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Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy. [ABSTRACT FROM AUTHOR]

Background: We identified that Stanford Health Care had a significant number of patients who after discharge are found by the utilization review committee not to meet Center for Mediare and Medicaid Services (CMS) 2-midnight benchmark for inpatient status. Some of the charges incurred during the care of these patients are written-off and known as Medicare 1-day write-offs. This study which aims to evaluate the use of a Best Practice Alert (BPA) feature on the electronic medical record, EPIC, to ensure appropriate designation of a patient's hospitalization status as either inpatient or outpatient in accordance with Center for Medicare and Medicaid services (CMS) 2 midnight length of stay benchmark thereby reducing the number of associated write-offs. Method: We incorporated a best practice alert (BPA) into the Epic Electronic Medical Record (EMR) that would prompt the discharging provider and the case manager to review the patients' inpatient designation prior to discharge and change the patient's designation to observation when deemed appropriate. Patients who met the inclusion criteria (Patients must have Medicare fee-for-service insurance, inpatient length of stay (LOS) less than 2 midnights, inpatient designation as hospitalization status at time of discharge, was hospitalized to an acute level of care and belonged to one of 37 listed hospital services at the time of signing of the discharge order) were randomized to have the BPA either silent or active over a three-month period from July 18, 2019, to October 18, 2019. Result: A total of 88 patients were included in this study: 40 in the control arm and 48 in the intervention arm. In the intervention arm, 8 (8/48, 16.7%) had an inpatient status designation despite potentially meeting Medicare guidelines for an observation stay, comparing to 23 patients (23/40, 57.5%) patients in the control group (p = 0.001). The estimated number of write-offs in the control arm was 17 (73.9%, out of 23 inpatient patients) while in the intervention arm was 1 (12.5%, out of 8 inpatient patient) after accounting for patients who may have met inpatient criteria for other reasons based on case manager note review. Conclusion: This is the first time to our knowledge that a BPA has been used in this manner to reduce the number of Medicare 1-day write-offs. [ABSTRACT FROM AUTHOR]

Background: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada.Methods: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models.Results: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74).Conclusions: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 3 article‐registration‐date‐day 9 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_226.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with limited response to cytotoxic chemoradiotherapy, as well as newer immunotherapies. The PDA tumor microenvironment contains infiltrating immune cells including cytotoxic T cells; however, there is an overall immunosuppressive milieu. Hypoxia is a known element of the solid tumor microenvironment and may promote tumor survival. Through various mechanisms including, but not limited to, those mediated by HIF‐1α, hypoxia also leads to increased tumor proliferation and metabolic changes. Furthermore, epithelial to mesenchymal transition is promoted through several pathways, including NOTCH and c‐MET, regulated by hypoxia. Hypoxia‐promoted changes also contribute to the immunosuppressive phenotype seen in many different cell types within the microenvironment and thereby may inhibit an effective immune system response to PDA. Pancreatic stellate cells (PSCs) and myofibroblasts appear to contribute to the recruitment of myeloid derived suppressor cells (MDSCs) and B cells in PDA via cytokines increased due to hypoxia. PSCs also increase collagen secretion in response to HIF‐1α, which promotes a fibrotic stroma that alters T cell homing and migration. In hypoxic environments, B cells contribute to cytotoxic T cell exhaustion and produce chemokines to attract more immunosuppressive regulatory T cells. MDSCs inhibit T cell metabolism by hoarding key amino acids, modulate T cell homing by cleaving L‐selectin, and prevent T cell activation by increasing PD‐L1 expression. Immunosuppressive M2 phenotype macrophages promote T cell anergy via increased nitric oxide (NO) and decreased arginine in hypoxia. Increased numbers of regulatory T cells are seen in hypoxia which prevent effector T cell activation through cytokine production and increased CTLA‐4. Effective immunotherapy for pancreatic adenocarcinoma and other solid tumors will need to help counteract the immunosuppressive nature of hypoxia‐induced changes in the tumor microenvironment. Promising studies will look at combination therapies involving checkpoint inhibitors, chemokine inhibitors, and possible targeting of hypoxia. While no model is perfect, assuring that models incorporate the effects of hypoxia on cancer cells, stromal cells, and effector immune cells will be crucial in developing successful therapies. [ABSTRACT FROM AUTHOR]

Using confocal Raman microspectroscopy, we derive parameters for bilayer water transport across an isolated nanoliter aqueous droplet pair. For a bilayer formed with two osmotically imbalanced and adherent nanoliter aqueous droplets in a surrounding oil solvent, a droplet interface bilayer (DIB), the water permeability coefficient across the lipid bilayer was determined from monitoring the Raman scattering from the C≡N stretching mode of K3Fe(CN)6 as a measure of water uptake into the swelling droplet of a DIB pair. We also derive passive diffusional permeability coefficient for D2O transport across a droplet bilayer using O–D Raman signal. This method provides a significant methodological advance in determining water permeability coefficients in a convenient and reliable way. [ABSTRACT FROM AUTHOR]

