cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of breast milk in acquisition of cytomegalovirus infection: recent advances.

PURPOSE OF REVIEW Congenital infection with cytomegalovirus is a major cause of disability in newborns. Recently, there has been increased emphasis on the study of postnatally acquired cytomegalovirus infection. One route by which cytomegalovirus infections are acquired in newborns is via consumption of breast milk from cytomegalovirus-seropositive, lactating mothers. The purpose of this review is to summarize recent studies of breast-milk-acquired cytomegalovirus infections in newborns, particularly in low-birth-weight premature infants. RECENT FINDINGS Nearly all cytomegalovirus-seropositive women will reactivate and shed cytomegalovirus during lactation, as demonstrated by sensitive polymerase chain reaction techniques, as well as by viral culture of breast milk. A substantial proportion of infants exposed to cytomegalovirus in breast milk will acquire a primary cytomegalovirus infection. Although acquisition of cytomegalovirus by this route is seldom of consequence in healthy term infants, cytomegalovirus infections in low-birth-weight premature infants have been demonstrated to cause symptomatic illness, including hepatitis, neutropenia, thrombocytopenia, and a 'sepsis-like' state. SUMMARY Cytomegalovirus is commonly shed in human milk, and cytomegalovirus-seropositive women can transmit this infection via breast-feeding. The benefits of breast-feeding greatly outweigh the minimal risk, if any, of infections transmitted to term infants. Caution is warranted, however, in low-birth-weight premature infants, who are at increased risk of cytomegalovirus disease. Interventions to screen breast milk, or to attempt to render breast milk noninfectious through treatments such as freezing, may be warranted in high-risk premature infants.
Effective Load Demand of Electric Vehicles in Power System Adequacy Assessment

The continuous increase of electric vehicles (EVs) has led to several challenges for the reliability of power systems. These challenges are mostly related to the variability of the charging time, duration, and location. Determining the required resources to maintain the reliability of power systems is a key factor in addressing these challenges. This paper introduces the concept of “Effective Load Demand” of EVs (ELD-EVs) in power system adequacy assessment. The ELD-EVs is defined as the amount of extra generation needed to restore the initial reliability level (i.e., the reliability level prior to adding the load of EVs). Also, this paper establishes a load profile that depicts the charging time, duration, and location of EVs. The load profile is represented in terms of weekly, daily, and hourly charging load data over one year. The estimation of the ELD-EVs is demonstrated on the IEEE Reliability Test System for several case studies. In all case studies, an equivalent load of 30,000 EVs with different charging patterns is determined. Monte Carlo simulations are used to evaluate the well-known power system reliability indices and the ELD-EVs. The resulting ELD-EVs can be used to determine the amount of the extra generation needed to maintain the reliability of a power system.
The Association Between Patient Satisfaction and Patient-Reported Health Outcomes.

Objective:Although patient satisfaction is increasingly used to rate hospitals, it is unclear how patient satisfaction is associated with health outcomes. We sought to define the relationship of se...
Outcomes for matched patients with metastatic colitis-associated cancers versus sporadic colorectal cancer receiving chemotherapy.

e15534Background: Colitis-associated cancers (CAC) develop in the setting of inflammatory bowel disease (IBD) and have a distinct pathogenesis and genomic features compared to sporadic colorectal c...
Navigating Americanized Identities: Bicultural Ethnicity, Race, and the Incorporation Experience

This paper reports on the complex ways in which immigrant young adults make sense of their Americanized ethnic and racial identities. The analysis draws on a large set of in-depth interviews (N = 233) collected with immigrants between the ages of 18 and 29 across three regions in the US (California, New York, and Minnesota) in the early 2000s and is in dialogue with emerging new theories of immigrant incorporation which combine the insights of traditional assimilation and racialization frameworks. The identity narratives that emerge from these interviews demonstrate the overarching significance of racial and ethnic identification for young adults across various immigrant communities. The narratives also highlight some of the contextual factors involved in the construction of an ethnic identity in the US such as experiences with discrimination; or the presence of co-ethnic communities. The final substantive section explores how young American immigrants in the transition to adulthood attempt to cultivate hybrid, bicultural identities that balance their American-ness with the ongoing experience of living in a deeply racialized society. The paper concludes by discussing implications for the literature on identity formation and the transition to adulthood as well as on the immigrant incorporation experience.
Establishment of Slice Cultures as a Tool to Study the Cancer Immune Microenvironment

