bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgene expression produced by biolistic‐mediated, site‐specific gene integration is consistently inherited by the subsequent generations
Authors: Chawla Rekha , Ariza‐Nieto Magnolia , Wilson Andrea J. , Moore Sarah K. , Srivastava Vibha
Published: November 2005

The efficient production of stable transgenic plants is important for both crop improvement and functional genomics. Site‐specific integration of foreign genes into a designated genomic position is an attractive tool for minimizing expression variability between transgenic lines. Here, we studied the utility of a Cre‐mediated, site‐specific integration approach, facilitated by particle bombardment, for streamlining the production of stable transgenic plants, using rice as a model species. Using this method, we generated 18 different transgenic lines containing a precise integration of a single copy of β‐glucuronidase gene (gusA) into a designated genomic location. Eleven of these lines contained no illegitimate integration in the background (single‐copy lines), and seven contained illegitimate integrations in addition to the site‐specific integration (multicopy lines). We monitored gusA expression in these lines up to three to four successive generations. Each of the single‐copy lines expressed the gusA gene at consistent levels and nearly doubled the expression level in the homozygous state. In contrast, multicopy lines displayed expression variation and gene silencing. In about half of the multicopy lines, however, expression of the site‐specific integration locus could be reactivated and stabilized on segregation of the illegitimate integrations, whereas, in the remaining half, expression could not be restored, as they contained genetically linked illegitimate integrations. This study demonstrates that biolistic‐mediated, site‐specific gene integration is an efficient and reliable tool for streamlining the production of stable transgenic plants.
Correlation between academic and skills‐based tests in computer networks
Authors: Buchanan William
Published: November 2005

Computing‐related programmes and modules have many problems, especially related to large class sizes, large‐scale plagiarism, module franchising, and an increased requirement from students for increased amounts of hands‐on, practical work. This paper presents a practical computer networks module which uses a mixture of online examinations and a practical skills‐based test to assess student performance. For widespread adoption of practical assessments, there must be a level of checking that the practical assessments are set at a level that examinations are set at. This paper shows that it is possible to set practical tests so that there can be a strong correlation between practical skills‐based tests and examination‐type assessments, but only if the practical assessment are set at a challenging level. This tends to go against the proposition that students who are good academically are not so good in a practice test, and vice versa. The paper shows results which bands students in A, B, C, and FAIL groups based on two online, multiple‐choice tests, and then analyses the average time these students took to complete a practical online test. It shows that there is an increasing average time to complete the test for weaker students. Along with this, the paper shows that female students in the practical test outperform male students by a factor of 25%.
‘Blended’ education and the transformation of teachers: a long‐term case study in postgraduate UK Higher Education
Authors: Motteram Gary
Published: November 2005

This paper discusses the role of blended learning in teacher education on a Master's programme at Manchester University. Blended learning is the bringing together of traditional physical classes with elements of virtual education. The paper focuses on one particular module of the degree and attempts to capture students’ experiences of using a number of online tools. As our students are primarily in‐service teachers, this experience is particularly relevant and equips them to make use of educational technology in the language classroom. Some comparisons are also made with a cohort of teachers studying the programme at a distance. The paper explores a range of issues that currently feature in the adult education literature, namely, deep and surface learning, communities of practice, and the importance of educational dialogue. The paper illustrates how important the blended nature of this module is for the teachers to get a balanced programme that upgrades skills and knowledge, but which also enables them to reflect on past and future practice. A transformative education scale is used to show that teachers can be transformed. The paper is a case study that makes use of data that explore the student perspective on a series of research questions.
The use of ICT by adults with learning disabilities in day and residential services
Authors: Parsons Sarah , Daniels Harry , Porter Jill , Robertson Christopher
Published: November 2005

The use of Information and Communication Technology (ICT) by adults with learning disabilities has been positively promoted over the past decade. More recently, policy statements and guidance from the UK government have underlined the importance of ICT for adults with learning disabilities specifically, as well as for the population in general, through the potential it offers for social inclusion. The aim of the present study was to provide a picture of how ICT is currently being used within one organisation providing specialist services for adults with learning disabilities and more specifically to provide a picture of its use in promoting community participation. Nine day and 14 residential services were visited as part of a qualitative study to answer three main questions: What kinds of computer programs are being used? What are they being used for? Does this differ between day and residential services? Computers and digital cameras were used for a wide range of activities and ‘mainstream’ programs were used more widely than those developed for specific user groups. In day services, ICT was often embedded in wider projects and activities, whilst use in houses was based around leisure interests. In both contexts, ICT was being used to facilitate communication, although this was more linked to within‐service activities, rather than those external to service provision.
Discontinuities in university student experiences of learning through discussions
Authors: Ellis Robert A. , Calvo Rafael A.
Published: November 2005

