bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonparametric Functional Mapping of Quantitative Trait Loci
Authors: Yang Jie , Wu Rongling , Casella George
Published: June 2008

SummaryFunctional mapping is a useful tool for mapping quantitative trait loci (QTL) that control dynamic traits. It incorporates mathematical aspects of biological processes into the mixture model‐based likelihood setting for QTL mapping, thus increasing the power of QTL detection and the precision of parameter estimation. However, in many situations there is no obvious functional form and, in such cases, this strategy will not be optimal. Here we propose to use nonparametric function estimation, typically implemented with B‐splines, to estimate the underlying functional form of phenotypic trajectories, and then construct a nonparametric test to find evidence of existing QTL. Using the representation of a nonparametric regression as a mixed model, the final test statistic is a likelihood ratio test. We consider two types of genetic maps: dense maps and general maps, and the power of nonparametric functional mapping is investigated through simulation studies and demonstrated by examples.
Aneuploidy, but not Ki‐67 or EGFR expression, is associated with recurrences in basal cell carcinoma
Authors: Janisson‐Dargaud Delphine , Durlach Anne , Lorenzato Marianne , Grange Florent , Bernard Philippe , Birembaut Philippe
Published: June 2008

Background:  Basal cell carcinoma (BCC), the most common skin cancer, has an overall excellent prognosis, but recurrences are frequent. The value of classical clinical and histological prognostic factors to predict recurrences remain limited.

Methods:  In order to evaluate the prognostic value of Epidermal Growth Factor Receptor (EGFR) expression, Ki‐67 antigen expression and DNA ploidy, we compared primary tumors in 20 patients who had subsequent local recurrences and 20 matched controls without recurrences. DNA ploidy was determined by image cytometry, and EGFR and Ki‐67 expression were studied by immunohistochemistry.

Results:  Statistical analysis of the intensity and the percentage of EGFR expression and Ki‐67 antigen expression did not show any significant difference between the two groups. In contrast, we found that 78% of primary BCC in patients who experienced recurrences vs. 32% in the control group were aneuploid (p = 0.005).

Conclusions:  Aneuploidy is a risk factor for recurrences. This factor should be useful in clinical practice and require evaluation in further studies.
Comparative Policy Brief: Status of Intellectual Disabilities in the Islamic Republic of Iran
Authors: Samadi Sayyed Ali
Published: June 2008

Abstract In the Islamic Republic of Iran, considerable stigma is attached to the presence of a family member with intellectual disabilities, and even in Iran's new constitution, a word with traditional, negative connotation has been retained to refer to persons with intellectual disabilities. While two government organizations have recently become involved with children who have intellectual disabilities, it is estimated that each reaches only a small number of those who need assistance. Applying a prevalence estimate of 2% means that around 360,000 children aged less than 15 years have intellectual disabilities, but just 1.3% of these are known to the Iranian Special Education Organisation. There are no data available on the population of adults with intellectual disabilities. All Iranian children deemed “educable” have the right to 8 years of free education, and those described as “trainable” receive healthcare and rehabilitation services chiefly provided by nongovernmental organizations (NGOs). NGOs have been established to promote the education and welfare of those persons with intellectual disabilities. For adults, there are very limited opportunities either for work or for care. While laws about the rights of people with disabilities have been formulated, there is no mechanism to ensure that they are implemented. Key issues are to widen access to inclusive education; to provide early intervention based on community‐based rehabilitation methods; and to help families and society to initiate ways of providing employment for adults.
Comparative Policy Brief: Status of Intellectual Disabilities in the Republic of Poland
Authors: Wapiennik Ewa
Published: June 2008

Abstract  The prevalence of intellectual disability (ID) in Poland is estimated at 47.8/10,000 among the population aged over 15 years. Although progress has recently been documented in the development of more positive attitudes toward integration of people with disabilities in society, social distance toward those with ID is persistent. Several Acts of Parliament apply to Polish people with intellectual and other disabilities, for example, in respect to pensions, healthcare, and education. It is possible for families to place a child with ID in one of 103 social welfare homes which are not part of the education system. There is no widespread inclusion of children with ID in mainstream schools, although precise data are not available. Adults with ID may receive a pension if they can demonstrate inability to work. Some may be placed in social welfare homes if families are not in a position to provide care. It is estimated that many adults do not take part in any organized social or vocational activity. Three key issues in Poland are an absence of appropriate professional training or other supports to promote inclusive education for children; disincentives for enabling adults to enter the workforce; and a relatively high level of institutionalization with corresponding gaps in community‐based services.
Dynamics, stability and iron‐binding activity of frataxin clinical mutants
Authors: Correia Ana R. , Pastore Chiara , Adinolfi Salvatore , Pastore Annalisa , Gomes Cláudio M.
Published: June 2008

