bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacovigilance of antimalarial treatment in Uganda: community perceptions and suggestions for reporting adverse events
Authors: Bukirwa Hasifa , Nayiga Susan , Lubanga Rosalind , Mwebaza Norah , Chandler Clare , Hopkins Heidi , Talisuna Ambrose O. , Staedke Sarah G.
Published: August 2008

Objectives  The deployment of new antimalarials in Africa provides an important opportunity to develop systems for pharmacovigilance. To inform strategies for reporting adverse events in Uganda, we investigated local perceptions and experiences with antimalarial treatment, and evaluated existing and potential systems for pharmacovigilance.

Methods  Focus group discussions (FGD) were conducted with community members and health workers from urban and rural Uganda exploring knowledge of fever/malaria, perceptions and expectations of treatment, understanding of adverse effects, and experiences with adverse events. Sessions were recorded, transcribed into English, and analysed using a coding scheme developed from pre‐defined topics together with themes emerging from the data.

Results  Between April and July 2006, we conducted 25 FGDs; 16 with community members and nine with health workers. All respondents had extensive experience with malaria and its treatment. Community members commonly recognized adverse effects of antimalarial therapy. However, events were uncommonly reported, and certain events were often interpreted as signs of successful treatment. Community members often felt that the costs of reporting or seeking additional care outweighed the potential benefits. Health workers were unfamiliar with formal pathways for reporting, and were deterred by the additional work of reporting and fear of incrimination. Respondents provided suggestions for incentives and methods of reporting, emphasizing that pharmacovigilance should ideally encompass the public and private sector, and the community.

Conclusions  To be successful, pharmacovigilance relying on voluntary reporting will require active participation of patients and health workers. Addressing the costs and benefits of reporting, and providing sensitization, training and feedback will be important.
Assessing debt‐to‐health swaps: a case study on the Global Fund Debt2Health Conversion Scheme
Authors: Cassimon Danny , Renard Robrecht , Verbeke Karel
Published: August 2008

The Debt2Health Conversion Scheme of the Global Fund to Fight AIDS, Tuberculosis and Malaria is used to reassess a range of recent initiatives that propose debt relief in exchange for spending in the health sector. The experience with debt swaps in the mid 1990s was far from positive, and recent improved insight in the economics of debt relief suggests extreme caution. We argue that the recent spade of debt swap proposals, even if targeting countries and debt titles that fall outside current major international debt relief mechanisms, share most of the design faults of previous initiatives. Proposals such as Debt2Health do not constitute efficient vehicles to increase net transfers to poor countries, to reduce the economic disadvantages of indebtedness, or to strengthen public health systems of partner countries. For debt relief to constitute a valuable mechanism to provide aid, it should be designed as a large‐scale and comprehensive operation, with spending earmarked to broad country‐established priorities, and reinforce rather than undermine national implementation systems.
Development and testing of a de novo clinical staging system for podoconiosis (endemic non‐filarial elephantiasis)
Authors: Tekola Fasil , Ayele Zewdu , Mariam Dereje Haile , Fuller Claire , Davey Gail
Published: August 2008

Objective  To develop and test a robust clinical staging system for podoconiosis, a geochemical disease in individuals exposed to red clay soil.

Methods  We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re‐iterative field tests conducted in an area of high‐podoconiosis prevalence in Southern Ethiopia. The system has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the 1‐week repeatability and the inter‐observer agreement of the final staging system.

Results  The five‐stage system is readily understood by community workers with little health training. Kappa for 1‐week repeatability was 0.88 (95% CI 0.80–0.96), for agreement between health professionals was 0.71 (95% CI 0.60–0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52–0.78).

Conclusions  This simple staging system with good inter‐observer agreement and repeatability can assist in the management and further study of podoconiosis.
Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta‐analysis of randomized, double‐blind, placebo‐controlled, clinical trials
Authors: Penagos M. , Compalati E. , Tarantini F. , Baena‐Cagnani C. E. , Passalacqua G. , Canonica G. W.
Published: August 2008

Rationale:  Several randomized, double‐blind, placebo‐controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta‐analysis to determine the overall treatment effect.

Methods:  A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double‐blind, placebo‐controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non‐nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta‐analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software.

Data synthesis:  Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD −0.49, 95% CI: −0.60 to −0.38; P < 0.00001; I2 = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (−0.41; 95% CI: −0.56 to −0.27), rhinorrhoea (−0.44; 95% CI: −0.66 to −0.21), sneezing (−0.40; 95% CI: −0.57 to −0.23) and nasal itching (−0.39; 95% CI: −0.53 to −0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (−0.30; 95% CI: −0.43 to −0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81–1.20; P = 0.91).

