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OBJECTIVES In the United States, autistic individuals experience disproportionate physical and mental health challenges relative to non-autistic individuals, including higher rates of co-occurring and chronic conditions and lower physical, social, and psychological health-related quality of life. The Autism Intervention Research Network on Physical Health (AIR-P) is an interdisciplinary, multicenter research network for scientific collaboration and infrastructure that aims to increase the life expectancy and quality of life for autistic individuals, with a focus on underserved or vulnerable populations. The current paper describes the development of the AIR-P Research Agenda. METHODS Development of the research agenda involved an iterative and collaborative process between the AIR-P Advisory Board, Steering Committee, and Autistic Researcher Review Board. The methodology consisted of 3 phases: (1) ideation and design, (2) literature review and synthesis; and (3) network engagement. RESULTS Six core research priorities related to the health of autistic individuals were identified: (1) primary care services and quality, (2) community-based lifestyle interventions, (3) health systems and services, (4) gender, sexuality, and reproductive health, (5) neurology, and (6) genetics. Specific topics within each of these priorities were identified. Four cross-cutting research priorities were also identified: (1) neurodiversity-oriented care, (2) facilitating developmental transitions, (3) methodologically rigorous intervention studies, and (4) addressing health disparities. CONCLUSIONS The AIR-P Research Agenda represents an important step forward for enacting large-scale health-promotion efforts for autistic individuals across the lifespan. This agenda will catalyze autism research in historically underrepresented topic areas while adopting a neurodiversity-oriented approach to health-promotion.

Canadian health leaders can benefit from greater involvement in the design and production of Health Technology Assessment (HTA) through enhanced working relationships with HTA producers. The HTA producers and health leaders have a shared interest in the appropriate use of pharmaceuticals, healthcare devices, and procedures which benefit patients and support sustainable health systems. This article highlights the shared responsibility of HTA producers and decision makers in the appropriate use of these healthcare interventions through an examination of a HTA-informed policy and practice change in the management diabetes in elderly residents in long-term care settings. Consideration is given to the role of the co-responsibility model and LEADS in a Caring Environment framework (LEADS) in helping to facilitate partnerships between decision-makers and HTA producers in the realization of HTA-informed policy and practice.

The goal of this study was to add to the existing literature by examining the effect of 1:1 iPad integration on the achievement of Canadian Grade 7 students. The school board we worked with...

This study explores the implementation of technology to facilitate students’ persuasive writing skills within elementary school classrooms. Five teachers were interviewed regarding their experiences teaching persuasive writing to students using technology-mediated feedback. Teachers perceived the influence of technology on students’ persuasive writing, on their own teaching practice, and on students’ experiences as valuable for skill development for both themselves and for their students. However, students’ unfamiliarity with technology was at times a hindrance.

© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. Processing of auditory information in the cortex continues to develop into later childhood and adolescence. Recent research has indicated that intraclass correlation (ICC) is the best method for capturing maturation in auditory event-related potentials (AEPs) of school-age children. However, the sensitivity of the ICC approach in discerning AEP changes in children has not been consistently demonstrated and positive results have not been replicated. We attempted this replication and further explored whether AEP maturation estimated using the ICC approach predicts cognitive and linguistic abilities in addition to chronological age. We measured AEPs in response to simple tones in groups of 7-, 8-, 9- and 10-year olds with typical development (N = 67) and used ICC to estimate the age equivalent of each child's AEP (AEP-age). Results indicated that ICC differentiated 7- to 8-year-old children from 9- to 10-year-old children and that AEP-age predicted both chronological age and significant, unique variance in language ability, but not in nonverbal IQ. Our findings support the view that auditory organization in children reflects both general developmental maturation and more specific development of language skills, and support the future use of AEP-age to identify and understand individual differences in brain maturation in typically developing and clinical populations.