Although immunotherapy is currently being widely applied to treat a variety of cancers, there is great heterogeneity in the response to these treatments. Many in the field hypothesize that this may be attributable to the characteristics of each individual tumor immune microenvironment, in addition to systemic immune factors. Therefore, understanding the immune cell microenvironment in a variety of tumors is critically important. Specifically, the interactions among immune, stromal, and cancer cells, along with other factors in tumors, may hold the key to developing rational personalized combinations of immunotherapeutic drugs. We recently developed an organotypic slice culture technique, which enables precise study of the pancreatic ductal adenocarcinoma (PDA) tumor microenvironment. We used a Vibratome to cut fresh human tumor tissue into 250 μm thick slices, and cultured slices on cell culture inserts with 0.4 μm pore to produce our tumor slice culture (TSC) system. We showed that TSC maintained many elements of the original tumor microenvironment and architecture for approximately one week. Using this slice culture technique for PDA, we demonstrated that immune cells, including T cells and macrophages, cancer cells, and stromal myofibroblasts were present throughout the culture period. TSCs were functionally responsive to drug treatment. Live PDA slices could be stained for multicolor immunofluorescence imaging of each of the primary cellular constituents of the tumor. Finally, autologous CFSE-labeled splenocytes were observed to readily migrate into cocultured tumor slices.
Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL cholesterol

Lecithin:cholesterol acyltransferase (LCAT) and LCAT-activating small molecules are being investigated as treatments for coronary heart disease (CHD) and familial LCAT deficiency (FLD). Herein we report the crystal structure of LCAT bound to a potent activator and an acyl intermediate-like inhibitor, thereby revealing an active conformation of LCAT and that the activator is bound exclusively to its membrane-binding domain (MBD). Functional studies indicate that the compound does not modulate the affinity of LCAT for HDL, but instead stabilizes residues in the MBD and likely facilitates channeling of substrates into the active site. By demonstrating that these activators increase the activity of an FLD variant, we show that compounds targeting the MBD have therapeutic potential. In addition, our data better define the acyl binding site of LCAT and pave the way for rational design of LCAT agonists and improved biotherapeutics for augmenting or restoring reverse cholesterol transport in CHD and FLD patients.
Croconaine Rotaxane Dye with 984 nm Absorption: Wavelength‐Selective Photothermal Heating

Croconaines are an emerging class of near-infrared dyes that are useful for various sensing, photothermal, optoelectronic, and photoacoustic applications. Previous work encapsulated a dumbbell-shaped croconaine dye whose structure contains two thiophene flanking units inside a tetralactam macrocycle and produced a croconaine rotaxane 1 with a narrow 824 nm absorption band. Herein, a new rotaxane 2 is reported that encapsulates a croconaine dye with two thienothiophene flanking units. The new croconaine rotaxane 2 exhibits a narrow 984 nm absorption band that is distinct from the 824 nm absorption of rotaxane 1. Photothermal heating experiments showed that an 830 nm diode laser selectively heats a solution containing rotaxane 1, with no heating of a solution containing rotaxane 2. Conversely, a 980 nm diode laser selectively heats a solution containing rotaxane 2, with no heating of a solution containing rotaxane 1. The new croconaine rotaxane 2 shows no fatigue after four cycles of laser heating and cooling.
Just Transitions/Design for Transitions: Preliminary Notes on a Design Politics for a Green New Deal

Mobilizations occurring around just transitions and design for transition contain many potential points of overlap. They are presently remarkably disengaged. This article seeks to rectify this situ...
Understanding Teacher Candidate Misconceptions and Concerns about Differentiated Instruction.

AbstractWhile teacher education programs are expected to teach effective methods of differentiating instruction, limited research to date has examined the meaning-making processes through which can...
IQ, CULPABILITY, AND THE CRIMINAL LAW’S “GRAY AREA”: WHY THE RATIONALE FOR REDUCING THE CULPABILITY OF JUVENILES AND INTELLECTUALLYDISABLED ADULTS SHOULD APPLY TO LOW-IQ ADULTS

For too long, the criminal law has only provided legal protections for defendants who exist on the margins, namely, those who suffer from mental retardation, insanity, or are too young to appreciate the consequences of criminal conduct. In so doing, the criminal law has failed to address the gray area in which most defendants reside, and for which all defendants lack sufficient legal protections. For example, at the guilt/innocence phase of a criminal trial, the legal system offers little, if any protections, for defendants afflicted with mental illnesses, personality disorders, neurological impairments, and borderline intellectual functioning. This is fundamentally unjust, contrary to relevant empirical evidence regarding the effects of cognitive, psychiatric, and psychological disorders on culpability, and results in profoundly unjust sentences that, in many cases, are entirely disproportionate to a defendant’s culpability. As such, the time has arrived for the courts and legislators to recognize that defendants need not be intellectually disabled, insane, or under the age of eighteen to trigger legal and constitutional protections at the guilt/innocence phase that account for a defendant’s reduced or, even, zero culpability in certain cases.
Holographic near-eye displays based on overlap-add stereograms