Friedreich’s ataxia results from a deficiency in the mitochondrial protein frataxin, which carries single point mutations in some patients. In the present study, we analysed the consequences of different disease‐related mutations in vitro on the stability and dynamics of human frataxin. Two of the mutations, G130V and D122Y, were investigated for the first time. Analysis by CD spectroscopy demonstrated a substantial decrease in the thermodynamic stability of the variants during chemical and thermal unfolding (wild‐type > W155R > I154F > D122Y > G130V), which was reversible in all cases. Protein dynamics was studied in detail and revealed that the mutants have distinct propensities towards aggregation. It was observed that the mutants have increased correlation times and different relative ratios between soluble and insoluble/aggregated protein. NMR showed that the clinical mutants retained a compact and relatively rigid globular core despite their decreased stabilities. Limited proteolysis assays coupled with LC‐MS allowed the identification of particularly flexible regions in the mutants; interestingly, these regions included those involved in iron‐binding. In agreement, the iron metallochaperone activity of the Friedreich’s ataxia mutants was affected: some mutants precipitate upon iron binding (I154F and W155R) and others have a lower binding stoichiometry (G130V and D122Y). Our results suggest that, in heterozygous patients, the development of Friedreich’s ataxia may result from a combination of reduced efficiency of protein folding and accelerated degradation in vivo, leading to lower than normal concentrations of frataxin. This hypothesis also suggests that, although quite different from other neurodegenerative diseases involving toxic aggregation, Friedreich’s ataxia could also be linked to a process of protein misfolding due to specific destabilization of frataxin.
The effect of FloSeal on post‐tonsillectomy pain: a randomised controlled pilot study
Authors: Blackmore K.J. , O’Hara J. , Flood L.M. , Martin F.W.
Published: June 2008

Objectives:  To determine whether FloSeal as a haemostatic agent in tonsillectomy is associated with less postoperative pain than conventional haemostasis with ligatures.

Design:  Randomised, controlled, single‐blinded pilot study.

Setting:  James Cook University Hospital, Middlesbrough, Cleveland, UK.

Participants:  Thirty patients over 16 years of age undergoing tonsillectomy for recurrent tonsillitis were recruited for the study. At surgery both tonsils were removed by cold steel dissection. Following randomisation one tonsil fossa had FloSeal applied and the other ligatures for haemostasis.

Main outcome measures:  The primary outcome measure was postoperative pain following tonsillectomy measured on a visual analogue scale. Pain was recorded three times a day for the first 10 days following surgery. Haemorrhage rates were also recorded as a secondary outcome.

Results:  Complete data was analysed for 26 patients (87%). The data was grouped into distinct time periods: 0–2, 3–6 and 7–10 days. The sum of the visual linear analogue scale over the time periods for each patient was calculated. Using Wilcoxon Signed Ranks Test, the data was analysed and it was found that there was no statistically significant difference in postoperative pain scores between the control and treatment side at any time. There was a postoperative reactionary haemorrhage rate of 6.7% on the FloSeal side.

Conclusion:  In our pilot study there was no reduction in pain on the FloSeal side in the first 10 days following tonsillectomy which contrasts with previous findings in the literature.
Pre‐treatment haemoglobin level predicts response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients
Authors: Baghi M. , Wagenblast J. , Hambek M. , Moertel S. , Gstoettner W. , Strebhardt K. , Knecht R.
Published: June 2008

Objective:  To investigate the prognostic value of the pre‐treatment haemoglobin level in patients with advanced squamous cell head and neck cancer treated with induction polychemotherapy.

Design:  Seventy‐two patients with advanced squamous cell head and neck cancer received primary combination chemotherapy consisting of docetaxel 75 mg/m² on day 1, cisplatin 100 mg/m² on day 1, and 5‐fluorouracil (5‐FU) 1000 mg/m²/day on days 1–4 (total dose 4000 mg/m²), repeated on days 1, 22 and 43 followed by chemoradiation. The data collected included pre‐treatment haemoglobin, response to treatment, disease‐free and overall survival.

Results:  The pre‐treatment haemoglobin level was found to be a significant predictor of response to induction chemotherapy (P = 0.01) and an independent predictor of overall survival [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58–1.03, P = 0.0001] and disease free survival (HR 2.09, 95% CI 1.41–3.09, P = 0.0001). Furthermore N‐stage was found to be a significant prognostic factor of overall survival (HR 9.24, 95% CI 6.90–21.34, P = 0.005). The Eastern Cooperative Oncology Group performance status scale was also found to be significant for disease free survival (HR 7.66, 95% CI 2.61–22.46, P = 0.003).

Conclusion:  In patients with advanced squamous cell head and neck cancer, the haemoglobin level prior to induction chemotherapy is significantly related to outcome including response and survival.
Conservative management of vestibular schwannomas: third review of a 10‐year prospective study
Authors: Hajioff D. , Raut V.V. , Walsh R.M. , Bath A.P. , Bance M.L. , Guha A. , Tator C.H. , Rutka J.A.
Published: June 2008

Keypoints

Seventy‐two patients with a unilateral vestibular schwannoma have been treated conservatively for a median of 121 months. They have been followed prospectively by serial clinical examination, MRI scans and audiometry.

Twenty‐five patients (35%, 95% CI: 24–47) failed conservative management and required active intervention during the study. No factors predictive of tumour growth or failure of conservative management could be identified. Seventy‐five per cent of failures occurred in the first half of the 10‐year study.

The median growth rate for all tumours at 10 years was 1 mm/year (range −0.53–7.84). Cerebellopontine angle tumours grew faster (1.4 mm/year) than intracanalicular tumours (0 mm/year, P < 0.01); 92% had growth rates under 2 mm/year.

Hearing deteriorated substantially even in tumours that did not grow, but did so faster in tumours that grew significantly (mean deterioration in pure tone average at 0.5, 1, 2 and 3 kHz was 36 dB; speech discrimination scores deteriorated by 40%).