Phytohemagglutinin (PHA) is commonly used to evaluate cell-mediated immunocompetence. In chickens, PHA is typically injected intradermally (i.d.) into the skin (e.g., wing web, wattle, or footpad), and the tissue swelling response is monitored, whereby the extent of tissue swelling positively relates to the individual's cell-mediated immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell and basophil infiltration to the site of injection, reports on temporal, qualitative, and quantitative aspects of the local cutaneous PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test site to assess and monitor the type and relative amounts of leukocytes present in the pulp of PHAinjected GF. For this study, male, non-vaccinated Lightbrown Leghorn chickens reared at the Arkansas Experiment Station Poultry Health Laboratory were used. At 9 wk of age, the dermis of 20 18-day-old regenerating GF was injected with 10 μL of either PBS diluent or 300 μg/mL PHA-P (5 chickens per treatment). GF were collected from each chicken before (zero) and at 0.25, 1, 2, 3, 4, 5, and 7 d post injection. At each time point, one GF was collected for immunofluorescent staining of pulp cell suspensions and leukocyte population analysis by flow cytometry, and another GF for histological analysis. Histological analysis confirmed participation of granulocytes and mononuclear cells, primarily lymphocytes, in the cutaneous PHA response. As revealed by flow cytometric cell population analysis, T cells, especially CD4+ T cells, constituted the major portion of the mononuclear cell infiltrate. Levels of CD4+ T cells were greatly elevated in PHA-injected GF within 6 h and remained elevated throughout the 7-day examination period. γδ T cells, CD8+ T cells, and B cells also infiltrated in response to PHA although at lower levels and with different time-course patterns from CD4+ T cells. The dominant presence of CD4+ T cells at the site of PHA injection further affirms this polyclonal response as an indicator of cell-mediated immunity. [ABSTRACT FROM AUTHOR]

The article discusses situations in which both indemnitors and indemnitees have opinions to support for or go against finding a waiver for the attorney-client privilege. It mentions that the consensus regarding subject-matter waiver issues is very difficult to achieve. It adds that a joint-defense agreement which clearly mentions the party's expectation may help and indemnitors and indemnitees are required to follow developments in law cases which are decided and moved forward with care.

The article offers suggestions for insurance policyholder attorneys on insurance coverage issues. The suggestions include policyholder attorneys informing their clients about the importance of complying with the conditions found in virtually all liability policies, altering policyholders to the adverse consequences of failing to build a solid foundation to support their coverage claim, and preparing a well thought out risk management and insurance program.

Urolith formation has been documented in giraffes and goats. As research in giraffes poses logistical challenges, 16 buck goats were used as a model. The impact of two commercially available, pelleted feeds used for giraffes, ADF-16 and Wild Herbivore (WH), as well as the impact of alfalfa hay and pellet proportions (20% hay:80% pellets, 80P or 80% hay:20% pellet, 20P) on the formation of urolithogenic precursors in goat urine was accomplished in a 2 × 2 factorial balance study. Complete diets contained 0.60, 0.32, 0.35 and 0.26% phosphorus (P) with calcium:P ratios of 1.60, 4.16, 3.06 and 5.23, for 80P-ADF-16, 20P-ADF-16, 80P-WH and 20P-WH respectively. Total faeces and urine were collected over two 5-day periods to assess N and mineral balance. Fresh urine samples were collected and evaluated microscopically for urolithic crystal content. Urinary nitrogen (N) was lower and N retention was higher in goats fed 80P diets (p < 0.05). Intake of P was greatest for goats fed 80P-ADF-16; however, urinary P excretion and P retention were not affected by treatment. Crystal scores were higher in animals receiving 80P diets (p = 0.08), with crystals being composed predominantly of calcium phosphate. Urine pH was alkaline (>8) for all treatments. Urinary P concentration, a risk factor for urolithiasis, was highest (p ≤ 0.06) in the 80P-ADF-16 treatment (0.38 vs. 0.01, 0.02 and 0.04 mg/dl for 20P-ADF-16, 80P-WH and 20P-WH respectively), reflecting its highest dietary P level. Further investigation is recommended to determine the long-term effects of these diets on urolithogenic compound formation. [ABSTRACT FROM AUTHOR]

This work combines electrophoretic deposition (EPD) withdirect-inkwriting (DIW) to prepare thin films of Al/CuO thermites onto patternedtwo- and three-dimensional silver electrodes. DIW was used to writethe electrodes using a silver nanoparticle ink, and EPD was performedin a subsequent step to deposit the thermite onto the conductive electrodes.Unlike conventional lithographic techniques, DIW is a low-cost andversatile alternative to print fine-featured electrodes, and addsthe benefit of printing self-supported three-dimensional structures.EPD provides a method for depositing the composite thermite only ontothe conductive electrodes, and with controlled thicknesses, whichprovides fine spatial and mass control, respectively. EPD has previouslybeen shown to produce well-mixed thermite composites which can packto reasonably high densities without the need for any postprocessing.Homogeneous mixing is particularly important in reactive composities,where good mixing can enhance the reaction kinetics by decreasingthe transport distance between the components. Several two- and three-dimensionaldesigns were investigated to highlight the versatility of using DIWand EPD together. In addition to energetic applications, we anticipatethat this combination of techniques will have a variety of other applications,which would benefit from the controlled placement of a thin film ofone material onto a conductive architecture of a second material. [ABSTRACT FROM AUTHOR]

