bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer
Authors: Redjimi Nassima , Gaudin Françoise , Touboul Cyril , Emilie Dominique , Pallardy Marc , Biola-Vidamment Armelle , Fernandez Hervé , Prévot Sophie , Balabanian Karl , Machelon Véronique
Published: October 2009

Background

Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.

Results

GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P < 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, P < 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.

Conclusion

The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.
Papular xanthomas and erosive arthritis in a 3 year old girl, is this a new MRH variant?
Authors: Matiz Catalina , Ferguson Polly J , Zaenglein Andrea , Groh Brandt , Bingham Catherine April
Published: October 2009

Xanthomatous skin lesions and arthritis in children are not a common association. We present the case of a 3 year old girl who presented with xanthomatous lesions in the periungual region of both hands, around the nares and on her forehead, associated with significant arthritis that was clinically compatible with multicentric reticulohistiocytosis. However, pathology of the xanthomatous lesions was more suggestive of papular xanthoma, a disease that is not associated with arthritis. Based on her presentation and the negative lipid workup, she was treated for presumed multicentric reticulohistiocytosis. Multiple treatment strategies were utilized, with improvement on a combination of infliximab, methotrexate, and prednisone. We review the different diagnoses that should be considered in children with xanthomas and arthritis as well as the different pharmacologic therapies used in children with multicentric reticulohistiocytosis.
Consanguinity and reproductive health among Arabs
Authors: Tadmouri Ghazi O , Nair Pratibha , Obeid Tasneem , Al Ali Mahmoud T , Al Khaja Najib , Hamamy Hanan A
Published: October 2009

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.
Blood feeding by the Rocky Mountain spotted fever vector, Dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding CD4+ T cells
Authors: Boppana Venkata D , Thangamani Saravanan , Alarcon-Chaidez Francisco J , Adler Adam J , Wikel Stephen K
Published: October 2009

Background

Tick modulation of host defenses facilitates both blood feeding and pathogen transmission. Several tick species deviate host T cell responses toward a Th2 cytokine profile. The majority of studies of modulation of T cell cytokine expression by ticks were performed with lymphocytes from infested mice stimulated in vitro with polyclonal T cell activators. Those reports did not examine tick modulation of antigen specific responses. We report use of a transgenic T cell receptor (TCR) adoptive transfer model reactive with influenza hemagglutinin peptide (110-120) to examine CD4+ T cell intracellular cytokine responses during infestation with the metastriate tick,Dermacentor andersoni, or exposure to salivary gland extracts.

Results

Infestation with pathogen-freeD. andersoninymphs or administration of an intradermal injection of female or male tick salivary gland extract induced significant increases of IL-4 transcripts in skin and draining lymph nodes of BALB/c mice as measured by quantitative real-time RT-PCR. Furthermore, IL-10 transcripts were significantly increased in skin while IL-2 and IFN-γ transcripts were not significantly changed by tick feeding or intradermal injection of salivary gland proteins, suggesting a superimposed Th2 response. Infestation induced TCR transgenic CD4+ T cells to divide more frequently as measured by CFSE dilution, but more notably these CD4+ T cells also gained the capacity to express IL-4. Intracellular levels of IL-4 were significantly increased. A second infestation administered 14 days after a primary exposure to ticks resulted in partially reduced CFSE dilution with no change in IL-4 expression when compared to one exposure to ticks. Intradermal inoculation of salivary gland extracts from both male and female ticks also induced IL-4 expression.

Conclusion

This is the first report of the influence of a metastriate tick on the cytokine profile of antigen specific CD4+ T cells. Blood feeding byD. andersonipathogen-free nymphs or intradermal injection of salivary gland extracts programs influenza hemagglutinin influenza peptide specific TCR transgenic CD4+ T cells to express IL-4.
Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis
Authors: Barba Maddalena , Yang Li , Schünemann Holger J , Sperati Francesca , Grioni Sara , Stranges Saverio , Westerlind Kim C , Blandino Giovanni , Gallucci Michele , Lauria Rossella , Malorni Luca , Muti Paola
Published: October 2009

Objective

To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio.

Methods

We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method.

Results

We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90).

Conclusion

Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.
Outcome of Different Nevirapine Administration Strategies in Preventin g Mother‐to‐Child Transmission (PMTCT) Programs in Tanzania and Uganda
Authors: Karcher Heiko , Kunz Andrea , Poggensee Gabriele , Mbezi Paulina , Mugenyi Kizito , Harms Gundel
Published: October 2009

Objective

Prevention‐of‐mother‐to‐child transmission (PMTCT) interventions based on single‐dose nevirapine (NVP) are widely implemented in Africa, but strategies differ regarding how and when to administer the drug to women and infants. The aim of this study was to analyze the outcome of different strategies with regard to NVP intake in pregnant women and their infants in Tanzania and Uganda.

