bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Turbulent Kinetic Energy Dissipation Rate with a Lagrangian Float
Authors: Lien Ren-Chieh , D'Asaro Eric A.
Published: August 2006

This study tests the ability of a neutrally buoyant float to estimate the dissipation rate of turbulent kinetic energy ɛ from its vertical acceleration spectrum using an inertial subrange method. A Lagrangian float was equipped with a SonTek acoustic Doppler velocimeter (ADV), which measured the vector velocity 1 m below the float's center, and a pressure sensor, which measured the float's depth. Measurements were taken in flows where estimates of ɛ varied from 10−8 to 10−3 W kg−1. Previous observational and theoretical studies conclude that the Lagrangian acceleration spectrum is white within the inertial subrange with a level proportional to ɛ. The size of the Lagrangian float introduces a highly reproducible spectral attenuation at high frequencies. Estimates of the dissipation rate of turbulent kinetic energy using float measurements ɛfloat were obtained by fitting the observed spectra to a model spectrum that included the attenuation effect. The ADV velocity measurements were converted to a wavenumber spectrum using a variant of Taylor's hypothesis. The spectrum exhibited the expected −5/3 slope within an inertial subrange. The turbulent kinetic energy dissipation rate ɛADV was computed from the level of this spectrum. These two independent estimates, ɛADV and ɛfloat, were highly correlated. The ratio ɛfloat/ɛADV deviated from one by less than a factor of 2 over the five decades of ɛ measured. This analysis confirms that ɛ can be estimated reliably from Lagrangian float acceleration spectra in turbulent flows. For the meter-sized floats used here, the size of the float and the noise level of the pressure measurements sets a lower limit of ɛfloat > 10−8 W kg−1.
Derivation of the Water Vapor Content from the GNSS Radio Occultations Observations
Authors: Vespe Francesco , Persia Teresa
Published: August 2006

The present work investigates the possibility of retrieving humidity using the bending angle data obtained from radio occultation of GPS signals without additional external information. In particular, with the proposed approach, the dry pressure profiles are obtained by fitting the bending angles of the outer-troposphere layers (from h = h250K up to the stratopause) using the Hopfield dry atmosphere model. The ground pressure and temperature are the parameters of the model to be estimated. In the second step the humidity profiles are extracted by subtracting the contribution resulting from the dry atmosphere from the measured bending angles. Such derivation implies a complex mathematical treatment of the relationship between the bending angle and the refractivity, which is fully explained herein. Furthermore, the method was applied on Challenging Minisatellite Payload (CHAMP) profiles. The CHAMP profiles are achieved by applying heuristic retrieval algorithms based on the canonical transform. The algorithms are applied to minimize the negative refractivity bias that is observed for low-latitude GNSS RO. Thus, the results are shown and discussed in the second part of the paper. Finally, it is widely discussed how the proposed method is able to retrieve refractivity profiles without using the Abel inversion.
One-Lag Estimators for Cross-Polarization Measurements
Authors: Melnikov Valery M.
Published: August 2006

Estimators of the linear depolarization ratio (LDR) and cross-polarization correlation coefficients (ρxh) free from noise biases are devised. The estimators are based on the 1-lag correlation functions. The 1-lag estimators can be implemented with radar with simultaneous reception of copolar and cross-polar returns. Absence of noise biases makes the 1-lag estimators useful in eliminating variations of the system gain and in observations of heavy precipitation with enhanced thermal radiation. The 1-lag estimators allow for measurements at lower signal-to-noise ratios than the conventional algorithms.

The statistical biases and standard deviations of 1-lag estimates are obtained via the perturbation analysis. It is found that both the 1-lag and conventional estimates of ρxh experience strong statistical biases at ρxh less than 0.3 (i.e., at low canting angles of oblate hydrometeors), and a procedure to correct for this bias is proposed.
Scope and Patterns of Metropolitan Governance in Urban America
Authors: Wood Curtis
Published: August 2006

The author explores the scope and patterns of metropolitan governance in the Kansas City region by examining how 46 cities deliver 28 different public services. The hypotheses that intergovernmental service-delivery arrangements will be more common than in-house delivery and contracting with the nongovernmental sector, that intergovernmental service-delivery arrangements will be more common for system maintenance services than for lifestyle services, and that central cities and at-risk suburbs will be more likely to enter into intergovernmental service-delivery arrangements than are bedroom developing and affluent job centers are examined and tested. The findings support the first hypothesis but not the last two hypotheses.
Humor and Older Adults
Authors: Kruse Barbara G. , Prazak Mark
Published: August 2006