The aims of this article are (1) to describe the prevalence of disclosure of HIV serostatus to sex partners among a racially/ethnically diverse sample of HIV-positive women living in Hawai'i and Seattle, Washington; and (2) to examine factors related to disclosure and condom use with those sex partners. HIV-positive women have difficulties consistently disclosing serostatus to sex partners and using condoms. Little is known about the disclosure practices of women from Hawai'i or Seattle. A cross-sectional design with convenience and snowball sampling was used, and up to three recent sex partner experiences were assessed among the HIV-positive participants (N = 84). A total of 133 recent sex partners were reported, with disclosure and condom use frequencies of 75.2 and 59.9%, respectively. Women who knew when it was safe to disclose were more likely to disclose. Women who disclosed to recent sex partners were less likely to use condoms, while those in casual/anonymous partnerships were more likely to use condoms. Hawaiian/part Hawaiian women had the lowest proportion of condom use. Health care personnel should routinely discuss disclosure and sexual transmission risk behaviors with seropositive women and offer strategies to enhance condom use, especially among those in committed partnerships. Culturally tailored interventions focused on strengthening efficacy beliefs for disclosure and condom use in Native Hawaiians are needed. [ABSTRACT FROM AUTHOR]

Children with early and continuously treated phenylketonuria (ECT-PKU) remain at risk of developing executive function (EF) deficits. There is some evidence that a high phenylalanine to tyrosine ratio (phe:tyr) is more strongly associated with impaired EF development than high phenylalanine alone. This study examined EF in a sample of 11 adolescents against concurrent and historical levels of phenylalanine, phe:tyr, and tyrosine. Lifetime measures of phe:tyr were more strongly associated with EF than phenylalanine-only measures. Children with a lifetime phe:tyr less than 6 demonstrated normal EF, whereas children who had a lifetime phe:tyr above 6, on average, demonstrated clinically impaired EF. [ABSTRACT FROM AUTHOR]

Abstract: Aluminum is traditionally used as the primary fuel in nanocomposite energetic systems due to its abundance and high energy release. However, thermodynamically boron releases more energy on both a mass and volumetric basis. Kinetic limitations can explain why boron rarely achieves its full potential in practical combustion applications, and thus has not replaced aluminum as the primary fuel in energetic systems. In particular, the existence of the naturally formed boron oxide (B2O3) shell is believed to play a major role in retarding the reactivity by acting as a liquid barrier if it cannot be efficiently removed. In this paper we demonstrate from constant-volume combustion experiments that nanoboron can be used to enhance the reactivity of nanoaluminum-based Metastable Intermolecular Composites (MICs) when the boron is of the fuel. It was also observed that an enhancement was not achieved when micronboron (700 nm) was used. Thermodynamic calculations showed that the aluminum reaction with CuO was sufficient to raise the temperature above in those mixtures which showed an enhancement. This is above both the boiling point of B2O3 (2338 K) and the melting point of boron (2350 K). A heat transfer model investigates the heating time of boron for temperatures (the region where the enhancement is achieved), and includes three heating times; sensible heating, evaporation of the B2O3 oxide shell, and the melting of pure boron. The model predicts the removal of the B2O3 oxide shell is fast for both the nano- and micronboron, and thus its removal alone cannot explain why nanoboron leads to enhancement while micronboron does not. The major difference in heating times between the nano- and micronboron is the melting time of the boron, with the micronboron taking a significantly longer time to melt than nanoboron. Since the oxide shell removal time is fast for both the nano- and micronboron, and since the enhancement is only achieved when the primary reaction (Al/CuO) can raise the temperature above 2350 K, we conclude that the melting of boron is also necessary for fast reaction in such formulations. Nanoboron can very quickly be heated relative to micronboron, and on a timescale consistent with the timescale of the Al/CuO reaction, thus allowing it to participate more efficiently in the combustion. The results indicate that sufficiently small boron can enhance the reactivity of a nanoaluminum-based MIC when added as the minor component (<50% by mole) of the fuel. [Copyright &y& Elsevier]

Debate continues as to why executive function (EF) continues to show impairments in children with early and continuously treated phenylketonuria (ECT-PKU). Using a mixed model, we measured EF in 10 adolescent children with ECT-PKU and 6 sibling controls, and examined associations between EF and (1) phenylalanine (phe) and (2) the phenylalanine : tyrosine ratio (phe : tyr). Measurements were taken on two occasions anticipated to yield variation in concurrent biochemistry resulting from changes in dietary compliance (i.e. holiday vs non-holiday period). A repeated measuresanova using the Behaviour Rating Inventory of Executive Function yielded the following results: no significant interactions; two significant group effects of substantially impaired working memory and initiation skills in children with ECT-PKU compared with controls, irrespective of occasion and two significant time effects, suggestive of slightly poorer non-holiday planning and organization scores in both groups. Further analyses revealed that phe levels were not significantly different on these occasions, suggesting that holiday dietary compliance may be better than expected. Correlations between EF and biochemistry in children with PKU showed that participant’s lifetime phe : tyr ratio was positively and significantly associated with EF impairment, more so than phe-only measures. [ABSTRACT FROM AUTHOR]

We describe the case of a man with Fragile X tremor/ataxia syndrome, whose ataxia and imbalance improved with the use of varenicline (Chantix®) and reverted to baseline 10 days after varenicline was discontinued. Varenicline was started as part of a smoking cessation program. [ABSTRACT FROM AUTHOR]