Methods

In an observational study carried out between March 2002 and December 2004, we compared a directly observed NVP administration strategy in Tanzania (supervised NVP intake for women and infants at a health unit) and a semi‐observed administration strategy (self‐administered NVP for women at home and supervised intake for infants at a health unit) in Uganda.

Results

The proportions of HIV‐positive women accepting receipt of NVP from the health units were similar in the 2 countries (42.4% in Tanzania vs 45.6% in Uganda; P = .06). NVP intake in infants was significantly higher in Tanzania than in Uganda (43.7% vs 24.1%; P < .001). In a multivariate analysis, maternal age above 25 years, secondary education, Catholic faith, and having undergone PMTCT counseling at a hospital were independently associated with infant NVP intake.

Conclusion

In our settings, the directly observed administration strategy resulted in a higher NVP intake in infants. The semi‐observed strategy, which implies that, after home delivery, the infant has to be presented to a health unit for NVP administration, was less successful.
Genomic and Nongenomic Cross Talk between the Gonadotropin-Releasing Hormone Receptor and Glucocorticoid Receptor Signaling Pathways
Authors: Kotitschke Andrea , Sadie-Van Gijsen Hanél , Avenant Chanel , Fernandes Sandra , Hapgood Janet P.
Published: October 2009

The GnRH receptor (GnRHR), a member of the G protein-coupled receptor family, is a central regulator of reproductive function in all vertebrates. The peptide hormone GnRH exerts its effects via binding to the GnRHR in pituitary gonadotropes. We investigated the mechanisms of regulation of transcription of the mGnRHR gene in the mouse pituitary gonadotrope LβT2 cell line by GnRH and dexamethasone (dex). Reporter assays with transfected mGnRHR promoter show that both dex and GnRH increase transcription of the mGnRHR gene via an activating protein-1 (AP-1) site. Real-time PCR confirmed this on the endogenous mGnRHR gene, and small interfering RNA experiments revealed a requirement for the glucocorticoid receptor (GR) for both the dex and GnRH response. Chromatin immunoprecipitation (ChIP) and immunofluorescence assays provide evidence that both GnRH and dex up-regulate the GnRHR gene via nuclear translocation and interaction of the GR with the AP-1 region on the mGnRHR promoter. We show that GnRH activates the unliganded GR by rapid phosphorylation of the GR at Ser-234 in a GnRHR-dependent fashion to transactivate a GRE reporter gene in LβT2 and COS-1 cells. Using kinase inhibitors, we established a direct link between GnRH-induced protein kinase C and MAPK activation, leading to unliganded GR phosphorylation at Ser-234 and transactivation of the glucocorticoid response element. Furthermore, we show that GnRH and dex synergistically activate the endogenous GnRHR promoter in LβT2 cells, via a mechanism involving steroid receptor coactivator-1 recruitment to the GnRHR AP-1 region. Our results suggest a novel mechanism of rapid nongenomic cross talk between the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes via GnRHR-dependent phosphorylation and activation of the unliganded GR in response to GnRH.
Further observations, mainly serological, on a cohort of women with or without pelvic inflammatory disease
Authors: Taylor-Robinson D , Stacey C M , Jensen J S , Thomas B J , Munday P E
Published: October 2009

An analysis was undertaken of data pertaining to over 100 women with lower abdominal pain who were laparoscoped. Prior to laparoscopy, 11 of the women were considered to almost certainly have salpingitis, of whom six (55%) had salpingitis at laparoscopy; 17 to probably have salpingitis, of whom six (35%) did; 28 to possibly have salpingitis, of whom five (18%) did; and 56 to be very unlikely to have salpingitis, of whom five (9%) did. Of the 22 women who had salpingitis at laparoscopy, 14 (64%) had a Chlamydia trachomatis IgG antibody titre of ≥1:128 and might reasonably be regarded as having chlamydial disease on this basis; six without such a titre probably did not have chlamydial disease as C. trachomatis could not be detected at any genital site. At laparoscopy, 18 women had adhesions without obvious tubal inflammation; clinically, 15 of them had been regarded as possibly having salpingitis or unlikely to have it, with 12 having chronic pelvic pain. Twelve (67%) of the 18 women had a chlamydial IgG antibody titre of ≥1:128. IgM antibody was also detected most often in the ‘salpingitis’ group. Of 49 women without any abnormality detected at laparoscopy, nine (18%) had a high chlamydial IgG antibody titre. Overall, a woman who had a high titre of chlamydial IgG antibody and acute pelvic pain, together with a clinical picture of pelvic inflammation, was more likely to have salpingitis than adhesions alone. Likewise, a woman who had a high titre of chlamydial IgG antibody and chronic pelvic pain, together with a clinical picture suggesting that salpingitis was unlikely, was more likely to have adhesions alone than acute chlamydial salpingitis. However, while antibody measurement and seeking cervical C. trachomatis may help in formulating a diagnosis, there seems no simple way of detecting the small proportion of women who are infected by C. trachomatis in the upper genital tract but whose laparoscopic findings indicate normality. So far as patient care is concerned, the only way of preventing damage to the upper genital tract is to treat early on the basis of suspicion.
The evolution of an integrated sexual health service
Authors: Creighton S , Apea V
Published: October 2009