Laughter, the physical response to perceived humor, has demonstrated positive effects on physical and psychological well-being. Studies that focus on effects of humor on health and well-being of older adults are scarce. No studies were found that examine what older adults find humorous. The purpose of this descriptive study was to explore the humor stimulus in a population of older adults. One hundred thirty (130) hospital auxiliary personnel aged 50 and older were asked the question What makes you laugh? Content analysis of responses revealed nine themes in two major categories, which were (a) people or animals and (b) situations or events. Children represented the largest category of people (30%), and telling jokes represented the largest category of situations or events (51%). Humor can be used by nurses as an effective therapeutic tool when caring for older adults if appropriate sources of humor are identified and applied.
Dementia management in France
Authors: Cantegreil-Kallen Inge , Turbelin Clément , Angel Pierre , Flahault Antoine , Rigaud Anne-Sophie
Published: August 2006

In France, a wide range of care and support services exist for community dwelling people with Alzheimer's disease (AD). These are coordinated by the general practitioner (GP). We investigated interventions that were ‘prescribed’ by French GPs and analysed their perceived barriers to arranging these. Thirty-nine percent of GPs responded to a postal survey, which was sent to 1105 physicians belonging to the Sentinel GP Research Network and to 524 GPs consulting in the Rhône-Alpes region of France. Fifty percent of patients were treated with acetyl-cholinesterase inhibitors and the following other support services were used: home help (63%), nursing care (48%) and physiotherapy (35%). Although GPs acknowledged carers' need for emotional support, only minimal levels of other interventions such as day care (12%) and psychotherapeutic interventions (12%) were prescribed. Reasons for under-use included non-availability and carers' reluctance to undergo psychotherapy. Lack of integrated community care services, insufficient information on services, lack of collaboration between health professionals and the frequent absence of a reliable carer were considered the most important barriers to the effective support of people with dementia in primary health care settings.
Receiving a diagnosis of dementia
Authors: Vernooij-Dassen Myrra , Derksen Els , Scheltens Philip , Moniz-Cook Esme
Published: August 2006

There are strong opinions about the advantages and disadvantages of a disclosure of dementia to the individual affected, but little is known about how they and their families understand and respond to this information. This article reports and examines the impact of receiving a diagnosis of dementia, by comparing descriptions of its impact at two weeks, with descriptions explored at 12 weeks. Interviews were undertaken on two occasions with 18 couples, one of whom had received a diagnosis of dementia, the other being a family member. The interviews revealed a gradual process of realization of what the diagnosis meant, resulting in important subtle changes in understandings of dementia and personal relationships. Disclosure of dementia occurs at one point in time, but its impact should be seen as a process. Suggestions are made on how the process of diagnosis and its sharing may enhance family partnerships and social relationships through support of both individuals with dementia and families.
Muscle Strength, Body Composition, and Physical Activity in Women Receiving Chemotherapy for Breast Cancer
Authors: Visovsky Constance
Published: August 2006

There is evidence to suggest that treatment of breast cancer with chemotherapy can induce metabolic changes in skeletal muscle. Women undergoing treatment for breast cancer with certain chemotherapeutic agents can experience declines in lean body mass and muscle strength and a subsequent increase in body weight. These alterations not only can lead to declines in physical function but also predispose women to weight-related chronic illness. Excess body weight may also play a role in the development or recurrence of breast cancer. There is evidence that physical exercise may improve body composition and enhance muscular endurance, flexibility, and quality of life (QOL) in women with breast cancer. While studies of aerobic, resistance, and combinations of aerobic and resistance exercise for women with breast cancer have been conducted, most studies employed supervised aerobic exercise sessions. Few studies have examined the role of resistance exercise or the combination of resistance and aerobic exercise in maintaining or increasing muscle strength while preserving lean body mass in this population. The relatively small sample sizes and short duration of physical activity interventions in previous studies make it difficult to detect dose responses to exercise training. Physical activity interventions with larger sample sizes and of longer duration are necessary to achieve long-term health outcomes. Physical activity interventions that include the older or more obese women with breast cancer are also needed, as this population may be most at risk of functional decline and the development of chronic illness. Interventions appropriate for women treated for breast cancer who have comorbid disease are also needed. Newer, more intense chemotherapy regimens may induce a differential effect on muscle strength and body composition. However, the role of physical activity during dose-dense chemotherapy protocols has not been established.
Protective Effect of Andrographis paniculata and Andrographolide on Cyclophosphamide-Induced Urothelial Toxicity
Authors: Sheeja K. , Kuttan Girija
Published: August 2006