Aim. This paper is a report of a study to explore patients' experiences of having chemotherapy in a day hospital. Background. The nature of cancer care has changed dramatically in recent years with most patients receiving chemotherapy in a day hospital. Despite recognition of the need to explore patients' experience of cancer treatment, little research has been undertaken in this specific area. Method. A qualitative approach was adopted with a convenience sample of 30 patients diagnosed with cancer and receiving chemotherapy in a day hospital. Data were collected from January 2002 to March 2003 using unstructured tape-recorded interviews and analysed using a narrative framework. Findings. Participants viewed their experiences of chemotherapy treatment from the initial perspective of having to face their need to have chemotherapy. Their experiences in the day hospital had both positive and negative dimensions. Positive aspects related to maintaining a sense of normality and absence of the sick role, whilst negative aspects were related to the dehumanizing, factory-like system in the day hospital. Organizational issues also influenced experiences, including the sense of comradeship with other patients. Participants indicated the need to remain positive about the future and to learn to 'work around' the treatment. Conclusion. More effective methods are needed to develop patients' confidence and motivation to realize their self-care potential, together with increased awareness of organizational influences on patient experiences. Nurses need to focus on the 'here and now' concerns of patients as opposed to a biomedical perspective relating to treatment regimes, survival and prognosis. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of the study was to investigate the nature, extent, and predictors of stroke knowledge amongst people at risk of stroke. METHOD: A total of 273 questionnaires were distributed to three types of sites in metropolitan Brisbane (retirement villages, senior citizens and bowls clubs), and this strategy yielded a response rate of 37%. Of the surveys returned, 75 were retained in this study on the basis that: (a) participants met our criteria for being at risk of stroke (i.e., they reported one or more modifiable stroke risk factor, such as hypertension), and (b) they returned a completed Stroke Knowledge Test (SKT). RESULTS: Descriptive analyses revealed the overall level of stroke knowledge in this group was fair (approximately 50% of SKT items answered correctly, on average). SKT performance trends showed that participants did not have misconceptions about stroke but that more than 50% of the sample did not know the answer to seven out of 20 SKT items. Some overlap was identified regarding the issues about which participants in this and other previously researched groups admit they lack knowledge, such as the extent of increased stroke risk associated with smoking; however, the number of knowledge gaps identified in this sample was almost double that reported previously amongst stroke survivors and the general community. Analyses undertaken to explore determinants of stroke knowledge revealed age and education but not risk factor variables as significant predictors. CONCLUSION: Overall, findings suggest that it is presently difficult to predict an individual's understanding of stroke and that there is a need to increase stroke education, especially if this can address issues that people at risk of stroke admit they do not understand. [ABSTRACT FROM AUTHOR]

AIMS AND OBJECTIVES: This study sought to explore the nurses' experience of a day hospital chemotherapy service in an acute general hospital in Northern Ireland and how this compared with their experience of working in an inpatient setting. BACKGROUND: Despite the many changes taking place in cancer care delivery, little research has been conducted on nurses' experience of working in more acute cancer treatment settings. Research conducted to date has tended to focus on the role of nurses in wards, hospices and palliative care settings. DESIGN: This Heideggerian hermeneutic phenomenological study explored nurses' lived experience of day hospital chemotherapy service. METHOD: Face-to-face focused in-depth interviews were conducted with the total population of nurses who worked in the day hospital at the time of data collection (n = 10). Data analysis involved a two-staged approach, the analysis of narratives and narrative analysis, based on the work of Polkinghorne (1995). CONCLUSIONS: The nurses' viewed their experience of the chemotherapy day hospital as having both positive and negative dimensions. The positive dimensions included an increased sense of autonomy and the challenge of developing new skills, while the negative dimension included a perceived decrease in their caring role: (i) The individual characteristics of the nurse were seen to have a key influence on caring experience; (ii) Role changes led to a perceived dichotomy between their actual and aspired role and their caring and clinical role. RELEVANCE TO CLINICAL PRACTICE: There is a need to achieve a balance between delivering a clinical role (administering chemotherapy) while maintaining the centrality of the nurse-patient relationship. This can be likened to achieving a balance between 'nursing the clinic' alongside 'nursing the patient'. These findings have implications for the discourse on caring within other outpatient type clinics and discourse on cancer nursing as therapy and the culture of the cancer clinic. [ABSTRACT FROM AUTHOR]

AIM: This paper reports a study exploring district nurses' experiences of providing palliative care for patients with cancer and their families. BACKGROUND: There is an increasing demand for palliative care in the community, as many patients wish to die at home. District nurses are central to providing palliative care in the community, but there is a dearth of literature on district nurses' experiences in palliative care. METHOD: A Husserlian phenomenological approach was adopted with a purposive sample of 25 female district nurses. Data were collected using unstructured, tape-recorded interviews and analysed using Colaizzi's seven stages of data analysis. FINDINGS: Four themes were identified: the communication web; the family as an element of care; challenges for the district nurse in symptom management and the personal cost of caring. CONCLUSIONS: District nurses' experiences of providing palliative care to family units was challenging but rewarding. The emotive nature of the experience cannot be under-estimated, as many district nurses were touched by the varying situations. Whilst acknowledging the need to maintain an integrated approach to care, district nurses should be identified as the key workers in the complex situation of palliative care. [ABSTRACT FROM AUTHOR]