Conclusions:  This meta‐analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.
Single cell electroporation method for axon tracing in cultured slices
Authors: Uesaka Naofumi , Nishiwaki Maki , Yamamoto Nobuhiko
Published: August 2008

Axon tracing is an essential method to reveal neuronal connection patterns and characteristics of growing axons during development. Here we introduce an electroporation‐based gene transfer technique with a fluorescent protein (FP), which enables us to observe a small number of axons. The result also demonstrates that dynamics of axon behavior can be followed for more than a week. Thus, such labeling with FP is a powerful tool for axon tracing.
Labeling embryonic mouse central nervous system cells by in utero electroporation
Authors: Tabata Hidenori , Nakajima Kazunori
Published: August 2008

During cerebral development, neurons are generated near the ventricle and then migrate toward the pial surface. In this review, we describe the method of in utero electroporation, this method allows the morphology of the migrating neurons to be visualized and the effect of overexpression or knock down of any gene to be examined. After electroporation of a green fluorescent protein (GFP) expression vector by this method, GFP‐positive cells are first found in the ventricular zone, and their distribution then gradually shift toward the pial surface. A few days later, most of the GFP positive cells were aligned beneath the marginal zone, with the normal course of cortical neuronal migration.
Targeted gene expression by the Gal4‐UAS system in zebrafish
Authors: Asakawa Kazuhide , Kawakami Koichi
Published: August 2008

Targeted gene expression by the Gal4‐UAS system is a powerful methodology for analyzing function of genes and cells in vivo and has been extensively used in genetic studies in Drosophila. On the other hand, the Gal4‐UAS system had not been applied effectively to vertebrate systems for a long time mainly due to the lack of an efficient transgenesis method. Recently, a highly efficient transgenesis method using the medaka fish Tol2 transposable element was developed in zebrafish. Taking advantage of the Tol2 transposon system, we and other groups developed the Gal4 gene trap and enhancer trap methods and established various transgenic fish expressing Gal4 in specific cells. By crossing such Gal4 lines with transgenic fish lines harboring various reporter genes and effector genes downstream of UAS (upstream activating sequence), specific cells can be visualized and manipulated in vivo by targeted gene expression. Thus, the Gal4 gene trap and enhancer trap approaches together with various UAS lines should be important tools for investigating roles of genes and cells in vertebrates.
Transferring genes into cultured mammalian embryos by electroporation
Authors: Takahashi Masanori , Nomura Tadashi , Osumi Noriko
Published: August 2008

Mammalian whole embryo culture (WEC) was developed long before transgenic and gene targeted animals are widely used. Electroporation (EP) into cultured rodent embryos has expanded the potential to analyze gene functions in mammalian embryos by transferring exogenous plasmid vectors or small nucleotides in region‐ and stage‐specific ways. This method is quite simple, and therefore enables us to analyze gene functions more quickly than genetic manipulation. In this review, we introduce combinatorial methods of WEC and EP, and summarize various applications in developmental neurobiology.
Congenic method in the chick limb buds by electroporation
Authors: Suzuki Takayuki , Ogura Toshihiko
Published: August 2008

Electroporation is a powerful tool with which to study limb development. Limb development, however, remains an intricate series of events, requiring the precise dissection of developmental processes using relevant transgenes. In this review, we describe the anatomy of the limb field as the basis of targeted electroporation, and specific expression vectors are discussed. We share a useful protocol for electroporation of chick limb buds, and the expression pattern of enhanced green fluorescent protein in the limb buds is used to demonstrate relevant embryonic patterning. Finally, useful trouble‐shooting techniques are described.
Androgens upregulate aquaporin 9 expression in the prostate
Authors: Wang Jianbo , Tanji Nozomu , Sasaki Toyokazu , Kikugawa Tadahiko , Song Xishuang , Yokoyama Masayoshi
Published: August 2008

Objectives:  Aquaporins (AQP) function as selective pores allowing water, glycerol and other small solutes to pass through the cell membrane. We previously reported that AQP are expressed in the prostates of both humans and rats. The present study investigated the androgen‐dependent expression of AQP9 in the prostate in vivo and in vitro.

Methods:  Rat ventral prostate tissue specimens and a normal human prostatic epithelial cell line (PNT2) were used. AQP9 messenger ribonucleic acid (mRNA) and protein expression were examined using real‐time polymerase chain reaction, Western blotting and immunohistochemical methods. Androgen modulation was achieved by surgical castration, treatment with testosterone propionate (5 µg/g bodyweight) or bicalutamide (20 µg/g bodyweight), and the ribonucleic acid interference (RNAi) method of the androgen receptor (AR). The synthetic small interfering RNA was transfected into PNT2 at a concentration of 10 nM, and the RNAi effect was evaluated using a Western blotting analysis.

Results:  AQP9 mRNA and protein were expressed in the rat prostate. Surgical castration or bicalutamide treatment significantly decreased their expression. In addition, the treatment with testosterone propionate after castration restored the expression to the level of the controls. An RNAi experiment in PNT2 also decreased the expression.

Conclusions:  AQP9 expression in the prostate is controlled by androgens.
The effectiveness of tamsulosin in treating women with voiding difficulty
Authors: Chang Shang‐Jen , Chiang I‐Ni , Yu Hong‐Jeng
Published: August 2008

Objectives:  To prospectively evaluate the effectiveness of tamsulosin in treating women with voiding difficulty.

