cssi/SciSciGPT-SciSciNet huggingface dataset:
Photorefractive keratectomy for anisometropic amblyopia in children.

Purpose To assess the safety and efficacy of photorefractive keratectomy (PRK) in children with anisometropic amblyopia and to define the characteristics of children who may be candidates for PRK. Methods This thesis comprises four parts: (1) a retrospective analysis of risk factors predictive of amblyopia treatment failure in 104 children, (2) a prospective study of pachymetry in 198 eyes of 108 children, (3) development and implementation of a protocol to perform PRK under general anesthesia, and (4) a prospective interventional case-comparison study of PRK in 11 noncompliant children with anisometropic amblyopia to evaluate safety and long-term outcomes. Compliant and noncompliant children with anisometropic amblyopia were analyzed as controls. Results Factors associated with conventional anisometropic amblyopia treatment failure were poor compliance (P = .004), age 6 years or older (P = .01), astigmatism > or = 1.5 diopters (P = .0002), and initial visual acuity of 20/200 or worse (P = .02). Central and paracentral pachymetry measurements were similar to published adult values. The general anesthesia protocol was efficient, and the laser functioned properly in all cases. All children did well with no anesthesia-related or treatment-related complications. Two years following PRK, the mean reduction in refractive error was 9.7 +/- 2.6 diopters for myopes (P = .0001) and 3.4 +/- 1.3 diopters for hyperopes (P = .001). The cycloplegic refractive error in 9 of 11 treated eyes was within 3 diopters of that in the fellow eye. Uncorrected visual acuity in the amblyopic eye improved by > or = 2 lines in seven of nine children; best-corrected visual acuity improved by > or = 2 lines in six of nine children. Stereopsis improved in five of nine children. The mean visual acuity of the PRK patients at last follow-up was significantly better than that of noncompliant controls (P = .003). The safety and efficacy indices for PRK in this study were 1.24 and 1.12, respectively. Conclusions Photorefractive keratectomy can be safely performed in children with anisometropic amblyopia. Visual acuity and stereopsis improved in most eyes, even in older children. Photorefractive keratectomy may have an important role in the management of anisometropic amblyopia in noncompliant children.
Mechanism and Function of a Newly Identified CpG DNA Motif in Human Primary B Cells

The vertebrate immune system recognizes bacterial DNA based on the presence of unmethylated CpG-dinucleotides in particular base contexts ("CpG motifs"). In contrast to mice, knowledge about CpG-mediated effects on human B cells is poor. In the present study we identify and determine an optimal human CpG motif. A phosphodiester oligonucleotide containing this motif strongly stimulated CD86, CD40, CD54, and MHC class II expression, IL-6 synthesis, and proliferation of primary human B cells. These effects required internalization of the oligonucleotide and endosomal maturation. The molecular mechanism of action of this CpG motif was associated with the sustained induction of the NF-kappaB p50/p65 heterodimer and of the transcription-factor complex AP-1. Transcription-factor activation by CpG DNA was preceded by increased phosphorylation of the stress kinases c-Jun N-terminal kinase and p38, and of activating transcription factor-2. In contrast to CpG, signaling through the B cell receptor led to activation of extracellular receptor kinase and to phosphorylation of a different isoform of c-Jun N-terminal kinase. These studies define the structure of a highly active human CpG motif and characterize its molecular mechanism of action in primary human B cells.
Improvements in the differentiation method of spectrum unfolding

Abstract Numerical differentiation of experimental data is widely used in obtaining neutron and gamma-ray energy spectra from measurements performed with proton-recoil proportional counters and scintillators. Most differentiation unfolding codes use various least-squares fits of polynomials to estimate the derivative of the measured proton-recoil or Compton-recoil spectra. Simple examples are presented to illustrate errors in unfolded energy spectra that can result from the use of least-squares differentiation. An alternative method of numerical differentiation is presented which is not prone to such errors.
The problems in scaling adult drug doses to children

Background: Many drugs are unlicensed in children and consequently their doses have been scaled down from those used in adults. Objective: To compare the performance of three scaling models in predicting maintenance doses for children from those used in adults. Methods: Three scaling models based on body weight (BW), body surface area (BSA) and BW 0.75 were used to predict maintenance doses across the paediatric age band from the equivalent adult doses for 30 different drugs. The predicted doses were compared with those in the British National Formulary for children 2006 (BNFc). Percentage error and mean squared prediction error were used as a measure of precision, and mean prediction error was used as a measure of bias. Results: In the 1-month and 12-month age groups, the different approaches ranked on their bias (least bias first) were BW 0.75 BW 0.75 >BSA. The BSA and BW 0.75 methods predicted doses up to 2.86-fold higher than the BNFc in the 1-month and 1-year age group. In the 7-year and 12-year age groups, BW 0.75 and BSA performed better than BW for precision and bias, and no predictions were more than 1.8-fold higher than the BNFc. The BW method tended to also under-predict dose across the paediatric age range. Conclusions: Dose scaling should only be used as a last resort for determining a suitable dose in children. No single method was suitable across the entire paediatric age range.
Comment on the effect of pressure on the structure of Ge III and Si III

Calculations of the bulk modulus of Si III and Ge III are presented. They are based on Keating's expression for the elastic energy. A numerical procedure is used to relax the structures to equilibrium at various volumes. The results indicate that, for reasonable force constants, the Ge III (or ST-12) structure is about twice as compressible as the diamond cubic and Si III (or BC-8) structure. This is due to the contribution from large internal displacements, which must consequently be carefully calculated in any analysis of pressure-dependent properties of Ge III.
Evaluation of the University of Virginia Leadership in Academic Medicine Program.