Patients who failed conservative management had clinical outcomes that were not different from those who underwent primary treatment without a period of conservative management.
Evaluation of inter‐observer variability in the grading of oral dysplasia using two different grading systems
Authors: Srinivasan R.T. , Snead D. , Matthews P. , Williams H. , Webster K. , Griffin D. , El‐Lalani N. , Mehanna H.
Published: June 2008

Objectives.  To compare the inter‐observer variability in grading of oral dysplasia between two consultant pathologists specialising in head and neck cancer, and one non‐specialist, using both the WHO classification 2005 and the Binary Grading system (proposed by Kujan et al. 2005).

Methods.  Eighty archived oral biopsy slides consisting of cases with different grades of dysplasia treated and followed up in a tertiary regional centre, were reviewed by three pathologists, blinded to the initial diagnosis and the clinical outcome. The H&E slides were graded according to the criteria of both systems. Inter‐observer reliability and variation were computed with kappa coefficient analysis.

Results.  The overall inter‐observer kappa agreement for the WHO grading system was κ = 0.21(95% CI: 0.10–0.34) and for the binary system was κ = 0.55(95% CI: 0.42–0.71). There was closer correlation in grading of the lesions between the two experts (WHO κ = 0.40, 95% CI: 0.28–0.53 and Binary κ = 0.59, 95% CI: 0.34–0.80), when compared to that between an expert and the non‐expert (WHO κ = 0.18 95% CI: 0.05–0.30 and Binary κ = 0.32 95% CI: 0.15–0.50) Kappa agreements between the three observers on individual architectural and cytological features of the binary system showed great variability, the highest agreement being in increased mitotic figures (κ = 0.49,95% CI: 0.25–0.72) and the lowest on atypical mitotic figures (κ = 0.15,95% CI: 0.01–0.32).

Conclusions.  There was closer agreement between all three pathologists when using the binary system in comparison to the WHO system, but both systems showed at best only moderate agreement. Improved agreement of scoring of individual features of the binary system should improve overall agreement of this system.
Health beliefs and expectations amongst chronic catarrh sufferers
Authors: Cathcart R. , Wilson J. , May C.
Published: June 2008

Background.  The mere presence of catarrh does not, in itself, compel medical help‐seeking: many experience catarrh and never seek help for it, while others do so after months or even years. We aimed to explore the triggers of help‐seeking in chronic catarrh patients, along with their general health beliefs and the expectations that they hold about the health services that they approach.

Method.  A qualitative study using digitally taped semi‐structured interviews of 19 chronic catarrh patients, with full ethical approval. Narrative analysis was performed on the transcribed interviews, using a constant comparative technique approach to the generation of grounded theory, through a process of manual coding and categorisation. Emergent categories were checked for goodness of fit.

Results.  Catarrh came to prominence for sufferers through a global shift in body concerns or a relative shift in symptom heirarchy subsequent to a lack of explanation or treatments. Catarrh sufferers had narrow, family‐based lay networks which they found to be frequently dismissive. Temporalisation and worsening of symptoms were the predominant triggers for seeking help. Sufferers attended GPs for a ‘quick‐fix’ and hospitals for ‘investigations’. Short‐term sufferers sought a cure for their symptoms whilst long‐term sufferers accepted reassurance.

Conclusions.  Explanantion and closure should be primary aims in managing catarrh patients. Although resolution of symptoms is the pervading hope of chronic catarrh sufferers, a significant majority of interviewees, particularly long‐term sufferers, admitted that they could live with their symptoms so long as they could be given reassurance that pathology was absent and no treatment option overlooked.
Do neonates have a nasal cycle?
Authors: Olarinde O. , Banerjee A. , O’Callaghan C.O.
Published: June 2008

Objectives.  To study the dynamic behaviour of the nasal mucosa in neonates.

Method.  Although the nasal cycle has been described in adults,1 studies regarding the nasal cycle physiology in neonates are scarce. Acoustic rhinometry (RHIN 2000 miniprobe) was carried out in ten neonates over periods ranging from 165 to 255 min at 15‐min intervals. Inclusion criteria were babies with no upper airway symptoms and no abnormality on anterior rhinoscopy. All examinations were carried out by the same examiner under similar conditions. The minimum cross sectional area (MCA10–40) and volume of nasal cavity (Vol10–40) were analysed for correlation using the Pearson's correlation coefficient.

Results.  Correlation (alternating pattern) between the right and left sides was found to be significant in one baby.

Conclusions.  Ninety percent of the neonates we examined did not demonstrate a nasal cycle. We demonstrated an alternating pattern in one baby. Neonates probably do not have a nasal cycle as demonstrated in adults.

Reference.  1 Fisher E.W., Scadding G.K. & Lund V.J. (1993) The role of acoustic rhinometry in studying the nasal cycle. Rhinology 2, 57–61
Immunological responses of laryngeal mucosa to short‐term endotracheal intubation
Authors: Hughes O.R. , Ayling S.M. , Birchall M.A.
Published: June 2008

Objectives.  Short‐term intubation (<4 h) is common in elective surgery and has been associated with post‐operative changes to the voice. Furthermore, short‐term endotracheal intubation is often used in microlaryngoscopy. Therefore research into laryngeal physiology requires an understanding of the changes to mucosal biology that result from intubation. Very little is known of the early cellular processes involved in laryngeal injury. We aim to establish how the cells of the innate immune system in the larynx are influenced by short‐term intubation.