The protective effect of Andrograhis paniculata and andrographolide (ANDLE) against cyclophosphamide (CTX)-induced urothelial toxicity was investigated in this study. Pretreatment of Swiss albino mice with A paniculata extract (10 mg/dose/animal intraperitoneally [ip]) and ANDLE (500 μg/dose/animal ip) could significantly reduce CTX (1.5 nmol/kg body weight)-induced urothelial toxicity. Morphological and histopathological analysis of urinary bladder of CTX-treated mice showed severe inflammation and dark coloration, whereas A paniculata and ANDLE-treated mice showed almost normal bladder morphology. Elevation of urinary protein level (7.33±0.3 g/L) by CTX administration was reduced by A paniculata (3.78 ± 0.4 g/L) and ANDLE treatment (4.19 ± 0.1 g/L). Urinary urea N2level, which was elevated after 48 hours of CTX administration (24.25 ± 0.2 g/L) was found to be reduced by the treatment with A paniculata (14.19 ± 0.5 g/L) and ANDLE (15.79 ± 0.4 g/L). A decreased level of reduced glutahione (GSH) content in liver (2.81 ± 0.1 nmol/mg protein) and bladder (1.20 ± 0.2 nmol/mg protein) after CTX administration was also increased by the treatment with A paniculata (liver: 5.78 ± 0.3 nmol/mg protein; bladder: 2.96 ± 0.2 nmol/mg protein) and ANDLE (liver: 5.14 ± 0.3 nmol/mg protein; bladder: 2.84 ± 0.2 nmol/mg protein). Production of the proinflammatory cytokine, tumor necrosis factor-α, which was elevated during CTX administration, was found to be inhibited by A paniculata and ANDLE treatment. The lowered level of interleukin-2 and interferon-γ during CTX treatment was elevated by the administration of A paniculata and ANDLE.
Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton
Authors: Kalfa Theodosia A. , Pushkaran Suvarnamala , Mohandas Narla , Hartwig John H. , Fowler Velia M. , Johnson James F. , Joiner Clinton H. , Williams David A. , Zheng Yi
Published: August 2006

Actin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as well as distinct roles in hematopoietic cells; therefore, we studied their role in red blood cells (RBCs). Conditional gene targeting with a loxP-flanked Rac1 gene allowed Crerecombinase–induced deletion of Rac1 on a Rac2 null genetic background. The Rac1–/–;Rac2–/– mice developed microcytic anemia with a hemoglobin drop of about 20% and significant anisocytosis and poikilocytosis. Reticulocytes increased more than 2-fold. Rac1–/–;Rac2–/– RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and aggregates under confocal microscopy. Transmission electron microscopy of the cytoskeleton demonstrated junctional aggregates and pronounced irregularity of the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal changes in Rac1–/–;Rac2–/– erythrocytes were associated with significantly decreased cellular deformability. The composition of the cytoskeletal proteins was altered with an increased actin-to-spectrin ratio and increased phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and phosphorylated adducin of Rac1–/–;Rac2–/– erythrocytes were more easily extractable by Triton X-100, indicating weaker association to the cytoskeleton. Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization.
Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states
Authors: Krispin Alon , Bledi Yaniv , Atallah Mizhir , Trahtemberg Uriel , Verbovetski Inna , Nahari Efrat , Zelig Orly , Linial Michal , Mevorach Dror
Published: August 2006

Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells.
Heat shock protein expression in canine malignant mammary tumours
Authors: Romanucci Mariarita , Marinelli Alessia , Sarli Giuseppe , Salda Leonardo Della
Published: August 2006

Background

Abnormal levels of Heat Shock Proteins (HSPs) have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS), in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value.

Methods

Immunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10in situcarcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes). A semi-quantitative method was used for the analysis of the results.

Results

Widespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01) expression was observed as well as a significant reduction in Hsp73 (P < 0.01) immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a strong positivity in infiltrating tumour cells and metaplastic squamous elements of invasive groups. High Hsp27 expression also appeared to be significantly correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90 expression was high in all tumours and, like Hsp73, it also showed an intense positivity in lymphatic emboli.

Conclusion

These results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and its high immunodetection in invasive tumours is indicative of a poorer clinical outcome.
Physical activity is related to quality of life in older adults
Authors: Acree Luke S , Longfors Jessica , Fjeldstad Anette S , Fjeldstad Cecilie , Schank Bob , Nickel Kevin J , Montgomery Polly S , Gardner Andrew W
Published: August 2006

Background

Physical activity is associated with health-related quality of life (HRQL) in clinical populations, but less is known whether this relationship exists in older men and women who are healthy. Thus, this study determined if physical activity was related to HRQL in apparently healthy, older subjects.