This article reports on research into the student experience of learning through discussions in a third‐year undergraduate engineering subject. Information engineering students studying e‐commerce were required to engage in face‐to‐face and online discussions as a key aspect of their learning experience. This study investigates the quality of the experience of learning through those discussions using quantitative methodologies from Student Learning Research. Analyses of student ratings on the closed‐ended questionnaires identify qualitatively different approaches to learning through discussions, both in face‐to‐face contexts and online. Relationships are found among the variation in the quality of these approaches and how students perceive issues such as workload, what they thought they were learning through discussions and performance. Implications arising from these results identify different suggestions for teaching students to discuss successfully in different contexts.
Where do educational technologists really publish? An examination of successful emerging scholars’ publication outlets
Authors: Carr‐Chellman Alison A.
Published: November 2005

This study engages the question of where successful emerging (pretenure) scholars are most likely to publish their research. Spurred on by findings of a survey of leaders in the field of educational technology/instructional design and technology (ET/IDT) to determine the advisability of a rank‐ordered list of journals for the purposes of decision making about tenure and promotion, this document analysis presents the results of measuring the conventional wisdom against the actual practices of emerging scholars. Findings suggest that pretenure scholars publish in a wide variety of outlets including some, but not all of those identified in earlier surveys. While it is understood that the tenure decision is a complicated one—based on many criteria (eg, teaching, service, grantsmanship, etc), research and scholarship remain primary determinants. Therefore, these findings will be useful to emerging scholars and to those decision makers seeking direction regarding research outlets. The study is limited by a focus from an original survey conducted in 2003 to primarily North American scholars as participants, however, international considerations are included. The findings indicate that a list of journals for tenure decision making may not be advisable at this point in the development of the field of ET/IDT.
The equivalence of online and traditional testing for different subpopulations and item types
Authors: MacCann Robert
Published: November 2005

A trial of pen‐and‐paper and online modes of a computing skills test was conducted for volunteer students of ages 15–16 in New South Wales, Australia. The tests comprised Matching, True/False and 4‐option Multiple‐Choice items. The aims were to determine whether gender, socioeconomic status (SES), or the type of item interacted with testing mode. No interactions were found for gender and item type, but the SES interaction was statistically significant. For low SES students, the online mode mean was 1 percent lower than the pen‐and‐paper mean, whereas high SES students had near equivalent means. These findings should be treated with caution as the groups in the study were self‐selected, rather than random samples from the student population.
Media effectiveness, essentiality, and amount of study: a mathematical model
Authors: Burt Gordon
Published: November 2005

An in‐depth investigation of the relationship between media effectiveness, essentiality, and amount of study was presented. Overall, effectiveness explains 48% of the variation in the amount of study. Students who found the media more effective studied the media more. Those media that were more effective were studied more. The relationship between effectiveness and amount of study is different for each medium. This is because media differ in their degree of ‘essentiality‐versus‐optionality’. Thus, the amount of study depends on a combination of effectiveness and essentiality. The relationship between effectiveness, essentiality, and amount of study is different for each student. This is because students differ in their ‘sensitivities’—their sensitivity to effectiveness and to essentiality. The final equation used effectiveness, essentiality, and sensitivity to explain 74% of the variation in the amount of study. The analysis was informed by a mathematical model.
Technology affordances: the ‘real story’ in research with K‐12 and undergraduate learners
Authors: Kay J. Wijekumar , Meyer Bonnie J.F. , Wagoner Diane , Ferguson Lon
Published: November 2005

Computer technologies for learning environments have been introduced with great expectations for improved learning outcomes. However, the great improvements have not materialised; some of these extant studies are examined. Of all the explanations for these disappointing results, the least examined are the affordances of the computer tools. This paper provides a rationale for studying affordances and presents two studies in K‐12 and undergraduate settings showing how powerful affordances are in affecting outcomes. Finally, the paper presents guidelines on how to gradually move students from a game affordance of a computer to a learning mode.
Cervical screening in HIV‐positive women: characteristics of those who default and attitudes towards screening
Authors: Shah S , Montgomery H , Smith C , Madge S , Walker P , Evans H , Johnson M , Sabin C
Published: November 2005

Objectives

To determine the characteristics of HIV‐positive women who undergo cervical screening and to identify negative attitudes and experiences of these women to screening and the factors associated with these.

Methods

We compared the Royal Free Cohort data from 59 newly diagnosed HIV‐infected women, 31 of whom did and 28 of whom did not attend for cervical screening in 2001, and from 227 women under active cervical screening follow‐up (at least one cervical screen since June 2001) and 88 HIV‐infected women lost to follow‐up (not screened since January 2001). Attitudes to screening were investigated with the aid of a questionnaire given to all women attending clinic who had had a previous colposcopy.