The objective of the study was to assess the contributions of different providers across an integrated sexual health-care network to the diagnosis of sexually transmitted infections (STIs). The method employed was retrospective cross-sectional survey of laboratory tests for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis between 01 April 2004 and 31 March 2007. The total number of STI screens in all venues rose from 17,126 to 23,679. The proportion of STI screens occurring in the genitourinary (GU) medicine clinic fell from 75% to 55% ( P < 0.0001). There was an 11% increase in male screens performed in the community. The number of STIs diagnosed rose from 2354 in 2004 to 3128 in 2007, with an upward trend of community-diagnosed STIs. In conclusion, the role of community services increased during the evolution of the integrated sexual health network, although the majority of STIs were diagnosed within in the GU medicine clinic. Male screens accounted for one-third of those performed. A gap in male attendances remains despite the plurality of services.
Obstructive endo-bronchial pseudotumour due to herpes simplex type 2 infection in an HIV-infected man
Authors: Plowman G M , Watson M W , D'Souza H , Thomas M G
Published: October 2009

We report a 31-year-old man with an obstructive bronchial lesion due to herpes simplex type 2 infection, who responded promptly to endoscopic resection and oral treatment with acyclovir. Exophytic lesions of the respiratory tract are rare, potentially life-threatening, but readily treated complication of herpes simplex virus infection in HIV-infected individuals.
Cardiovascular risk factors and ultrasound evaluation of carotid atherosclerosis in patients with HIV-1 infection
Authors: Calza L , Verucchi G , Pocaterra D , Pavoni M , Alfieri A , Cicognani A , Manfredi R , Serra C , Chiodo F
Published: October 2009

A cross-sectional study was performed to evaluate classical risk factors for cardiovascular diseases and subclinical atherosclerosis by carotid ultrasonography in HIV-positive subjects, naïve or treated with antiretroviral agents. A total of 66 patients were enrolled into the study: 21 subjects were naïve to all antiretroviral agents (group A) and 45 patients were treated with antiretroviral therapy for ≧36 months (group B). The prevalence of carotid plaques was significantly higher in group B than in group A (44.7% versus 0%; P = 0.014). In group B, patients with high 10-year risk of coronary heart disease showed a significantly higher intima-media thickness and prevalence of carotid lesions than those with low risk. Moreover, carotid lesions were structurally comparable to classical atherosclerotique plaques observed in the general population, with iso-hyperechonegic aspects and irregular surfaces. The prevalence of carotid atherosclerosis in experienced patients is higher than in those naïve to highly active antiretroviral therapy and seems mostly associated with a longer duration of HIV infection, more severe lipid metabolism alterations, presence of lipodystrophy syndrome and a more elevated 10-year risk of cardiovascular diseases.
Profile of direct walk-in and referred clients attending Integrated Counselling and Testing Centre
Authors: Kashyap B , Bhalla P , Sharma A , Saini S
Published: October 2009

The HIV pandemic has had a profound impact on the health and economic conditions of individuals, and people living with HIV/AIDS are faced with the task of maintaining optimal health status despite an increasing insult to their immune status. The aim of the present study was to study the profile of direct walk-in and referred patients attending the Integrated Counselling and Testing Centre (ICTC) of a tertiary care hospital, which may provide important clues to understanding the epidemiology of the disease in a particular region. The study included all the attendees of the ICTC referred from the hospital or direct walk-in from January 2007 to December 2007. Three rapid HIV tests were used and the samples showing positive results in all the three tests were declared HIV positive. The results were analysed to correlate between HIV positivity, age, sex, route of transmission and direct walk-in/referred patients. A low proportion of ICTC attendees (27%) in our study were direct walk-ins. As regards HIV positivity, 312 (8.3%) out of 2440 males and 164 (4.3%) out of 1315 females were HIV positive. Among the referred HIV-positive patients 162 were males and 62 females, whereas among the direct walk-in HIV-positive patients, 150 were males and 102 females. Integrated counselling and testing is now seen as a key entry point for HIV prevention. In addition to scaling up ICTC services, it is also important to raise awareness by aggressive health education programmes and integration of ICTC into various community organizations.
Bronzino's ‘Allegory of Venus and Cupid’: an exemplary image for contemporary sexual health promotion?
Authors: Porter S , Kelly C
Published: October 2009