Methods

Measures were obtained from 112 male and female volunteers (70 ± 8 years, mean ± SD) recruited from media advertisements and flyers around the Norman, Oklahoma area. Data was collected using a medical history questionnaire, HRQL from the Medical Outcomes Survey short form-36 questionnaire, and physical activity level from the Johnson Space Center physical activity scale. Subjects were separated into either a higher physically active group (n = 62) or a lower physically active group (n = 50) according to the physical activity scale.

Results

The HRQL scores in all eight domains were significantly higher (p < 0.05) in the group reporting higher physical activity. Additionally, the more active group had fewer females (44% vs. 72%, p = 0.033), and lower prevalence of hypertension (39% vs. 60%, p = 0.041) than the low active group. After adjusting for gender and hypertension, the more active group had higher values in the following five HRQL domains: physical function (82 ± 20 vs. 68 ± 21, p = 0.029), role-physical (83 ± 34 vs. 61 ± 36, p = 0.022), bodily pain (83 ± 22 vs. 66 ± 23, p = 0.001), vitality (74 ± 15 vs. 59 ± 16, p = 0.001), and social functioning (92 ± 18 vs. 83 ± 19, p = 0.040). General health, role-emotional, and mental health were not significantly different (p > 0.05) between the two groups.

Conclusion

Healthy older adults who regularly participated in physical activity of at least moderate intensity for more than one hour per week had higher HRQL measures in both physical and mental domains than those who were less physically active. Therefore, incorporating more physical activity into the lifestyles of sedentary or slightly active older individuals may improve their HRQL.
Characterisation of the immune response to type I collagen in scleroderma
Authors: Warrington Kenneth J , Nair Usha , Carbone Laura D , Kang Andrew H , Postlethwaite Arnold E
Published: August 2006

This study was conducted to examine the frequency, phenotype, and functional profile of T lymphocytes that proliferate in response to type I collagen (CI) in patients with scleroderma (SSc). Peripheral blood mononuclear cells (PBMCs) from SSc patients, healthy controls, and rheumatoid arthritis disease controls were labeled with carboxy-fluorescein diacetate, succinimidyl ester (CFSE), cultured with or without antigen (bovine CI) for 14 days, and analysed by flow cytometry. Surface markers of proliferating cells were identified by multi-color flow cytometry. T-cell lines were derived after sorting for proliferating T cells (CFSElow). Cytokine expression in CI-responsive T cells was detected by intracellular staining/flow cytometry and by multiplex cytokine bead assay (Bio-Plex). A T-cell proliferative response to CI was detected in 8 of 25 (32%) SSc patients, but was infrequent in healthy or disease controls (3.6%; p = 0.009). The proliferating T cells expressed a CD4+, activated (CD25+), memory (CD45RO+) phenotype. Proliferation to CI did not correlate with disease duration or extent of skin involvement. T-cell lines were generated using in vitro CI stimulation to study the functional profile of these cells. Following activation of CI-reactive T cells, we detected intracellular interferon (IFN)-γ but not interleukin (IL)-4 by flow cytometry. Supernatants from the T-cell lines generated in vitro contained IL-2, IFN-γ, GM-CSF (granulocyte macrophage-colony-stimulating factor), and tumour necrosis factor-α, but little or no IL-4 and IL-10, suggesting that CI-responsive T cells express a predominantly Th1 cytokine pattern. In conclusion, circulating memory CD4 T cells that proliferate to CI are present in a subset of patients with SSc, but are infrequent in healthy or disease controls.
Estrogen receptor-α and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands
Authors: Booth Brian W , Smith Gilbert H
Published: August 2006

Introduction

Stem cells of somatic tissues are hypothesized to protect themselves from mutation and cancer risk through a process of selective segregation of their template DNA strands during asymmetric division. Mouse mammary epithelium contains label-retaining epithelial cells that divide asymmetrically and retain their template DNA.

Method

Immunohistochemistry was used in murine mammary glands that had been labeled with [3H]thymidine during allometric growth to investigate the co-expression of DNA label retention and estrogen receptor (ER)-α or progesterone receptor (PR). Using the same methods, we investigated the co-localization of [3H]thymidine and ER-α or PR in mammary tissue from mice that had received treatment with estrogen, progesterone, and prolactin subsequent to a long chase period to identify label-retaining cells.