Methods.  Biopsies were taken from the supraglottis and subglottis of five pairs of NIH minipigs fully matched at the major histocompatibility complex (MHC) locus. One of each pair was intubated 48 h prior to laryngeal biopsy; the other had not received previous intubation. Multiple‐colour immunofluorescence histology was used to quantify the numbers of immunologically active mucosal cells at each site.

Results.  At 48 h following endotracheal intubation, there was no significant difference (P > 0.05) in total number of myeloid cells immunologically active in the supraglottic or subglottic mucosa. In the subglottis there was a small increase in the number of CD14+ and CD16+ cells in three out of four pairs following intubation; largest percentage increase in CD14+ and CD16+ expression between pairs was 74% (P = 0.011) and 72% (P = 0.007) respectively.

Conclusions.  At 48 h post‐intubation our results points to a continued innate immune response in the subglottis; this is consistent with previous histological and clinical studies that have identified the subglottis as the focus for post‐intubation injury.

References.  1 Gould S.J. & Howard S. (1985) The histopathology of the larynx in the neonate following endotracheal intubation. J. Pathol. 146, 301–311

2 Beckford N.S., Mayo R., Wilkinson A. & Tierney M. (1990) Effects of short‐term endotracheal intubation on vocal function. Laryngoscope 100, 331–336
Biopolymer nanoparticles as antigen delivery vehicles for immunotherapy of head and neck squamous cell carcinoma (HNSCC)
Authors: Prasad S. , Cody V. , Hanlon D. , Edelson R.L. , Saltzman M. , Sasaki C.T. , Birchall M.A.
Published: June 2008

Objective.  To determine whether nanoparticles (NP) made from FDA‐approved biopolymers could be incorporated into a novel clinically translatable dendritic cell (DC)‐based therapy for HNSCC.

Methods.  Head and neck squamous cell carcinoma lines were used to make lysates employing multiple techniques, and with varying amounts of protein so as to improve encapsulation within differing molecular weights of Poly (lactic‐co‐glycolic acid) (PLGA) polymers. NP were fabricated by a double emulsion solvent‐evaporation technique with flash freeze‐lyophilization. Encapsulation and release profile were studied to determine the ideal formulation. These findings were adopted for encapsulating tumour material from five patients with advanced HNSCC. Pattern of protein release was detected using Silver stained SDS‐PAGE gels and immunoblotting for p53. GM‐CSF/IL‐4 DC made from blood monocyte precursors were loaded with either the soluble or encapsulated versions of tumour lysate, and used for stimulation of magnetic bead‐isolated autologous CD8+ T‐cells. Differences in Th1/Th2 responses were estimated by Cytometric bead array (CBA). NP morphology and DC loading were evaluated by scanning electron microscopy.

Results.  Optimal release was recorded from 80 K PLGA NP containing a lysate made using four cycles of freeze‐thaw plus 15‐s sonication followed by brief lyophilization. NP were small enough to be phagocytosed by DC. Encapsulation and release was directly proportional to the lysate concentration with no major antigen degradation. In four patients, CBA showed significantly increased IFN‐γ or decreased IL‐10 (P = 0.012) production associated with NP encapsulation.

Conclusions.  Biopolymer NP can efficiently deliver the panoply of unknown tumour antigens. This strategy has been optimized for use in a clinical trial.

References.  1 Sandor M., Enscore D., Weston P et al. (2001) Effect of protein molecular weight on release from micron‐sized PLGA microspheres. J. Control. Release 76, 297–311

2 Elamanchili P., Lutsiak C., Hamdy S et al. (2007) ‘Pathogen‐mimicking’ nanoparticles for vaccine delivery to dendritic cells. J. Immunother.30, 378–395
The perceptual assessment of voice in post‐laryngectomy tracheoesophageal speakers
Authors: Hurren A. , Hildreth A. , Carding P.N.
Published: June 2008

Objectives.  To investigate the inter and intra rater reliability of expert raters concerning two alaryngeal voice parameters: ‘overall grade’ and ‘neoglottal tonicity’. Reliable perceptual assessment is essential for surgical and therapeutic outcome measurement but has been minimally researched to date.

Method.  Nine speech and language therapists and four ENT surgeons judged audio recordings of 55 tracheoesophageal speakers. ‘Overall grade’ was rated with a 0–3 equally appearing interval scale and ‘neoglottal tonicity’ with an 11 point bipolar semantic scale. Ratings were repeated one‐month later. Weighted kappa reliability co‐efficients were calculated with StatXact.

Results.  The effect of ‘neoglottal’ tonicity on ‘overall grade’ was examined via linear regression using the combined grades of the 4 senior SLT's. R2 coefficient = 0.62, implying that 62% of the variance in ‘overall grade’ is attributable to tonicity.

Conclusions.  Strength of agreement1 was good for inter and intra rater reliability for ‘overall grade’. Intra‐rater agreement for ‘neoglottal tonicity’ was also good but inter‐rater judgements were only moderate. However experienced therapists demonstrated good inter rater reliability for ‘neoglottal tonicity’ suggesting this group may be the optimal judges for alaryngeal voice assessment. The R2 coefficient indicates ‘tonicity’ is a good predictor of ‘overall grade’ for experienced SLT raters.

Reference. 1 Landis J.R. & Koch G.G. (1977) The measurement of observer agreement for categorical data. Biometrics 33, 159–174
Localisation training of unilateral cochlear implanted children
Authors: Murphy J. , Summerfield A.Q. , O’Donoghue G.M. , Moore D.R.
Published: June 2008

Objectives.  Spatial hearing is a particularly important ability for normal development. It aids appropriate orientation of a child towards a target sound and segregation of targets from noise, thus facilitating listening, especially in complex, acoustic environments (e.g. classrooms). Our aim was to investigate the potential of behavioural training to improve the localisation ability of children using unilateral cochlear implant (CI).