Results

Of the 59 newly HIV diagnosed women, 31 (53%) underwent cervical screening. These 31 women were more likely to be heterosexual (100 vs 89%, P=0.05), to have lower median viral loads (< 50 vs 3210 HIV‐1 RNA copies/mL) and to be receiving antiretrovirals (ARVs) (74 vs 54%, P=0.1) than those not screened. Of the 315 women who had at least one screen, 72% returned for further follow‐up. There were no differences in age or ethnicity between these groups. Those under active follow‐up had a higher CD4 count (P=0.04) and lower viral load (P=0.0001) at their last visit. They were also more likely to be on highly active antiretroviral therapy (HAART) (68 vs 52%, P=0.006). A total of 78 of 104 questionnaires (75%) were returned. Women participating in the questionnaire study were mainly of back ethnicity (68%), did not speak English as their first language (59%) and were taking ARVs (76%). Most agreed that regular smears and colposcopy were valuable. Women of white ethnicity, and those speaking English as a first language, were more likely to dislike colposcopy compared with those of nonwhite ethnicity (87 vs 25%, respectively, P=0.0007) and not speaking English as a first language (74 vs 26%, respectively, P=0.002). Those of white ethnicity were more likely to find smears and colposcopy painful (60 and 73%) compared with those of black ethnicity (46 and 51%, P=0.47 and 0.28, respectively).

Conclusions

Our results suggest that women on HAART with better disease control, older women, and those of black African ethnicity are more likely to take up cervical screening. Cervical screening experience varies by ethnicity and language.
Determinants of response to first HAART regimen in antiretroviral‐naïve patients with an estimated time since HIV seroconversion
Authors: Thiébaut R , Jacqmin‐Gadda H , Walker S , Sabin C , Prins M , Del Amo J , Porter K , Dabis F , Chêne G ,   the CASCADE Collaboration
Published: November 2005

Objective

To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV‐1 seroconversion.

Design

Data from HIV‐cohort studies where dates of seroconversion have been reliably estimated.

Methods

In previously untreated patients, short‐ and long‐term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow‐up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout.

Results

In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short‐term virological response (2.54 vs 2.13 log10 HIV‐1 RNA copies/mL at 1.5 months, P=0.03) and poorer long‐term immunological response (522 vs 631 cells/μL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/μL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/μL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long‐term virological response (0.67 log10 copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion.

Conclusion

Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow‐up carried out in high‐risk subgroups such as IDUs who have poorer responses.
Impact of highly active antiretroviral therapy on blood pressure in HIV‐infected patients. A prospective study in a cohort of naive patients
Authors: Palacios R , Santos J , García A , Castells E , González M , Ruiz J , Márquez M
Published: November 2005

Objectives

To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment.

Methods

A prospective, observational study of 95 HIV‐positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow‐up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg] was defined according to international criteria.

Results

Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4‐cell count on SBP increase.

Conclusions

Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV‐infected patients on HAART.
Pronounced lipoatrophy in HIV‐infected men receiving HAART for more than 6 years compared with the background population
Authors: Hansen AB , Lindegaard B , Obel N , Andersen O , Nielsen H , Gerstoft J
Published: November 2005

Objectives

To establish the prevalence and quantify the severity of body fat redistribution and dyslipidaemia in HIV‐infected men after long‐term highly active antiretroviral therapy (HAART) compared with the background population.

Methods

In a cross‐sectional study, we included 87 HIV‐infected men who had received HAART for at least 6 years and 34 HIV‐negative men. Regional body composition was assessed using dual‐energy X‐ray absorptiometry. Fasting metabolic parameters were obtained. Associations between regional body fat distribution and metabolic parameters were evaluated.

Results

HIV‐infected patients and controls did not differ with regard to height and lean body mass. Compared with controls, HIV‐infected men had reduced total fat mass (median 12.3 versus 19.2 kg, P<0.001), limb fat mass (4.3 versus 7.9 kg, P<0.001), and trunk fat mass (6.7 versus 10.8 kg, P<0.001) and higher trunk/limb fat ratio (1.7 versus 1.2, P<0.001). Also, patients without clinical lipodystrophy had reduced amounts of limb and trunk fat. In HIV‐infected men, triglyceride levels were higher (2.0 versus 1.2 mmol/L, P<0.001), high‐density lipoprotein (HDL)‐cholesterol levels were lower (1.2 versus 1.3 mmol/L, P<0.05) and insulin levels were higher (40.8 versus 29.9 pmol/L, P<0.01) than in controls. All adverse metabolic parameters correlated with increased trunk/limb fat ratio, and insulin levels correlated positively with trunk fat mass (P<0.01).