Aqueous phase processing of biomass derived sugar alcohols is one of the promising routes to convert biomass into fuels and chemicals. Bifunctional catalysts are critical in the aqueous phase hydrodeoxygenation of sugar alcohol. Understanding the interaction between metal and acidic metal oxides as well as the hydrodeoxygenation pathways will help develop more efficient bifunctional catalysts. Here, tungstated zirconia supported palladium catalysts were prepared and further characterized using nitrogen sorption, X-ray diffraction, FT-IR analysis of adsorbed pyridine, CO chemisorption and diffuse reflectance UV–vis. Strong interaction between palladium and WO3 in addition to a synergetic effect of the acidic and metallic sites were found to promote the aqueous phase hydrodeoxygenation of ethylene glycol. H-D exchange experiments using 13C{1H} NMR spectroscopy confirmed that the aqueous phase hydrodeoxygenation follows a dehydration–hydrogenation pathway. The hydrogenation of the dehydration products shifts the dehydration–hydration equilibrium toward the dehydration pathway and leads to highly selective C O cleavage.

Technology continues to form an important part of the educational landscape, although the value of portable devices as learning tools is still being explored and debated. In light of the technology-based teaching methods suddenly brought into effect in response to the COVID-19 pandemic, the deliberate use of technology for learning is increasingly significant. The purpose of this article is to highlight student perspectives of learning with portable devices to inform the use of portable technology in the Canadian school system going forward. To gather student perceptions, the research team surveyed 704 students in grades 6 to 9 about their use of iPads in the classroom during a 1:1 technology initiative. While students were enthusiastic about the presence of portable technology, they also shared mixed feelings about the use of such technology as a learning tool. Key themes fell into three categories—engagement, inclusivity, and learning—as students shared their insight into the academic, social, and physical barriers that exist as a result of the technology. In the discussion, we identify lessons learned, especially in the area of self-regulation, and make recommendations on how to harness the power of this multi-faceted learning tool and minimize the chaos it can create when not utilized deliberately and carefully.

© 2014 Elsevier Ltd. All rights reserved. Clinical anecdotes suggest that children with autism spectrum disorder (ASD) often show an atypical language profile in which expressive language exceeds receptive language competency. However, the few studies to directly explore this language profile have yielded inconsistent findings. This meta-analysis examined 74 studies that reported the receptive and expressive language performances of children and youth with ASD. Four potential predictors (age, language domain, source of language data, method of ASD diagnosis) were separately analyzed for their contribution to the relative receptive and expressive language impairment in ASD. Contrary to popular belief, the current meta-analyses found no evidence that an expressive advantage is common in ASD. Overall, children and youth with ASD showed equally impaired receptive and expressive language skills, both falling roughly 1.5 SD below peers with typical development. No discrepancies were found in receptive and expressive language across developmental stages, cognitive abilities, vocabulary, global language skills, caregiver report measures, clinician-administered measures, mixed method measures, or method of ASD diagnosis. Although some individual children with ASD may have an expressive-better-than-receptive language profile, this profile is not common enough to be a useful marker of ASD.

This paper examines the impact of a school board’s one-to-one iPad initiative on equity and inclusion. Data include: questionnaires from Grade 7–9 students, teachers, and administrators; focus groups with inclusion coaches; and interviews with classroom teachers. The results show that the iPads have supported equity among students in the district; there is now less disparity in terms of access to technology on the basis of families’ socio-economic status. The results show that the iPads have also supported the academic and social inclusion of students with exceptionalities; themes that arose across the data sources include: differentiation of content, access to grade-level curriculum, the appearance of sameness, communication and collaboration among students with and without exceptionalities, and positive student affect. Negative implications included the potential for students who struggle with self-regulation to be negatively affected and the potential for the technology to be used in socially exclusionary ways.

