bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring vigabatrin in head injury patients by cerebral microdialysis: obtaining pharmacokinetic measurements in a neurocritical care setting
Authors: Shannon Richard J. , Timofeev Ivan , Nortje Jürgens , Hutchinson Peter J. , Carpenter Keri L. H. 
Published: May 2014

AimsThe aims were to determine blood–brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; γ‐vinyl‐γ‐aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of γ‐aminobutyric acid (GABA) concentration in brain extracellular fluid.MethodsSevere TBI patients (n = 10) received VGB (0.5 g enterally, every 12 h). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 h before and 2, 4 and 11.5 h after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB.ResultsAfter the first VGB dose, the maximum concentration of VGB (Cmax) was 31.7 (26.9–42.6) μmol l−1 (median and interquartile range for eight patients) in plasma and 2.41 (2.03–5.94) μmol l−1 in brain microdialysates (nine patients, 11 catheters), without significant plasma–brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24–7.14) μmol l−1 (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration.ConclusionsVigabatrin, given enterally to severe TBI patients, crosses the blood–brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood.
Clinical pharmacology of AMG 181, a gut‐specific human anti‐α4β7 monoclonal antibody, for treating inflammatory bowel diseases
Authors: Pan Wei‐Jian , Köck Kathleen , Rees William A. , Sullivan Barbara A. , Evangelista Christine M. , Yen Mark , Andrews Jane M. , Radford‐Smith Graham L. , Prince Peter J. , Reynhardt Kaz O. , Doherty David R. , Patel Sonal K. , Krill Christine D. , Zhou Kefei , Shen Jing , Smith Lynn E. , Gow Jason M. , Lee Jonathan , Treacy Anthony M. , Yu Zhigang , Platt Virginia M. , Borie Dominic C. 
Published: May 2014

AimsAMG 181 pharmacokinetics/pharmacodynamics (PK/PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double‐blind, placebo‐controlled study.MethodsHealthy male subjects (n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis (UC) subjects (n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti‐AMG 181‐antibody (ADA), α4β7 receptor occupancy (RO), target cell counts, serum C‐reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3–9 months after dose.ResultsFollowing s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2–10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose‐proportionally and approximately dose‐proportionally, respectively, within the 70–210 mg s.c. and 70–420 mg i.v. ranges. The linear β‐phase t1/2 was 31 (range 20–48) days. Target‐mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml−1. The PD effect on α4β7 RO showed an EC50 of 0.01 μg ml−1. Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181‐treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo‐treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment‐related serious adverse events were observed.ConclusionsAMG 181 has PK/PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases.
Laparoscopic radical prostatectomy for high‐risk prostate cancer
Authors: Di Benedetto Antonina , Soares Ricardo , Dovey Zach , Bott Simon , McGregor Roy G. , Eden Christopher G. 
Published: May 2014