Conclusion

Peripheral as well as central fat loss is a general characteristic of HIV‐infected men after long‐term HAART. Although lipoatrophy was the dominant morphological presentation, the adverse metabolic parameters were mainly associated with the increased ratio of trunk/limb fat.
Depletion of mitochondrial DNA copies/cell in peripheral blood mononuclear cells in HIV‐1‐infected treatment‐naïve patients
Authors: Maagaard A , Holberg‐Petersen M , Kvittingen EA , Sandvik L , Bruun JN
Published: November 2005

Objectives

Mitochondrial toxicity is believed to be the main reason for adverse effects related to nucleoside reverse transcriptase inhibitors (NRTIs). The aim of the present study was to compare mitochondrial toxicity in NRTI‐treated HIV‐positive patients, HIV‐positive treatment‐naïve patients and HIV‐negative controls by comparing mitochondrial DNA (mtDNA) copies/cell in peripheral blood mononuclear cells (PBMCs) and lactate/pyruvate (L/P) ratios in the different groups.

Methods

We enrolled 60 participants in the study: 31 patients on combined antiretroviral therapy (CART), 14 HIV‐positive treatment‐naive patients and 15 HIV‐negative controls. mtDNA (copies/cell) in peripheral blood was analysed using quantitative real‐time polymerase chain reaction (PCR). Standard curves and serial dilutions of plasmid‐cloned mitochondrion and retinoblastoma (RB1) PCR products with known concentrations were generated to estimate the mtDNA and nuclear DNA (nDNA) copy numbers in each sample. The L/P ratio was enzymatically and spectrophotometrically analysed in samples from individuals in a fasted, non‐exercise state.

Results

The median mtDNA copy number was 63 copies/cell (interquartile range 33–94) in HIV‐positive patients and 153 (132–283) in HIV‐negative controls (P<0.001). No significant difference was seen between the HIV‐positive NRTI‐exposed patients and the HIV‐positive treatment‐naive patients. Current use of didanosine was negatively correlated with depletion of mtDNA (r=−0.36, P=0.046). HIV‐positive patients also had a higher L/P ratio compared with HIV‐negative controls (P=0.004).

Conclusions

The number of mtDNA copies/cell in PBMCs was depleted in HIV‐positive treatment‐naive patients as well as in HIV‐positive NRTI‐exposed patients. HIV‐positive patients also had a higher L/P ratio compared with HIV‐negative controls, which supports this conclusion. The study suggests that neither mtDNA in PBMCs nor L/P ratio is a good marker of NRTI‐associated mitochondrial toxicity.
Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real‐life situation in 2002
Authors: Fischer A , Karasi J‐C , Kibibi D , Omes C , Lambert C , Uwayitu A , Hemmer R , Van Den Ende J , Schmit J‐C , Arendt V
Published: November 2005

Our study aimed to complete the published data on ARV therapy in Africa by describing the baseline situation in Rwanda before the launch of a large ARV programme (ESTHER). Prescription habits, frequency and reasons for treatment interruptions but also antiviral efficay, resistance to ARVs and genotypic variability of the viruses present in Rwanda were analysed. Among the 233 patients included in the study, it appeared that a vast majority (91%) were under triple therapy and that half of them had experienced at least one treatment interruption caused mainly by drug shortage or financial difficulties. Among 60 blood samples analysed, 26 were in virological failure with a viral load above 1000 RNA copies/ml and 11 presented major drug resistance mutations.

Finally, virological failure could mainly be explained by the high frequency of treatment interruptions but also by the emergence of drug resistance mutations. Consequently the major objective for the ESTHER programme to improve the situation in Rwanda will be to reduce the drug shortage and facilitate the financial accessibility of the treatments.
Effect of GB virus C on response to antiretroviral therapy in HIV‐infected Brazilians*
Authors: Souza IE , Zhang W , Diaz RS , Chaloner K , Klinzman D , Stapleton JT
Published: November 2005

Objectives

GB virus C (GBV‐C) infection is associated with delayed mortality in HIV‐infected people in most, but not all, studies. Previous investigations of the effect of GBV‐C viraemia on response to antiretroviral therapy (ART) were inconclusive. To determine the effect of GBV‐C on ART, we retrospectively analysed plasma samples taken from patients in a prospective randomized clinical trial of ART in HIV‐positive Brazilians.

Methods

GBV‐C viraemia was characterized by testing stored serum samples from 175 participants by reverse transcriptase–polymerase chain reaction (RT‐PCR). Subjects were randomized to receive indinavir (n=59), zidovudine and lamivudine (n=58), or zidovudine, lamivudine and indinavir (n=58). The effect of GBV‐C viraemia on the average change in HIV viral load and CD4 count following initiation of therapy was evaluated in a multiple regression analysis.