Background: Developing effective transformational leaders is essential for a diverse and complex academic medical system. The purpose of this study is to elicit faculty perspectives on their leadership skills before and after participation in a Leadership in Academic Medicine (LAM) Program. Summary: The two-part study consisted of a prospective Pre- and Immediate Post-LAM Survey distributed to 32 participants in the 2008 Program and a Long-Term Post-LAM Survey distributed to 110 prior participants (2004–2007). Both surveys were designed to assess participant leadership perspectives and career outcomes. Institutional Review Board approval was obtained. Data were analyzed quantitatively and qualitatively. All participants reported improved leadership skills, but the percentages were lower for Long-Term Post-LAM participants than for the Immediate Post-LAM participants. In addition, although 58% of Immediate Post-LAM women, compared with 19% of Immediate Post-LAM men (p < .05), were actively seeking leadersh...
Syndecans and HIV-1 pathogenesis.

Abstract The exploitation of receptors represents a common microbial strategy to survive in the hostile environment of the host. A growing body of evidence suggests that HIV-1 exploits a specific class of receptors—the syndecans—to facilitate colonization of the host.
General moment functions and a density version of the central limit theorem

1. Introduction . We shall employ the customary abbreviations: p.d.f. for probability density function ; d.f. for distribution function ; c.f. for characteristic function .
Crowdsourcing, big data and homeland security

This paper discusses ways that crowdsourcing can help homeland security. It reviews some successes in this area, suggests some directions and points out some obstacles. Short abstract.
Advances in radio frequency tumor ablation therapy: technical considerations, strategies for increasing coagulation necrosis volume, and preliminary clinical results

Radiofrequency (RF) tumor ablation has been demonstrated as a reliable method for creating thermally induced coagulation necrosis using either a percutaneous approach with image- guidance or direct surgical application of thin electrodes into treated tissues. Early clinical trials with this technology have studied the treatment of hepatic, cerebral, and bony malignancies. The extent of coagulation necrosis induced with conventional monopolar radiofrequency electrodes is dependent on overall energy deposition, the duration of RF application, and RF electrode tip length and gauge. This article will discuss these technical considerations with the goal of defining optimal parameters for RF ablation. Strategies to further increase induced coagulation necrosis including: multiprobe and bipolar arrays, and internally-cooled RF electrodes, with or without pulsed-RF or cluster technique will be presented. The development and laboratory results for many of these radiofrequency techniques, initial clinical results, and potential biophysical limitations to RF induced coagulation, such as perfusion mediated tissue cooling (vascular flow) will likewise be discussed.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Incidence and Clinical Outcome of Patients with Teratoma in the Retroperitoneum Following Primary Retroperitoneal Lymph Node Dissection for Clinical Stages I and IIA Nonseminomatous Germ Cell Tumors

ABSTRACTPurpose: We determined the incidence and clinical outcome of patients with clinical stages I and IIA nonseminomatous germ cell tumors (NSGCT), and teratoma in the retroperitoneum following primary retroperitoneal lymph node dissection (RPLND).Materials and Methods: Between January 1989 and February 1998, 294 patients with clinical stages I (209) and IIA (85) underwent primary RPLND at our institution. The primary tumor had teratomatous elements in 179 (61%) cases. Median followup was 27.8 months.Results: The overall incidence of teratoma in the retroperitoneum was 9% (25 of 294), and 21% (25 of 118) in patients with pathological stage II disease. The incidence of teratoma in the retroperitoneum increased from 3% (6 of 209) in clinical stage I to 22% (19 of 85, chi-square test p <0.0001) in clinical stage IIA. The incidence of teratoma in patients with pN1/N2/N3 disease increased from 9% (6 of 64) in clinical stage I to 35% (19 of 54) in clinical stage IIA (chi-square test p = 0.0006). All 25 patie...
Existence of global solutions to a model of a myelinated nerve axon

The main result is a proof of the existence of solutions which are global in time for a.differential equation arising in the theory of myelinated nerves. The equation differs from the usual reaction-diffusion equations occurring in nerve models in that the second derivative operator in the spatial direction is replaced at a sequence of discrete nodes by an operator defined as the jump in the first derivative in the spatial direction across the node. The nonlinear dynamics are assumed to be concentrated at the nodes. Local existence of solutions is obtained via semigroup theory; global bounds and hence global existence via energy or Lyapunov methods.
Regression including anorexia nervosa in a Down's syndrome adult: a seven year follow up.