Diabetic peripheral polyneuropathy is characterized by axonal degeneration and regeneration as well as by Schwann cell and microvascular changes. These changes have been described at both the light (LM) and the electron microscopic (EM) levels; however, EM has not been applied to large clinical trials. Our goal was to adapt the rigorous techniques used for quantifying human biopsies with LM image analysis to accommodate ultrastructural analyses. We applied digital image capture and analysis to the ultrastructural examination of axons in sural nerve biopsies from diabetic patients enrolled in a multicenter clinical trial. The selection of sural nerve biopsies was based on the quality of specimen fixation, absence of physical distortion, and nerve fascicle size (≥100 000; ≤425 000 µm2). Thin sections were collected on formvar-coated slot grids, stabilized with carbon and scanned on a Phillips CM100 transmission electron microscope. Digital images were captured with a Kodak Megaplus 1.6 camera. A montage was constructed using software derived from aerial mapping applications, and this virtual image was viewed by EM readers. Computer-assisted analyses included identification and labeling of individual axons and axons within regenerating clusters. The average density of regenerating myelinated axon clusters per mm2 was 65.8 ± 5.1, range of 0–412 ( n = 193). These techniques increase the number of samples that may be analyzed by EM and extend the use of this technique to clinical trials using tissue biopsies as a primary endpoint. [ABSTRACT FROM AUTHOR]

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; however, both biological and psychological factors have been implicated in establishing or maintaining this condition. People with CFS report significant and disabling cognitive difficulties such as impaired concentration that in some cases are exacerbated by exposure to chemical triggers. The aim of this study was to determine if neuropsychological deficits in CFS are triggered by exposure to chemicals, or perceptions about the properties of these substances. Participants were 36 people with a primary diagnosis of CFS, defined according to Centers for Disease Control (CDC) criteria. A randomized, double-blind, placebo-controlled, crossover design was used, with objective assessment of neuropsychological function and participant rating of substance type, before and after exposure to placebo or chemical trigger. Results showed decrements in neuropsychological tests scores on three out of four outcome measures when participants rated the substance they had been exposed to as 'chemical.' No change in performance was found based on actual substance type. These results suggest that cognitive attributions about exposure substances in people with CFS may be associated with worse performance on neuropsychological tasks. In addition, these findings suggest that psychological interventions aimed at modifying substance-related cognitions may reduce some symptoms of CFS. [ABSTRACT FROM AUTHOR]

A qualitative descriptive study was developed to gain an insight into the experiences of patients with operable cancer of the oesophagus and the information they received. Through semistructured interviews, participants related details about different aspects of information-giving. Key sources of information were the consultant surgeon and other patients. Nurses, other medical staff, physiotherapists and dieticians were then mentioned. Family/friends were poor sources. Positive and negative aspects of the verbal and written information given were described, but there was minimal support for audiovisual information. Participants were given information relating to a number of key areas: treatment details, side-effects, extent of their disease, cure and prognosis and return to normality. A number of problem areas were identified. The findings indicate a need for a thoracic nurse specialist, updating of the information booklet and development of a staff education programme. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This article compares the quality of care provided by managed care plans (MCPs) and indemnity (or fee-for-service [FFS]) plans since 1980. METHODS: The 44 studies examined are the studies that Miller and Luft cited in their 1994 and 1997 reviews of the literature comparing MCPs with FFS plans. These studies are examined to determine how well they met Miller and Luft's selection criteria and, in addition, whether they controlled for differences in the breadth of insurance coverage. RESULTS: The 44 studies generated 57 observations. MCPs scored better than FFS plans on 10 of these, equally well on 25, and worse on 22. However, only 44 of these observations met the Miller-Luft criteria plus the coverage criterion. Four of these indicated that MCP care was better, 19 that MCP and FFS care were equivalent, and 21 that MCP care was worse. CONCLUSIONS: The small body of reliable studies comparing the quality of MCP care with that of FFS care indicates that the quality of care provided by MCPs tends to be equal or inferior to that provided by FFS plans. [ABSTRACT FROM AUTHOR]

Presents information on a study that measured the concentration and speciation of mercury (Hg) in the surface and deep ocean waters of the South and equatorial Atlantic. Information on the methylated Hg species; Methods; Results and discussion of the study.

The importance of information giving has been recognized and promoted in political, ethical and professional arenas and this has ultimately resulted in the publication of a vast amount of literature relating to the subject. This literature review considers the functions of patient information and the factors influencing information seeking for patients who have been diagnosed with cancer. Methods of providing information are discussed and the nurse's role in information giving is examined. A number of core problems are highlighted in relation to information giving. These problems, and possible reasons for them, are subsequently critically analysed. Finally, the literature relating to information needs of patients with cancer is evaluated and five key needs identified. [ABSTRACT FROM AUTHOR]