Results

The prevalence of GBV‐C viraemia was similar to that observed in previous studies (24%). HIV viral load decreased following ART to a significantly greater extent in patients with GBV‐C viraemia (by 0.48 log10 HIV‐1 RNA copies/mL, P=0.009, adjusting for age, ART group, and baseline CD4 count). Although there was no significant difference in change in CD4 count between individuals with and without GBV‐C viraemia overall, CD4 counts were higher following 48 weeks of therapy in GBV‐C viraemic individuals receiving the least potent ART regimen (zidovudine and lamivudine) compared with those without GBV‐C infection.

Conclusions

GBV‐C viraemia is associated with an enhanced reduction of HIV viral load in response to ART. In this study of treatment‐naive individuals during 48 weeks of follow up, patients with GBV‐C viraemia had reductions in HIV viral load that were approximately 0.5 log copies/mL greater than those found in patients without GBV‐C viraemia. This is similar to reductions observed with nucleoside reverse transcriptase inhibitors.
Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co‐infection
Authors: Cooper CL , Breau C , LaRoche A , Lee C , Garber G
Published: November 2005

Objectives

Despite the benefits of HAART, initiation of antiretroviral therapy in HIV‐HCV co‐infected patients is often delayed as a consequence of patient and physician concern pertaining to liver toxicity. It is unclear whether this is justified.

Methods

We retrospectively evaluated treatment duration and outcome in 186 patients initiating a first HAART regimen.

Results

Despite frequent HIV RNA suppression and CD4 T‐cell increase following initiation of HAART, the median duration of therapy was only 8 months. Therapy was discontinued primarily for gastrointestinal intolerance (26%), poor adherence (19%), neurocognitive side effects (13%), and substance abuse (6%). Regimes were changed to reduce pill burden and/or frequency of dosing as well (11%). Only six (4%) subjects interrupted therapy as a result of clinically apparent liver toxicity. None were on low dose ritonavir‐containing therapy. In those subjects remaining on HAART for at least 12 months, the median ALT level increased marginally from a baseline of 44 IU/mL to 56 IU/mL. The median AST was 44 IU/mL at baseline and at month 12.

Conclusions

These results support our contention that regimen potency, durability, and extrahepatic side effect profile should remain the paramount considerations related to the selection of HAART regimen in HIV‐HCV co‐infection.
Potentiation strategies for treatment‐resistant depression
Authors: Ros S. , Agüera L. , de la Gándara J. , E. Rojo J. , de Pedro J. M.
Published: November 2005

Objective:  To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy.

Method:  Literature searches were undertaken and the results reviewed.

Results:  Treatment‐resistant depression is common (15–30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second‐generation antipsychotics, psychostimulants, hormones and anticonvulsants.

Conclusion:  Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.
Combined antidepressants: clinical experience
Authors: Rojo J. E. , Ros S. , Agüera L. , de la Gándara J. , de Pedro J. M.
Published: November 2005

Objective:  To review the current literature on the use of combinations of antidepressive agents.

Method:  Literature searches were undertaken and reviewed on the use of combinations of antidepressants.

Results:  Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine.

Conclusion:  Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.
Use of antidepressant combinations: which, when and why? Results of a Spanish survey
Authors: de la Gándara J. , Agüera L. , Rojo J. E. , Ros S. , de Pedro J. M.
Published: November 2005

Objective:  The present study uses the data from a large survey conducted to examine the general practice of Spanish psychiatrists on the use of antidepressant combinations in the treatment of depressive disorders.

Method:  The sample was drawn from specialists and psychiatric residents practicing in Spain who were respondents to a questionnaire distributed during an annual national psychiatry meeting and sent by mail.

Results:  A total of 1032 questionnaires were collected; following the data‐filtering, 831 were analysed. Most psychiatrists (89%) believe that many patients do not respond to the first treatment; in such cases of non‐response, 58% choose a combination of antidepressants as the next treatment option. Reasons for using the combined treatments include greater efficacy (57%), overcoming resistance to the first antidepressant (27%), faster onset of action (21%) and avoidance of side effects (17%). The most sought after pharmacological profile was serotonergic‐noradrenergic (96%) and the most popular combinations were selective serotonin reuptake inhibitor (SSRI) + mirtazapine, SSRI + reboxetine and SSRI + tricyclic antidepressant.

Conclusion:  Antidepressant combinations are frequently used in clinical practice. Pharmacological profiles are always considered and SSRIs + mirtazapine is the option usually chosen.
Nurses’ short‐term prediction of violence in acute psychiatric intensive care
Authors: Björkdahl A. , Olsson D. , Palmstierna T.
Published: November 2005

Objective:  To evaluate the short‐term predictive capacity of the Brøset Violence Checklist (BVC) when used by nurses in a psychiatric intensive care unit.