Recent sexual health promotion strategies have veered between a negative emphasis on the deleterious consequences of sexually transmitted infections, and a more positive, eroticized approach to safer sex. The differences in approach are starkly reflected in the images chosen to illustrate them. We note that there are problems with both approaches. The main purpose of this review is to demonstrate how this dichotomy was transcended by the sixteenth century Florentine Mannerist painter, Agnolo Bronzino, in his allegory on syphilis.
The psychological impact caused by genital warts: has the Department of Health's choice of vaccination missed the opportunity to prevent such morbidity?
Authors: Lawrence S , Walzman M , Sheppard S , Natin D
Published: October 2009

This study evaluated the psychological impact caused by genital warts and whether this altered over time. Eighty-four patients with genital warts and a group of 28 appropriately matched volunteers from the local general population were recruited. The patients were divided into three groups of 28 according to the Health Protection Agency classification codes for genital warts. A comprehensive health questionnaire was completed by all participants. Patients with first attack genital warts experienced significantly more distress, anxiety and depression and were less satisfied with their lives than all the other groups. They also reported less satisfaction with the practical support they received. The recurrent episode genital warts group experienced significantly high levels of emotional distress and the re-registered group reported significantly less emotional and practical support according to their needs. While the first attack genital warts group experienced the most psychological effects, it is clear that those effects did not disappear as an individual came to terms with their diagnosis. The choice of vaccine to prevent cervical cancer will not prevent clinical warts occurring and therefore will not help prevent the psychological morbidity associated with this condition.
A review of cervical cytology in genitourinary medicine clinics in England between 1997 and 2008
Authors: Markos A R
Published: October 2009

The current cervical screening guidelines lay the duty of care of women under 25 years of age on genitourinary (GU) medicine clinics. To date there has not been an extensive review of cervical cytology results sourced from GU medicine departments. We reviewed the annual reports of the cervical screening programme, with their extensive and comparative data, including records of cervical cytology from GU medicne. There is a clear and progressive trend of rising percentages of ‘severe dyskaryosis’ in laboratory reported GU medicine cervical smears. The trend and observations indicate that GU medicine physicians should take young women's concern on cervical cancer seriously. The programme of opportunistic cervical screening in GU medicine should not be discouraged.
What do patients want most from sexual health services?
Authors: Hitchings S , Allotey J , Pittrof R
Published: October 2009

Changes to sexual health clinics have recently been driven by government waiting time targets. However, patients' needs and expectations should be equally important when making service alterations. This study sought to determine what patients valued most when attending an integrated sexual health clinic. During February 2009, 252 patients attending a sexual health clinic in outer London completed an anonymous questionnaire. The questionnaire asked for their views on different aspects of sexual health care. The results showed that the most highly valued aspects of care were confidentiality (18.47% of points allocated) followed by speed of service (13.1%) and rapid test results (12.12%). These aspects were more important than being seen within 48 hours (7.78%), technical expertise (6.26%) or other patient-centred aspects of care. These findings, which represent patients' views, have important implications for service design.
Factors associated with unprotected anal intercourse between HIV-positive men and regular male partners in a Sydney cohort
Authors: Begley K , Chan D J , Jeganathan S , Batterham M , Smith D E
Published: October 2009

Blood plasma HIV-RNA load (BPVL) is the strongest predictor of HIV-1 transmission during sex. Unprotected anal intercourse (UAI) is the highest risk activity for transmission among men who have sex with men (MSM). Awareness of BPVL may influence rates of UAI. We assessed whether optimism towards antiretroviral therapy (ART) and/or biomedical factors influenced sexual activities with regular partners. Questionnaires were administered to 109 HIV-positive MSM participating in a cross-sectional study of BPVL and seminal viral load. The survey assessed HIV transmission beliefs and sexual practices with regular male partners in the past three months. Sixty-nine of 109 (63.3%) had been in a regular relationship and 42 reported having had anal sex. Unprotected receptive anal intercourse without ejaculation (URAI − e) was associated with awareness that their most recent BPVL was detectable (>50 RNA copies/mL) and not taking ART. Receptive UAI with ejaculation (URAI + e) was associated with not taking ART, having a sexually transmissible infection and having an HIV-positive partner; the latter was also associated with insertive UAI with ejaculation (UIAI + e). Treatment optimism was not associated with UAI. In this cohort, sexual practices were based more upon knowledge of biomedical factors rather than attitudes regarding transmission risks.
Concurrent sexual partnerships among individuals in HIV sero-discordant heterosexual couples
Authors: Eaton A , van Der Straten A
Published: October 2009