Methods.  Five unilateral CI users (10–16 years old) participated in a single 2‐h training session. Localisation training was presented via a 24 loudspeaker ring. Pre‐ and post‐training assessments employed, five video monitors, paired with five loudspeakers (30° angular separation), each displayed a talker saying ‘Hello, what toy is this?’ The task of the listener was to identify the only talker whose image was co‐located with the sound. In Phase 1 training two loudspeakers separated by 120° were used and participants were coached to use head movements facilitating greater access to dynamic loudness cues. An above chance performance provided entry into Phase 2. Here the stimulus separation varied adaptively between 120–30° to facilitate training around threshold levels.

Results.  Our data indicate that unilateral CI users’ pre‐training performance (P (correct) 0.45) improved in the final assessment (P (correct) 0.55) following a period of training. A likelihood ratio test showed P < 0.01.

Conclusions.  In just a single session it was possible to train implant users on a skill that may help them in their everyday life. Further research is needed to show whether the training is long lasting enough to be truly useful.
Accuracy of CT in the measurement of stapes prostheses using a temporal bone model
Authors: Rowlands R.G. , Beale T. , Wright A.
Published: June 2008

Objectives.  To evaluate whether it would be possible to measure accurately a range of stapes prostheses of different lengths and makes using spiral CT imaging and a radiologist who would report the images in a blinded fashion. To establish the distance from the tip of each prosthesis to the metallic component in metal – plastic prostheses.

Method.  Eight stapes prostheses (2 fluoroplastic‐stainless steel; 2 fluoroplastic‐platinum; 2 fluoroplastic‐nitinol; 2 fluoroplastic only) were selected and placed onto the long process of the incus and over the oval window of a dried temporal bone preparation. CT scans were then performed and multiplanar reformatting techniques used to allow measurement of the length of the prostheses. The prostheses were then photographed and measured using high definition digital prints after slicing them in half to expose the central metallic component.

Results.  The median difference between the actual and observed length of the 6 metallic/fluoroplastic stapes prostheses was 0.25 mm (0.05–0.55 mm). In contrast the 2 fluoroplastic prostheses were accurately measured as 4 and 5 mm respectively. The median distance of the metallic component from the end of the prosthesis was found to be 1.75 mm (1.5–1.9 mm).

Conclusion.  Modern spiral CT scanners can visualise the fluoroplastic component of stapes prostheses to assess its position. However, our series shows that the length of mixed metallic/fluoroplastic prostheses may be still be inaccurately measured by up to 0.55 mm. Reliance on measuring the metallic component of the prosthesis may also overestimate the proportion of prostheses that are short of the footplate.

References.  1 Kosling S. & Bootz F. (2001) CT and MR imaging after middle ear surgery. Eur. J. Radiol. 40, 113–118

2 Pickuth D., Brandt S., Berghaus A., Spielmann R.P. & Heywang‐Kobrunner S.H. (2000) Vertigo after stapes surgery: the role of high resolution CT. Br. J. Radiol. 73, 1021–1023
Oil Migration in Chocolate–Peanut Butter Paste Confectionery as a Function of Chocolate Formulation
Authors: McCarthy K.L. , McCarthy M.J.
Published: June 2008

ABSTRACT: Migration of oil from high oil content filling to the chocolate coating can result in undesirable quality changes in filled chocolate confectionery products. The objective of this study was to monitor and model peanut oil migration in a 2‐layer chocolate–peanut butter paste model confectionery. Spatial and temporal oil content changes were evaluated using magnetic resonance imaging. Five formulations of chocolate, which varied in chocolate particle size, milk fat content, and emulsifier level, were assessed at 2 temperatures, 20 and 30 °C. The spatial and temporal experimental data were modeled using a Fickian‐based diffusion model, fitting for the diffusion coefficient,D, over a time frame of 17 d. Values of the diffusion coefficient ranged from 1.82 to 3.23 × 10−11m2/s for the chocolate formulations stored at 30 °C. No significant mass transfer took place in the 20 °C samples over the experimental time frame. This study describes the dynamic nature of the interface between the chocolate and peanut butter paste layers, quantifies the mass transfer from the peanut butter paste to the chocolate, and reinforces the importance of temperature control.
Invasive Infections with Community-Associated Methicillin-Resistant
Staphylococcus aureus
after Kidney Transplantation
Authors: Adeyemi Oluwadamilola A. , Qi Chao , Zembower Teresa R. , Ison Michael G. , Grant Thomas H. , Hartigan Brian J. , Malczynski Michael , Stosor Valentina
Published: June 2008

We report two cases of invasive infections caused by Panton-Valentine leukocidin-positive, community-associated, methicillin-resistant
Staphylococcus aureus
(CA-MRSA) after kidney transplantation. This report emphasizes the clinical importance of considering CA-MRSA as a causative agent in the differential diagnosis of infections of the skin and soft tissues in organ transplant recipients.
Herpes Simplex Virus Type 2 Displays Atypical Melting-Temperature Profiles at Low Viral Titers
Authors: LeBlanc Jason J. , Campbell Sarah , Pettipas Janice , Hatchette Todd F. , Davidson Ross J.
Published: June 2008