Method:  Seventy‐three patients were assessed according to the BVC three times daily. Violent incidents were recorded with the Staff Observation Aggression Scale, revised version.

An extended Cox proportional hazards model with multiple events and time‐dependent covariates was estimated to evaluate how the highest BVC sum of the last 24 h and its separate items affect the risk for severe violence within the next 24 h.

Results:  With a BVC sum of one or more, hazard for severe violence was six times higher than if the sum was zero. Four of the six separate items significantly increased the risk for severe violence with hazard ratios between 3.0 and 6.3.

Conclusion:  Risk for in‐patient violence in a short‐term perspective can to a high degree be predicted by nurses using the BVC.
Protective effect of the apo ɛ2 allele in major depressive disorder in Taiwanese
Authors: Fan P.‐L. , Chen C.‐D. , Kao W.‐T. , Shu B.‐C. , Lung F.‐W.
Published: November 2005

Objective:  Major depression is an important comorbidity in Alzheimer's disease, which is definitely associated with the apolipoprotein E (apo E) polymorphism. The aim of this study was to explore the role of the different apo E polymorphisms in major depressive disorder (MDD) in a Taiwanese population.

Method:  We examined apo E genotypes in 273 Taiwanese patients with MDD and 429 healthy community controls, and compared their polymorphism distribution.

Results:  The allelic frequency of apo ɛ2 was significantly lower in patients with MDD than in the controls, whereas no significant difference in apo ɛ4 allelic frequency between these two groups was found.

Conclusion:  The apo ɛ4 allele was not associated with MDD in this study. However, the finding of a lower frequency of the apo ɛ2 allele in MDD could lead to the conclusion that the apo ɛ2 allele likely provides a protective effect against MDD in the Taiwanese population.
Pre‐vitamin D3 effective ultraviolet transmission through clothing during simulated wear
Authors: Parisi A. V. , Wilson C. A.
Published: November 2005

Background/purpose: Clothing is an important protective layer used to reduce ultraviolet (UV) exposures to the skin surface. However, not all UV exposure is linked to detrimental health effects with some exposure to UVB wavelengths below 316 nm required for the synthesis of pre‐vitamin D3. The aim of the current research was to investigate the effect of fabric type, color, fit, and wetness on the transmission of pre‐vitamin D3 effective UV through garments during simulated wear, in a high UV exposure environment.

Methods: Dosimeters fabricated from polysulfone film were positioned at eight selected body sites on the skin surface and clothing surface of identically designed, loose and fitted, black and white T‐shirts made up in two knitted fabric types and tested when both dry and when drying after initial wetting (n=3 replicates). The T‐shirts were placed on manikins set to simulate humans in the sun between 09:30 and 12:30 Eastern Standard Time during the Southern Hemisphere summer period. The post‐exposure absorbance was measured and the dosimeters were calibrated for biologically effective UV for pre‐vitamin D3 synthesis with a UV spectroradiometer. The effect of fit, fabric type, color, and wetness on pre‐vitamin D3 effective UV transmission during simulated wear was assessed.

Results: Irradiances varied among body sites with the highest erythemal exposures to a horizontal plane over the 3 h period reaching approximately 14.5 minimal erythema dose (MED) while the highest exposure under the garment was 0.22 MED which may not be above the threshold for pre‐vitamin D3 synthesis for the time period investigated. Fabric and fit were the main variables affecting transmission of pre‐vitamin D3 effective UV. Some interactions were identified between the fabric color and wetness and between fabric type and color; however, while significantly modifying transmission these effects were small.

Conclusion: Transmission of pre‐vitamin D3 effective UV occurred through the high UPF knitted fabrics investigated. However, the length of exposure will influence whether the irradiances are sufficient to be above the threshold for pre‐vitamin D3 synthesis. The main effect on transmission of pre‐vitamin D3 effective UV was the fit of the T‐shirt and its fabric type (probably structure) rather than color or degree of wetness.
Topical aminolevulinic acid‐photodynamic therapy for the treatment of acne vulgaris
Authors: Hong Seok‐Beom , Lee Mu‐Hyoung
Published: November 2005

Background: Photodynamic therapy (PDT) is useful for the treatment of epidermal neoplasia but may also have use in the treatment of inflammatory dermatoses. The purpose of this study was to evaluate the safety and efficacy of PDT in the treatment of acne on the face.

Methods: Eight patients with mild‐to‐moderate acne vulgaris on the face were treated with one session of topical aminolevulinic acid (ALA)‐PDT using a red light. Each patient's face was divided into two areas (right side and left side) for ALA‐PDT and untreated control. Twenty percent topical ALA was applied with 4 h occlusion, and 18 J/cm2 red light (630±63 nm) was administered. Each patient's acne was visually assessed by a spot count of both inflamed and non‐inflamed lesions at baseline and at 1, 3, and 6 months following PDT.