Previous studies of students with high-functioning autism spectrum disorder (HFASD) have shown great variability in their writing abilities. Most previous studies of students with HFASD have combined individuals with linguistic impairments (HF-ALI) and individuals without linguistic impairments (HF-ALN) into a single group. The current study was the first to compare the persuasive writing of students with HF-ALN with controls, without confounding the effects of language ability and autism on writing achievement, and while considering possible cognitive underpinnings of their writing skills. Twenty-five students with HF-ALN and 22 typically developing controls completed measures of oral language, nonverbal IQ, social responsiveness, theory of mind, integrative processing and persuasive writing. The persuasive texts were coded on 19 variables across six categories: productivity, grammatical complexity, lexical diversity, cohesiveness, writing conventions, and overall quality. The texts were reliably different between groups across measures of productivity, syntactic complexity, lexical complexity and persuasive quality. Specifically, the texts of students with HF-ALN scored lower on overall quality (d = −0.6 SD), contained shorter and simpler sentences (d = −1.0), and had less repetition of content words (d = −0.8 SD). For the HF-ALN group, integrative processing, language ability and age predicted 77% of the variance in persuasive quality.

Background: There is growing interest in identifying changes in ways of practice associated with the growth of professional expertise. Research on highly experienced or expert teachers and therapists (i.e. occupational, physical and behavioural therapists) can provide insights into how they approach practice, providing guidance for new practitioners. Purpose: The objective was to compare and contrast children’s mental health therapists’ and elementary/secondary schoolteachers’ perceptions of changes in perspectives and approaches related to the development of expertise. Sample: Nine children’s mental health therapists and five teachers/principals took part. Design and methods: Using a nested sampling design, therapists and teachers/principals were selected based on years of experience and peer reputation, and participated in two separate focus groups. Similarities and differences between the practice groups were examined qualitatively, using cross-group analysis. Results: Common reported changes in perspective included the development of open, broad, flexible and relational perspectives. Changes in approach included a focus on children’s needs/desires, psychosocial issues/outcomes and realistic goals. Conclusions: The findings indicated how expert practitioners viewed their practice as changing over time, contributing to a better understanding of the nature and development of expertise in children’s service practitioners. The findings suggest the importance of paying attention to children’s needs/desires, cultivating awareness of their motivation and psychosocial issues, and setting realistic goals. Practitioners linked these changes in perspective and approach to more positive life and learning outcomes for children, which may have implications for guiding the practice of more novice teachers and therapists.

Chlamydia trachomatis is an obligate intracellular bacteria and the infectious agent responsible for the sexually transmitted disease Chlamydia. Infection with Chlamydia can lead to serious health sequelae such as pelvic inflammatory disease and reproductive tract scarring contributing to infertility and ectopic pregnancies. Additionally, chlamydial infections have been epidemiologically linked to cervical cancer in patients with a prior human papilomavirus (HPV) infection. Chlamydial infection of cultured cells causes multinucleation, a potential pathway for chromosomal instability. Two mechanisms that are known to initiate multinucleation are cell fusion and cytokinesis failure. This study demonstrates that multinucleation of the host cell by Chlamydia is entirely due to cytokinesis failure. Moreover, cytokinesis failure is due in part to the chlamydial effector CPAF acting as an anaphase promoting complex mimic causing cells to exit mitosis with unaligned and unattached chromosomes. These lagging and missegregated chromosomes inhibit cytokinesis by blocking abscission, the final stage of cytokinesis.

Impurities present in commercially available ionic liquids display prominent catalytic functions toward carbohydrate conversion. Little conversion was observed at 180 °C with high purity [EMIM]Cl ionic liquid whereas significant conversion was observed for ionic liquids of lower purity levels. Addition of metal halides to high purity [EMIM]Cl catalyze cellulose conversion with drastically different product selectivities dependent on the metal ions. CuCl2 is an active catalyst for hydrolyzing cellulose and further degrading the products. CrCl2 is an active and a selective catalyst for the formation of 5-hydroxymethylfurfural (5-HMF). CrCl2 also helps stabilize the 5-HMF product. FeCl2 does not show catalytic activity. Metal impurities in ionic liquid correlate to the activities observed when similar metals were added to high purity ionic liquids.