Abstract In this study we discuss the results at a 7 year follow-up of a treatment package for regression including anorexia nervosa. The findings revealed that the client, a mentally retarded woman, was able to maintain treatment gains. Collateral benefits were also seen in social, vocational and self-help areas. The maintenance of these improved skills across response classes and settings suggests that the woman's behavior had come under the influence of natural reinforcers in her environment.
Probing cellular mechanobiology in three-dimensional culture with collagen-agarose matrices

The study of how cell behavior is controlled by the biophysical properties of the extracellular matrix (ECM) is limited in part by the lack of three-dimensional (3D) scaffolds that combine the biofunctionality of native ECM proteins with the tunability of synthetic materials. Here, we introduce a biomaterial platform in which the biophysical properties of collagen I are progressively altered by adding agarose. We find that agarose increases the elasticity of 3D collagen ECMs over two orders of magnitude with modest effect on collagen fiber organization. Surprisingly, increasing the agarose content slows and eventually stops invasion of glioma cells in a 3D spheroid model. Electron microscopy reveals that agarose forms a dense meshwork between the collagen fibers, which we postulate slows invasion by structurally coupling and reinforcing the collagen fibers and introducing steric barriers to motility. This is supported by time lapse imaging of individual glioma cells and multicellular spheroids, which shows that addition of agarose promotes amoeboid motility and restricts cell-mediated remodeling of individual collagen fibers. Our results are consistent with a model in which agarose shifts ECM dissipation of cell-induced stresses from non-affine deformation of individual collagen fibers to bulk-affine deformation of a continuum network.
Alkali Metal Control over N–N Cleavage in Iron Complexes

Though N2 cleavage on K-promoted Fe surfaces is important in the large-scale Haber–Bosch process, there is still ambiguity about the number of Fe atoms involved during the N–N cleaving step and the interactions responsible for the promoting ability of K. This work explores a molecular Fe system for N2 reduction, particularly focusing on the differences in the results obtained using different alkali metals as reductants (Na, K, Rb, Cs). The products of these reactions feature new types of Fe–N2 and Fe-nitride cores. Surprisingly, adding more equivalents of reductant to the system gives a product in which the N–N bond is not cleaved, indicating that the reducing power is not the most important factor that determines the extent of N2 activation. On the other hand, the results suggest that the size of the alkali metal cation can control the number of Fe atoms that can approach N2, which in turn controls the ability to achieve N2 cleavage. The accumulated results indicate that cleaving the triple N–N bond to n...
Reduced-order controllers inH∞-Optimal synthesis methods of the first kind

It has often been believed that inH∞-optimal synthesis methods, the resulting controllers have order much greater than the order of the plant. Recently, Limebeer and Hung [9] have shown that inH∞-optimal synthesis problems of the “first kind” both optimal as well as suboptimal controllers have order which is no greater than the order of the plant. However, those authors do not provide any explicit algorithm for computing these controllers. In this paper we derive an explicit procedure for computing suboptimal controllers in problems of the first kind. These controllers have order no greater than the order of the plant and can be computed by solving only two Riccati and two Lyapunov equations.
Acoustic Rhinometric Measurements of Changes in Velar Positioning

Abstract Acoustic rhinometry as a means to detect changes in velar position was examined in this study. Videofluoroscopic recordings were made of two normal speakers maintaining velopharyngeal open and velopharyngeal closed (silent /f/) targets. Simultaneous acoustic rhinometric recordings were made during the production of each stimulus. Determinations of changes in velar positioning during the closed samples were made from fluoroscopic recordings and compared to nasal cavity-nasopharynx changes detected by rhinometry. The excellent agreement between the measures from the two procedures (less than 1 cm) indicates that acoustic rhinometry is capable of detecting changes in velar positioning during “silent” speech. Implications for assessment and future research are discussed.
On the gap structure of sequences of points on a circle

Abstract Considerable mathematical effort has gone into studying sequences of points in the interval [0, 1) which are evenly distributed, in the sense that certain intervals contain roughly the correct percentages of the first n points. This paper explores the related notion in which a sequence is evenly distributed if its first n points split a given circle into intervals which are roughly equal in length, regardless of their relative positions. The sequence x k =(log 2 (2 k −1) mod 1) was introduced in this context by De Bruijn and Erdos. We will see that the gap structure of this sequence is uniquely optimal in a certain sense, and optimal under a wide class of measures.
Accurate assessment of aootic stenosis severity by Doppler echocardiography independent of aortic jet velocity