Methods:  Female patients presenting chronic, bothersome voiding symptoms, combined with subnormal uroflow were treated with 0.2 mg tamsulosin daily for six weeks. Outcome analyses included the International Prostate Symptom Score and uroflowmetry with post‐void residual urine. Patients achieving a 50% or greater reduction in their voiding symptom score, combined with a 30% or greater increment in their maximal flow rate were regarded as having a good therapeutic response. Subgroup analysis was performed in patients classified as having bladder outlet obstruction, or detrusor underactivity based on pressure‐flow study, excluding those with indwelling catheterization or intermittent self‐catheterization as well as those with anatomic obstruction.

Results:  Ninety‐seven patients met the study inclusion criteria and were enrolled. Significant improvements in voiding symptom score, storage symptom score, maximal flow rate, post‐void residual urine and voiding efficiency were observed in all patients while on tamsulosin. A good therapeutic response was observed in 35.1% of patients. Of these, 33 were classified as having bladder outlet obstruction and 52 had detrusor underactivity. Although both groups experienced significant reduction in their voiding symptom scores, patients with bladder outlet obstruction were more likely to achieve a reduction of their voiding symptom score. The magnitude of improvement in uroflow parameters as well as the proportion of patients achieving a good therapeutic response (39.4% for bladder outlet obstruction vs 32.7% for detrusor underactivity, P = 0.69) were similar between the two groups. Adverse events were mild and tolerable.

Conclusions:  Tamsulosin has beneficial effects in a significant proportion of women with voiding difficulty.
Ejaculatory dysfunction caused by the new α1‐blocker silodosin: A preliminary study to analyze human ejaculation using color Doppler ultrasonography
Authors: Nagai Atsushi , Hara Ryoei , Yokoyama Teruhiko , Jo Yoshimasa , Fujii Tomohiro , Miyaji Yoshiyuki
Published: August 2008

Objectives: In order to clinically investigate the mechanism of ejaculatory dysfunction attributable to the α1‐blocker silodosin, a real‐time observation of ejaculation by healthy males was performed.

Methods: Following intake of silodosin, a newly developed selective α1‐blocker for benign prostatic hypertrophy, ejaculation was dynamically observed using color Doppler ultrasound in three healthy males. Normal ejaculation was also investigated in the same manner.

Results: With silodosin intake, no antegrade ejaculation was observed in cases 1 or 2. In case 1, seminal fluid slowly but continuously flowed out from the seminal vesicles into the bladder. In case 2, only a small amount of seminal fluid flowed into the bladder during the ejaculatory sensation. In case 3, ejection of a small amount of semen from the external urethral orifice was observed and inflow of a small amount of seminal fluid into the bladder was also captured. Without silodosin intake, all three subjects exhibited antegrade ejaculation.

Conclusions: The mechanism of ejaculatory dysfunction is intricately related to retrograde ejaculation (retrograde inflow of seminal fluid), insufficient contraction of the seminal vesicles, and insufficient rhythmic contraction of the muscles of the pelvic floor.
Epigenetic markers as promising prognosticators for bladder cancer
Authors: Kim Young Kyoon , Kim Wun‐Jae
Published: August 2008

Transitional cell carcinomas of the urinary bladder have diverse biological and functional characteristics. Surveillance strategies for bladder cancer recurrence have historically relied on the diagnostic combination of cystoscopy and urinary cytology. However, the accuracy of both tests depends on subjective and operator‐dependent interpretations of the visible findings. In contrast, promoter hypermethylation of CpG islands is strongly associated with tumor development and prognosis of bladder cancer. Detection of DNA methylation in voided urine may be feasible and more sensitive than conventional urine cytology. Ultimately, all types of urological cancers may be screened in urine using a candidate panel of hypermethylated genes. The epigenetic silencing of tumor suppressor genes is interest from a clinical point of view because it is possible to reverse epigenetic changes and restore gene function to a cell. Methylation markers might therefore be more useful than conventional molecular markers for the treatment and prevention of bladder cancer.
Salvage radiotherapy following radical prostatectomy
Authors: Chalasani Venu , Iansavichene Alla E , Lock Michael , Izawa Jonathan I
Published: August 2008

Recurrent disease following radical prostatectomy will occur in approximately 20% of patients, for whom the therapeutic options include surveillance, salvage radiotherapy, or hormonal therapy. This review will focus on the evidence for salvage radiotherapy. Efficacy results of 30–50% have been reported from multiple retrospective series, with minimal morbidity. Unfortunately there are no randomized or prospective studies in this area. Results of salvage radiotherapy improve when given earlier, ideally with the serum prostate‐specific antigen < 1 ng/mL. Other positive prognosticators are positive margins at radical prostatectomy, longer prostate‐specific antigen doubling times, lower radical prostatectomy Gleason scores, and the absence of lymph node metastases. Current standard dosage is 64 Gy or slightly higher, although the optimal dosage has yet to be defined with prospective randomized trials. Salvage radiotherapy can provide a durable response when given early, and patients with recurrent disease should be considered for treatment or enrolment in clinical trials.
Prospective assessment of the efficacy of single dose versus traditional 3‐day antimicrobial prophylaxis in 12‐core transrectal prostate biopsy
Authors: Cam Kamil , Kayikci Ali , Akman Yavuz , Erol Ali
Published: August 2008

Objectives:  To prospectively evaluate the efficacy of single dose antibiotic prophylaxis in 12‐core transrectal ultrasonography (TRUS) guided prostate biopsy.