Intravenous immune globulin (IVIG) has been used with success to prevent and treat infection in patients with immunodeficiencies of humoral immune function. More recently, IVIG has been shown to modulate immune responses and to treat successfully several autoimmune diseases. Initial trials in bone marrow transplant recipients were aimed at the prevention of cytomegalovirus (CMV) disease. Although most studies showed such a benefit, CMV prophylaxis is now commonly provided by use of CMV-negative blood products or ganciclovir prophylaxis in, respectively, CMV-seronegative and CMV-seropositive patients. Acute and chronic graft-versus-host disease (GVHD) and associated infections remain critical barriers to the wider application of allogeneic blood or marrow transplantation, especially among patients given HLA-disparate grafts. To date, four controlled clinical trials have shown a significant reduction in acute GVHD in patients given IVIG (500-1000 mg/kg) weekly until 90-120 days post-transplant. in addition, bacterial infection in the early transplant period appears reduced. Meta-analysis of controlled trials reporting acute GVHD end points in 379 patients found a relative risk of acute GVHD of 0.68 (95% CI, 0.45-1.02) in IVIG recipients compared to untreated controls. Overall mortality reported in 809 patients in these trials showed an odds ratio of mortality of 0.74 (0.55-0.99) in IVIG recipients compared to controls (values <1.0 suggest that IVIG was effective in preventing the event). More recently it has been shown that in the absence of hypogammaglobulinaemia, IVIG (500 mg/kg) given monthly from day 90 to 360 did not reduce the incidence of chronic GVHD or late complications. Future research is aimed at characterizing the mechanism of action of suppression of acute GVHD with weekly IVIG prophylaxis and the role of IVIG prophylaxis in patients receiving unrelated marrow grafts. [ABSTRACT FROM AUTHOR]

Background: Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation.Methods: In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin. By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors.Results: Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64). Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021). Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients. Neither survival nor the risk of relapse was altered by immunoglobulin. However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs. 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs. 30 percent; P = 0.023).Conclusions: Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation. [ABSTRACT FROM AUTHOR]

This article is in direct response to a recently published article entitled Electrophoretic deposition and mechanistic studies of nano-Al/CuO thermites (K. T. Sullivan et al., J. Appl. Phys., 112(2), 2012), in which we introduced a non-dimensional parameter as the ratio of gas production to gas escape within a thin porous thermite film. In our original analysis, we had treated the problem as Fickian diffusion of gases through the porous network. However, we believe a more physical representation of the problem is to treat this as pressure-driven flow of gases in a porous medium. We offer a new derivation of the non-dimensional parameter which calculates gas velocity using the well-known Poiseuille's Law for pressure-driven flow in a pipe. This updated analysis incorporates the porosity, gas viscosity, and pressure gradient into the equation. [ABSTRACT FROM AUTHOR]

Electrophoretic deposition was used to deposit thin films (∼10-200 μm) of nano-aluminum/copper oxide thermites, with a density of 29% the theoretical maximum. The reaction propagation velocity was examined using fine-patterned electrodes (0.25 × 20 mm), and the optimum velocity was found to correspond to a fuel-rich equivalence ratio of 1.7. This value did not correlate with the calculated maximum in gas production or temperature, and it is suggested that it is a result of enhanced condensed-phase transport, which is speculated to increase for fuel-rich conditions. A ∼25% drop in propagation velocity occurred above an equivalence ratio of 2.0, where Al2O3 is predicted to undergo a phase change from liquid to solid. This is expected to hinder the kinetics by decreasing the mobility of condensed-phase reacting species. The effect of film thickness on propagation velocity was investigated, using the optimum equivalence ratio. The velocity was seen to exhibit a two-plateau behavior, with one plateau between 13 and 50 μm film thickness, and the other above ∼120 μm. The latter had nearly an order of magnitude faster velocity than the former, 36 m/s vs. 4 m/s, respectively. For film thicknesses in the 50-120 μm range, a linear transitional regime was observed. Images from the combustion studies showed an increase in forward-transported particles as the film thickness increased, along with more turbulent behavior of the flame. It was suggested that the two-plateau behavior indicated a shift in the energy transport mechanism. While nanocomposite thermites have been traditionally thought to exhibit convective energy transport, we find in this work that particle advection may also be important. The velocity of particles ejected through a thin slit mounted above a thermite strip was measured, and was found to be even faster (∼2-3×) than the flame propagation velocity. The morphology of captured particles was examined with an electron microscope, and indicated that reactive sintering had occurred. A non-dimensional number (A) was used to relate the rate of gas pressurization (1/τp) to the rate of gas escape by Fickian diffusion (D/L2), A = L2/(D*τp). For small values of A, gases rapidly escape and do not accumulate within the thermite films. Thus, the resultant energy transport is relatively slow. For large values of A, gases are entirely trapped, thus activating enhanced energy transport via oscillating pressure buildup and unloading of the material. This analysis is suitable for thermites which can produce sufficient gas to raise the local pressure above some critical value to overcome material adhesion strength, inducing pressure-driven unloading and resulting in enhanced energy transport. We suggest that further improvements in nanocomposite thermites can be made by examining the coupling of multiple length scales. Not only is nano-scale mixing important, in this work we found that a second length scale (∼120 μm) was necessary to fully activate a pressure buildup/unloading mechanism, which significantly enhances the reactivity. [ABSTRACT FROM AUTHOR]

The role of pro-inflammatory cytokines in systemic lupus erythematosus (SLE) remains somewhat controversial Several studies have shown increased production of TNFα and IL-6 in patients with SLE. Increased production of IL-6, TNFα, and IL-1 soluble receptors have also been reported. This finding is provocative because the soluble receptors have the capacity to act as antagonists. Several other inflammatory disorders are also associated with increased production of soluble TNFα receptors suggesting that this may be a general compensatory mechanism designed to down-regulate inflammation. The recent identification of an SLE disease susceptibility locus near the TNFR2 locus (TNFR p75) suggested the hypothesis that genetically driven differences in soluble TNFR2 production could play a role in the genetic susceptibility to SLE. We therefore characterized the frequency of a genetic polymorphism in the 3' untranslated region of the TNFR2 gene in Caucasoid SLE patients and geographically matched controls. No difference in the gene frequency of the two base-pair polymorphism in SLE patients compared to controls was found, nor was there any association with any particular clinical phenotype. [ABSTRACT FROM AUTHOR]