Holographic near-eye displays are a key enabling technology for virtual and augmented reality (VR/AR) applications. Holographic stereograms (HS) are a method of encoding a light field into a hologram, which enables them to natively support view-dependent lighting effects. However, existing HS algorithms require the choice of a hogel size, forcing a tradeoff between spatial and angular resolution. Based on the fact that the short-time Fourier transform (STFT) connects a hologram to its observable light field, we develop the overlap-add stereogram (OLAS) as the correct method of "inverting" the light field into a hologram via the STFT. The OLAS makes more efficient use of the information contained within the light field than previous HS algorithms, exhibiting better image quality at a range of distances and hogel sizes. Most remarkably, the OLAS does not degrade spatial resolution with increasing hogel size, overcoming the spatio-angular resolution tradeoff that previous HS algorithms face. Importantly, the optimal hogel size of previous methods typically varies with the depth of every object in a scene, making the OLAS not only a hogel size-invariant method, but also nearly scene independent. We demonstrate the performance of the OLAS both in simulation and on a prototype near-eye display system, showing focusing capabilities and view-dependent effects.
Innovative Approaches to Emergency Medical Services Fellowship Challenges

Author(s): Weston, Benjamin W.; Gaither, Joshua; Schulz, Kevin; Srinivasen, Saranya; Smith, Jennifer J.; Colella, M. Riccardo | Abstract: Introduction: Since the development of an Accreditation Council of Graduate Medical Education (ACGME)-accredited emergency medical services (EMS) fellowship, there has been little published literature on effective methods of content delivery or training modalities. Here we explore a variety of innovative approaches to the development and revision of the EMS fellowship curriculum.Methods: Three academic, university-based ACGME-accredited EMS fellowship programs each implemented an innovative change to their existing training curricula. These changes included the following: a novel didactic curriculum delivery modality and evaluation; implementation of a distance education program to improve EMS fellows’ rural EMS experiences; and modification of an existing EMS fellowship curriculum to train a non-emergency medicine physician.Results: Changes made to each of the above EMS fellowship programs addressed unique challenges, demonstrating areas of success and promise for more generalized implementation of these curricula. Obstacles remain in tailoring the described curricula to the needs of each unique institution and system.Conclusion: Three separate curricula and program changes were implemented to overcome specific challenges and achieve educational goals. It is our hope that our shared experiences will enable others in addressing common barriers to teaching the EMS fellowship core content and share similar innovative approaches to educational challenges.
Colon and Rectum; Anatomy and Development

Abstract This article provides an introductory description of the appearance, structure, histologic layers, anatomic positioning, and function of the segments of the colon and rectum (large intestines). We also describe specific clinical circumstances where knowledge of these basic concepts is critical to medical care. Next, we outline the normal steps that the colon undergoes during embryologic development in order to form and position itself within the abdomen. We then follow that by describing congenital conditions that result from failure of the colon to undergo normal development at different points within this process.
Twelve tips for interfacing with the new generation of medical students: iGen

iGen, or Generation Z, is the newest generation of health professions students to enter the classroom. This generation represents the first cohort of students in which technology has been present in all aspects of their lives. Since birth, they have been influenced by the boom of social media and wide-spread internet availability, leading to decreased face-to-face interactions and a desire for immediate access to information. Health professions educators should recognize the unique attributes of iGen students in order to foster student success and create a more positive learning environment. The following twelve tips examine the research-based distinctive characteristics of iGen students and highlight important concepts to consider when modifying current pedagogy to better support their needs. Incorporating these tips as an educator can promote lifelong learning and skill development for iGen students and empower this generation to thrive.
Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in post-liver transplant patients with previous direct-acting antiviral failure: Six case reports.

Background Direct-acting antiviral (DAA) therapy regimens are highly effective at eliminating hepatitis C virus (HCV) infection but rates of sustained virologic response (SVR) are lower in patients with decompensated cirrhosis or hepatocellular carcinoma. Since many of these patients will be referred for liver transplant, they will require retreatment after transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data. Case summary We present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant. Conclusion This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients achieving SVR, it was well tolerated, and there were minimal drug-drug interactions with their immunosuppressants.
Faculty preceptors' strategies for teaching clinical reasoning skills in the advanced pharmacy practice experience setting.

Abstract Introduction Clinical reasoning is essential to providing quality patient care. However, advanced pharmacy practice experience (APPE) students may struggle with the real-life aspects of patient care, and it may be difficult to quickly identify these students in order to make meaningful interventions. The purpose of this study was to explore pharmacy faculty preceptors' strategies for identifying gaps and teaching clinical reasoning in the APPE setting. Methods A qualitative study utilizing 30-min, one-on-one phone interviews was conducted with faculty members from two schools of pharmacy. Faculty participants were invited based on their APPE preceptor role and expertise in adult general medicine. Interview questions collected faculty demographics and reflections on evaluation and instruction of clinical reasoning skills. Demographics were analyzed using descriptive statistics. Thematic analysis was completed to identify themes from qualitative interview data. Results Fifteen faculty preceptors participated. The cohort had an average of 17.1 pharmacy practice years and an average of 11.9 faculty member years. Interviews yielded a 7735-word document for data analysis, which resulted in 11 themes. Conclusions This study explored pharmacy faculty preceptors' strategies for identifying gaps in clinical reasoning and their instructional methods to improve those skills, which resulted in 11 themes. Future directions include implementation of a standardized clinical reasoning assessment tool in the APPE setting and exploration of targeted educational interventions.
Shape From Shading: A Non-iterative Method Using Neural Networks