Results: At 1, 3, and 6 months, the mean percentage reduction in inflamed lesions count was 27.6%, 37.9%, and 41.9%, respectively, in the ALA‐PDT‐treated area, whereas in the control area, it was 8.0%, 14.7%, and 15.4%, respectively, compared with the baseline. This showed a higher reduction of a spot count of inflamed lesions in the ALA‐PDT‐treated area, which was statistically significant (P<0.05). There was a slightly higher reduction of a spot count of non‐inflamed lesions in the ALA‐PDT‐treated area, which was statistically not significant (P>0.05). The adverse effects were minimal.

Conclusion: ALA‐PDT with red light was found to be effective in the reduction of the number of inflamed lesions in patients with mild‐to‐moderate acne vulgaris, with no significant short‐term adverse effects.
Clinical and immunohistochemical evaluation of psoriatic plaques treated with topical 5‐aminolaevulinic acid photodynamic therapy
Authors: Fransson Jessica , Ros Anne‐Marie
Published: November 2005

Background/purpose: The aims of this study were to investigate the clinical and immunohistochemical events of psoriatic plaques during photodynamic therapy (PDT) using topical application of 5‐aminolaevulinic acid (ALA).

Methods: Twelve psoriatic patients were recruited for this study. Four of them dropped out because of pain during treatment. The effect of PDT was evaluated in the remaining eight. One plaque was selected in each patient and treated once weekly with PDT 10–30 J/cm2 two to five times. It was evaluated by using the scale, erythema and induration (SEI) index (maximal score per patient=9). Pain during treatment was assessed by a visual analogue scale (VAS), ranging from 0 to 10. Skin biopsies were taken before treatment, after two treatments and after completion of treatment, and were evaluated by immunohistochemistry.

Results: Median SEI scores were significantly reduced from 7 (range 5–9) before to 1.5 (range 0–3) following treatment (P<0.0001). The median pain during PDT was 7. The number of vessels in the subpapillary dermis, identified by antibodies against Factor VIII and endoglin, increased during and/or after treatment in six of eight patients. Before treatment, the epidermal growth factor (EGF) receptor was displayed throughout the epidermis, keratin 16 suprabasally, involucrin from the stratum granulosum to the lower spinous layers and filaggrin in stratum granulosum with focal absence. There was a moderate dermal infiltrate of CD4+ cells and a sparse one of CD8+. Following treatment, the EGF receptor was still displayed throughout the epidermis in seven of eight specimens. Cytokeratin 16 expression decreased markedly. Involucrin was not seen as deep in the spinous layers as before PDT. Filaggrin was expressed throughout the stratum granulosum and often weakly in the upper stratum spinosum. The number of CD4+ and CD8+ dermal cells decreased.

Conclusion: PDT improved psoriasis and induced dermal neovascularization. Although a good clinical response was seen in most of our patients, the high frequency of discomfort during treatment limits the usefulness of ALA‐PDT for psoriasis. The mechanism of the neovascularization is unknown. It may be owing to an indirect effect of PDT on the microvasculature and immune system or recovery phenomena.
Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early‐stage mycosis fungoides: a right–left comparative study
Authors: El‐Mofty M. , El‐Darouty M. , Salonas M. , Bosseila M. , Sobeih S. , Leheta T. , Nada H. , Tawdy A. , Amin I. , El‐Enany G.
Published: November 2005

Background: Psoralen ultraviolet A (PUVA) is a widely used first‐line therapy for treatment of early cutaneous T‐cell lymphoma. Narrow band UVB (UVB‐NB) (311 nm) has been recently introduced as another effective line of treatment. It is postulated that the efficacy of UVB‐NB could be enhanced by addition of psoralen.

Aim: The aim of the present work was to compare the clinical and histopathologic efficacy of PUVA and UVB‐NB in the treatment of early‐stage MF (stages IA, IB and IIA), and to evaluate whether psoralen adds to the efficacy of UVB‐NB or not.

Patients and Methods: Twenty patients (stage IA, IB or IIA) were divided into two equal groups: group I received UVB‐NB on the right body half vs. PUVA on the left side of the body for 48 sessions, and group II received PUVB‐NB on the right side of the body vs. PUVA on the left side for 36 sessions. The sessions were administered three times weekly.

Results: In group I, almost equal results were obtained on both sides, i.e., UVB‐NB and PUVA were equally effective in the treatment of early stages of MF, both clinically and histopathologically. In group II, PUVB‐NB was found to be as effective as conventional PUVA in the treatment of early‐stage mycosis fungoides, also on both clinical and histopathological grounds.