ObjectiveTo investigate the results of performing laparoscopic radical prostatectomy (LRP) in patients with high‐risk prostate cancer (HRPC): PSA level of ≥20 ng/mL ± biopsy Gleason ≥8 ± clinical T stage ≥2c.Patients and MethodsOf a total of 1975 patients having LRP during a 159‐month period from 2000 to 2013, 446 (22.6%) had HRPC; all patients were staged by preoperative magnetic resonance imaging or computed tomography and isotope bone scanning. The median (range) patient age was 64.0 (36–79) years; body mass index 27.0 (18–43) kg/m2; PSA level 8.1 (0.1–93) ng/mL and biopsy Gleason 8 (6–10). All patients had a pelvic lymphadenectomy, which was done using an extended template after April 2008 (53.3%). Neurovascular bundle (NVB) preservation was done in 41.5% (bilateral 26.3%; unilateral 15.2%) of patients; an incremental or partial nerve‐sparing technique was used in 99 of the 302 (32.8%) NVBs preserved.ResultsThe median (range) gland weight was 58.5 (20–161) g; operating time 180 (92–330) min; blood loss 200 (10–1400) mL; postoperative hospitalisation 3.0 (2–7) nights; catheterisation time 14 (2–35) days; complication rate 7.6%; lymph node (LN) count 16 (2–51); LN positivity 16.2%; LN involvement 2 (1–8); positive surgical margin (PSM) rate 26.0%; up‐grading 2.5%; down‐grading 4.3%; up‐staging from T1/2 to T3, 24.7%; down‐staging from T3 to T1/2, 6.1%. No cases were converted to open surgery and three patients were transfused (0.7%) after surgery. At a mean (range) follow‐up of 24.9 (3–120) months, 79.2% of patients were free of biochemical recurrence, 91.8% were continent and 64.4% of previously potent non‐diabetic men aged <70 years were potent after bilateral nerve preservation.ConclusionThe low morbidity, 55.4% specimen‐confinement rate, 26.0% PSM rate, 79.2% biochemical disease‐free survival, 91.8% continence rate and 64.4% potency rate, at 35.2 months in the present study serve as evidence firstly that surgery is an effective treatment for patients with HRPC, curing many and representing the first step of multi‐modal treatment for others, and that LRP for HRPC appears to be as effective as open RP in this context.
Modified transurethral resection of the prostate (TURP) for men with moderate lower urinary tract symptoms (LUTS) before brachytherapy is safe and feasible
Authors: Brousil Philip , Hussain Muddassar , Lynch Mark , Laing Robert W. , Langley Stephen E.M. 
Published: May 2014

ObjectiveTo report the urinary toxicity outcomes for patients at greater risk of voiding symptoms and retention who received a modified limited transurethral resection of the prostate (TURP) before low‐dose rate (LDR) brachytherapy.Patients and MethodData were analysed from patients receiving the above procedures between 2006 to present, taken from the prospective brachytherapy database of 2000 patients at the St. Luke's Cancer Centre. The limited TURP (TURPBXT) was performed at a median (range) of 64 (25–205) days before seed implantation with a median resection weight of 1.15 g. Selection criteria were based on patients with moderate lower urinary tract symptoms, poor flow or post‐void residual urine volume (PVR), or a prominent middle lobe or high bladder neck on transrectal ultrasonography. Baseline prostate cancer characteristics, uroflowmetry, International Prostate Symptom Score (IPSS) and quality‐of‐life QoL scores were collected and compared with follow‐up IPSS and QoL scores.ResultsData for 112 patients was gathered from the database. The TURPBXT resulted in statistically significant improvements before LDR brachytherapy in maximum urinary flow rate (Qmax) and PVR, IPSS and QoL scores (the mean Qmax before vs after the TURPBXT was 11.3 vs 16.7 mL/s). The IPSS and QoL scores at 6 months after seed implantation were increased compared with baseline values before the TURPBXT (mean IPSS at 6 months 11.7 vs 9.2 before TURPBXT), but no difference at 1 year (mean IPSS 9), and improved scores at 2, 3, 4 and 5 years follow‐up (mean IPSS of 7.9, 5.6, 5.3 and 7.4, respectively).ConclusionThe present study suggests patients at increased risk of deteriorating voiding symptoms, including urinary retention, are no longer contraindicated against LDR brachytherapy if they receive a modified TURP before seed implantation. This procedure does not appear to carry the risk of urinary incontinence thought to be associated with a conventional TURP before LDR brachytherapy.
Clay mineral occurrence and burial transformations: reservoir potential of the Permo‐Triassic sediments of the Iberian Range
Authors: Marfil R. , La Iglesia A. , Herrero M. J. , Scherer M. , Delgado A. 
Published: May 2014