Shape from shading is an important domain of computer vision and one of the approaches of 3D reconstruction. In this paper we propose a new method to reconstruct the surface of an object using neural networks. This approach ignores the details of the image for a big gain in noise resistance. It is based on the available boundary information of the surface of the shape to be reconstructed. We will use a neural network to evaluate the variation of the surface for a pixel based on the adjacent pixels. The small number of neurons ensures the speed of the algorithm. The approach is tested on synthetic and real images .
Cybersecurity: Of Heterogeneity and Autarky

The Internet is an almost organic mix of actors and their machines, an eclectic scheme of government and private decision-making, of nonprofits and for-profits. As in any integrated system, my choices affect your life in a very direct way. So “Zombie PC Army Responsible for Big-Name Web Blackout” sounds like a headline from a bad Hollywood B movie when instead it means that computer users could not access the websites of Apple, Google, Microsoft and Yahoo because a Trojan horse program – which, by definition, had been placed surreptitiously on thousands of personal computers, turning those machines into zombie computers under the control of their cybermaster – launched a simultaneous attack on a key piece of the domain name system infrastructure (Lemos and Hu 2004). Here we have perhaps one bad actor, thousands of sloppy computer users, and externalities galore. Taking down prominent websites is one way for a malicious computer programmer to seek fame (perhaps infamy), but spam provides perhaps a more meaningful way in which the day-to-day computer experience is degraded by our shared network decisions. Some estimates suggest that 80% of spam arises from zombie machines (Sandvine Inc. 2004). Many of these are residential PCs with broadband hookups. Why? This is the dark side of Yochai Benkler's (2004) work on shareable goods. From the consumer's perspective, both the PC and the broadband connection are shareable goods. Given the lumpiness of processing power, the average PC user has power to spare.
Design of a Barrel-Vault Cofferdam

A unique proposal for the construction of a cofferdam for repair work on the walls of a canal consists of a ring-reinforced steel barrel-vault with rubber bearing pads and seals at the edges and end. The general instability of the skin-ring combination commonly is checked by comparing the line load equivalent to a tributary length times the pressure with the ring-buckling line load. The ring in this case has its ends free to slide and in addition may be affected by eccentricity at the ends, by initial movement or elastic support of the ends or by out-of-roundness. These and other effects are analyzed and discussed with the problems of design of such a cofferdam in view.
Digitization Programs at STScI

The Space Telescope Science Institute (STScI) continues with its programs of digitization, cataloging and data distribution. These were defined earlier, at the Geneva and the Edinburgh workshops (Jaschek 1989; MacGillivray & Thomson 1992), and this report, by necessity of space, is incremental upon them.
Propagation characteristics of ground based urban communications in the military UHF band

A series of experiments were conducted to characterize the propagation characteristics in an urban canyon setting between ground-based communicators operating within the military ultrahigh frequency band (225 to 450 MHz). The experiments were conducted over a two-day period in downtown Philadelphia. Profiles of received power versus distance were generated along a variety of straight and L-shaped paths for different radio frequencies and antenna heights. The results were analyzed to determine the dependency of the received power on street width, RF frequency, antenna height, and corner distance (the distance between the transmitter and the corner on an L-shaped path). The results showed well-defined dependencies on all of the parameters except antenna height, which did not appear to affect the results over the range of values considered in this study. The results are compared with similar measurements by other investigators operating at higher frequencies in an attempt to identify the impact of RF frequency on urban propagation. This study addresses an important but largely overlooked propagation environment
Check list of the plants of Rhum, inner hebrides (V.-C. 104, North Ebudes)

(1965). Check list of the plants of Rhum, inner hebrides (V.-C. 104, North Ebudes) Transactions of the Botanical Society of Edinburgh: Vol. 40, No. 1, pp. 20-59.
Extracting a climate signal from the skeletal geochemistry of the Caribbean coral Siderastrea siderea

[1] The first bimonthly time series of paired δ18O and Sr/Ca from the slow-growing coral Siderastrea siderea, from the Dry Tortugas, Florida, has been generated that documents that robust proxy climate records of the tropical Atlantic and IntraAmerican Seas can be produced from this massive coral. The time series contain a 20-year-long calibration window (1973–1992) for both δ18O and Sr/Ca and a 73-year-long verification window (1900–1972) for Sr/Ca. These time series permit the quantification of the relationship between coral δ18O-SST and Sr/Ca-SST and the assessment of the stability of the proxy relationships over time. Both coral geochemical records are highly correlated with the augmented instrumental SST record through the calibration period, and Sr/Ca remains highly correlated through the verification period both at the bimonthly (r = −0.97) and annual average resolution (r = −0.72). Coral δ18O and Sr/Ca are highly reproducible within the same core, and Sr/Ca exhibits no extension-related vital effects. This study sets the stage for generating multicentury scale climate records from the tropical Atlantic Ocean using the skeletal geochemistry of this massive, but slow growing coral.
Use of the exponential multipath profile model to predict the performance of indoor radio systems using combined antenna and spread-spectrum diversity