Real-time PCR is a powerful tool for the detection and typing of herpes simplex virus (HSV). HSV types 1 and 2 can be distinguished by using the differences in the melting temperatures (
T

m

s) of the hybridization probes. The efficacy of
T

m

profiling with low DNA concentrations was evaluated in this study.
DNA gag/Adenovirus Type 5 (Ad5) gag and Ad5 gag/Ad5 gag Vaccines Induce Distinct T-Cell Response Profiles
Authors: Cox Kara S. , Clair James H. , Prokop Michael T. , Sykes Kara J. , Dubey Sheri A. , Shiver John W. , Robertson Michael N. , Casimiro Danilo R.
Published: June 2008

Results from Merck's phase II adenovirus type 5 (Ad5) gag/pol/nef test-of-concept trial showed that the vaccine lacked efficacy against human immunodeficiency virus (HIV) infection in a high-risk population. Among the many questions to be explored following this outcome are whether (i) the Ad5 vaccine induced the quality of T-cell responses necessary for efficacy and (ii) the lack of efficacy in the Ad5 vaccine can be generalized to other vector approaches intended to induce HIV type 1 (HIV-1)-specific T-cell responses. Here we present a comprehensive evaluation of the T-cell response profiles from cohorts of clinical trial subjects who received the HIV CAM-1 gag insert delivered by either a regimen with DNA priming followed by Ad5 boosting (
n
= 50) or a homologous Ad5/Ad5 prime-boost regimen (
n
= 70). The samples were tested using a statistically qualified nine-color intracellular cytokine staining assay measuring interleukin-2 (IL-2), tumor necrosis factor alpha, macrophage inflammatory protein 1β, and gamma interferon production and expression of CD107a. Both vaccine regimens induced CD4
+
and CD8
+
HIV gag-specific T-cell responses which variably expressed several intracellular markers. Several trends were observed in which the frequencies of HIV-1-specific CD4
+
T cells and IL-2 production from antigen-specific CD8
+
T cells in the DNA/Ad5 cohort were more pronounced than in the Ad5/Ad5 cohort. Implications of these results for future vaccine development will be discussed.
Role of Interferon in the Replication of Human Parainfluenza Virus Type 1 Wild Type and Mutant Viruses in Human Ciliated Airway Epithelium
Authors: Bartlett Emmalene J. , Hennessey Margaret , Skiadopoulos Mario H. , Schmidt Alexander C. , Collins Peter L. , Murphy Brian R. , Pickles Raymond J.
Published: June 2008

Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease in the upper and lower airways. An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology. In HAE, type I interferon (IFN) is induced following infection with an HPIV1 mutant expressing defective C proteins with an F170S amino acid substitution, rHPIV1-C
F170S
, but not following infection with wild-type HPIV1. IFN induction coincided with a 100- to 1,000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for the inhibition of the innate immune response. Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE. The vaccine candidates, rHPIV1-C
R84G/Δ170
HN
T553A
L
Y942A
and rHPIV1-C
R84G/Δ170
HN
T553A
L
Δ1710-11
, which contain temperature-sensitive (
ts
) attenuating (
att
) and non-
ts att
mutations, were highly restricted in growth in HAE at permissive (32°C) and restrictive (37°C) temperatures. The viruses grew slightly better at 37°C than at 32°C, and rHPIV1-C
R84G/Δ170
HN
T553A
L
Y942A
was less attenuated than rHPIV1-C
R84G/Δ170
HN
T553A
L
Δ1710-11
. The level of replication in HAE correlated with that previously observed for African green monkeys, suggesting that the HAE model has potential as a tool for the preclinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.
Competition Model for Upregulation of the Major Histocompatibility Complex Class II-Associated Invariant Chain by Human Immunodeficiency Virus Type 1 Nef
Authors: Mitchell Richard S. , Chaudhuri Rittik , Lindwasser O. Wolf , Tanaka Kristie A. , Lau David , Murillo Rudy , Bonifacino Juan S. , Guatelli John C.
Published: June 2008

The human immunodeficiency virus type 1 (HIV-1) Nef protein upregulates the expression of the invariant chain (Ii)/major histocompatibility complex class II (MHC-II) complex at the cell surface. This complex appears to reach the antigen-loading endosomal compartment at least in part via an indirect pathway in which it is internalized from the cell surface via the adaptor protein 2 (AP-2) complex. Here we provide evidence for a competition model to explain how Nef upregulates the expression of Ii at the cell surface. In this model, Nef and Ii compete for binding to AP-2. In support of this model, Nef decreased the rate of internalization of Ii from the cell surface. The AP-binding dileucine motif in Nef, ENTSLL
165
, was necessary and sufficient for the upregulation of Ii. In addition, two leucine-based AP-binding motifs in the Ii cytoplasmic tail, DDQRDLI
8
and EQLPML
17
, were critical for the efficient upregulation of Ii by Nef. Experiments using Nef variants in which the native dileucine-based sorting motif was replaced with similar motifs from cellular transmembrane proteins allowed modulation of AP-binding specificity. Analysis of these variants suggested that the binding of Nef to AP-2 is sufficient to upregulate Ii at the plasma membrane. Finally, interference with the expression of AP-2 caused an upregulation of Ii at the plasma membrane, and this decreased the effect of Nef. These data indicate that Nef usurps AP-2 complexes to dysregulate Ii trafficking and potentially interfere with antigen presentation in the context of MHC-II.
Structural Biology of Pectin Degradation byEnterobacteriaceae
Authors: Abbott D. Wade , Boraston Alisdair B.
Published: June 2008