AbstractThe diagenetic evolution of Permian (Autunian and Saxonian) and Triassic (Buntsandstein) sandstones and mudrocks have been studied over 1000 m sequence from the Sigüenza 44‐3 drill core in the Iberian Range, Spain. We compare and contrast the diagenetic processes in these different lithologies and the timing of clay mineral formation. Moreover, we establish the relationship between clay mineral diagenesis and reservoir potential. Both the Permian and Triassic successions are characterised by conglomerates, sandstones and interbedded mudstones of fluvial origin that change upwards into distal deposits of a fluvio‐deltaic system. The clay minerals are illite, illite‐smectite mixed layers, kaolinite and dickite. The illite content in all sequences is not related to diminished feldspars; it is owing to the initial detrital mineralogical composition of the Autunian sandstones. The effect of feldspar alteration to kaolin minerals has a strong influence on the lost of porosity‐permeability in the Saxonian facies. In contrast, illite and mixed layers illite‐smectite are the main clay rims preserving porosity in the Buntsandstein sandstones. However, fibrous illite is the dominant pore‐filling in the Permian Autunian facies, closing porosity and permeability. Kaolinite and dickite show opposite trends: dickite increases yet kaolinite decreases from Triassic to Permian sandstones. Dickite replaced kaolinite during burial‐thermal evolution of the succession. The δD and δ18O isotopic signatures from silt and clay fractions indicate a mixture of meteoric and marine waters, and suggest a minimum temperature range between 60 and 150 °C for diagenetic pore fluids. The Permian δD values (−24‰ to −44‰) are relatively similar to Buntsandstein values (−24‰ to −37‰). However, the Permian δ18O values (+7.6 and +15.3, average of +13.3‰) are generally higher by ca. 6.2‰ compared to the Buntsandstein data (4.8–10.1‰, average +7.1‰). Such a variation is interpreted as the result of mesodiagenetic pore fluid changes. The extensive dickitisation of kaolinite is attributed to increased hydrogen ions resulting from maturation of organic matter. The vitrinite reflectance of organic matter and the modelled thermal history suggest a maximum burial of 3400 m, accomplished 70 Ma ago. The Permo‐Triassic reached the gas window shortly before major uplift, at 65 Ma, when further maturation and hydrocarbon expulsion ceased.
The road to recovery: Comparing Canada and US recovery strategies for shared endangered species
Authors: Olive Andrea 
Published: May 2014

AbstractCanada and the United States share 30 endangered or threatened species. This paper examines the recovery process for species at risk under the two country's domestic laws: Canada's Species at Risk Act and the American Endangered Species Act. These two countries could be working together to recover shared species, especially migratory and cross‐border species. Through comparing the recovery strategies and plans for the 30 species, and interviewing recovery team members on both sides of the border, it is shown that cross‐border collaboration is limited. The paper argues that more collaboration, data sharing, and cross‐border recovery teams are needed. Biodiversity loss is an increasing problem in both countries.
New MT‐ND1 pathologic mutation for Leber hereditary optic neuropathy
Authors: Martínez‐Romero Íñigo , Herrero‐Martín M Dolores , Llobet Laura , Emperador Sonia , Martín‐Navarro Antonio , Narberhaus Bernat , Ascaso Francisco J , López‐Gallardo Ester , Montoya Julio , Ruiz‐Pesini Eduardo 
Published: May 2014