Results

Label-retaining epithelial cells (LRECs) comprised approximately 2.0% of the entire mammary epithelium. ER-α-positive and PR-positive cells represented about 30–40% of the LREC subpopulation. Administration of estrogen, progesterone, and prolactin altered the percentage of LRECs expressing ER-α.

Conclusion

The results presented here support the premise that there is a subpopulation of LRECs in the murine mammary gland that is positive for ER-α and/or PR. This suggests that certain mammary LRECs (potentially stem cells) remain stably positive for these receptors, raising the possibility that LRECs comprise a hierarchy of asymmetrically cycling mammary stem/progenitor cells that are distinguished by the presence or absence of nuclear steroid receptor expression.
Reappraisal of Pseudomonas aeruginosa hospital-acquired pneumonia mortality in the era of metallo-β-lactamase-mediated multidrug resistance: a prospective observational study
Authors: Zavascki Alexandre Prehn , Barth Afonso Luís , Fernandes Juliana Fernandez , Moro Ana Lúcia Didonet , Gonçalves Ana Lúcia Saraiva , Goldani Luciano Zubaran
Published: August 2006

Introduction

Hospital-acquired pneumonia (HAP) due to Pseudomonas aeruginosa is associated with high mortality rates. The metallo-β-lactamases (MBLs) are emerging enzymes that hydrolyze virtually all β-lactams. We aimed to assess P. aeruginosa HAP mortality in a setting of high-rate MBL production

Methods

A prospective cohort study was performed at two tertiary-care teaching hospitals. A logistic regression model was constructed to identify risk factors for 30-day mortality.

Results

One-hundred and fifty patients with P. aeruginosa HAP were evaluated. The 30-day mortality was 37.3% (56 of 150): 57.1% (24 of 42) and 29.6% (32 of 108) for patients with HAP by MBL-producing P. aeruginosa and by non-MBL-producing P. aeruginosa, respectively (relative risk, 1.93; 95% confidence interval (CI), 1.30–2.85). The logistic regression model identified a higher Charlson comorbidity score (odds ratio, 1.21; 95% CI, 1.04–1.41), presentation with severe sepsis or septic shock (odds ratio, 3.17; 95% CI, 1.30–7.72), ventilator-associated pneumonia (odds ratio, 2.92; 95% CI, 1.18–7.21), and appropriate therapy (odds ratio, 0.24; 95% CI, 0.10–0.61) as independent factors for 30-day mortality. MBL production was not statistically significant in the final model.

Conclusion

MBL-producing P. aeruginosa HAP resulted in higher mortality rates, particularly in patients with ventilator-associated pneumonia, most probably related to the less frequent institution of appropriate antimicrobial therapy. Therapeutic approaches should be reviewed at institutions with a high prevalence of MBL.
SOFA is superior to MOD score for the determination of non-neurologic organ dysfunction in patients with severe traumatic brain injury: a cohort study
Authors: Zygun David , Berthiaume Luc , Laupland Kevin , Kortbeek John , Doig Christopher
Published: August 2006

Introduction

The objective of the present study was to compare the discriminative ability of the Sequential Organ Failure Assessment (SOFA) and Multiple Organ Dysfunction (MOD) scoring systems with respect to hospital mortality and unfavorable neurologic outcome in patients with severe traumatic brain injury admitted to the intensive care unit.

Method

We performed a prospective cohort study at Foothills Medical Centre, the sole adult tertiary care trauma center servicing southern Alberta (population about 1.3 million). All patients aged 16 years or older with severe traumatic brain injury and intensive care unit length of stay greater than 48 hours between 1 May 2000 and 31 April 2003 were included. Non-neurologic organ dysfunction was measured using the SOFA and MODS scoring systems. Determination of organ dysfunction for each non-neurologic organ system was compared between the two systems by calculating the proportion of patients with SOFA and MOD component score defined organ failure. Consistent with previous literature, organ system failure was defined as a component score of three or greater.

Results

The odds of death and unfavorable neurologic outcome in patients with SOFA defined cardiovascular failure were 14.7 times (95% confidence interval [CI] 5.9–36.3) and 7.6 times (95% CI 3.5–16.3) that of those without cardiovascular failure, respectively. The development of SOFA-defined cardiovascular failure was a reasonable discriminator of hospital mortality and unfavorable neurologic outcome (area under the receiver operating characteristic [ROC] curve 0.75 and 0.73, respectively). The odds of death and unfavorable neurologic outcome in patients with MOD-defined cardiovascular failure were 2.6 times (95% CI 1.24–5.26) and 4.1 times (95% CI 1.3–12.4) that of those without cardiovascular failure, respectively. The development of MOD-defined cardiovascular failure was a poor discriminator of hospital mortality and unfavorable neurologic outcome (area under the ROC curve 0.57 and 0.59, respectively). Neither SOFA-defined nor MOD-defined respiratory failure was significantly associated with hospital mortality.