Abstract The present investigation was designed to derive an accurate pulsed Doppler method of assessing aortic stenosis severity that does not rely on measurement of aortic jet velocity. Left ventricular ET and SV were determined from pulsed Doppler recordings of flow velocity at the aortic anulus in 44 mostly normotensive patients with aortic stenosis. Aortic valve area at catheterization ranged between 0.3 and 2.13 cm2. A predicted ET was derived from Doppler-determined SV with the use of a regression equation previously described by Harley et al. A significant inverse quadratic relation was observed between the ET difference (ΔET), defined as measured ET minus predicted ET, and valve area at catheterization (r = −0.87; valve area = 1.4 − 15 ΔET + 60 ΔET2; SEE = 0.23 cm2). An ET difference of ≥0.060 second was 88% sensitive, 89% specific, and 89% accurate for detecting critical aortic stenosis. Thus the ET difference, derived from measurements of SV and ET by pulsed Doppler, is a sensitive index for detection of critical aortic stenosis that is independent of determination of aortic jet velocity. This index should complement the Doppler evaluation of aortic stenosis, especially in cases where interrogation of the stenotic jet with continuous wave Doppler is inadequate.
The disappearance of chlorobromuron in ensilage.

Chlorobromuron, 3-(4-bromo,3-chlorophenyl)-l-methoxy-l-methylurea is a preemergent and postemergent herbicide used for the control of many annual broadleaf weeds and grasses in field corn and soybean production. Both corn and soybeans are very common forage crops used for ensilage production and feeding to farm animals. The ensilage process involves a fermentation wherein the aerobic organism utilize quickly the available oxygen in the silo causing the atmosphere to become anaerobic allowing the fermentation and subsequent acid production to proceed. Hence the procedure is a preservative measure minimizing putrefication. In practice, corn plants, including stalk, leaves and ears, or mixtures of corn plants, legumes, soybeans or other grasses are chopped and packed into air-tight silos. The period of 48-72 hours is one of great fermentive activity with the production of considerable heat and pressure. The organisms responsible for the fermentation are streptococci and lactobacilli producing lactic acid, butyric, propionic and acetic acid with small amounts of alcohol. A pH of 5.2 or less is generally necessary to prevent decomposition of the ensilage. As is common with most, if not all chemicals used in crop production, small but measurable amounts of herbicides and/or their metabolic products are present as residues in plant materials. Because of the great importance in assessing the potential for the production of hazardous substances or unwanted residues, a study of the stability of chlorobromuron in the ensilage process was undertaken. Materials
Optical trap activation in a photorefractive polymer.

Optical trap activation has been observed to increase the steady-state diffraction efficiency by a factor of 3 in a photorefractive (PR) polymer, poly(methylmethacrylate):(l,3-dimethyl-2,2-tetramethylene-5-nitrobenzimidazoline):C60 (PMMA:DTNBI:C60). The increased diffraction efficiency is accompanied by an increase in the PR storage lifetime but also by an increase in the characteristic grating growth time of the PR grating. The optical activation of the deep trapping sites is observed to be a sublinear function of the optical irradiation power. Both spatially uniform trap activation and spatial patterning of the photorefractive response of the material are demonstrated.
A National Analysis of the Relationship Between Hospital Volume, Academic Center Status, and Surgical Outcomes for Abdominal Hysterectomy Done for Leiomyoma

Background Volume-to-outcomes relationships have been established for high-risk surgical procedures. To determine whether hospital volume and academic center status affect surgical outcomes in a lower-risk procedure, morbidity and mortality in patients undergoing abdominal hysterectomy for leiomyoma were evaluated. Study Design Administrative data from the National Inpatient Sample were used to conduct a retrospective analysis of 172,344 individuals who had primary diagnoses of leiomyomata (ICD-9 diagnosis codes of 218.x in the first 2 positions) and who underwent abdominal hysterectomy (ICD-9 procedure codes 68.4 in the first 2 positions) from 1999 to 2003. Comparison was made between teaching hospitals versus nonteaching hospitals and annual case volume in quintiles. Morbidity was considered to be any postoperative condition that is not an expected outcome of hysterectomy and defined as instances in which a patient suffered hemorrhage, ureteral injury, bladder injury, intestinal injury, wound dehiscence, wound infection, deep vein thrombosis, pulmonary embolism, or required blood transfusion. Results A total of 37 deaths were observed. Mortality was not significantly related to hospital volume or academic medical center status. In contrast, morbidity was found to have a positive association with academic medical center status (odds ratio=1.34; 95% CI, 1.23 to 1.45), although an inverse relationship between volume and morbidity was observed for extended length of stay (> 3 days) and blood transfusion outcomes in the first 3 (lowest) volume quintiles and for pulmonary embolism in the highest-volume quintile. No important association with volume was found for hemorrhage, ureteral injury, bladder injury, or intestinal injury. Conclusions Unlike high-risk procedures, such as esophagectomy, pediatric cardiac surgery, and pancreaticoduodenectomy, mortality for abdominal hysterectomy done for benign indication does not improve with hospital volume or academic center status. The statistically significant positive association between academic medical center status and morbidity merits additional characterization to target areas for improvement.
Predicting Resident Intentions to Support Community Tourism: Toward an Integration of Two Theories

Community tourism (CT) commonly influences the lives of local residents, and their attitudes in turn greatly affect the tourist experience. This study addresses a gap in the existing literature on CT by proposing a framework that integrates social exchange theory with the theory of reasoned action in order to map residents' decision-making processes about CT development. The results show that the attitude of community residents is a valid predictor of their intention to support tourism. In addition, perceived benefits for residents have a larger impact on attitudes about CT than perceived costs. Finally, the study concludes that the marketing program of a specific community had little impact on resident perceptions of CT development.
Understanding transmitted HIV resistance through the experience in the USA.