Pectin is a structural polysaccharide that is integral for the stability of plant cell walls. During soft rot infection, secreted virulence factors from pectinolytic bacteria such asErwiniaspp. degrade pectin, resulting in characteristic plant cell necrosis and tissue maceration. Catabolism of pectin and its breakdown products by pectinolytic bacteria occurs within distinct cellular environments. This process initiates outside the cell, continues within the periplasmic space, and culminates in the cytoplasm. Although pectin utilization is well understood at the genetic and biochemical levels, an inclusive structural description of pectinases and pectin binding proteins by both extracellular and periplasmic enzymes has been lacking, especially following the recent characterization of several periplasmic components and protein-oligogalacturonide complexes. Here we provide a comprehensive analysis of the protein folds and mechanisms of pectate lyases, polygalacturonases, and carbohydrate esterases and the binding specificities of two periplasmic pectic binding proteins fromEnterobacteriaceae. This review provides a structural understanding of the molecular determinants of pectin utilization and the mechanisms driving catabolite selectivity and flow through the pathway.
Optimal Time and Size for Smolt Migration in Wild Sea Trout (Salmo trutta)
Authors: Bohlin Torgny , Dellefors Claes , Faremo Ulo
Published: June 2008

A tagging programme, in which wild sea trout (Salmo trutta) were marked at the parr stage with internal tags in winter and recaptured during smolt migration in a trap in the following spring, was conducted for three seasons in a small stream in southwestern Sweden, individuals that were initially smaller migrated later, grew more in length, and were smaller at migration than those initially bigger. Body length at migration decreased with migration time during the season for tagged as well as nontagged trout. A model for optimal time of and size at migration is proposed, based on the assumption that the expression (body length at the end of the season) × (survival over the season) is maximized and that migratory and postmigratory survival is positively size dependent. The qualitative predictions on the relationship between initial size and time of and size at migration are supported by the tagging data. Pre- and postmigratory growth rates are predicted to have opposite effects on migration time, so the migration timing is expected to depend strongly on the degree of dependence between these.
An Extension of Stock Composition Analysis to include Marking Data
Authors: Brodziak Jon
Published: June 2008

Population characteristics and man-made marks have been applied separately to gather information on the stock composition of mixed-stock fisheries. This paper develops an extension of the finite mixture problem with learning samples model of Fournier et al. (1984. Can. J. Fish. Aquat. Sci. 41: 400–408) to include marking data as well as morphometric, meristic, or biochemical genetic data for stock composition analyses. Simulation studies are used to test the model on a previously described "problem cluster" that consists of stocks that exhibit high levels of genetic affinity. The test results show that the inclusion of marking data can improve the accuracy of stock composition estimates.
Convergence of Acoustic, Optical, and Net-Catch Estimates of Euphausiid Abundance: Use of Artificial Light to Reduce Net
Authors: Sameoto D. , Cochrane N. , Herman A.
Published: June 2008

Euphausiid concentrations in the Scotian Shelf basins were sampled with BIONESS, a multinet sampling system, and quantitatively assessed simultaneously with an in situ optical zooplankton counter (OPC) mounted on BIONESS and with an acoustic backscattering system operating simultaneously at 50, 122, and 200 kHz. Supplementary observations were made with vertically dropped video cameras and video and 35-mm frame cameras mounted on a remotely operated vehicle (ROV). The use of a light source on BIONESS during sampling increased the catch of euphausiids by 10–20 times by reducing active avoidance reactions to the net. Consequently, conventional net sampling has greatly underestimated euphausiid concentrations, a conclusion suggested by previous acoustic measurements. Experimental acoustic target strengths for 28-mm euphausiids averaged −77.5, −73.4, and −68.4 dB at 50, 122, and 200 kHz, respectively, using measured Sv levels and assuming 100% net sampling efficiency. Theoretical scattering models based on randomly oriented cylinders require the euphausiids to be oriented within about 5° of the horizontal to approximate both the experimentally observed target strength amplitudes and their frequency dependence. Acoustic interpretation has been enhanced by incorporation of transducer sensitivity versus temperature corrections and modeling techniques that allow for finite transducer beam widths.
Megalopal Spatial Distribution and Stock Separation in Dungeness Crab (Cancer magister)
Authors: Jamieson G. S. , Phillips A.
Published: June 2008

During the day, Dungeness crab (Cancer magister) megalopae from off the outer coasts of Vancouver Island and Washington are aggregated at about 25 m whereas those from the Strait of Georgia are at about 160 m. At night, both populations of megalopae seem to be mostly in the top metre of water. Juan de Fuca Strait, which connects the Strait of Georgia to the Pacific Ocean, typically has an estuarine circulation, with outflow in the top 50–100 m and deeper inflow. Because the daylight to dark ratio when megalopae are present is about 3:1, the Strait of Georgia and outer-coast megalopae are mostly retained within their own systems by currents at their daytime depths. Occasional intrusions of outer-coast megalopae into Juan de Fuca Strait may occur when estuarine flow in the Strait temporarily breaks down following sustained, strong, southwesterly winds; such intrusions are typically restricted to the south and head of Juan de Fuca Strait, and even extensive ones do not carry megalopae far into the Strait of Georgia. The daily movement of larval crab to cold (<10 °C), deep water in the Strait of Georgia may explain, at least partially, the delay in seasonal timing of settlement and their smaller physical size at settlement compared with outer-coast megalopae.
Loss of Bacillus thuringiensis var. israelensis Larvicidal Activity and Its Distribution in Benthic Substrates and Hyporheic Zone of Streams
Authors: Tousignant M. E. , Boisvert J. L. , Chalifour A.
Published: June 2008