The performance of an indoor wireless spread-spectrum communication system is conveniently analyzed assuming that the multipath profile is a constant function of delay. However, experimental measurements appear to fit an exponential profile better. Assuming flat Rayleigh fading and an exponential multipath profile, we derive a closed form expression for the bit error rate of BPSK with spread-spectrum and antenna diversity. Comparison of these results with simulated results based on actual channel measurements shows that the exponential profile model differs from the simulation model by only 1-2 dB whereas the constant profile model differs by as much as 5 dB. >
Reticulocalbin-1 Facilitates Microglial Phagocytosis

Phagocytosis is critical to the clearance of apoptotic cells, cellular debris and deleterious metabolic products for tissue homeostasis. Phagocytosis ligands directly recognizing deleterious cargos are the key to defining the functional roles of phagocytes, but are traditionally identified on a case-by-case basis with technical challenges. As a result, extrinsic regulation of phagocytosis is poorly defined. Here we demonstrate that microglial phagocytosis ligands can be systematically identified by a new approach of functional screening. One of the identified ligands is reticulocalbin-1 (Rcn1), which was originally reported as a Ca2+-binding protein with a strict expression in the endoplasmic reticulum. Our results showed that Rcn1 can be secreted from healthy cells and that secreted Rcn1 selectively bound to the surface of apoptotic neurons, but not healthy neurons. Independent characterization revealed that Rcn1 stimulated microglial phagocytosis of apoptotic but not healthy neurons. Ingested apoptotic cells were targeted to phagosomes and co-localized with phagosome marker Rab7. These data suggest that Rcn1 is a genuine phagocytosis ligand. The new approach described in this study will enable systematic identification of microglial phagocytosis ligands with broad applicability to many other phagocytes.
CAD Using Green's Functions and Finite Elements and Comparison to Experimental Structures for Inhomogeneous Microstrip Circulators

Publisher Summary Computer aided design (CAD) has become indispensable in the microwave electronic industry—an industry devoted to producing reliable, lightweight, compact, and efficient circuits for commercial and military applications. Use of CAD to solve physics and engineering design problems for components used in electromagnetic communication equipment has been the norm today for components, such as filters, resonators, isolators, limiters, oscillators, transmission lines, couplers, attenuators, and amplifiers, as well as circulators. The microstrip circulator is a basic building-block device in many microwave and millimeter wave circuits because it provides nonreciprocal port control in the planar format, presently, the technology of choice for all advanced hybrid and monolithic integrated circuits. CAD techniques that lead to realistic engineering design imply that all the modeling tools to be used must allow rapid redesign trials of device structures. The Green's function approaches meet this criterion as they allow analytical integration at several stages of derivation and lead to expressions that may be evaluated to determine electromagnetic fields and s-parameters.
Topology design for metropolitan area network

A new topology that is highly suitable for a metropolitan area network is presented. The topology can be designed for any number of nodes in the network and is incremently expandable. It has a good node connectivity and a small diameter. The diameter of the topology in presence of node failure increases only by a small constant quantity. Algorithms for data routing both in the presence and absence of node failures in the network are presented. >
Islamic Law in Action: A Historical Discussion

This review essay engages Kristen Stilt's recent book, Islamic Law in Action: Authority, Discretion, and Everyday Experiences in Mamluk Egypt (2011), in a fashion that highlights its contributions to the study of Islamic law. In particular, it underlines the methodological arguments made in the book that might help us think about Islamic legal practice in sophisticated and historically grounded ways. As elaborated in the article, these arguments have important implications for modern as well historical settings. Specifically, Stilt's discussion of “Islamic law in action” reveals the inherent flexibility of Islamic legal practice to accommodate political change. The article also discusses how further research on the topic could benefit from specific approaches and orientations.
Effect of hand sanitizer location on hand hygiene compliance