Efficient hydrolytic depolymerization of crystalline cellulose to sugars is a critical step and has been a major barrier for improved economics in the utilization of cellulosic biomass. A novel catalytic system involving CuCl2 (primary metal chloride) paired with a second metal chloride, such as CrCl2, PdCl2, CrCl3 or FeCl3 in 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) ionic liquid solvent has been found to substantially accelerate the rate of cellulose depolymerization under mild conditions. These paired metal chlorides are particularly active for the hydrolytic cleavage of 1,4-glucosidic bonds when compared to the rates of acid-catalyzed hydrolysis at similar temperatures (80–120 ◦C). In contrast, single metal chlorides with the same total molar loading showed much lower activity under similar conditions. Experimental results illustrate the dramatic effect of the second metal chloride in the paired catalytic system. An array of characterization techniques, including electron paramagnetic resonance (EPR) spectroscopy, differential scanning calorimetry (DSC), X-ray absorption fine structure (XAFS) spectroscopy, and X-ray absorption near edge structure (XANES) spectroscopy, in combination with theoretical calculations at the DFT level, was used to reveal a preliminary understanding of possible mechanisms involved in the paired CuCl2/PdCl2 catalytic system. We discovered that Cu(II) was reduced during the course of the reaction to Cu(I) only in the presence of a second metal chloride and a carbohydrate source such as cellulose in the ionic liquid system. Our results suggest that Cu(II) generates protons by hydrolysis of water to catalyze the depolymerization step, and serves to regenerate Pd(II) reduced to Pd(0) by side reactions. Pd(II) likely facilitates the depolymerization step by coordinating the catalytic protons, and also promotes the formation of hydroxymethylfurfural (HMF). Our results also suggest that the C2-proton

Membrane trafficking and cargo delivery are essential for axonal and dendritic growth and guidance. Neurons have numerous diverse post-Golgi vesicles and recent advances have clarified their identity and regulation. Combinatorial approaches using in vivo imaging of ‘intracellular cargo address labels' and functional perturbation have provided insight into these processes. In particular, the UNC-51 kinase regulates the trafficking of early endosomes and their axon guidance molecular cargos in several types of neurons in multiple organisms. Vesicular compartments bearing features of recycling endosomes, late endosomes or lysosomes also contribute to membrane addition and protein trafficking during neurite outgrowth and extension. New work shows that ubiquitylation of cargos and Rab effectors further specifies the trafficking routes of post-Golgi vesicles. These findings have begun to provide a more detailed view of the molecular mechanisms involved in neurite outgrowth and guidance. Additionally, high-resolution light microscopy imaging promises greater temporal and spatial understanding of vesicular exchange and maturation in neurons in the near future.

The syntheses of barium, cadmium, calcium, lead, and strontium apatites were performed in anhydrous polar organic solvents such as DMSO, anisole, pyridine, glacial acetic acid, ethanol, methanol, and DMF. Reactions took place under anhydrous conditions at temperatures ranging from 80 to 120 °C and for durations of 1–6 days. Ten apatites were synthesized in nonaqueous solvents and three (PbApF, PbApCl, SrApCl) were obtained using trimethylphosphate as the phosphate source. The use of nonaqueous solvents alleviates the formation of hydrogen phosphates which occurs in aqueous solution for some divalent cations. The limited solubility of even alkali metal salts in many of the solvents also produces nonapatitic double salts such as NaPb4(PO4)3, NaPbPO4, KPb4(PO4)3, Cd(OH)NO3, and NaBaPO4.

How endosomes contribute to the maintenance of vesicular structures at presynaptic terminals remains controversial and poorly understood. Here, we have investigated synaptic endosomal compartments in the presynaptic terminals of C. elegans GABAergic motor neurons. Using RAB reporters, we find that several subsynaptic compartments reside in, or near, presynaptic regions. Loss of function in the C. elegans JIP3 protein, UNC-16, causes a RAB-5-containing compartment to accumulate abnormally at presynaptic terminals. Ultrastructural analysis shows that synapses in unc-16 mutants contain reduced number of synaptic vesicles, accompanied by an increase in the size and number of cisternae. FRAP analysis revealed a slow recovery of RAB-5 in unc-16 mutants, suggestive of an impairment of RAB-5 activity state and local vesicular trafficking. Overexpression of RAB-5:GDP partially suppresses, whereas overexpression of RAB-5:GTP enhances, the synaptic defects of unc-16 mutants. Our data demonstrate a novel function of UNC-16 in the regulation of synaptic membrane trafficking and suggest that the synaptic RAB-5 compartment contributes to synaptic vesicle biogenesis or maintenance.