Objective Posttraumatic Stress Disorder (PTSD) is vulnerable to feigning. This presents a major challenge for clinicians who must differentiate between genuine and feigned presentations. Past studies have shown that in genuine PTSD the symptom profiles varies as a function of trauma type. It is not yet clear if this variation also occurs for feigned PTSD. Method Sixty participants were each randomly assigned to one of two experimental conditions. Both conditions provided: i) coaching about PTSD and ii) instructions to feign PTSD as if for financial gain. The trigger event in the conditions was either sexual assault (SA) or a motor vehicle collision (MVC), and it was manipulated in a written vignette. Outcomes were assessed via standardized measures for PTSD symptoms (PCL-5) and profile invalidity (Structured Inventory of Malingered Symptomology [SIMS]). Results All participants exceeded the PCL-5 and SIMS cut scores, indicating a plausible PTSD symptom profile with over-reported (detectable) symptoms. However, there were no statistically significant group differences on the PCL-5 or SIMS at the overall, subscale, or profile levels (all p's > 0.05). Conclusions Unlike genuine PTSD, in simulated PTSD the symptom profile did not differ by trauma type. The feigned performance was detected on the SIMS which could recommend this test, and this requires further investigation. If understanding of the genuine PTSD profiles for different trauma types is further developed and if our result is replicated, the future use of profile-analyses could assist clinicians when evaluating feigned PTSD. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with limited response to cytotoxic chemoradiotherapy, as well as newer immunotherapies. The PDA tumor microenvironment contains infiltrating immune cells including cytotoxic T cells; however, there is an overall immunosuppressive milieu. Hypoxia is a known element of the solid tumor microenvironment and may promote tumor survival. Through various mechanisms including, but not limited to, those mediated by HIF-1α, hypoxia also leads to increased tumor proliferation and metabolic changes. Furthermore, epithelial to mesenchymal transition is promoted through several pathways, including NOTCH and c-MET, regulated by hypoxia. Hypoxia-promoted changes also contribute to the immunosuppressive phenotype seen in many different cell types within the microenvironment and thereby may inhibit an effective immune system response to PDA. Pancreatic stellate cells (PSCs) and myofibroblasts appear to contribute to the recruitment of myeloid derived suppressor cells (MDSCs) and B cells in PDA via cytokines increased due to hypoxia. PSCs also increase collagen secretion in response to HIF-1α, which promotes a fibrotic stroma that alters T cell homing and migration. In hypoxic environments, B cells contribute to cytotoxic T cell exhaustion and produce chemokines to attract more immunosuppressive regulatory T cells. MDSCs inhibit T cell metabolism by hoarding key amino acids, modulate T cell homing by cleaving L-selectin, and prevent T cell activation by increasing PD-L1 expression. Immunosuppressive M2 phenotype macrophages promote T cell anergy via increased nitric oxide (NO) and decreased arginine in hypoxia. Increased numbers of regulatory T cells are seen in hypoxia which prevent effector T cell activation through cytokine production and increased CTLA-4. Effective immunotherapy for pancreatic adenocarcinoma and other solid tumors will need to help counteract the immunosuppressive nature of hypoxia-induced changes in the tumor microenvironment. Promising studies will look at combination therapies involving checkpoint inhibitors, chemokine inhibitors, and possible targeting of hypoxia. While no model is perfect, assuring that models incorporate the effects of hypoxia on cancer cells, stromal cells, and effector immune cells will be crucial in developing successful therapies. [ABSTRACT FROM AUTHOR]

Background: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. Methods: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. Results: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. Conclusions: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. Methods: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. Results: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07–3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23–3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12–7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56–6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07–5.62], p ≤ 0.05) among those who met the GWI case criteria. Conclusion: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population. [ABSTRACT FROM AUTHOR]

The poem "Thrashing" by K. M. A. Sullivan is presented. First Line: 111 start with the way my youngest rubs the center of my forehead; Last Line: and rivers.

Aims The increasing use of highly conformal radiation techniques to treat meningioma confers a greater need for accurate targeting. Several groups have shown that positron emission tomography/computed tomography (PET/CT) information alters meningioma targets contoured by single observers, but whether this translates into improved accuracy has not been defined. As magnetic resonance imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous PET/MRI may be superior to PET/CT. We assessed whether 68 Ga DOTATATE PET imaging (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma target volume contouring. Materials and methods Ten patients with meningioma underwent simultaneous 68 Ga DOTATATE PET/MRI followed by PET/CT. They were selected as it was anticipated that target volume definition in their cases would be particularly challenging. Three radiation oncologists contoured target volumes according to an agreed protocol: gross tumour volume (GTV) and clinical target volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative differences between PET(CT) and PET(MRI) were evaluated. Results There was substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38, CT/MRI+PET(MRI) 0.39 ( P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35, CT/MRI+PET(MRI) 0.35 ( P = 0.04 for all groups; P > 0.05 for individual pairs). One observer consistently contoured largest and one smallest. Observers rarely decreased volumes in relation to PET. Most IOV occurred in bone followed by dural tail, postoperative bed and venous sinuses. Tumour edges were qualitatively clearer on PET(MRI) versus PET(CT), but this did not affect contouring. Conclusion IOV in contouring challenging meningioma cases was large and only slightly improved with the addition of 68 Ga DOTATATE PET. Simultaneous PET/MRI for meningioma contouring is feasible, but did not improve IOV versus PET/CT. Whether volumes can be safely reduced according to PET requires evaluation. [ABSTRACT FROM AUTHOR]