Background Hand hygiene is the most important intervention to prevent infection in hospitals. Health care workers should clean their hands at least before and after contact with patients. Hand sanitizer dispensers are important to support hand hygiene because they can be made available throughout hospital units. The aim of this study was to determine whether the usability of sanitizer dispensers correlates with compliance of staff in using the sanitizer in a hospital. This study took place in a Midwest, 404-bed, private, nonprofit community hospital with 15 inpatient care units in addition to several ambulatory units. Methods The usability and standardization of sanitizers in 12 participating inpatient units were evaluated. The hospital measured compliance of staff with hand hygiene as part of their quality improvement program. Data from 2010-2012 were analyzed to measure the relationship between compliance and usability using mixed-effects logistic regression models. Results The total usability score ( P = .0046), visibility ( P = .003), and accessibility of the sanitizer on entrance to the patient room ( P = .00055) were statistically associated with higher observed compliance rates. Standardization alone showed no significant impact on observed compliance ( P = .37). Conclusion Hand hygiene compliance can be influenced by visibility and accessibility of dispensers. The sanitizer location should be part of multifaceted interventions to improve hand hygiene.
Histologic prognostication in soft tissue sarcomas: Grading versus subtyping or both? A comprehensive review of the literature with proposed practical guidelines

Despite the validation of many histologic grading systems for soft tissue sarcomas, none have been universally accepted. Because of the overall rarity of specific histologic sarcoma subtypes, evaluation of grading systems and their prognostic significance have tended to base the results on sarcomas as a general group, diminishing the value and significance of histologic subtyping. A representative review of the literature regarding histologic grading of soft tissue sarcomas and its relationship to histologic subtype, stage, and prognosis is analyzed and discussed. Histologic grading of many soft tissue sarcomas appears to be a valuable predictor of patient survival, as confirmed by the literature. However, accurate histologic subtyping is essential for accurate histologic grading. Histologic grading in some sarcoma subtypes is probably not applicable and may underestimate biologic behavior. Clinicians and pathologists should be aware of the limitations, prognostic significances, and relationships of histologic subtyping and histologic grading in the therapeutic management and prognostication of soft tissue sarcomas.
Great works for the 21st century: a critical role for the modern research university

As we enter the 21st century, there can be no doubt that our world faces an enormous range of social, technological, and political challenges. For example, with almost 3 billion people on the planet earning less than $2/day, over one billion people still lack access to clean drinking water. If we want to stabilize global warming at 2oC, we will need the ability to produce 30-60 terawatts of carbon-free power by 2050 -- the equivalent of a large, carbon-free power plant every day between now and the year 2050. As daunting as these challenges seem, we must remember that individuals, governments, and foundations are capable of "great works" that lead to economic and social progress and improvements in our quality of life. Examples in the 20th century include Andrew Carnegie's decision to fund public libraries, the GI Bill, the Marshall Plan, the eradication of smallpox, and the Green Revolution.Throughout history, the major research universities in the world have played a leading role in informing public debate, identifying key issues, performing basic research that has led to many of the major developments of our age and, last but not least, educating our global leaders. Today, a growing number of faculty at major research universities throughout the world are interested in pursuing research, education and service that addresses the major domestic and global challenges we all face. As an example at Berkeley, this is reflected in multidisciplinary initiatives such as our Center for Information Technology Research in the Interest of Society (CITRIS). Obviously, such an agenda does not supplant the need for continued excellence in individual disciplines and for basic, curiosity-driven research.In this presentation I will describe a set of candidate Great Works for the 21st Century and will sketch an outline of how the world's leading research universities could collaborate to determine a global research agenda, to identify and prioritize the problems we face, and to develop an international public-private partnership to tackle them.
Cat scratch‐induced Pasteurella multocida necrotizing cellulitis in a dog

Background In humans, rapidly developing Pasteurella multocida cellulitis after a cat scratch or bite is a well-known entity that sometimes progresses to necrotizing fasciitis and can be fatal. Case report A 3-year-old female spayed whippet dog developed ecchymosis, swelling and pain within 24 h of being scratched by a cat on the ventral thorax. Over the following days, while being treated only with pain medications, the lesions rapidly progressed into haemorrhagic bullae with expanding skin necrosis. A heavy growth of P. multocida was seen on bacterial cultures, and histological examination showed marked, suppurative panniculitis with necrosis of the epidermis, dermis and panniculus. Special histological stains highlighted a moderate amount of Gram-negative coccobacilli admixed with inflammatory cells. Complete resolution was achieved with surgical debridement, skin grafting and intravenous antibiotic treatment. Positive bacterial culture for P. multocida, in conjunction with the history, clinical findings, histology results and the rapid response to therapy, strongly supports a diagnosis of P. multocida necrotizing cellulitis. Conclusions and clinical importance Complications of cat bite-associated P. multocida infections in humans are well known. To the authors' knowledge, this is the first documentation of P. multocida necrotizing cellulitis in a dog following a cat scratch wound. This case highlights the rapidity and severity of P. multocida cellulitis, if not recognized and treated early. Veterinarians should include P. multocida in the differential diagnosis of any local wound infection following a cat scratch.
Partial purification and characterization of a nerve trophic factor regulating muscle acetylcholinesterase activity