AbstractBackgroundMutations causing Leber hereditary optic neuropathy are usually homoplasmic, show incomplete penetrance, and many of the affected positions are not well conserved through evolution. A large percentage of patients harbouring these mutations have no family history of disease. Moreover, the transfer of the mutation in the cybrid model is frequently not accompanied by the transfer of the cellular, biochemical and molecular phenotype. All these features make difficult their classification as the etiologic factors for this disease. We report a patient who exhibits typical clinical features of Leber hereditary optic neuropathy but lacks all three of the most common mitochondrial DNA mutations.MethodsThe diagnosis was made based on clinical studies. The mitochondrial DNA was completely sequenced, and the candidate mutation was analysed in more than 18 000 individuals around the world, its conservation index was estimated in more than 3100 species from protists to mammals, its position was modelled in the crystal structure of a bacteria ortholog subunit, and its functional consequences were studied in a cybrid model.ResultsGenetic analysis revealed an m.3472T>C transition in the MT‐ND1 gene that changes a phenylalanine to leucine at position 56. Bioinformatics, molecular‐genetic analysis and functional studies suggest that this transition is the etiological factor for the disorder.ConclusionsThis mutation expands the spectrum of deleterious changes in mitochondrial DNA‐encoded complex I polypeptides associated with this pathology and highlights the difficulties in assigning pathogenicity to new homoplasmic mutations that show incomplete penetrance in sporadic Leber hereditary optic neuropathy patients.
Reliability of cone counts using an adaptive optics retinal camera
Authors: Bidaut Garnier Mélanie , Flores Mathieu , Debellemanière Guillaume , Puyraveau Marc , Tumahai Perle , Meillat Mathieu , Schwartz Claire , Montard Michel , Delbosc Bernard , Saleh Maher 
Published: May 2014

AbstractBackgroundTo assess the reproducibility and repeatability of cone imaging in healthy human eyes, using the RTx‐1 Adaptive Optics Retinal Camera and its proprietary cone‐counting software.DesignSingle‐centre, prospective study.ParticipantsTen healthy adults.MethodsMacular cones were imaged. Intrasession repeatability was assessed by comparing 10 consecutive acquisitions obtained by the same operator from each subject. For the intersession study, each subject was imaged five consecutive days. Interoperator reproducibility was also evaluated by comparing the images obtained from 10 different subjects by two independent operators. Finally, intergrader agreement was evaluated by comparing the cone counts measured by two masked graders.Main Outcome MeasuresMean cone density (cells/mm2), spacing between cells (μm) and percentage of cones with six neighbours calculated on Voronoi diagrams were measured. Correlation coefficients, intraclass correlation coefficients, and coefficients of variation were calculated.ResultsCorrelation coefficient and intraclass correlation coefficient were respectively 0.81 and 0.96 between operators, and 0.97 and 0.98 between the two graders. The intrasession and intersession coefficients of variation were under 7%. The percentage of cells with six neighbours and the spacing between cones varied in the same proportion (coefficients of variation ranged from 1.66 to 10.05%).ConclusionsOverall, the test–retest variability of RTx‐1 and its software was good in normal human eyes. Further studies in the normal clinical setting are mandatory.
Understanding and checking the assumptions of linear regression: a primer for medical researchers
Authors: Casson Robert J , Farmer Lachlan DM 
Published: May 2014

AbstractLinear regression (LR) is a powerful statistical model when used correctly. Because the model is an approximation of the long‐term sequence of any event, it requires assumptions to be made about the data it represents in order to remain appropriate. However, these assumptions are often misunderstood. We present the basic assumptions used in the LR model and offer a simple methodology for checking if they are satisfied prior to its use. In doing so, we aim to increase the effectiveness and appropriateness of LR in clinical research.
Impact of trastuzumab on wound healing in experimental glaucoma surgery
Authors: Turgut Burak , Eren Kenan , Akin Mehmet M , Bilir Can Nagehan , Demir Tamer 
Published: May 2014