The extraction of soy oil from soybean flakes in industry requires large amounts of hexane solvent and results in significant losses and energy consumption during the distillative removal of the solvent. Hexanes and related hydrocarbon extractants are also becoming an environmental and health concern. A new method for extraction of the oil is sought, that would require neither hexane nor distillative removal of solvent. This article presents a preliminary assessment of several new methods for soy oil extraction and subsequent solvent removal from the oil. The most promising are (a) extraction by an amidine switchable solvent that can then be removed from the soy oil by carbonated water and (b) extraction by a moderately hydrophilic solvent that can then be removed from the oil by water.

SummaryC. elegans RPM-1 (for Regulator of Presynaptic Morphology) is a member of a conserved protein family that includes Drosophila Highwire and mammalian Pam and Phr1. These are large proteins recently shown to regulate synaptogenesis through E3 ubiquitin ligase activities. Here, we report the identification of an RCC1-like guanine nucleotide exchange factor, GLO-4, from mass spectrometry analysis of RPM-1-associated proteins. GLO-4 colocalizes with RPM-1 at presynaptic terminals. Loss of function in glo-4 or in its target Rab GTPase, glo-1, causes neuronal defects resembling those in rpm-1 mutants. We show that the glo pathway functions downstream of rpm-1 and acts in parallel to fsn-1, a partner of RPM-1 E3 ligase function. We find that late endosomes are specifically disorganized at the presynaptic terminals of glo-4 mutants. Our data suggest that RPM-1 positively regulates a Rab GTPase pathway to promote vesicular trafficking via late endosomes.

Replacing petroleum feedstocks by biomass requires efficient methods to convert carbohydrates to a variety of chemical compounds. We report the catalytic conversion of sugars giving high yield to 5-hydroxymethylfurfural (HMF), a versatile intermediate. Metal halides in 1-alkyl-3-methylimidazolium chloride are catalysts, among which chromium (II) chloride is found to be uniquely effective, leading to the conversion of glucose to HMF with a yield near 70%. A wide range of metal halides is found to catalyze the conversion of fructose to HMF. Only a negligible amount of levulinic acid is formed in these reactions.

Cotton linters were partially hydrolyzed in dilute acid and the morphology of remaining macrofibrils was studied with scanning electron microscopy (SEM) under various magnifications. The crystalline region in cellulose is composed of microfibril bundles instead of separated microfibrils. These microfibril bundles in the macrofibrils were exposed by removing amorphous cellulose on and near the surface of the macrofibers. XRD suggests that the microfibril bundles have diameters of 20–30 nm. Cellulose apparent crystallinity was not altered by hydrolysis, as indicated by XRD and NMR results. These facts suggest that amorphous cellulose in the bulk (not on the surface) is not accessible to hydrolysis and that microfibril bundles are hydrolyzed through a surface reaction process. The observed agglomerization of macrofibers could be the result of the high surface potential from the remaining microfibrils or acid catalyzed intermolecular surface dehydration between macrofibrils.

Kinesin-1 is a heterotetramer composed of kinesin heavy chain (KHC) and kinesin light chain (KLC). The Caenorhabditis elegans genome has a single KHC, encoded by the unc-116 gene, and two KLCs, encoded by the klc-1 and klc-2 genes. We show here that UNC-116/KHC and KLC-2 form a complex orthologous to conventional kinesin-1. KLC-2 also binds UNC-16, the C. elegans JIP3/JSAP1 JNK-signaling scaffold protein, and the UNC-14 RUN domain protein. The localization of UNC-16 and UNC-14 depends on kinesin-1 (UNC-116 and KLC-2). Furthermore, mutations in unc-16, klc-2, unc-116, and unc-14 all alter the localization of cargos containing synaptic vesicle markers. Double mutant analysis is consistent with these four genes functioning in the same pathway. Our data support a model whereby UNC-16 and UNC-14 function together as kinesin-1 cargos and regulators for the transport or localization of synaptic vesicle components.