Conclusion

In patients with brain injury, the SOFA scoring system has superior discriminative ability and stronger association with outcome compared with the MOD scoring system with respect to hospital mortality and unfavorable neurologic outcome.
A quantitative analysis of the mechanism that controls body size in Manduca sexta
Authors: Nijhout HF , Davidowitz G , Roff DA
Published: August 2006

Background

Body size is controlled by mechanisms that terminate growth when the individual reaches a species-specific size. In insects, it is a pulse of ecdysone at the end of larval life that causes the larva to stop feeding and growing and initiate metamorphosis. Body size is a quantitative trait, so it is important that the problem of control of body size be analyzed quantitatively. The processes that control the timing of ecdysone secretion in larvae of the moth Manduca sexta are sufficiently well understood that they can be described in a rigorous manner.

Results

We develop a quantitative description of the empirical data on body size determination that accurately predicts body size for diverse genetic strains. We show that body size is fully determined by three fundamental parameters: the growth rate, the critical weight (which signals the initiation of juvenile hormone breakdown), and the interval between the critical weight and the secretion of ecdysone. All three parameters are easily measured and differ between genetic strains and environmental conditions. The mathematical description we develop can be used to explain how variables such as growth rate, nutrition, and temperature affect body size.

Conclusion

Our analysis shows that there is no single locus of control of body size, but that body size is a system property that depends on interactions among the underlying determinants of the three fundamental parameters. A deeper mechanistic understanding of body size will be obtained by research aimed at uncovering the molecular mechanisms that give these three parameters their particular quantitative values.
Correspondence from substance misuse services – what do general practitioners really want?
Authors: Shyam Devatha Radhae , Williams Hugh
Published: August 2006

Aims and Method

To improve the quality of correspondence by identifying what general practitioners (GPs) regarded as the important attributes in patient letters from a substance misuse service. A postal questionnaire survey was carried out to determine the views of general practitioners in Brighton and Hove City.

Results

Responses were obtained from 32 out of 45 GP surgeries (71%) and indicated that correspondence should be prompt, concise and regular. An assessment summary, management plan and clear medication prescribing arrangements between primary and secondary services were considered particularly important.

Clinical Implications

New quality standards for correspondence to GPs have been implemented by the Brighton Substance Misuse Service. These might be of interest to other such services.
Five-year study (2000–2004) of trainees' publications in the Psychiatric Bulletin
Authors: George Sanju , Dhaya Ditesh , Oyebode Femi
Published: August 2006

Aims and Method

We explored the contribution of trainees to the Psychiatric Bulletin by estimating the nature and proportion of papers by trainees published during a 5-year period: 2000–2004.

Results

Nearly a third (30.7%) of all papers published during the 5 years were authored/co-authored by trainees. The predominant contribution was to education and training papers (66% of all the papers in this section), original papers (46%) and drug information quarterly papers (30%). The proportions of papers by trainees remained fairly consistent across the 5 years.

Clinical Implications

Overall, the Psychiatric Bulletin appears to be ‘trainee-friendly’ and this should encourage trainees to submit papers to the Bulletin.
Novel Fibroblast Growth Factor Receptor 1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism with and without Anosmia
Authors: Trarbach Ericka Barbosa , Costa Elaine Maria Frade , Versiani Beatriz , de Castro Margaret , Baptista Maria Tereza Matias , Garmes Heraldo Mendes , de Mendonca Berenice Bilharinho , Latronico Ana Claudia
Published: August 2006

Context: Kallmann syndrome is a clinically and genetically heterogeneous disorder. To date, loss-of-function mutations in the genes encoding anosmin-1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the X-linked and autosomal dominant forms of this syndrome, respectively.

Objective: The objective was to investigate genetic defects in the KAL1 and FGFR1 genes in patients with congenital isolated hypogonadotropic hypogonadism (IHH).

Patients: Eighty patients (71 males and nine females) with IHH were studied, of which 30 were familial. Forty-six of them had olfactory abnormalities.

Methods: The coding regions of both KAL1 and FGFR1 genes were amplified and automatically sequenced. The KAL1 mutations were investigated only in patients with olfactory abnormalities, whereas FGFR1 was studied in the entire group.