Transmitted drug resistance is an emerging phenomenon with important clinical and public health implications. It has been reported in 3.4% to 26% of HIV-infected persons in the USA. Most cases affect non-nucleoside reverse transcriptase inhibitors or nucleos(t)ide reverse transcriptase inhibitors. Transmitted protease inhibitor or multi-class resistance is uncommon, occurring in <5% of cases. The genital tract may function as a reservoir of transmissible drug-resistant variants or a site for low-level viral replication at a time plasma HIV is suppressed. Transmitted drug-resistant HIV variants, including those that exist in very low titers (minority populations), are associated with suboptimal virologic response to initial antiretroviral therapy. Baseline resistance testing, preferably genotype, appears to be cost-effective and is recommended for all treatment-naive patients in the USA, although prospective trials have not been performed. It appears transmitted drug resistance is still relatively low in developing countries, but there is a dearth of information.
Ultrastructural, histochemical, and morphometric analysis of skeletal muscle in a murine model of type I diabetes.

Background. Since peripheral nerves are damaged in diabetes mellitus, morphological changes occur within the diabetic muscle in response to the diabetic neuropathy. The aim of this study was to examine the extensor digitorum longus (EDL) from a 42-day streptozotocin-induced diabetic Swiss Webster mouse (STZ) and compare the muscle morphology and histochemistry to age-matched, nondiabetic controls. Methods. The EDL was evaluated using electron microscopy in order to investigate the morphological integrity of the myofibers and neuromuscular junctions. Histochemical analysis was completed using the myofibrillar CA + +-ATPase reaction of Doriguzzi et al. (1983. Histochemistry, 79 :289–294) for use in computer-assisted morphometric analysis of fiber size using Bioquant System 4 software. Results. Ultrastructural analysis of the diabetic EDL (N = 5, 225 myofibers/animal) showed a significant number of abnormal myofibers, exhibiting various degrees of degeneration, signs of denervation, and necrosis. The STZ myofibers exhibited excessive lipid accumulations and abnormal mitochondrial arrangements. Histochemical analysis of the STZ EDL revealed a significant shift in fiber type profile (53.6% type 2A and 46.4% type 2B- STZ myofibers; 47.5% type 2A, 52.5% type 2B nondiabetic controls). Morphometric analysis of myofiber size by fiber type (200 myofibers/muscle/fiber type) indicated a significant decrease in myofiber size for both type 2A and type 2B fibers in the STZ diabetic mouse. Conclusion. The degeneration and necrosis of myofibers concomitant with the sever atrophy of both the type 2A and 2B myofibers in the STZ muscle could account for the functional alterations seen in diabetic muscle. © 1994 Wiley-Liss, Inc.
Width dependence of substrate and gate currents in MOSFET's

Width dependence of hot-electron currents in MOSFET's fabricated with LOCOS, non-LOCOS, and a modified LOCOS processes are studied. The experimental results show that the substrate and gate currents are apparently enhanced in narrow width devices. The enhancement, however, is due to different voltage drops across the source-drain series resistance. The voltage drops are usually larger in wider devices. After correcting for the resistance effect, the substrate and gate currents scale with the device width. With this typical LOCOS process, the bird's beak and in-diffusion of field implant dopants do not cause excess hot-electron activities along the channel/field edges as has been suspected. Some other LOCOS process could, of course, produce a different result. Studies using wide test devices must consider the series resistance effect. With this precaution taken, models derived from wide-channel data will be applicable to narrow-channel devices, at least for some processes.
Cardiothoracic surgery residency training: past, present, and future.

Background A dramatic transformation of cardiothoracic surgical education has evolved over the past few decades. Methods We begin by presenting recognized catalysts of this change, organized by whom they primarily affect: the trainees, the trainers, and the profession as a whole. Our trainees' prior training is different, and their current demographics and priorities have changed. There is less incentive to teach, with time-honored traditions of education inadequate to meet the needs of trainees. Concurrently, our profession has to adjust to new regulations, increasing financial constraints, and an expanding body of knowledge and technology. To address these issues requires developing new models of education and assessment that can thrive in today's environment. We discuss efforts in the United States and abroad, including new training paradigms ranging from restructuring existing models to novel approaches (eg, competency-based training). Training tools are being developed, such as online instruction, simulation-based learning, and regular student-centered assessments. Finally, models that recognize and reward teaching as a scholarly activity are being implemented. Conclusions Like the radical advances we have witnessed in surgical therapy, surgical education requires creative and perhaps disruptive changes if we are to continue to produce well-trained additions to our professional ranks.
Synthesis of a Reconfigurable Four-Bar Mechanism with Variable Joints