AbstractBackgroundTo investigate the effects of subconjunctivally administered trastuzumab on wound healing in experimental glaucoma filtration surgery.DesignComparative, experimental study.SamplesTwenty eight eyes.MethodsTwenty‐eight male New Zealand white rabbits were randomly assigned to four groups, each including seven rabbits: The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the mitomycin‐C group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL mitomycin‐C was applied intraoperatively to the scleral surgical site for 3 min. The rabbits in the trastuzumab group underwent trabeculectomy and were injected subconjunctivally once with 1.2 mg/0.1 mL of the drug. On day 14 of the experiment, the operated and control eyes were enucleated and immunohistochemically analyzed.Main Outcome MeasuresMean values of fibroblast, mononuclear cell and immunostaining intensities of the transforming growth factor‐β, fibroblast growth factor‐β, and platelet derived growth factor.ResultsThe mean cell numbers and immunostaining intensities in the sham group were higher than those of the control group (P < 0.01). The mean cell numbers and immunostaining intensities in the mitomycin‐C group and trastuzumab group were statistically significantly lower than those of the sham group (P < 0.01) while mean cell numbers and immunostaining intensities in the mitomycin‐C group and trastuzumab group were similar (P > 0.05).ConclusionSubconjunctival trastuzumab injection effectively suppressed subconjunctival scarring after experimental glaucoma filtration surgery.
Uncontrolled eating is associated with reduced executive functioning
Authors: Calvo D. , Galioto R. , Gunstad J. , Spitznagel M. B. 
Published: May 2014

SummaryAccumulating evidence indicates obesity is associated with reduced cognitive functioning, particularly attention and executive function, as well as maladaptive eating behaviour such as uncontrolled eating. The current study examined relationships between eating patterns and attention/executive function test performance in lean and obese individuals. Sixty‐two (32 lean, 30 obese) healthy young adults (21.13 ± 2.31 years; 56.5% female) completed the abbreviated Three‐Factor Eating Questionnaire (TFEQ‐R18) to assess eating patterns, including uncontrolled eating, cognitive restraint, and emotional eating. The Go/No‐Go (GNG), Running Memory Continuous Performance Test (RCMPT) and Standard Continuous Performance Test from the Automated Neuropsychological Assessment Metrics‐4 were administered as measures of executive functioning and attention. An independent samples t‐test revealed greater report of uncontrolled eating in obese compared with lean participants (t[60] = −2.174, P < 0.05; d = −0.55) but no differences in cognitive restraint or emotional eating. Multivariate analysis of variance revealed cognitive differences between lean and obese groups (F[6, 54] = 3.86, P < 0.005; λ = 0.70; ηp2 = 0.30), which were driven by GNG reaction time (F[1, 59] = 8.36, P < 0.01, d = 0.74). Pearson bivariate correlations revealed a positive correlation between uncontrolled eating and reaction time on GNG (r = 0.343, P < 0.05) and RMCPT (r = 0.267, P < 0.05) in all participants. Relative to lean participants, obese individuals reported higher levels of uncontrolled eating and exhibited slower performance on a task of inhibitory control. In the full sample, greater self‐reported dyscontrol in eating behaviour was related to slower inhibitory control and working memory. Results support a link between executive function and control of eating behaviour. Obese individuals may be more vulnerable to difficulties in these domains relative to those who are lean.
The cost‐effectiveness of the LighterLife weight management programme as an intervention for obesity in England
Authors: Lewis L. , Taylor M. , Broom J. , Johnston K. L. 
Published: May 2014

SummaryLighterLife Total is a very low calorie diet total dietary replacement weight reduction programme that provides Foodpacks, behavioural change therapy and group support appropriate for people with a body mass index of 30 kg m−2 or above. A model was built to assess the cost‐effectiveness of LighterLife Total, compared with (i) no treatment, Counterweight, Weight Watchers and Slimming World, as a treatment for obesity in those with a body mass index of 30 kg m−2 or above, and (ii) no treatment, gastric banding and gastric bypass in those with a body mass index of 40 kg m−2 or above. Change in body mass index over time was modelled, and prevalence of comorbidities (diabetes, coronary heart disease and colorectal cancer) was calculated. Costs (of intervention and treatment for comorbidities) and quality‐adjusted life years were calculated. LighterLife Total was cost‐effective against no treatment, Counterweight, Weight Watchers and Slimming World in the 30+ kg m−2 group (incremental cost‐effectiveness ratios: £11 895, £12 453, £12 585 and £12 233, respectively). In the 40+ kg m−2 group, LighterLife Total was cost‐effective against no treatment (incremental cost‐effectiveness ratio: £4356), but less effective than gastric banding and bypass.