Methods:  A total of 400 patients who underwent prostate biopsy with TRUS guidance were included. The patients were prospectively randomized in three groups regarding antibiotic prophylaxis. The first group (139 patients) received a single gram of intramuscular ceftriaxone, while the second group (131 patients) had a 3‐day course of oral ciprofloxacin. The third group (130 patients) had single oral 500 mg of ciprofloxacin. All patients had urine cultures prior to biopsy and on the second day after biopsy.

Results:  The study groups were compared in terms of the results of urine cultures and clinical parameters. Overall, only seven patients (1.8% of the cases) had positive urine cultures with no difference between these three groups. Additionally, no significant difference was observed regarding morbidity rates in all groups. Only eight patients (2%) developed major complications requiring hospitalization. There was no increase in the rate of infectious complications when the biopsy core numbers were increased up to 12.

Conclusions:  The current study suggests that a single oral dose of antimicrobial prophylaxis is reasonable in TRUS prostate biopsy even in the case of 12‐core sampling.
Clinical characteristics of vulvovaginal candidiasis and antifungal susceptibilities of Candida species isolates among patients in southern China from 2003 to 2006
Authors: Fan Shang Rong , Liu Xiao Ping , Li Jian Wu
Published: August 2008

Aim:  To determine the clinical characteristics of vulvovaginal candidiasis (VVC), the Candida species involved and the antifungal susceptibility of Candida species isolated from patients with VVC.

Methods:  Candida organisms were cultured from samples obtained from patients who presented with VVC to the Gynecology Department, Peking University Shenzhen Hospital. Antifungal susceptibility testing was performed using a commercial agar diffusion test.

Results:  Of the 1070 cases of VVC reported in this study, 36.5% were uncomplicated VVC, and 63.5% were complicated VVC. Twenty‐four patients were identified as having two species of Candida. Candid albicans alone was isolated from 89.5% of cases (n = 958). Candida glabrata was isolated from 85 cases (7.9%), Candida tropicalis from 10 (0.9%), Saccharomyces cerevisiae from eight (0.7%), Candida parapsilosis from six (0.6%), Candida famata from two (0.2%), and Candida krusei from one case (0.1%). All isolates of Candida albicans were susceptible to nystatin. The resistant rate of Candida albicans to azole agents was 0–4.9%.

Conclusion:  Candida albicans was the predominant Candida species isolated from this series of patients with VVC. Resistance of vaginal Candida albicans isolates to antifungal agents was infrequent.
Predictive factors for faecal incontinence after third or fourth degree obstetric tears: a clinico‐physiologic study
Authors: Tjandra J. J. , Chan M. K. Y. , Kwok S. Y. , Yeh C. H. , Tan J. J. Y. , Sloane K. , Carey M. P.
Published: August 2008

Objective This is a prospective study to review the natural history of anorectal dysfunction after primary repair for third or fourth degree obstetric tear and to identify the predictive factors for significant faecal incontinence.

Method From January 2003 to December 2005, 121 consecutive women (mean age 29.9 ± 4.7) who sustained third or fourth degree obstetric tears were assessed. All had primary repair by obstetricians. They were assessed using anorectal physiology testing and endoanal ultrasound. Short‐term (3‐month postpartum) and medium‐term (mean 18.8 ± 7.7 months) Wexner’s continence scores were obtained.

Results Among the 121 women, seven were excluded because of incomplete follow‐up. At short‐term assessment, 25 out of 114 women were incontinent. One of them underwent another sphincter repair for significant faecal incontinence. Twenty‐one and three patients respectively, had mild (Wexner’s score 1–4) and moderate (Wexner’s score 5–8) symptoms. At medium‐term assessment, 24 patients remained incontinent; of these, 20 had mild symptoms (Wexner’s score 1–4) and four had moderate incontinence (Wexner’s score 5–8). The parity (P = 0.04), degree of obstetric tear (P = 0.036) and short‐term Wexner’s scores at 3 months postpartum (P < 0.0001) were significantly related to the change in Wexner’s scores at medium‐term assessment. However, the short‐term Wexner’s score was the only identifiable predictive factor for significant faecal incontinence.

Conclusion Most women suffering from third or fourth degree obstetric tear were continent or mildly incontinent. Poor Wexner’s score at short‐term assessment at 3 months postpartum was predictive of faecal incontinence in the medium‐term.
PROCEED: Prospective Obesity Cohort of Economic Evaluation and Determinants: baseline health and healthcare utilization of the US sample*
Authors: Wolf A. M. , Finer N. , Allshouse A. A. , Pendergast K. B. , Sherrill B. H. , Caterson I. , Hill J. O. , Aronne L. J. , Hauner H. , Radigue C. , Amand C. , Despres J.‐P.
Published: August 2008

Aim:  To summarize baseline characteristics, health conditions, resource utilization and resource cost for the US population for the 90‐day period preceding enrolment, stratified by body mass index (BMI) and the presence of abdominal obesity (AO).