In 2014, the Australian Government established the Teacher Education Ministerial Advisory Group (TEMAG) to advise on how teacher education programmes could ensure new teachers were adequately prepared for the classroom. Following this, the Australian Government endorsed a key recommendation of the TEMAG Action Now: Classroom Ready Teachers report, the inclusion of specialisations in primary Initial Teacher Education (ITE). This research was conducted at an Australian public university that, in 2016, had embedded specialisations in a revised primary teacher programme structure and was one of the first ITE institutions in Australia to graduate primary teachers with a specialisation. Using a mixed-methods case study design with convenience sampling, this study sought to investigate these primary graduates' perceptions of undertaking a specialisation in relation to the development of content knowledge and pedagogical knowledge in the specialist area, as well as perceived employment advantages. This research took place over 4 years with participants having completed a Bachelor of Education (Primary) at least three months prior to participating. The participants reported benefits to having completed a primary specialisation but expressed concerns about their preparedness to teach their specialisation and whether it would result in any advantages for employment. Recommendations from the participants included teaching practice in their area of specialisation, consideration of specialist skills and changing the timetabling of the specialisation in the programme. Ultimately, there is a need for ongoing research in this area to determine the extent to which primary specialisations deliver the intended outcomes and impacts at both the policy driver level and the university level. [ABSTRACT FROM AUTHOR]

Objective. Autoimmune diseases offer unique opportunities to measure disease burden and response to immunomodulation with haematopoietic cell transplantation (HCT). To study baseline impairments in health-related quality of life (HR-QOL), we analysed correlates of HR-QOL indices among patients with diffuse SSc participating in the SCOT (Scleroderma: Cyclophosphamide Or Transplantion) trial.Methods. Subjects with poor prognosis SSc were enrolled in the ongoing multicentre trial comparing immunosuppression with 12 monthly infusions of CYC (750 mg/m2) vs immunoablation followed by CD34-selected autologous HCT. Entry criteria are detailed at the study website (www.sclerodermatrial.org). Validated HR-QOL indices included the short-form 36 (SF-36) physical component summary (PCS) and mental component summary (MCS), HAQ-disability index (HAQ-DI) and the UCLA gastrointestinal instrument (GIT 2.0). We assessed Pearson correlations between HR-QOL indices and objective disease measures. Coefficients >0.30 were considered moderate associations.Results. Sixty-seven subjects were tested at randomization: 45 were females; mean age was 46.2 years and disease duration was 1.6 years; mean (s.d.) per cent predicted forced vital capacity (FVC) was 74.6 (15.7) and mean modified Rodnan Skin Score (mRSS) was 30.3 (9.6). Baseline mean PCS (n = 57) was 27.7, which is 2.2 s.d. below the US general population. The 67 patients had moderate functional disability (mean HAQ-DI 1.4), whereas the mean total GIT (n = 25) was 0.57 (0.4 signifies moderate severity). For comparison, subjects with diffuse SSc enrolled in the Scleroderma Lung Study (comparing CYC with placebo; Tashkin, NEJM 2006) had a higher (better) baseline PCS (32.1) and lower (better) HAQ-DI (1.02; (Khanna, Arthritis Rheum 2005). Table 1 presents correlations between mRSS and FVC with QOL measures.Conclusions. Patients in the SCOT study had marked baseline impairments in physical health. Objective disease measures of dermal and pulmonary involvement correlated with reported symptom burden (DLCO data not shown). Longitudinal analysis at study completion (14 test repetitions over 72 months) will offer unique rigor in HCT trials, provide a rich basis for comparisons with immune and mechanistic studies, and characterize alterations in HR-QOL indices across the two treatments of SSc. Table 1.VariablesmRSSFVCSHAQ HAQ-DI (n = 65)0.59*0.05 Pain VAS (n = 65)0.100.07SF-36 (n = 57) SF-36 PCS−0.50*0.03 SF-36 MCS−0.020.06 SF-36 physical functioning−0.51*0.07 SF-36 role limitations−0.44*−0.04 SF-36 pain−0.130.08 SF-36 general health−0.17−0.11 SF-36 vitality−0.130.08 SF-36 social functioning−0.210.01 SF-36 role emotional−0.120.08 SF-36 mental health−0.080.02UCLA GIT 2.0 (n = 25) Reflux scale−0.270.30 Distention scale−0.370.20 Diarrhea0.14−0.09 Constipation0.16−0.09 Emotional well-being−0.04−0.05 Sociaf functioning0.130.26 GIT total score−0.180.19For SF-36, higher scores denote better HR-QOL. For HAQ-DI and GIT 2.0, higher scores denote worse HR-QOL. *P < 0.05. [ABSTRACT FROM PUBLISHER]