Olympia oysters Ostrea conchaphila have declined markedly during the last century and are a focus of restoration in many embayments, including the San Francisco Bay (SFB) estuary. Oysters were collected from 17 sites in this estuary and nearby Tomales Bay in an effort to charac- terize diseases that may impact recovery of this species and captive rearing programs. Three diseases/disease agents including a Mikrocytos-like protist (microcell), a haplosporidian and hemic neoplasia were observed from several sites along the western margins of the SFB estuary suggesting a geographic localization of disease presence. Based on fluoresecent in situ hybridization (FISH) assays, the microcell is distinct from M. mackini and Bonamia spp. These data highlight the need for further elucidation of the haplosporidian and for careful health management of a declining species destined for captive rearing and supplementation.

Background Primary cutaneous Paget's disease of the vulva is an intraepithelial adenocarcinoma most likely arising from a cutaneous stem cell with sweat gland epithelial differentiation or can be of sweat gland origin. Primary vulvar Paget's disease, however, can be mimicked by an internal noncutaneous neoplasm htat has extended to secondarily involve the vulva. Most commonly, this is due to an anal or rectal adenocarcinoma or a urothelial carcinoma. These malignancies may be detected in a vaginal or vulvar cytologic smear. Case An 81-year-old woman with a past history of urothelial carcinoma in situ of the bladder presented severalyears subsequent to treatment for bladder cancer with extensive vulvar and vaginal disease, clinically interpreted as primary vulvar Paget's disease involving the vagina. Vaginal cytology showed a high grade malignancy. The patient subsequently underwent radical (total deep) vulvectomy and vaginal excision. Subsequent investigation of her bladder showed recurrent urothelial carcinoma in situ with extensive spread to the vagina and vulva, simulating primary cutaneous vulvar Paget's disease. Conclusion It is important to recognize secondary vulvar Paget's disease, although uncommon, because of the difference in therapy for primary and secondary vulvar Paget's disease. Certain cytologic characteristics in a vaginal or vulvar smear in a patient with suspected vulvar Paget's disease may aid in distinguishing them.

The existence of pure‐phase transition metal hydroxy apatites of zinc, copper, manganese, and cobalt could not be verified by repeated attempts to duplicate the few literature procedures reported for their preparation in aqueous solution. Variations of temperature, time of reactions, pH, and use of decomplexation also did not produce apatitic compounds. In the case of zinc, the product resulting from the addition of zinc nitrate to ammonium dihydrogen phosphate in solutions brought to pH >9 with ammonia appears to be a zinc ammonia complex with phosphate as the counter ion. Extensive drying removed ammonia to produce the phosphate. At pH

Objectives: To describe the utility of image guided surgery in the diagnosis of pterygopalatine fossa lesions and to discuss the varied pathologic diagnoses from this area. Study Design: Case series presentation. Methods: Three cases of pterygopalatine fossa lesions were accessed and biopsied by way of a middle meatus antrostomy approach into the pterygopalatine fossa under image guidance for rapid localization. Results: The diagnoses of melanoma, squamous cell carcinoma, and schwannoma were obtained with minimal morbidity with image guidance. More extensive external approaches were avoided, and appropriate treatment was started without delay. The utility of the image guided approach will be discussed along with the varied pathologies encountered in the pterygopalatine fossa. Conclusions: 1) One must recognize the diverse, yet related, symptoms of patients presenting with pterygopalatine fossa lesions. Early recognition as well as skull-base imaging is crucial. 2) Biopsy, in addition to imaging, is necessary for diagnosis and may be achieved with little morbidity and increased accuracy using the image guided surgery middle meatus antrostomy approach to the pterygopalatine fossa. 3) The origin of lesions that involve the pterygopalatine fossa may be difficult to identify. Involvement of the pterygopalatine fossa by malignancy may be by contiguous spread, by way of metastasis, or by perineural invasion.