Results: Two novel KAL1 mutations, an intragenic deletion of exons 3–6 and a splicing mutation IVS7 + 1G>A, were identified in two of 46 patients with Kallmann syndrome. Eight novel heterozygous FGFR1 mutations (G48S, L245P, R250W, A343V, P366L, K618fsX654, P722S, and V795I) were identified in nine of 80 patients with IHH. Eight of them had olfactory abnormalities. Interestingly, the G48S mutation was identified in a normosmic IHH patient. Two unrelated females, who carried FGFR1 mutations, had anosmia and normal reproductive function.

Conclusion: We identified novel mutations in KAL1 and FGFR1 genes in IHH patients. FGFR1 mutations were identified in 17% of the patients with olfactory abnormalities and in one of 34 normosmic IHH patients. In addition, isolated anosmia was identified in two unrelated females as a partial phenotypic manifestation of FGFR1 defects.
Letrozole Reduces Estrogen and Gonadotropin Exposure in Women with Breast Cancer Undergoing Ovarian Stimulation before Chemotherapy
Authors: Oktay Kutluk , Hourvitz Ariel , Sahin Gulnaz , Oktem Ozgur , Safro Bradley , Cil Aylin , Bang Heejung
Published: August 2006

Context: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation.

Objective: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy.

Patients and Methods: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150–300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease.

Results: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean ± sd 483.4 ± 278.9 vs. 1464.6 ± 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17–18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery.

Conclusion: Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.
Persistent Intraprostatic Androgen Concentrations after Medical Castration in Healthy Men
Authors: Page Stephanie T. , Lin Daniel W. , Mostaghel Elahe A. , Hess David L. , True Lawrence D. , Amory John K. , Nelson Peter S. , Matsumoto Alvin M. , Bremner William J.
Published: August 2006

Context: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences.

Objective: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men.

Design: Thirteen male volunteers ages 35–55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone (T) gel (10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed.

Results: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls (P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression.

Conclusion: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20–30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study.
Polycystic Ovarian Morphology in Normal Women Does Not Predict the Development of Polycystic Ovary Syndrome
Authors: Murphy M. K. , Hall J. E. , Adams J. M. , Lee H. , Welt C. K.
Published: August 2006

Context: Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome (PCOS); however, the natural history of PCOM is unknown.

Objective: We hypothesized that the presence of PCOM predisposes the development of PCOS.

Design: The study was a longitudinal follow-up study over 8.2 ± 5.2 yr (mean ± sd; range 1.7–17.5 yr).

Setting: The study took place in an outpatient setting.

Subjects: Women who took part in a previous study as a normal control and had an ultrasound examination (n = 40) participated.

Intervention: Subjects underwent an interval menstrual history, physical exam, blood sampling, and repeat ultrasound in the follicular phase.

Main Outcome Measure: Development of PCOS was diagnosed by irregular menses and hyperandrogenism, in the absence of other disorders. Changes in ovarian morphology over time were evaluated.

Results: At the baseline visit, 23 women (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM no longer met the criteria for PCOM at follow-up. There was no factor that predicted the change to normal ovarian morphology at the follow-up visit.

Conclusions: These data suggest that PCOM in women with regular ovulatory cycles does not commonly predispose the development of PCOS. Although it is unusual to develop PCOM if the ovaries are normal on first assessment, ovaries in women with PCOM no longer meet the criteria for PCOM in approximately half of cases over time.
Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and αvβ5 integrin
Authors: Franco Paola , Vocca Immacolata , Carriero Maria V. , Alfano Daniela , Cito Letizia , Longanesi-Cattani Immacolata , Grieco Paolo , Ossowski Liliana , Stoppelli Maria P.
Published: August 2006

The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined `connecting peptide' (residues 132-158) and cell-surface integrin αvβ5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to αvβ5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-αvβ5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which - through individual domains - can engage two different surface receptors (uPAR and αvβ5 integrin), thus initiating and potentiating intracellular signaling and migration.
Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level
Authors: Hubert Antoine , Paris Sébastien , Piret Jean-Pascal , Ninane Noëlle , Raes Martine , Michiels Carine
Published: August 2006