The objective of the study was to assess the level at which individuals in HIV discordant couples engage in concurrent sexual partnerships and factors associated with this risk of transmitting HIV. By using data from a group of HIV discordant heterosexual couples ( n = 145), we examined the frequency of concurrent sexual partners and factors associated with such partnerships. The prevalence of concurrent partnerships with heterosexual partners was 16%. Fewer than half of individuals with concurrent partnerships reported that their main study partner knew about these relationships. Of individuals involved in concurrent partnerships, 30% reported inconsistent condom use in these relationships. Unmarried individuals in new HIV sero-discordant relationships were particularly at risk for concurrent partnerships. In conclusion, more frequent HIV testing may complement increased attention to communication, disclosure and condom use in this population that is especially vulnerable to acquiring and transmitting HIV infection.
Review of drug treatment for female sexual dysfunction
Authors: Wylie K , Malik F
Published: October 2009

Female sexual dysfunction (FSD) incorporates various sexual disorders including hypoactive sexual desire disorder, sexual arousal disorder, orgasmic and sexual pain disorders. Although many strategies have been formulated for the treatment of male sexual problems, FSD remains an area that warrants further research and trial studies to identify the most efficacious treatment options. Research has highlighted numerous pharmacological interventions that have been trialled and found to exhibit positive effects. These include hormonal therapies, prostaglandins, dopaminergic agonists, phosphodiesterase type-5 (PDE-5) inhibitors and melanocortin agonists.
Integration of diagnostic and communication technologies
Authors: Malik Nafees N
Published: October 2009

Three key areas in diagnostics will drive the convergence of diagnostic and communication technologies: point-of-care testing, micro-electromechanical systems and biomarker discovery. In addition, the communications revolution means that increasing numbers of people will be able to send data from their home to their doctor using the Internet. Also, the widespread availability of broadband opens up the possibly of realtime videoconferencing with clinicians. It is already possible for patients at home to monitor simple variables, such as heart rate and blood pressure, and send their results using communication technologies to their doctors, who can promptly review the information to diagnose problems. As diagnostic and communication technologies converge, it will be feasible for patients to transmit more complex health-care data periodically to their doctor, who will be able to identify problems early on and thus modify disease management to prevent exacerbations of patients' medical conditions. This will allow improved patient care in a wide range of health-care situations, from acute medical conditions to chronic disease.
Application of camera phones in telehaematology
Authors: McLean Richard , Jury Corrine , Bazeos Alexandra , Lewis S Mitchell
Published: October 2009

We investigated the use of camera phones for telehaematology. First, the minimum requirements for the camera phones to be used in telehaematology were investigated. A single image containing white cells, red cells and platelets was sent from a camera phone to 33 different camera phones. Nine of the camera phones were found to be unsuitable for telehaematology due to low display resolution or no zoom function of the image. Then we examined the agreement between a haematologist using a suitable camera phone for remote diagnosis and the blood film report made in the usual way. Blood samples were collected from nine patients who had conditions in which diagnostically important morphological abnormalities occurred. In seven of the nine cases, the telehaematology responses were similar to the documented blood film reports. We conclude that telehaematology using camera phones offers a quick and potentially valuable method of support for the diagnostic haematology laboratory.
Technologically-assisted behaviour change: a systematic review of studies of novel technologies for the management of chronic illness
Authors: Rosser Benjamin A , Vowles Kevin E , Keogh Edmund , Eccleston Christopher , Mountain Gail A
Published: October 2009

A systematic review was conducted to investigate the use of technology in achieving behaviour change in chronic illness. The areas reviewed were: (1) methods employed to adapt traditional therapy from a face-to-face medium to a computer-assisted platform; (2) targets of behaviour change; and (3) level of human (e.g. therapist) involvement. The initial literature search produced 2032 articles. A total of 45 articles reporting 33 separate interventions met the inclusion/exclusion criteria and were reviewed in detail. The majority of interventions reported a theoretical basis, with many arising from a cognitive-behavioural framework. There was a wide range of therapy content. Therapist involvement was reported in 73% of the interventions. A common problem was high participant attrition, which may have been related to reduced levels of human interaction. Instigating successful behaviour change through technological interventions poses many difficulties. However, there are potential benefits of delivering therapy in this way. For people with long-term health conditions, technological self-management systems could provide a practical method of understanding and monitoring their condition, as well as therapeutic guidance to alter maladaptive behaviour.
A comparison of in-person home care, home care with telephone contact and home care with telemonitoring for disease management
Authors: Bowles Kathryn H , Holland Diane E , Horowitz David A
Published: October 2009

