage in sport digital communication endures. In this study, structuration theory is employed to examine how social-media users exercise preferences in the creation of content as they respond to a variety of macrolevel factors pertaining to college football—the type of game, team strength, conference membership, market characteristics, etc. Through hierarchical regression analysis, the results indicate that the presence and timing of college football games, as well as team strength and game outcome, are significant determinants for the patterns of online content generation. As such, the study advances the theoretical, methodological, and managerial inquiry of user-generated content on sport social-media platforms through a Big Data analytics approach.
Comparison of Access to Eye Care Appointments Between Patients With Medicaid and Those With Private Health Care Insurance.

Importance Although low-income populations have more eye problems, whether they face greater difficulty obtaining eye care appointments is unknown. Objective To compare rates of obtaining eye care appointments and appointment wait times for those with Medicaid vs those with private insurance. Design, Setting, and Participants In this prospective, cohort study conducted from January 1, 2017, to July 1, 2017, researchers made telephone calls to a randomly selected sample of vision care professionals in Michigan and Maryland stratified by neighborhood (urban vs rural) and professional type (ophthalmologist vs optometrist) to request the first available appointment. Appointments were sought for an adult needing a diabetic eye examination and a child requesting a routine eye examination for a failed vision screening. Researchers called each practice twice, once requesting an appointment for a patient with Medicaid and the other time for a patient with Blue Cross Blue Shield (BCBS) insurance, and asked whether the insurance was accepted and, if so, when the earliest available appointment could be scheduled. Main Outcomes and Measures Rate of successfully made appointments and mean wait time for the first available appointment. Results A total of 603 telephone calls were made to 330 eye care professionals (414 calls [68.7%] to male and 189 calls [31.3%] to female eye care professionals). The sample consisted of ophthalmologists (303 [50.2%]) and optometrists (300 [49.8%]) located in Maryland (322 [53.4%]) and Michigan (281 [46.6%]). The rates of successfully obtaining appointments among callers were 61.5% (95% CI, 56.0%-67.0%) for adults with Medicaid and 79.3% (95% CI, 74.7%-83.9%) for adults with BCBS ( P P P P P P P = .03) or with an optometrist vs an ophthalmologist (OR, 8.00; 95% CI, 5.37-11.90; P Conclusions and Relevance Callers were less successful in trying to obtain eye care appointments with Medicaid than with BCBS, suggesting a disparity in access to eye care based on insurance status, although confounding factors may have contributed to this finding. Improving access to eye care professionals for those with Medicaid may improve health outcomes and decrease health care spending in the long term.
Making well-informed software design decisions

Design decisions software architects make directly impact system quality. Real-world systems involve a large number of such decisions, and each decision is typically influenced by others and involves trade-offs in system properties. This paper poses the problem of making complex, interacting design decision relatively early in the project's lifecycle and outlines a search-based and simulation-based approach for helping architects make these decisions and understand their effects.
Chapter 49 – Anticholinergic Bronchodilators

Publisher Summary This chapter considers the pharmacology, biochemistry, and potential anti-inflammatory actions of anticholinergic bronchodilators, including possible anti-inflammatory actions, as well as clinical trial evidence for the safety and efficacy of these therapies. Important outcome measures for LAMAs involve considerations of effects on symptoms, lung function, dynamic hyperinflation and exercise responses, quality of life, health economics, exacerbations, survival, and the natural history of chronic obstructive pulmonary disease (COPD). Anticholinergics are muscarinic receptor antagonists, inhibiting cholinergic reflex bronchoconstriction, and reducing vagal cholinergic tone, which is the main reversible component in COPD. Normal airways have a small degree of vagal cholinergic tone, but because the airways are patent this has no perceptible effect and does not reduce airflow. Anticholinergics may reduce mucus hypersecretion. Anticholinergics have no apparent effect on pulmonary vessels, and therefore do not cause a fall in Pao2, as may sometimes be seen with β2-agonists and theophylline. The existence of several subtypes of muscarinic receptor in human airways has suggested that more selective muscarinic antagonists may have advantages over nonselective agents, such as ipratropium bromide and oxitropium bromide. Interestingly, anticholinergic may benefit asthmatics with COPD-like inflammation in asthma, viral hyperreactivity, and emergency asthma.
The Impetus for Change: Why Entrepreneurial Universities Will Transform the Future (While Others Will Cease to Exist)

As leaders and innovators in educational institutions attempt to meet future learning needs, it is paramount that they reconsider both the structure and processes that have become legacy models in their academic infrastructure. One key challenge for higher education leadership (and those within the institution seeking to innovate for the future) is to incorporate the spirit and drive exhibited by entrepreneurs. Entrepreneurial spirit has driven much development in the economic annals and is key to future societal expansion. Universities can play a vital role in such expansion but only if they align internal structures and manage risk and ambiguity to support mechanisms for learner-centered approaches and leverage technology in the learning process. University leaders must challenge the status quo and address the urgency to balance forces involved in the creation of knowledge and processes for the dissemination of knowledge. Therefore, this chapter focuses on entrepreneurial considerations that impact the future of higher education.
The Culture Environment and Its Control of Myogenesis

The differentiation of striated muscle from embryonic myoblasts in cell culture reproduces the processes by which the structural and functional characteristics of differentiated muscle fibers are formed in the organism with remarkable fidelity. The one notable difference is the unusual degree of synchrony which can be achieved in cell culture.