Abstract A protein influencing acetylcholinesterase activity of newt triceps muscle in organ culture has been identified and partially purified from rat brain homogenates by gel filtration, ion-exchange chromatography, and isoelectric focusing. Muscles treated with fractions containing the active factor had higher acetylcholinesterase activity than paired untreated muscles after 1 week in organ culture. Analysis of the molecular forms of acetylcholinesterase by velocity sedimentation showed that the factor had the greatest effect on the 16.5 S acetylcholinesterase, increasing it more than 100% of untreated controls. With isoelectric focusing, activity was present in a fraction focusing at p H 8.3. On SDS-polyacrylamide gel electrophoresis, a protein with a molecular weight of 34,000 was present in active fractions and was the major component of the isoelectric focusing p H 8.3 fraction. These findings indicate that a small basic protein, which we have termed neurotrophin, mediates the neuronal trophic effect on skeletal muscle acetylcholinesterase.
A new lipase in regulating lipid mobilization: hormone-sensitive lipase is not alone

Three papers recently appeared simultaneously that identify a new triacylglycerol lipase. Zimmerman et al. identified this lipase as adipocyte triacylglycerol lipase (ATGL). Jenkins et al. identified it as the ζ-isoform of a calcium-independent phospholipase A 2 (iPLA 2 ), whereas Villena et al. found this enzyme and called it desnutrin. Interestingly, if, as implied, this lipase works in concert with hormone-sensitive lipase, then our concept of regulated fatty acid mobilization from triacylglycerols will have to be revised.
Proteoglycans and Hypertension: III: Aorta Proteoglycans in Dahl Salt-Sensitive Hypertensive Rats

The vascular proteoglycans probably have an important influence on the biomechanical properties of blood vessels and, therefore, may play a role in the development or maintenance of hypertension. In the aorta of the spontaneously hypertensive rat, the authors previously observed an increased content of chondroitin sulfate, an increased incorporation of [35S]sulfate into proteoglycans, and qualitative alterations in the [35S]polysaccharides compared to the normotensive Wistar Kyoto rat. To determine if these differences were related to hypertension or to strain variations, normotensive and hypertensive Dahl S rats were studied. There was a significant elevation (70%) in the aorta content of chondroitin sulfate, whereas the dermatan sulfate and hyaluronic acid contents were similar in the two groups. The in vitro incorporation of [35S]sulfate was increased 2.6-fold in the hypertensive animals. No differences between the two groups were observed with respect to the gel chromatographic profiles of the [35S]proteoglycans or the charge density of the [35S]glycosaminoglycans, as assessed by ion exchange chromatography. It was concluded that the increase in chondroitin sulfate and [35S]sulfate incorporation into proteoglycans occurred as a result of hypertension, regardless of genetic factors.
On the spatial pattern of casualties in earthquakes.

Comment on: GIS mapping of earthquake-related deaths and hospital admissions from the 1994 Northridge, California, Earthquake.Peek-Asa C, Ramirez MR, Shoaf K, Seligson H, Kraus JF. Ann Epidemiol. 2000 Jan; 10(1):5-13. Language: en
Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy.

Summary Purpose: Optical recording of intrinsic signals provides the highest combined spatial and temporal resolution with broad spatial sampling for measuring cerebral blood volume (CBV) and hemoglobin oxygenation in cerebral cortex. Few opportunities arise to apply this laboratory method to record spontaneous seizures in unanesthetized human brain during neurosurgery. We report such a rare opportunity in a man with recurrent focal epilepsy arising from a cavernous malformation. Methods: We recorded intrinsic optical signals (IOS) from human cortex intraoperatively during spontaneous seizures arising from brain surrounding a small cavernous malformation in an awake patient using only local anesthesia with simultaneous electrocorticography. The IOS was recorded at two wavelengths, one an isosbestic point for hemoglobin to measure CBV (570 nm) and the other at a wavelength more sensitive to deoxygenated hemoglobin (Hbr) (610 nm). A modified Beer-Lambert calculation was used on two separate but similar seizures to approximate changes in Hbr, CBV as well as oxygenated hemoglobin (HbO2). Results: Electrographically recorded seizures (n = 3) elicited a focal increase in both Hbr and CBV that lasted for the duration of the seizure, indicating that perfusion was inadequate to meet metabolic demand. Remarkably, these hemodynamic changes preceded the onset of the seizures by ∼20 s and occurred focally over the known location of the lesion and the seizure onsets. Discussion: These findings demonstrate that the hemoglobin becomes deoxygenated in spite of large increase in CBV during spontaneous human focal seizures and that optically recorded hemodynamic events can be used both to predict and localize human focal epilepsy. Such data may someday be useful to assist in the presurgical evaluation of patients considered for epilepsy surgery and to predict the timing and location of seizure onsets.
Costs of novel symptom management interventions and their impact on hospitalizations.