Methods:  PROCEED (Prospective Obesity Cohort of Economic Evaluation and Determinants) is a multinational, prospective cohort of control (BMI 20–24.0 kg/m2), overweight (BMI 25–29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) subjects with AO and without AO [non‐abdominal obesity (NAO)], defined by waist circumference (WC) >102 and 88 cm for males and females, respectively. Subjects were recruited from an Internet consumer panel. Outcomes were self‐reported online. Self‐reported anthropometric data were validated. Prevalence of conditions and utilization is presented by BMI class and AO within BMI class. Differences in prevalence and means were evaluated.

Results:  A total of 1067 overweight [n = 474 (NAO: n = 254 and AO: n = 220)] and obese [n = 493 (NAO: n = 39 and AO: n = 454)] subjects and 100 controls were recruited. Self‐reported weight (r = 0.92) and WC (r = 0.87) were correlated with measured assessments. Prevalence of symptoms was significantly higher in groups with higher BMI, as were hypertension (p < 0.0001), diabetes (p < 0.0001) and sleep apnoea (p < 0.0001). Metabolic risk factors increased with the BMI class. Among the overweight class, subjects with AO had significantly more reported respiratory, heart, nervous, skin and reproductive system symptoms. Overweight subjects with AO reported a significantly higher prevalence of diabetes (13%) compared with overweight subjects with NAO (7%, p = 0.04). Mean healthcare cost was significantly higher in the higher BMI classes [control ($456 ± 937) vs. overweight ($1084 ± 3531) and obese ($1186 ± 2808) (p < 0.0001)].

Conclusion:  An increasing gradient of symptoms, medical conditions, metabolic risk factors and healthcare utilization among those with a greater degree of obesity was observed. The independent effect of AO on health and healthcare utilization deserves further study with a larger sample size.
Latent autoimmune diabetes in adults (LADA) in South Wales: incidence and characterization
Authors: Davies H. , Brophy S. , Fielding A. , Bingley P. , Chandler M. , Hilldrup I. , Brooks C. , Williams R.
Published: August 2008

Aim  To define the incidence and characteristics of latent autoimmune diabetes in adults (LADA).

Methods  We estimated the incidence of LADA by examining the incidence of Type 2 diabetes and calculating the proportion that were antibody positive. The incidence of Type 2 diabetes was calculated by analysis of computer records of 35 out of 36 general practices in Swansea. In addition, thirty‐two practices participated in recruiting people with Type 2 diabetes to have glutamic acid decarboxylase (GAD) antibody testing.

Results  The crude proportion of Type 2 patients testing positive for GAD antibodies (GADA) was 4.0% (28/683). This figure did not change when we analysed only the practices that tested more than 60% of all eligible patients. In these practices, 79% (387/487) of all eligible patients were GADA tested and 14/387 [3.6% (95% confidence interval: 2.1–6.1%)] were classified as having LADA. This gives an incidence of LADA of 9 per 100 000 (95% confidence interval: 4.4–17.8 per 100 000) people per year registered with a general practitioner. Patients testing positive for GADA were more likely to have a lower body mass index, other antibodies, to present with acute symptoms and to have higher glycated haemoglobin.

Conclusions  This is the first study of the incidence of LADA in primary care. People with LADA make up a significant proportion of people with apparent Type 2 diabetes. Patients with LADA are likely to be symptomatic, have poorer glycaemic control and have other autoimmune antibodies.
Glycated haemoglobin and cardiovascular outcomes in people with Type 2 diabetes: a large prospective cohort study
Authors: Elley C. R. , Kenealy T. , Robinson E. , Drury P. L.
Published: August 2008

Aims  To investigate the association between long‐term glycaemic control, measured by glycated haemoglobin (HbA1c), and time to first cardiovascular disease (CVD) event for people with Type 2 diabetes in New Zealand.

Methods  A prospective cohort study including people with Type 2 diabetes but no previous CVD. The primary outcome measure was time to first recorded fatal or non‐fatal CVD event (ischaemic heart disease, cerebrovascular accident, transient ischaemic attack or peripheral vascular disease) as identified from linked primary care, hospital and mortality records between January 2000 and December 2005. A Cox proportional hazards model was used to examine the association between HbA1c and time to CVD event, adjusting for age at diagnosis, duration of diabetes, gender, ethnicity, socio‐economic status, smoking, blood pressure (BP), serum total cholesterol : high‐density lipoprotein ratio, body mass index (BMI) and urine albumin : creatinine ratio.

Results  Participants included 48 444 people with Type 2 diabetes. Fifty‐one per cent (n = 24 721) were women, median age 60 years. Median duration of diabetes was 3 years, median BMI 31 kg/m2, median HbA1c 7.1% and mean BP was 138/81 mmHg. During the study period (median follow‐up 2.4 years), there were 5667 first CVD events (11.7% of cohort). Each 1% increase in HbA1c was associated with an increase in hazard ratio (HR) for CVD of 1.08 (95% confidence interval 1.06–1.10, P < 0.001), myocardial infarction [HR 1.08 (1.04, 1.11)] and stroke [HR 1.09 (1.04, 1.13)].