This article introduces a reconfigurable four-bar mechanism. The mechanism uses a rotational-translational variable joint to switch between a RRRR four-bar and a RRRP1 four-bar. The ability to transition between two types of four-bar mechanisms allows the reconfigurable four-bar mechanism to complete a rigid body guidance task not possible by either a RRRR four-bar mechanism or a RRRP four-bar mechanism. The reconfigurable mechanism reduces the number of required actuators in the mechanism.Copyright © 2014 by ASME
Colorectal and Extracolonic Malignancy in Ulcerative Colitis

In a review of 1248 cases of ulcerative colitis seen at the Cleveland Clinic that were followed up to 1984 (mean, 14.4 years), 82 patients (6.5%) were subsequently found to have colorectal cancer and 48 (3.8%) had extracolonic malignancy, 6 of them with associated colorectal cancer. Most patients with colorectal cancer were men (2:1), and had extensive (90%) and long-lasting colitis (10 years or more in 93% of cases; mean 18 years). Colitis was inactive before the diagnosis of cancer in 48%. Acute onset of the first attack was rare (7%), and the disease had a remittent course in 92%. The mean age at diagnosis of cancer was 43 years. The cumulative risk of colorectal cancer was significantly higher in patients with extensive colitis than in those with left-sided disease (P < 0.0001: 11.9% vs. 1.8% at 20 years and 25.3% vs. 3.7% at 30 years). When comparing mean duration of disease, left-sided colitis (22 years) did not differ significantly from extensive disease. The tumor was multifocal in 13.5%, proximal to the splenic flexure in 44%, and poorly differentiated in 34% of the cases. The diagnosis was suspected clinically in 64% of cases. The prognosis of colorectal cancer in patients with ulcerative colitis appears to be similar to that in the general population. The cumulative 5-year survival rate was 54%. This study supports the concept that surveillance colonoscopy should be started after 8 to 10 years of extensive colitis and after 15 years of left-sided colitis. Among those with extracolonic malignancy, the incidence of bile duct carcinoma, leukemia, bone tumors, and endometrial cancer was significantly greater than expected (P < 0.01), whereas that of lung cancer was significantly lower than expected (P < 0.01). Cancer 58:1569-1574, 1986. OLORECTAL CANCER is known to be a complication C of ulcerative colitis with a reported incidence of 2% to 5%;'-13 however, the risk of cancer is cumulative with time5,6 and is higher in patients with extensive colitis of greater than 8 to 10 years duration.2-6 Early development of ~olitis~,~ and acute onset of the first attack6 are considered risk factors by some authors, but not others.' Some authors have stated that involvement of the left side of the colon only does not carry an increased risk of cancer2.'; others suggest that even in this group the risk is increased, particularly after the colitis has lasted 25 to 30 years.' In patients with ulcerative colitis, cancer frequently tends to be multicentric,'.6 right-~ided,~ and associated with a poor prognosis''; however, more recent studies suggest that the prognosis is no different than for that of colorectal cancer occumng in the general population.8,' ',I2 Subtotal colectomy offers no protection from the inherent risk of malignancy developing in the rectal ~tump.'~-'~ As a means of identifying subgroups of colitis patients who are at high risk of malignancy, Morson and Pang
Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation

The prokaryotic ubiquitin-like protein Pup is involved in the Mycobacterium tuberculosis proteasome pathway but is an intrinsically disordered protein, unlike eukaryotic Ub. Structural data now indicate that the Mycobacterium proteasomal ATPase (Mpa) binds Pup in an α-helical form, indicative of binding-induced folding of Pup upon reaching the proteasome in this system. Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an α-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.
Prostate-specific antigen screening in elderly men

Prostate cancer is the most common noncutaneous cancer in men, it predominantly afflicts elderly men and it will assume increasing importance as the population at large ages. Prostate cancer is variable in its behavior and represents a spectrum of aggressiveness. Prostate cancer screening with prostate-specific antigen (PSA) was first introduced in the early 1980s. Since its introduction, PSA has become not only the most commonly used biomarker for cancer screening, but also the most contentious. Robust, randomized studies elucidating the unequivocal benefits of PSA screening are lacking. The void of reliable evidence has created a confusing environment surrounding the potential advantages, disadvantages, overdiagnosis and overtreatment associated with PSA screening. Current recommendations from leading medical organizations disagree on the appropriateness of PSA screening in all men, especially elderly men; however, there appears to be a trend toward shared decision-making between patient and physician t...
Flocculated amorphous nanoparticles for highly supersaturated solutions.