We compared the effects of evidence-based disease management guidelines delivered to patients with heart failure and diabetes using three different modalities: in-person visits alone (Control), in-person visits and a telephone intervention (Telephone), and in-person visits and telemonitoring (Telemonitoring). Patients were randomized to the three groups. There were 112 patients in the Control group, 93 in the Telephone group and 98 in the Telemonitoring group. During the first 60 days, 10% of the Control group were rehospitalized, 17% of the Telephone group and 16% of the Telemonitoring group. Having heart failure and receiving more in-person visits were significantly related to readmission and time to readmission. However, after adjusting for diagnosis and visits, the differences between the three groups were non-significant. There was a trend for increased risk of readmission for the Telephone group compared to Control alone ( P = 0.07, risk ratio 2.2, 95% CI: 0.9 to 5.2) and for readmission sooner ( P = 0.02, risk ratio 2.3, 95% CI: 1.2 to 4.6). Patient rehospitalization and emergency department visit rates were lower than the national average, making it difficult to detect a difference between groups. Previous rehospitalization was a consistent predictor of those who were rehospitalized, suggesting that it may be a useful indicator for identifying patients likely to need additional attention.
A Brazilian educational experiment: teleradiology on web TV
Authors: Silva Angélica Baptista , de Amorim Annibal Coelho
Published: October 2009

Since 2004, educational videoconferences have been held in Brazil for paediatric radiologists in training. The RUTE network has been used, a high-speed national research and education network. Twelve videoconferences were recorded by the Health Channel and transformed into TV programmes, both for conventional broadcast and for access via the Internet. Between October 2007 and December 2009 the Health Channel website registered 2378 hits. Our experience suggests that for successful recording of multipoint videoconferences, four areas are important: (1) a pre-planned script is required, for both physicians and film-makers; (2) particular care is necessary when editing the audiovisual material; (3) the audio and video equipment requires careful adjustment to preserve clinical discussions and the quality of radiology images; (4) to produce a product suitable for both TV sets and computer devices, the master tape needs to be encoded in low resolution digital video formats for Internet media (wmv and rm format for streaming, and compressed zip files for downloading) and MPEG format for DVDs.
Interactive emergency communication involving persons in crisis
Authors: Nordby Halvor , Nøhr Øyvind
Published: October 2009

We studied the dialogue between telephone operators at medical emergency communication centres in Norway and parents of children later diagnosed with sudden infant death syndrome. The aim was to understand how the parents experienced the communication with the telephone operators. The qualitative method involved semi-structured interviews. We interviewed six respondents from urban areas and five from rural areas. An important finding was that all the parents were satisfied with the resuscitation instructions they received. It was also perceived as important that the emergency operators expressed empathy and care. We believe that it is not merely the quality of the resuscitation attempts that the operators' efforts should be measured against. It is also important that the operators provide good explanations and express emotional support. Our findings indicate that this will be enormously appreciated, even if callers do not feel that they are capable of performing optimum resuscitation.
Telehealth in clinical supervision: a comparison of supervision formats
Authors: Reese Robert J , Aldarondo Federico , Anderson Charlotte R , Lee Seong-Jik , Miller Thomas W , Burton Deborah
Published: October 2009

Nine counselling psychology students were enrolled in a 12-week pilot practicum (i.e. a work placement) for either one hour of course credit (six students) or three hours (three students). Group supervision was provided both in-person and by videoconferencing. Each trainee completed a measure evaluating their satisfaction with supervision (Supervisory Satisfaction Questionnaire, SSQ) and the supervisory relationship (Supervisory Working Alliance Inventory – Trainee Version, SWAI-T). The student's self-efficacy was also tracked during the semester (Counselling Self-Estimate Inventory, COSE). Trainees rated their satisfaction with videoconferencing similarly to the in-person format. The supervisory relationship also did not appear to be affected by the videoconferencing format. The COSE scores indicated that the students increased in counsellor self-efficacy by the end of the semester. Trainees reported that their supervisory needs were met and believed that videoconferencing was a viable format for supervision, although such a format still needed to be augmented by in-person contact. Providing better access to supervision and professional support using technology is one step towards improving health care in rural areas.
Feasibility of telemonitoring for active surveillance of influenza vaccine safety in the primary care setting in the Netherlands
Authors: Vrijhoef Hubertus JM , Janssen Joyce JM , Greenberg Michael E
Published: October 2009