HIF-1 (hypoxia-inducible factor-1) is the main transcription factor involved in the adaptation of cells to hypoxia. In addition to regulation of HIF-1α protein level, HIF-1 activity is also enhanced by several pathways involving asparagine hydroxylation and phosphorylation. Here, we investigated the relationship between casein kinase 2 (CK2), p53 and HIF-1. An increase in p53 protein level and transcriptional activity was observed when CK2 was inhibited by different inhibitors under normoxia and hypoxia. This increase was in parallel with a decrease in HIF-1 activity without changes in HIF-1α protein level, indicating a regulation of its transcriptional activity. Similar results were obtained using CK2α siRNA. Ectopic overexpression of p53 also led to an inhibition of HIF-1 activity. Conversely, CK2 inhibition had no effect in p53-null cells indicating that the inhibitory effect of CK2 inhibitors requires the presence of p53. p53 activity was not required because overexpression of a p53 mutated in its DNA-binding domain exerted the same effect as wild-type p53 and because the effect of CK2 inhibitors was still observed when p53 activity was inhibited by pifithrin-α. Since CK2 activity is increased in hypoxic conditions, this process provides one more mechanism to ensure enhanced HIF-1 activity under such conditions.
Temperature Coefficient of Corrosion Inhibition of Steel by Adenine
Authors: Gomma Gamal K , Wahdan Mostafa H
Published: August 2006

The inhibition of steel corrosion in 0.5 M sulfuric acid by adenine at different temperatures was shown to follow the Langmuir adsorption isotherm over a wide concentration range (10−5 to 10−3 M). The corrosion potential, corrosion current, corrosion rate, polarization resistance, as well as activation energy and thermodynamic parameters were calculated at different temperatures. From a comparison of the activation energies of uninhibited and inhibited corrosion reactions, the heat of adsorption of adenine may be obtained. The temperature coefficient for corrosion inhibition has a negative value, which may be explained by assuming that the corrosion reaction is no longer the simple metal/acid reaction, but involves the adsorbed species directly.
Photochemical Hole Burning of Tetraphenylporphine Glycosides
Authors: Suzuki Taro , Horie Kazuyuki , Yamashita Takashi , Bitoh Masami , Konishi Satoshi , Kishimoto Masanari
Published: August 2006

Glycosides of tetraphenylporphine were synthesized and studied by photochemical hole burning (PHB) spectroscopy. The derivatives with lactosyl groups in poly(vinyl alcohol) (PVA) shows excellent thermal stability against cyclic annealing, which is superior to that of sulfonated tetraphenylporphine (TPPS) in PVA. It is supposed that the hydroxyl groups of the glycosides as well as those of PVA would contribute to reducing irreversible structural relaxation by forming hydrogen bonds.
Pressure Dependence of the CN(B2Σ+–X2Σ+) Emission Spectra in an Ar Flowing Afterglow
Authors: Kanda Kazuhiro , Suzuki Kaoru , Ito Haruhiko , Kondow Tamotsu , Kuchitsu Kozo
Published: August 2006

The CN(B2Σ+–X2Σ+) emission spectrum produced in the reaction of Ar(3P2) with BrCN was observed by the use of a flowing afterglow method at argon pressures ranging from 9 mTorr to 2 Torr (1 Torr = 133.322 Pa). The pressure dependences of the intensity anomalies in the rotational lines due to the B2Σ+∼A2Πi and the B2Σ+∼4Σ+ perturbations were measured by introducing collision-partner gases in the reaction region. These pressure dependences can be explained by the “doorway” model. On the other hand, the measured pressure dependence of the effective rotational temperature in the CN(B2Σ+) state can also be reproduced by the collision-induced rotational relaxation model. The cross section for the rotational relaxation in the A2Πi state was found to be smaller than those in the B2Σ+ and 4Σ+ states. This finding is interpreted by the use of the dipole–induced dipole interaction model for the collision–induced rotational relaxation.
Syntheses of 1,2-Thiaphospholes and Their Thermal and Lewis Acid-Promoted Addition Reactions
Authors: Shinoda Ikuo , Takahashi Akihiko , Saito Takao , Uchida Tokiko
Published: August 2006

3,5-Di-substituted 1,2-thiaphospholes were efficiently prepared by treating 2,9-dithia-1-phosphabicyclo[4.3.0]nona-3,7-diene 1-sulfides with n-Bu3P. The thiaphospholes reacted thermally with norbornadiene, norbornene or diethyl azodicarboxylate to produce the 1 : 2 double Diels–Alder cycloadducts. With a mixture of norbornadiene and methyl acrylate or acrylonitrile, the crossed double Diels–Alder cycloadducts were obtained. In the presence of a Lewis acid, the thiaphospholes underwent, at the initial step, the Diels–Alder reaction with acrylic esters, methyl vinyl ketone or acrylonitrile, followed in tandem by the Michael addition of the 1 : 1 cycloadducts to another molecule of the reactant.