To recover polymer-stabilized amorphous nanoparticles from aqueous dispersions efficiently by salt flocculation and to show that the particles redisperse and dissolve rapidly to produce highly supersaturated solutions. Nanoparticle dispersions of itraconazole stabilized by nonionic polymers were formed by antisolvent precipitation and immediately flocculated with sodium sulfate, filtered and dried. The size after redispersion in water, crystallinity, and morphology were compared with those for particles produced by spray drying and rapid freezing. Particle drug loading increased to ∼90% after salt flocculation and removal of excess polymer with the filtrate. The formation of the flocs at constant particle volume fraction led to low fractal dimensions (open flocs), which facilitated redispersion in water to the original primary particle size of ∼300 nm. Amorphous particles, which were preserved throughout the flocculation–filtration–drying process, dissolved to supersaturation levels of up to 14 in pH 6.8 media. In contrast, both spray dried and rapidly frozen nanoparticle dispersions crystallized and did not produce submicron particle dispersions upon addition to water, nor high supersaturation values. Salt flocculation produces large yields of high surface area amorphous nanoparticle powders that de-aggregate and dissolve rapidly upon redispersion in pH 6.8 media, for supersaturation levels up to 14.
Factors predictive of improved overall survival following stereotactic radiosurgery for recurrent glioblastoma

The currently accepted standard of care for primary glioblastoma (GBM) consists of maximal surgical resection followed by fractionated external beam radiotherapy (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has typically been applied as a salvage therapy for GBM recurrence. This paper reviews our single institution experience using gamma knife radiosurgery (GKRS) for the treatment of GBM. Thirty-six patients treated with GKRS for pathologically proven GBM at LSU Health in Shreveport from February 2000 to December 2013 were identified and analyzed. Patient characteristics, treatment variables, and survival were correlated. Seven patients received GKRS in the immediate postoperative period for an average tumor volume of 10.9 cm3, and 29 patients were treated for a recurrent average tumor volume of 11.4 cm3 with a prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median overall survival was significantly higher in recurrence group compared to up-front group [7.9 months (0.77–32.1 months) vs. 3.5 months (range 0.23–11.7 months) respectively, (p = 0.018)]. The predictive factors for improved survival in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70 (p = 0.026), age ≤ 50 years (p = 0.006), absence of neurodeficits (p = 0.01), and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with GKRS following GBM recurrence demonstrates statistical superiority over immediate postoperative boost therapy.
Has implementation of the 80-hour work week made a career in surgery more appealing to medical students?

Abstract Background This study was conducted to determine if a surgical career became more appealing to medical students with the resident work week limited to 80 hours. Methods At the start and conclusion of each surgery clerkship rotation, students completed a survey addressing perception of surgeons, and surgery as a career. They were divided into the control groups (rotations before July 2003; n=109) and the experimental group (rotations after July 2003; n=108). Results Students in the experimental group had a significantly more favorable impression of a surgeon's lifestyle and work hours than those in the control group. This was especially true of female students post-rotation, who responded more positively to the statement that a surgical career would allow for a good balance between professional and personal life (1.87 vs 2.45, P Conclusion The new Accreditation Council for Graduate Medical Education (ACGME) regulation has had a positive impact on students' perceptions of the surgeon's lifestyle, but does not necessarily increase their interest in a surgical career.
A National Survey of Transition Services for Deaf and Hard of Hearing Students

This manuscript analyzed a survey of programs providing transition services to deaf and hard-of-hearing (D/HH) students. Quantitative analyses compared services offered by residential, large (35+ D...
Protein tolerance to random amino acid change

Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations to evolve novel proteins. To quantitate protein tolerance to random change, it is vital to understand the probability that a random amino acid replacement will lead to a protein's functional inactivation. We define this probability as the "x factor." Here, we develop a broadly applicable approach to calculate x factors and demonstrate this method using the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG). Three gene-wide mutagenesis libraries were created, each with 10(5) diversity and averaging 2.2, 4.6, and 6.2 random amino acid changes per mutant. After determining the percentage of functional mutants in each library using high-stringency selection (>19,000-fold), the x factor was found to be 34% +/- 6%. Remarkably, reanalysis of data from studies of diverse proteins reveals similar inactivation probabilities. To delineate the nature of tolerated amino acid substitutions, we sequenced 244 surviving AAG mutants. The 920 tolerated substitutions were characterized by substitutability index and mapped onto the AAG primary, secondary, and known tertiary structures. Evolutionarily conserved residues show low substitutability indices. In AAG, beta strands are on average less substitutable than alpha helices; and surface loops that are not involved in DNA binding are the most substitutable. Our results are relevant to such diverse topics as applied molecular evolution, the rate of introduction of deleterious alleles into genomes in evolutionary history, and organisms' tolerance of mutational burden.
Exemplification and Parthood