Conclusion  This study has confirmed in a large prospective cohort that increased HbA1c is an independent risk factor for cardiovascular disease after controlling for traditional risk factors.
Evolution and ecology of lizard body sizes
Authors: Meiri Shai
Published: August 2008

Aim  Body size is instrumental in influencing animal physiology, morphology, ecology and evolution, as well as extinction risk. I examine several hypotheses regarding the influence of body size on lizard evolution and extinction risk, assessing whether body size influences, or is influenced by, species richness, herbivory, island dwelling and extinction risk.

Location  World‐wide.

Methods  I used literature data and measurements of museum and live specimens to estimate lizard body size distributions.

Results  I obtained body size data for 99% of the world's lizard species. The body size–frequency distribution is highly modal and right skewed and similar distributions characterize most lizard families and lizard assemblages across biogeographical realms. There is a strong negative correlation between mean body size within families and species richness. Herbivorous lizards are larger than omnivorous and carnivorous ones, and aquatic lizards are larger than non‐aquatic species. Diurnal activity is associated with small body size. Insular lizards tend towards both extremes of the size spectrum. Extinction risk increases with body size of species for which risk has been assessed.

Main conclusions  Small size seems to promote fast diversification of disparate body plans. The absence of mammalian predators allows insular lizards to attain larger body sizes by means of release from predation and allows them to evolve into the top predator niche. Island living also promotes a high frequency of herbivory, which is also associated with large size. Aquatic and nocturnal lizards probably evolve large size because of thermal constraints. The association between large size and high extinction risk, however, probably reflects a bias in the species in which risk has been studied.
On the Concept and the Nature of Law
Authors: ALEXY ROBERT
Published: August 2008

Abstract.  The central argument of this article turns on the dual‐nature thesis. This thesis sets out the claim that law necessarily comprises both a real or factual dimension and an ideal or critical dimension. The dual‐nature thesis is incompatible with both exclusive legal positivism and inclusive legal positivism. It is also incompatible with variants of non‐positivism according to which legal validity is lost in all cases of moral defect or demerit (exclusive legal non‐positivism) or, alternatively, is affected in no way at all by moral defects or demerits (super‐inclusive legal non‐positivism). The dual nature of law is expressed, on the one hand, by the Radbruch formula, which says that extreme injustice is not law, and, on the other, by the correctness argument, which says that law's claim to correctness necessarily includes a claim to moral correctness. Thus, what the law is depends not only on social facts, but also on what the law ought to be.
Democratic Inclusion, Law, and Causes
Authors: BECKMAN LUDVIG
Published: August 2008

Abstract. In this article two conceptions of what it means to say that all affected persons should be granted the right to vote in democratic elections are distinguished and evaluated. It is argued that understanding “affected” in legal terms, as referring to the circle of people bound by political decisions, has many advantages compared to the view referring to everyone affected in mere causal terms. The importance of jurisdictions in deciding rights to democratic influence should hence be recognized more clearly than it currently is in democratic thinking.
PUTTING PARTICULARISM IN ITS PLACE
Authors: GERT JOSHUA
Published: August 2008

Abstract:The point of this paper is to undermine the support that particularism in the domain of epistemic reasons might seem to give to particularism in the domain of practical reasons. In the epistemic domain, there are two related notions: truth and the rationality of belief. Epistemic reasons are related to the rationality of belief, and not directly to truth. In the domain of practical reasons, however, the role of truth is taken by the notion of objective rationality. Practical reasons are directly relevant to this objective notion, and therefore the reasons to expect holism and particularism in the epistemic domain do not transfer to the domain of practical rationality.
AAN‐EFNS guidelines on trigeminal neuralgia management
Authors: Cruccu G. , Gronseth G. , Alksne J. , Argoff C. , Brainin M. , Burchiel K. , Nurmikko T. , Zakrzewska J. M.
Published: August 2008

Several issues regarding diagnosis, pharmacological treatment, and surgical treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy of Neurology and the European Federation of Neurological Societies launched a joint Task Force to prepare general guidelines for the management of this condition. After systematic review of the literature the Task Force came to a series of evidence‐based recommendations. In patients with TN MRI may be considered to identify patients with structural causes. The presence of trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal reflexes should be considered useful to disclose symptomatic TN, whereas younger age of onset, involvement of the first division, unresponsiveness to treatment and abnormal trigeminal evoked potentials are not useful in distinguishing symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) should be offered as first‐line treatment for pain control. For patients with TN refractory to medical therapy early surgical therapy may be considered. Gasserian ganglion percutaneous techniques, gamma knife and microvascular decompression may be considered. Microvascular decompression may be considered over other surgical techniques to provide the longest duration of pain freedom. The role of surgery versus pharmacotherapy in the management of TN in patients with multiple sclerosis remains uncertain.
Expression of the endogenous, nicotinic acetylcholine receptor ligand, SLURP‐1, in human colon cancer
Authors: Pettersson A. , Nordlander S. , Nylund G. , Khorram‐Manesh A. , Nordgren S. , Delbro D. S.
Published: August 2008

1 Secreted mammalian Ly‐6/urokinase plasminogen activator receptor‐related protein‐1 (SLURP‐1) is a recently discovered endogenous ligand at the α7 subunit of the nicotinic acetylcholine receptors. Previous reports have shown that SLURP‐1 is expressed in normal human keratinocytes seemingly with a pro‐apoptotic function. Conversely, such expression was markedly attenuated in transformed cells and it was suggested that the molecule could convey protection against malignant transformation.