OBJECTIVES: To determine whether body weight can be maintained or improved in dementia residents of special care units (SCUs) using a comprehensive intervention strategy. DESIGN: Quasi-experimental with an interventional site and a noninterventional site. SETTING: Four SCUs in two long-term care facilities in Ontario. PARTICIPANTS: The intervention site included 33 residents; the comparison site included 49 residents. MEASUREMENTS: Weight change over time was the primary outcome. Three time periods were compared: 9-month baseline period, 9-month intervention period (enhanced dietitian monitoring and menu changes at intervention site), and 12-month postintervention period (only menu changes at intervention site). Comparisons were made within and between sites. Full nutritional assessments were completed for the intervention group. Medical charts and basic anthropometric, behavioral, and cognitive measures were completed in both groups to determine baseline site differences. Weight change over time was analyzed with a repeated measures analysis, controlling for various covariates. Bivariate analyses were completed for other outcomes of death, number of infections, falls, and hospital days. RESULTS: The intervention period that included the dietitian time and menu changes significantly promoted weight gain, compared with the standard treatment at the comparison facility. Other covariates of pacing, type of dementia, sex, age, number of comorbid conditions, and medications were also significant predictors of weight change. Weight gain or maintenance regardless of site was associated with survival. CONCLUSION: Body weight can be maintained in residents of SCUs regardless of pacing and other clinical characteristics. The comprehensive intervention of clinical dietitian time and an enhanced menu designed to be individualized for ambulatory people with dementia promoted significant gains in body weight. A minimum 5% weight gain is associated with survival in these residents of SCUs.

We report a case of a 43-year-old man with known metastatic melanoma and two intracranial tumors, one of which was resected and confirmed to be melanoma. At autopsy, the second lesion was found to be a central neurocytoma harboring metastatic melanoma. To our knowledge, this represents the first reported case of tumor-to-tumor metastasis to a central neurocytoma. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms, in which an aggressive high-grade malignancy serves as the source tumor and a more indolent neoplasm serves as the recipient tumor, is affirmed by the present novel example.

Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease. However, vulvar Paget disease is in itself a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. The subtypes of vulvar Paget disease include primary Paget disease arising from a pluripotent stem cell within the epithelium of the vulva, and secondary Paget disease of the vulva. Secondary vulvar Paget disease results from spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulvar epithelium. We have recently proposed that these lesions be classified as primary (of cutaneous origin) or secondary (of extracutaneous origin). These subtypes can present similarly as eczematoid skin lesions and may appear similar on routine hematoxylin and eosin-stained slides. Immunohistochemical studies can help differentiate between them. Our current study includes 17 patients with a pathologic diagnosis of vulvar Paget disease. We performed a panel of immunohistochemical stains, including cytokeratin (CK) 7 and 20, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and uroplakin-III (UP-III). Of these 17 patients, 14 (80%) had primary intraepithelial cutaneous Paget disease, 13 without invasion and 1 with associated invasion. Three patients had urothelial carcinoma with spread to the vulva, manifesting as secondary vulvar Paget disease. Immunohistochemically, primary vulvar Paget disease is immunoreactive for CK 7 and GCDFP-15, but uncommonly for CK 20. Vulvar Paget disease secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP-15. Vulvar Paget disease secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP-15. In addition, we propose the use of a new, commercially available antibody, UP-III, which is specific for urothelium and, in our experience, is immunoreactive in secondary vulvar Paget disease of urothelial origin. The distinction between these 3 types of Paget and Paget-like lesions is essential in that the specific diagnosis has a significant influence on current treatment. The difference in surgical approach to the subtypes of vulvar Paget disease justifies classifying them into distinct lesions, which may be aided by the use of immunohistochemistry, including UP-III.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen and the second leading cause of sexually transmitted infections in the US. Infections cause significant morbidity and can lead to serious reproductive sequelae, including an epidemiological link to increased rates of reproductive cancers. One of the overt changes that infected cells exhibit is the development of genomic instability leading to multinucleation. Here we demonstrate that the induction of multinucleation is not conserved equally across chlamydial species; C. trachomatis L2 caused high levels of multinucleation, C. muridarum intermediate levels, and C. caviae had very modest effects on multinucleation. Our data show that at least two effector pathways together cause genomic instability during infection leading to multinucleation. We find that the highly conserved chlamydial protease CPAF is a key effector for one of these pathways. CPAF secretion is required for the loss of centrosome duplication regulation as well as inducing early mitotic exit. The second effector pathway involves the induction of centrosome position errors. This function is not conserved in three chlamydial species tested. Together these two pathways contribute to the induction of high levels of genomic instability and multinucleation seen in C. trachomatis infections.