We examined the feasibility of a commercial home telemonitoring system for monitoring adverse events related to vaccination and influenza-like illness (ILI) signs and outcomes in the primary care setting in the Netherlands. A prospective cohort of people eligible for influenza vaccination was monitored daily between mid-October 2007 and mid-March 2008. Adults from five primary care centres were invited to participate. A total of 245 people participated (response rate 75%). Their mean age was 61 years (SD = 15), 50% were female and 60% had a chronic disease. Most (73%) had no problems with installation of the system and 67% finished all sets of monitoring dialogues. The reported incidence of adverse events in the first week after vaccination was 8–38%. The reported incidence rates of ILI symptoms varied and were higher than reference data. A total of 39% of individuals consulted their general practitioner, 7% the hospital emergency department, 6% were hospitalized and 27% used medication. Of those in paid work, one-third reported absence of work due to ILI. Home telemonitoring appears to be feasible for monitoring vaccine adverse events and ILI symptoms and outcomes.
Players' Effects Under Limited Independence
Authors: Gradwohl Ronen , Reingold Omer , Yadin Ariel , Yehudayoff Amir
Published: October 2009

In a function that takes its inputs from various players, the effect of a player measures the variation he can cause in the expectation of that function. In this paper we prove a tight upper bound on the number of players with large effect, a bound that holds even when the players' inputs are only known to be pairwise independent. We also study the effect of a set of players, and show that there always exists a “small” set of players that, when eliminated, leaves every small set with little effect. Finally, we ask whether there always exists a player with positive effect, and show that, in general, the answer is negative. More specifically, we show that if the function is nonmonotone or the distribution is only known to be pairwise independent, then it is possible that all players have zero effect.
From CVaR to Uncertainty Set: Implications in Joint Chance-Constrained Optimization
Authors: Chen Wenqing , Sim Melvyn , Sun Jie , Teo Chung-Piaw
Published: October 2009

We review and develop different tractable approximations to individual chance-constrained problems in robust optimization on a variety of uncertainty sets and show their interesting connections with bounds on the conditional-value-at-risk (CVaR) measure. We extend the idea to joint chance-constrained problems and provide a new formulation that improves upon the standard approach. Our approach builds on a classical worst-case bound for order statistics problems and is applicable even if the constraints are correlated. We provide an application of the model on a network resource allocation problem with uncertain demand.
Data Envelopment Analysis as Nonparametric Least-Squares Regression
Authors: Kuosmanen Timo , Johnson Andrew L.
Published: October 2009

Data envelopment analysis (DEA) is known as a nonparametric mathematical programming approach to productive efficiency analysis. In this paper, we show that DEA can be alternatively interpreted as nonparametric least-squares regression subject to shape constraints on the frontier and sign constraints on residuals. This reinterpretation reveals the classic parametric programming model by Aigner and Chu [Aigner, D., S. Chu. 1968. On estimating the industry production function. Amer. Econom. Rev. 58 826–839] as a constrained special case of DEA. Applying these insights, we develop a nonparametric variant of the corrected ordinary least-squares (COLS) method. We show that this new method, referred to as corrected concave nonparametric least squares (C2NLS), is consistent and asymptotically unbiased. The linkages established in this paper contribute to further integration of the econometric and axiomatic approaches to efficiency analysis.
Establishing the Value of Flexibility Created by Training: Applying Real Options Methodology to a Single HR Practice
Authors: Berk Aleš , Kaše Robert
Published: October 2009

This paper refers to the conceptualizations of strategic flexibility, real options, and human resource (HR) options to build a model for valuing future-oriented and organizational flexibility-enhancing aspects of training. By adopting an indirect approach to measuring HR options by valuing particular investment projects in which human capital is involved, we satisfy the conditions for applying the Black-Scholes option valuation model and avoid the problematic measurement of the stand-alone value of human capital. The proposed valuation model is elucidated by a case study from the mobile telecommunications industry. The results indicate that in rapidly growing markets based on emerging technology, the generation of HR options based on training should be encouraged. Broader applicability and limitations of the valuation model are discussed and directions for further development of the valuation model are given.
Perspective—From Gaussian to Paretian Thinking: Causes and Implications of Power Laws in Organizations
Authors: Andriani Pierpaolo , McKelvey Bill
Published: October 2009