2 In this study, we demonstrated the mRNA expression (by RT‐PCR) and protein expression (by Western blotting and immunocytochemistry) of SLURP‐1 in the human colon cancer cell line, HT‐29.

3 Furthermore, we demonstrated the expression of SLURP‐1 (by immunohistochemistry) in tumour cells of human colon cancer tissue, and, to a greater extent, in immune and smooth muscle cells of adjacent, macroscopically tumour‐free colon tissue.

4 The current findings suggest that SLURP‐1 participates in the regulation of gut immune functions and motility, as well as possibly playing a role in colon carcinogenesis/cancer progression.
How starvation risk in Redshanks Tringa totanus results in predation mortality from Sparrowhawks Accipiter nisus
Authors: CRESSWELL WILL , WHITFIELD D. PHILIP
Published: August 2008

Redshanks Tringa totanus that are preyed upon by Sparrowhawks Accipiter nisus at the Tyninghame Estuary, Firth of Forth, Scotland, provide an example of how the starvation–predation risk trade‐off results in mortality. In this trade‐off, animals cannot always optimize anti‐predation behaviour because anti‐predation behaviours, such as avoiding predators, are usually incompatible with foraging behaviours that might maximize intake rates. Therefore, as animals compensate for starvation risk, predation risk increases. Sparrowhawks are the main direct cause of death in Redshanks at Tyninghame. Sparrowhawk attack rate is determined by Redshank vulnerability, and vulnerability decreases as group size and distance to cover increase, and probably as spacing decreases. But reduction of predation vulnerability reduces feeding rate because areas away from cover are less food‐profitable and grouping results in increased interference competition. Increased starvation risk in midwinter means Redshanks are forced to feed on highly profitable prey, Orchestia amphipods, the behaviour of which means that Redshanks are forced to feed vulnerably, in widely spaced groups, close to predator‐concealing cover. Therefore, it is the constraints that limit the ability of Redshanks to feed in large, dense flocks away from cover that ultimately lead to mortality. We investigate this hypothesis further by testing the prediction that mortality can be predicted directly by cold weather and population density. We demonstrate that the overall number of Redshanks and the proportion of Redshanks killed increase in cold months when controlling for population size. We also demonstrate that the proportion of Redshanks killed increases when there are fewer Redshanks present, because the success rate of hunting Sparrowhawks increases, probably because effective management of predation risk through flocking is constrained by a low population size. Redshanks therefore provide an example of how directly mortality caused by predation arises from starvation risk and other constraints that prevent animals from optimizing anti‐predation behaviour.
The starvation–predation risk trade‐off, body mass and population status in the Common Starling Sturnus vulgaris
Authors: MACLEOD ROSS , CLARK JACQUIE , CRESSWELL WILL
Published: August 2008

It is theoretically and empirically well established that body mass variation in small birds reflects a trade‐off between starvation risk and predation risk. This occurs because carrying increased fat reserves reduces starvation risk but also results in a higher predation risk due to reduced escape flight performance and/or the increased foraging exposure needed to maintain a higher body mass. In principle, therefore, the theory of mass‐dependent predation risk could be used to understand how a bird perceives and responds to the risks in its environment, because its mass will reflect the predictability of foraging opportunities and predation risk. Mass in birds may then provide a relatively straightforward way of assessing the foraging environment of birds and so the potential conservation problems a species faces. This study tests, for the first time for any species, how body mass changes in response to changing starvation risk, changing predation risk and changing population status. Common Starling Sturnus vulgaris mass varies as predicted by starvation–predation risk trade‐off theory: mass is lower when foraging conditions are more favourable and when predation risk is increased. The populations that are declining the most strongly have higher mass, which is most likely indicative of a poor foraging environment, leading to lower relative survival. The results suggest that increased mass in Starlings, and possibly in other species, may provide an indication of the poor quality of the foraging environment and/or rapidly declining populations.
Behavioural strategies of cormorants (Phalacrocoracidae) foraging under challenging light conditions
Authors: WHITE CRAIG R. , BUTLER PATRICK J. , GRÉMILLET DAVID , MARTIN GRAHAM R.
Published: August 2008