Background Mycobacterium tuberculosis (MTb) infection remains the cause of higher morbidity and mortality than any other infectious disease in the world. Intact cellular immunity is necessary to resist the disease, and therefore the AIDS epidemic has greatly contributed to the resurgence of MTb. Depending on the degree of immunosuppression, the presentation of MTb in patients with AIDS can be atypical and difficult to diagnose as compared to the classical presentation of MTb in the nonimmunocompromised population. Case A patient who was not known to be HIV positive had a clinical picture of extensive abdominal and pelvic lymphadenopathy without chest radiographic abnormalities. The diagnosis of MTb was made by fine needle aspiration (FNA) of a pelvic lymph node. Conclusion Miliary tuberculosis associated with AIDS may have an unusual clinical presentation and unusual cytologic features on ENA.

It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear. Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is down-regulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B.

BACKGROUND In the absence of metastases, there are no reliable microscopic features that distinguish malignant from benign pheochromocytomas. Because a common feature of malignancy is the loss of cell cycle regulation and normal growth arrest, the authors hypothesized that analysis of the cell cycle could be used to aid in the diagnosis of malignant pheochromocytoma. METHODS Cell cycle analysis of archival samples of 51 pheochromocytomas (40 sporadic, 11 familial) from 45 patients, including 6 malignant and 45 benign tumors, was conducted. Flow cytometry data and immunohistochemistry for markers of cell proliferation (proliferating cell nuclear antigen [PCNA] and MIB-1 [Ki-67]) were correlated with the authors' clinical data base records, with a mean follow-up of 66 months. RESULTS No correlation of DNA ploidy, S-phase fraction by flow cytometry, or PCNA with malignancy was observed. Staining for the MIB-1 nuclear proliferation marker was positive in 3 of 6 (50%) of the malignant pheochromocytomas and negative in all 45 benign tumors (P< 0.01). CONCLUSIONS Contrary to some previous reports, a diploid DNA pattern does not necessarily predict benign behavior of pheochromocytoma. In this study, cell cycle analysis and, in particular, assessment of the MIB-1 nuclear proliferation marker was useful in the histologic evaluation of pheochromocytoma, as MIB-1 was expressed only in malignant tumors. Cancer 1999;86:1583–9. © 1999 American Cancer Society.

Previous genetic and biochemical studies have led to the hypothesis that the essential mitotic bi- polar kinesin, KLP61F, cross-links and slides microtu- bules (MTs) during spindle assembly and function. Here, we have tested this hypothesis by immunofluo- rescence and immunoelectron microscopy (immu- noEM). We show that Drosophila embryonic spindles at metaphase and anaphase contain abundant bundles of MTs running between the spindle poles. These inter- polar MT bundles are parallel near the poles and anti- parallel in the midzone. We have observed that KLP61F motors, phosphorylated at a cdk1/cyclin B consensus domain within the BimC box (BCB), localize along the length of these interpolar MT bundles, being concentrated in the midzone region. Nonphosphory- lated KLP61F motors, in contrast, are excluded from the spindle and display a cytoplasmic localization. Immunoelectron microscopy further suggested that phospho-KLP61F motors form cross-links between MTs within interpolar MT bundles. These bipolar KLP61F MT-MT cross-links should be capable of orga- nizing parallel MTs into bundles within half spindles and sliding antiparallel MTs apart in the spindle mid- zone. Thus we propose that bipolar kinesin motors and MTs interact by a "sliding filament mechanism" during the formation and function of the mitotic spindle.