Although normal distributions and related current quantitative methods are still relevant for some organizational research, the growing ubiquity of power laws signifies that Pareto rank/frequency distributions, fractals, and underlying scale-free theories are increasingly pervasive and valid characterizations of organizational dynamics. When they apply, researchers ignoring power-law effects risk drawing false conclusions and promulgating useless advice to practitioners. This is because what is important to most managers are the extremes they face, not the averages. We show that power laws are pervasive in the organizational world and present 15 scale-free theories that apply to organizations. Next we discuss research implications embedded in Pareto rank/frequency distributions and draw statistical and methodological implications.
COLD-PCR–Enhanced High-Resolution Melting Enables Rapid and Selective Identification of Low-Level Unknown Mutations
Authors: Milbury Coren A , Li Jin , Makrigiorgos G Mike
Published: October 2009

Background: Analysis of clinical samples often necessitates identification of low-level somatic mutations within wild-type DNA; however, the selectivity and sensitivity of the methods are often limiting. COLD-PCR (coamplification at lower denaturation temperature–PCR) is a new form of PCR that enriches mutation-containing amplicons to concentrations sufficient for direct sequencing; nevertheless, sequencing itself remains an expensive mutation-screening approach. Conversely, high-resolution melting (HRM) is a rapid, inexpensive scanning method, but it cannot specifically identify the detected mutation. To enable enrichment, quick scanning, and identification of low-level unknown mutations, we combined COLD-PCR with HRM mutation scanning, followed by sequencing of positive samples.

Methods: Mutation-containing cell-line DNA serially diluted into wild-type DNA and DNA samples from human lung adenocarcinomas containing low-level mutations were amplified via COLD-PCR and via conventional PCR for TP53 (tumor protein p53) exons 6–8, and the 2 approaches were compared. HRM analysis was used to screen amplicons for mutations; mutation-positive amplicons were sequenced.

Results: Dilution experiments indicated an approximate 6- to 20-fold improvement in selectivity with COLD-PCR/HRM. Conventional PCR/HRM exhibited mutation-detection limits of approximately 2% to 10%, whereas COLD-PCR/HRM exhibited limits from approximately 0.1% to 1% mutant-to-wild-type ratio. After HRM analysis of lung adenocarcinoma samples, we detected 7 mutations by both PCR methods in exon 7; however, in exon 8 we detected 9 mutations in COLD-PCR amplicons, compared with only 6 mutations in conventional-PCR amplicons. Furthermore, 94% of the HRM-detected mutations were successfully sequenced with COLD-PCR amplicons, compared with 50% with conventional-PCR amplicons.

Conclusions: COLD-PCR/HRM improves the mutation-scanning capabilities of HRM and combines high selectivity, convenience, and low cost with the ability to sequence unknown low-level mutations in clinical samples.
Quantitative Transcription Factor Analysis of Undifferentiated Single Human Embryonic Stem Cells
Authors: Ståhlberg Anders , Bengtsson Martin , Hemberg Martin , Semb Henrik
Published: October 2009

Background: Human embryonic stem cells (hESCs) require expression of transcription factor genes POU5F1 (POU class 5 homeobox 1), NANOG (Nanog homeobox), and SOX2 [SRY (sex determining region Y)-box 2] to maintain their capacity for self-renewal and pluripotency. Because of the heterogeneous nature of cell populations, it is desirable to study the gene regulation in single cells. Large and potentially important fluctuations in a few cells cannot be detected at the population scale with microarrays or sequencing technologies. We used single-cell gene expression profiling to study cell heterogeneity in hESCs.

Methods: We collected 47 single hESCs from cell line SA121 manually by glass capillaries and 57 single hESCs from cell line HUES3 by flow cytometry. Single hESCs were lysed and reverse-transcribed. Reverse-transcription quantitative real-time PCR was then used to measure the expression POU5F1, NANOG, SOX2, and the inhibitor of DNA binding genes ID1, ID2, and ID3. A quantitative noise model was used to remove measurement noise when pairwise correlations were estimated.

Results: The numbers of transcripts per cell varied >100-fold between cells and showed lognormal features. POU5F1 expression positively correlated with ID1 and ID3 expression (P < 0.05) but not with NANOG or SOX2 expression. When we accounted for measurement noise, SOX2 expression was also correlated with ID1, ID2, and NANOG expression (P < 0.05).

Conclusions: We demonstrate an accurate method for transcription profiling of individual hESCs. Cell-to-cell variability is large and is at least partly nonrandom because we observed correlations between core transcription factors. High fluctuations in gene expression may explain why individual cells in a seemingly undifferentiated cell population have different susceptibilities for inductive cues.