Diving is indicative of foraging in cormorants (Phalacrocoracidae). We have investigated a range of parameters associated with diving in Great Cormorants Phalacrocorax carbo to provide insight into the bases of cormorant predatory strategies. We hypothesize that if vision is important in cormorant foraging behaviour, and if they are not constrained by the position of their prey in the water column, then diving behaviour will be modulated primarily in response to the diel variation in ambient light levels. Specifically, we propose that cormorants forage at shallower depths when light levels are low, and more deeply when light levels are high. We provide evidence that this is the case. We recorded the occurrence of cormorant diving behaviour using implanted data loggers and recorded ambient light levels and water temperature using leg‐mounted loggers in a sample of free‐living Great Cormorants in Greenland. Our results show that dives are shallower at the beginning and end of each day when light levels are lower. We suggest that these data support the hypothesis that cormorant foraging is visually‐guided even though recent evidence has shown that their underwater visual acuity is poor.
Impacts of birds of prey on gamebirds in the UK: a review
Authors: PARK KIRSTY J. , GRAHAM KATE E. , CALLADINE JOHN , WERNHAM CHRIS W.
Published: August 2008

The influence of predators on the distribution, density and dynamics of their prey species has long been of interest to ecologists and wildlife managers. Where the prey population is also utilized by humans, conflicts may arise through competition for a limited resource. Because gamebird shooting in the UK provides employment, recreation and income, the impact of birds of prey on gamebird populations has been the subject of intense debate for many years. Various approaches have been used to assess the impacts that raptors have on gamebird populations. Here we review the applicability and limitations of the methods used and assess the scientific evidence for population‐level and economic impacts of raptors on gamebird populations in the UK. Raptors may, in some situations, take large numbers of gamebirds and may be an important proximate cause of mortality, although few studies have addressed the impacts of raptors on either breeding or pre‐shooting densities. Two exceptions are studies of Hen Harrier Circus cyaneus, Peregrine Falcon Falco peregrinus predation on Red Grouse Lagopus lagopus scoticus on moorland in Scotland and Sparrowhawk Accipiter nisus predation on Grey Partridge Perdix perdix on farmland in England. Both these studies suggested that raptors could have population‐level impacts when their gamebird prey was already at low density. Studies on predation of captively bred gamebirds suggest that numbers taken by raptors at release pens vary considerably and in a few cases raptors have been documented killing relatively large numbers. On the whole, however, it appears that raptors account for a relatively small proportion of mortality among released birds and the impact on subsequent shooting bags is unknown. We summarize important gaps in current knowledge and recommend specific areas for future research.
Site‐specific production of TGF‐β in oral mucosal and cutaneous wounds
Authors: Schrementi Megan E. , Ferreira Ahalia M. , Zender Chad , DiPietro Luisa A.
Published: August 2008

Wound healing in the oral mucosa is clinically distinguished by rapid healing and lack of scar formation compared with dermal wounds. Mechanisms of favorable mucosal healing are yet to be elucidated. Utilizing a murine model of equivalent‐size mucosal and skin wounds, we verified the rapid reepithelializaton and reduction in scarring of oral wounds reported in humans. Collagen fibrillar structure in oral wounds rapidly approached the size of normal collagen fibrils, while the collagen ultrastructure in skin remained immature through the later phases of healing. To determine whether the transforming growth factor‐β (TGF‐β) contributes to the lack of scar formation in oral mucosa, we compared the expression and production in oral and skin wounds. The RNase protection assay demonstrated significantly lower levels of TGF‐β1 expression in oral wounds compared with dermal wounds, and no changes were observed in the expression levels of TGF‐β2 or TGF‐β3. ELISA analysis confirmed that oral wounds contained lower levels of TGF‐β1 levels compared with dermal wounds, along with a significant increase in the ratio of TGF‐β3 to ‐β1. These findings showed reduced scarring in oral wounds at the ultrastructural level, and provide evidence that site‐specific differences in TGF‐β production contributes to the superior healing of oral wounds.
Risk factors for pressure ulcers in acute care hospitals
Authors: Fogerty Mary D. , Abumrad Naji N. , Nanney Lillian , Arbogast Patrick G. , Poulose Benjamin , Barbul Adrian
Published: August 2008

Selection of patients for preventive measures to protect against pressure ulcers relies on clinical scales and provider judgment, which vary widely. Our objectives were to: (a) identify risk factors by clinical classification and report demographic differences in pressure ulcer risk and (b) develop criteria for identification of high‐risk patients. Patients with pressure ulcer as a discharge diagnosis were identified from the 2003 Nationwide Inpatient Sample (NIS). The effect of discharge diagnosis was examined using the Agency for Healthcare Research and Quality Clinical Classification Software (CCS). Multiple regression analysis for survey data was used to assess risk factors. The 2003 NIS listed 94,758 with a discharge diagnosis of pressure ulcer, identified as International Classification of Disease‐9 code 707.0–707.09, for an overall incidence of 143 per 10,000. Forty‐five CCS discharge diagnoses were present in at least 5% of these patients and 28 of these CCS diagnoses had odds ratios >2.0. African‐American race and advanced age were identified as risk factors for pressure ulcer diagnosis. Disorders of skin integrity, organ system failure, and infection were found to be broad categories of risk factors as well. Using the NIS, risk factors for pressure ulcer including diagnoses and demographic factors have been identified.