Conclusion: UVB‐NB phototherapy should be included among the initial therapeutic options of mycosis fungoides in view of its efficacy, convenience, and likelihood of fewer long‐term adverse effects. Addition of psoralen does not seem to enhance its therapeutic efficacy.
Does narrow‐band ultraviolet B phototherapy work in atopic dermatitis through a local or a systemic effect?
Authors: Yule S. , Dawe R. S. , Cameron H. , Ferguson J. , Ibbotson S. H.
Published: November 2005

The likely mechanisms of action of narrow‐band ultraviolet B (NB‐UVB) in atopic dermatitis are several. We attempted, in a 12 patient prospective intraindividually controlled study, to determine whether the effect of NB‐UVB in atopic dermatitis is primarily through systemic or local effects. Change in observer‐assessed severity of patches of dermatitis covered during each whole‐body NB‐UVB treatment was compared with change in uncovered neighbouring patches. We found great variation between patients in responses. Only in two (of 12) patients was there a large difference between directly exposed and covered patch dermatitis severity. We suspect that the balance of local and systemic effects important in determining response to NB‐UVB in atopic dermatitis varies from patient to patient. This study did not conclusively answer our original question, but did show that in some patients localized effects of NB‐UVB are important.
Determination of action spectrum for sparfloxacin‐photosensitized single‐strand breaks in plasmid pBR322 DNA
Authors: Sayama Katsuhide , Kobayashi Yuki , Fujita Hitoshi , Ito Atsushi , Tokura Yoshiki , Sasaki Masako
Published: November 2005

Background: Various drugs have been reported to induce photosensitivity as a side effect. Sparfloxacin (SPFX) is well known to trigger dermatological phototoxicity upon solar radiation exposure.

Purpose: To prevent SPFX‐induced phototoxicity, we determined the wavelength range responsible for SPFX phototoxicity.

Methods: The action spectrum for SPFX photosensitization was assessed by the formation of single‐strand breaks in plasmid pBR322 DNA.

Results: The wavelengths of light leading to the formation of single‐strand breaks were in the ultraviolet A (UVA) and visible ranges. In comparison with the absorption spectrum, we found that SPFX absorption primarily contributed to the action spectrum of single‐strand break formation, but it even expanded to the visible range (between 320 and 480 nm) beyond the absorption wavelengths.

Conclusion: The findings suggest that protection of skin from short wavelengths of visible light beyond the absorption wavelengths as well as UVA light is of primary importance in prevention against induction of SPFX phototoxicity.
Lymphocytes treated by extracorporeal photopheresis can down‐regulate cytokine production in untreated monocytes
Authors: Bladon John , Taylor Peter C.
Published: November 2005

Background:Pro‐inflammatory cytokines are actively involved in graft‐versus host‐disease (GvHD) aetiology. Treatment of GvHD, using extracorporeal photopheresis (ECP), has demonstrated clinical efficacy. ECP rapidly reduces the number of T cells that produce tumour necrosis factor α (TNFα), interferon γ (IFNγ) and interleukin (IL)2. ECP‐treated cells are re‐infused immediately after completion of treatment. This study attempted to determine the influence that ECP‐treated cells would have on untreated cells following re‐infusion.

Methods:Heparinized samples were taken from 10 chronic GvHD patients, pre‐ECP and immediately prior to re‐infusion (post‐ECP). Lymphocytes and monocytes were isolated using magnetic separation. The post‐ECP lymphocytes were mixed with pre‐ECP monocytes, while the post‐ECP monocytes and pre‐ECP lymphocytes were combined. After suitable stimulation, the T cells were tested for intracellular TNFα, IFNγ and IL2, while the monocytes were evaluated for TNFα, IL1α, IL1β, IL6 and IL8.

Results:Although cytokine secretion is decreased in T cells exposed to ECP, pre‐ECP T cells were unaffected by post‐ECP monocytes. Post‐ECP monocytes demonstrated a reduction in cytokine secretion. Furthermore, untreated monocytes down‐regulated cytokine production following exposure to ECP‐treated lymphocytes.

Conclusion:ECP has both a direct and indirect immunosuppressive action, both of which may be beneficial in the treatment of GvHD.
Multigenerational Transition in Family Businesses: A New Explanatory Model
Authors: Lambrecht Johan
Published: November 2005

This article presents an explanatory model for transfer of family businesses to following generations. Our research using 10 case studies shows that transfer of family businesses is a lifelong, continuous process, in which the family must address and foster the soft elements of the transfer process: enterpreneurship, freedom, values, outside experience, upbringing, and education. Furthermore, a business family can develop into a family dynasty only when it embraces sound governance as a fundamental principle; that is, the individual family member belongs to the family, which belongs to the business.