Abstract Four hundred thirty-seven patients with solid tumor cancer, undergoing chemotherapy, were enrolled, interviewed, and randomized to receive either a six-contact, eight-week, nurse-directed intervention or an automated telephone symptom management intervention. Patients were assessed at 10 and 16 weeks. Patients were queried at intake and at 10 and 16 weeks to determine the severity of their symptoms and if they had been hospitalized—if hospitalized, the number of hospitalizations and location of the hospital. The fixed and variable costs associated with the production of each arm were identified. Both total fixed and variable costs were greater for the nurse arm; total costs per patient were $69 and $167 for the automated and nurse arms, respectively. The overall symptom severity declined significantly over baseline and equally between the groups at 10 and 16 weeks. The relationship between reductions in symptom severity and the number of hospitalizations and days in the hospital was investigated using zero-inflated Poisson regression model. The cost of a hospitalization was estimated at $1,800 per day in 2004. At 16 weeks, those with 50% or greater reductions in severity had an adjusted mean of 1.1 days in the hospital, whereas those with increased symptom severity had a mean of 2.23. Reductions in hospitalizations related to lower severity suggest that the telephone arm could produce a net saving over cost of its development and implementation. Although promising, the links between reductions in severity of symptoms and fewer hospitalizations remain difficult to isolate.
Assessment and treatment of multiple behavior problems exhibited by a profoundly retarded adolescent

The severe aggression and noncompliance of a profoundly retarded blind male were subjected to extensive behavioral assessment in order to identify controlling variables. The assessment, conducted across settings and therapists, suggested that these inappropriate behaviors functioned to avoid or terminate nonpreferred activities. Intervention consisted of manual guidance when there was noncompliance with instructions and edible reinforcement upon compliance; there were no direct contingencies for the inappropriate behaviors. Treatment procedures were implemented in a multiple baseline design across therapists and settings. Results show that the intervention consistently increased compliance, with concurrent decreases in inappropriate behaviors. Edible reinforcement and neuroleptic medication were withdrawn systematically with no loss of therapeutic gains. Family members and school personnel were trained to use the intervention procedures. Results are discussed in terms of functional assessment, response covariation, compliance training, parent and staff training, and behavioral assessment of the effects of neuroleptic medication.
Structure of the R65Q Mutant of Yeast 3-Phosphoglycerate Kinase Complexed with Mg-AMP-PNP and 3-Phospho-d-glycerate†,‡

The structure of a ternary complex of the R65Q mutant of yeast 3-phosphoglycerate kinase (PGK) with magnesium 5'-adenylylimidodiphosphate (Mg-AMP-PNP) and 3-phospho-D-glycerate (3-PG) has been determined by X-ray crystallography to 2.4 angstrom resolution. The structure was solved by single isomorphous replacement, anamalous scattering, and solvent flattening and has been refined to an R-factor of 0.185, with rms deviations from ideal bond distance and angles of 0.009 angstrom and 1.78 degrees, respectively. PGK consists of two domains, with the 3-PG bound to a "basic patch" of residues from the N-terminal domain and the Mg-AMP-PNP interacting with residues from the C-terminal domain. The two ligands are separated by approximately 11 angstrom across the interdomain cleft. The model of the R65Q mutant of yeast PGK is very similar to the structures of PGK isolated from horse, pig, and Bacillus stearothermophilus (rms deviations between equivalent alpha-carbons in the individual domains < 1.0 angstrom) but exhibits substantial variations with a previously reported yeast structure (rms deviations between equivalent alpha-carbons in the individual domains of 2.9-3.2 angstrom). The most significant tertiary structural differences among the yeast R65Q, equine, porcine, and B. stearothermophilus PGK structures occur in the relative orientations of the two domains. However, the relationships between the observed conformations of PGK are inconsistent with a "hinge-bending" behavior that would close the interdomain cleft. It is proposed that the available structural and biochemical data on PGK may indicate that the basic patch primarily represents the site of anion activation and not the catalytically active binding site for 3-PG.
Utilization of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for structural studies related to biology and disease

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), because of its high sensitivity and relatively straightforward requirements for sample preparation, is contributing to the solution of structural problems in biology and to the development of therapeutic approaches through increased understanding of pharmacology and enhanced capabilities for quality control of pharmaceuticals. We are using a reflectron TOF- MS for the determination of molecular weights of individual compounds and the components of mixtures that are naturally occurring or are generated through enzymic digests, and employing the post-source decay mode to elucidate structural details. To maximize the sensitivity and information content of the spectra, varied matrices, derivative, and stepwise degradation procedures are being explored. Present studies include investigations of oligosaccharides, neutral glycolipids, gangliosides, glycoproteins, neuropeptides and proteins. Rules for fragmentation are being developed with model compounds and used for the structural elucidation of unknowns. When adequate sample amounts are available, the results are compared with low- and high-energy collision-induced decomposition spectra obtained with tandem MS in order to provide a data base for the correlation of spectral features and guidance in selection of approaches for scarce biological samples. Current projects include biophysical studies of glycoplipids, glycoproteins and oligosaccharides and investigations of the substance P receptor, transthyretin genetic variants and cisplatin-DNA interactions.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.