Numerous field trials have indicated that the effectiveness of Bacillus thuringiensis var. israelensis (B.t.i.) is limited to a short distance in streams, but the reasons for loss of toxicity have not been identified. Two streams were treated with B.t.i. and experiments were conducted to monitor the transfer of B.t.i. toxicity from the channel water to different compartments within the stream. These compartments included benthic substrates such as sediments, periphyton covering bedrocks, vegetation (moss and grass), and water samples taken from hyporheic probes (15, 35, and 65 cm depth). B.t.i. toxic activity was measured using bioassays with mosquito neonate larvae. Results indicated that loss to the hyporheic zone accounted for a significant fraction of B.t.i. removal from the open-channel water. Additional losses were attributable chiefly to moss, but sediments may play an important role in filtering or retaining B.t.i. toxic particles.
Inhibition of Candida albicans extracellular enzyme activity by selected natural substances and their application inCandidainfection
Authors: Yordanov M. , Dimitrova P. , Patkar S. , Saso L. , Ivanovska N.
Published: June 2008

Extracellular enzymes secreted by Candida albicans are claimed to be virulence factors responsible for penetration of the yeast into host cells. Substances able to inhibit lipolytic and proteinase activities of the fungus might be of therapeutic use in some pathologic conditions caused by C. albicans. In the present work, we have tested the influence of the flavonoid compounds apigenin and kaempferol, the indole alkaloid ibogaine, and the protoberberine alkaloid berberine on the in vitro enzyme activity of C. albicans. The substances showed complex suppressive effects concerning the processes of adherence to epithelial cells, secreted aspartyl proteinase activity, and the rate of cell wall protein glycosylation. Apigenin and kaempferol were administered in systemic C. albicans infection, demonstrating an increased number of survivors by kaempferol. The application of apigenin, kaempferol, ibogaine, and berberine in cutaneous infection suppressed the symptoms and accelerated elimination of the yeast from the site of inoculation.
Oxylipin and mitochondrion probes to track yeast sexual cells
Authors: Ncango Desmond M. , Swart Chantel W. , Goldblatt Monique E. , Pohl Carolina H. , Van Wyk Pieter W.J. , Botes Piet J. , Kock Johan L.F.
Published: June 2008

When oxylipin and mitochondrion probes, i.e., fluorescing antibodies specific for 3-hydroxy fatty acids (3-OH oxylipins) and rhodamine 123 (Rh123), were added to yeast cells, these probes accumulated mainly in the sexual cells (i.e., both associated with ascospores) and not in the vegetative cells. This suggests increased mitochondrial activity in asci, since 3-OH oxylipins are mitochondrially produced and it is known that Rh123 accumulates selectively in functional mitochondria that maintain a high transmembrane potential (ΔΨm). This increased activity may be necessary for the production and effective release of the many spores found in single-celled asci. These results may be useful in the rapid identification of asci and in yeast sexual spore mechanics, which may find application in yeast systematics as well as hydro-, aero-, and nano-technologies.
MULTIFRAGMENTATIONS OF TARGETS AT SPS ENERGY — EVIDENCE OF BOTH MONOFRACTALITY AND MULTIFRACTALITY
Authors: GHOSH DIPAK , DEV ARGHA , SARKAR SAMABRATA , HALDAR PRABIR KUMAR
Published: June 2008

This paper reports the fractal analysis of target residues in both ring- and jet-like events emitted from 32 S - AgBr interactions at 200 AGeV using Takagi's prescription. The study reveals a very interesting feature of emission process such as monofractality of target fragments in jet-like events and multifractality of target fragments in case of ring-like events.
Syneruptive features and sedimentary processes associated with pyroclastic currents entering the sea: the
ad
79 eruption of Vesuvius, Bay of Naples, Italy
Authors: MILIA ALFONSA , MOLISSO FLAVIA , RASPINI ARTURO , SACCHI MARCO , TORRENTE MAURIZIO M.
Published: June 2008

The ad 79 Plinian eruption of Vesuvius that buried Pompeii and Herculaneum began with pumice falls deposited towards the SE of the volcano followed by pyroclastic currents directed towards the SW. These currents reached Herculaneum and rapidly entered the sea, forming a fan. The interpretation of seismic reflection profiles and gravity cores collected off Herculaneum documents a submarine fan-shaped pyroclastic body at 10–140 m water depth that we interpret as the submarine counterpart of the onshore pyroclastic current deposits. This fan,
c
. 0.3 km
3
in volume, displays a chaotic seismic facies that changes seaward to parallel reflectors and then to wavy reflectors. Gravity cores reveal a succession consisting of centimetre-thick sand- or silt-sized ash couplets followed by a graded gravelly sand-sized bed up to 180 cm thick, containing shell fragments and beach-derived pebbles, overlain by centimetre-thick graded and laminated sandy ash layers. The depositional textures and sedimentary structures of the submarine pyroclastic fan have been interpreted as the product of the interactions between pyroclasts, water waves and tsunamis induced by the ad 79 pyroclastic density currents into the Bay of Naples.