Consider the things that exist—the entities—and let us suppose they are mereologically structured, that is, some are parts of others. The project of ontology within the bounds of bare mereology use this structure to say which of these entities belong to various ontological kinds, such as properties and particulars. My purpose in this paper is to defend the most radical section of the project, the mereological theory of the exemplification of universals. Along the way I help myself to several hypotheses: the existence of merely possible worlds; that particulars have thisnesses; and that mereology is far from classical. Moreover, the way I characterize instantiation might be judged too complicated to be plausible. At the end of the paper, I reply to these objections based on complexity.
Synthesis of Hantsch 1,4-dihydropyridines by fermenting bakers’ yeast

Abstract Hantsch 1,4-dihydropyridines are prepared by fermenting bakers’ yeast with alkyl acetoacetate and ammonium acetate.
A novel role for non-ubiquitinated FANCD2 in response to hydroxyurea-induced DNA damage

Fanconi anemia (FA) is a genetic disease of bone marrow failure, cancer susceptibility, and sensitivity to DNA crosslinking agents. FANCD2, the central protein of the FA pathway, is monoubiquitinated upon DNA damage, such as crosslinkers and replication blockers such as hydroxyurea (HU). Even though FA cells demonstrate unequivocal sensitivity to crosslinkers, such as mitomycin C (MMC), we find that they are largely resistant to HU, except for cells absent for expression of FANCD2. FANCD2, RAD51 and RAD18 form a complex, which is enhanced upon HU exposure. Surprisingly, although FANCD2 is required for this enhanced interaction, its monoubiquitination is not. Similarly, non-ubiquitinated FANCD2 can still support proliferation cell nuclear antigen (PCNA) monoubiquitination. RAD51, but not BRCA2, is also required for PCNA monoubiquitination in response to HU, suggesting that this function is independent of homologous recombination (HR). We further show that translesion (TLS) polymerase PolH chromatin localization is decreased in FANCD2 deficient cells, FANCD2 siRNA knockdown cells and RAD51 siRNA knockdown cells, and PolH knockdown results in HU sensitivity only. Our data suggest that FANCD2 and RAD51 have an important role in PCNA monoubiquitination and TLS in a FANCD2 monoubiquitination and HR-independent manner in response to HU. This effect is not observed with MMC treatment, suggesting a non-canonical function for the FA pathway in response to different types of DNA damage.
Duration discrimination and subjective duration for ramped and damped sounds.

The perception of stimuli with ramped envelopes (gradual attack and abrupt decay) and damped envelopes (abrupt attack and gradual decay) was studied in subjective and objective tasks. Magnitude estimation (ME) of perceived duration was measured for broadband noise, 1.0-kHz, and 8.0-kHz tones for durations between 10 and 200 ms. Damped sounds were judged to be shorter than ramped sounds. Matching experiments between sounds with ramped, damped, and rectangular envelopes also showed that damped sounds are perceived to be shorter than ramped sounds, and, additionally, the reason for the effect is a result of the damped sound being judged shorter than a rectangular-gated sound rather than the ramped sound being judged longer than a rectangular-gated sound. These matching studies also demonstrate that the size of the effect is larger for tones (factor of 2.0) than for broadband noise (factor of 1.5). There are two plausible explanations for the finding that damped sounds are judged to be shorter than ramped or rectangular-gated sounds: (1) the abrupt offset at a high level of the ramped sound (or a rectangular-gated sound) results in a persistence of perception (forward masking) that is considered in judgments of the subjective duration; and (2) listeners may ignore a portion of the decay of a damped sound because they consider it an “echo” [Stecker and Hafter, J. Acoust. Soc. Am. 107, 3358–3368 (2000)]. In another experiment, duration discrimination for broadband noise with ramped, damped, and rectangular envelopes was studied as a function of duration (10 to 100 ms) to determine if differences in perceived duration are associated with the size of measured Weber fractions. A forced-choice adaptive procedure was used. Duration discrimination was poorer for noise with ramped envelopes than for noise with damped or rectangular envelopes. This result is inconsistent with differences in perceived duration and no explanation was readily apparent.
Probing RNA in Vivo with Methylation Guide Small Nucleolar RNAs

Most box C/D small nucleolar RNAs (snoRNAs) direct the formation of 2'-O-methylated nucleotides in ribosomal RNA and, apparently, other RNAs present in the nucleolar complex. Sites to be modified are selected by a long (>10-nt) antisense guide sequence in the snoRNA and a distance measurement from a box D or D' element that follows the snoRNA guide sequence. Modification of the substrate occurs in the region of complementarity, at a position five nucleotides upstream from box D/D'. Methylation can be targeted to novel sites by expressing a snoRNA with a new guide sequence. In some cases methylation impairs the growth rate of the cell, indicating that a functionally important nucleotide has been altered. With a view to harnessing snoRNA-directed methylation for functional mapping, we have developed a method for constructing libraries of snoRNA genes that, in principle, can introduce methylation point mutations into any rRNA segment of interest. The strategy and procedures are described here, and preliminary results are presented that show the feasibility of using this technology to probe a region of the yeast large subunit rRNA that includes the core of the peptidyltransferase center.