bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary and maximal crossed product orders
Authors: Braun Amiram , Ginosar Yuval , Levy Amit
Published: May 2007

We first deal with classical crossed products

S
f

∗
G

S^f*G

, where

G
G

is a finite group acting on a Dedekind domain

S
S

and

S
G

S^G

(the

G
G

-invariant elements in

S
S

) a DVR, admitting a separable residue fields extension. Here

f
:
G
×
G
→

S
∗

f:G\times G\rightarrow S^*

is a 2-cocycle. We prove that

S
f

∗
G

S^f*G

is hereditary if and only if

S

/

Jac
⁡
(
S

)

f
¯

∗
G

S/\operatorname {Jac}(S)^{\bar {f}}*G

is semi-simple. In particular, the heredity property may hold even when

S

/

S
G

S/S^G

is not tamely ramified (contradicting standard textbook references). For an arbitrary Krull domain

S
S

, we use the above to prove that under the same separability assumption,

S
f

∗
G

S^f*G

is a maximal order if and only if its height one prime ideals are extended from

S
S

. We generalize these results by dropping the residual separability assumptions. An application to non-commutative unique factorization rings is also presented.
An infinite-dimensional integral identity for the Segal-Bargmann transform
Authors: Becnel Jeremy , Sengupta Ambar
Published: May 2007

We prove an infinite-dimensional integral identity equating the integral of a function on a subspace of a linear space to the integral of its Segal-Bargmann transform over the orthogonal complement.
Predicting functionally important residues from sequence conservation
Authors: Capra John A. , Singh Mona
Published: May 2007

Motivation: All residues in a protein are not equally important. Some are essential for the proper structure and function of the protein, whereas others can be readily replaced. Conservation analysis is one of the most widely used methods for predicting these functionally important residues in protein sequences.

Results: We introduce an information-theoretic approach for estimating sequence conservation based on Jensen–Shannon divergence. We also develop a general heuristic that considers the estimated conservation of sequentially neighboring sites. In large-scale testing, we demonstrate that our combined approach outperforms previous conservation-based measures in identifying functionally important residues; in particular, it is significantly better than the commonly used Shannon entropy measure. We find that considering conservation at sequential neighbors improves the performance of all methods tested. Our analysis also reveals that many existing methods that attempt to incorporate the relationships between amino acids do not lead to better identification of functionally important sites. Finally, we find that while conservation is highly predictive in identifying catalytic sites and residues near bound ligands, it is much less effective in identifying residues in protein–protein interfaces.

Availability: Data sets and code for all conservation measures evaluated are available at http://compbio.cs.princeton.edu/conservation/

Contact:  mona@cs.princeton.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Network Analysis and the Law: Measuring the Legal Importance of Precedents at the U.S. Supreme Court
Authors: Fowler James H. , Johnson Timothy R. , Spriggs James F. , Jeon Sangick , Wahlbeck Paul J.
Published: May 2007

We construct the complete network of 26,681 majority opinions written by the U.S. Supreme Court and the cases that cite them from 1791 to 2005. We describe a method for using the patterns in citations within and across cases to createimportance scoresthat identify the most legally relevant precedents in the network of Supreme Court law at any given point in time. Our measures are superior to existing network-based alternatives and, for example, offer information regarding case importance not evident in simple citation counts. We also demonstrate the validity of our measures by showing that they are strongly correlated with the future citation behavior of state courts, the U.S. Courts of Appeals, and the U.S. Supreme Court. In so doing, we show that network analysis is a viable way of measuring how central a case is to law at the Court and suggest that it can be used to measure other legal concepts.
Stroboscopy Versus High‐Speed Glottography: A Comparative Study
Authors: Olthoff Arno , Woywod Christina , Kruse Eberhard
Published: May 2007

Objectives: To evaluate and to compare the diagnostic value of videostroboscopy (VS) and high‐speed glottography (HGG) in dysphonic patients.

Study Design: Randomized, prospective study.

Methods: A total of 162 patients underwent indirect laryngoscopy using both methods (VS and HGG). The resulting 324 films were evaluated by two professionals (laryngologists, MDs) using a standardized protocol containing established criteria to classify vocal fold vibratory movement qualities.

Results: The rating “not assessable” was mentioned significantly more often in VS than in HGG (P < .001). In HGG, methodologic failures were less frequent, and the length of investigation was shorter. Even if the agreement between the two raters was higher in HGG (54%) compared with VS (42%), both percentage values show a low accordance in diagnostic findings.

Conclusions: Regardless of the method used (VS or HGG), perceptive evaluations of vibratory movements of vocal folds revealed a higher variability than assumed. This result supports the need for objective methods to analyze vocal fold vibratory movements. Therefore, real‐time imaging of vocal fold vibratory movements using HGG will be necessary.
Equivalent Noise Level Generated by Drilling Onto the Ossicular Chain as Measured by Laser Doppler Vibrometry: A Temporal Bone Study
Authors: Jiang Dan , Bibas Athanasios , Santuli Carlo , Donnelly Neil , Jeronimidis George , O'Connor Alec Fitzgerald
Published: May 2007

Background: Inadvertent drilling on the ossicular chain is one of the causes of sensorineural hearing loss (HL) that may follow tympanomastoid surgery. A high‐frequency HL is most frequently observed. It is speculated that the HL is a result of vibration of the ossicular chain resembling acoustic noise trauma. It is generally considered that using a large cutting burr is more likely to cause damage than a small diamond burr.

Aim: The aim was to investigate the equivalent noise level and its frequency characteristics generated by drilling onto the short process of the incus in fresh human temporal bones.

Methods and Materials: Five fresh cadaveric temporal bones were used. Stapes displacement was measured using laser Doppler vibrometry during short drilling episodes. Diamond and cutting burrs of different diameters were used. The effect of the drilling on stapes footplate displacement was compared with that generated by an acoustic signal. The equivalent noise level (dB sound pressure level equivalent [SPL eq]) was thus calculated.

Results: The equivalent noise levels generated ranged from 93 to 125 dB SPL eq. For a 1‐mm cutting burr, the highest equivalent noise level was 108 dB SPL eq, whereas a 2.3‐mm cutting burr produced a maximal level of 125 dB SPL eq. Diamond burrs generated less noise than their cutting counterparts, with a 2.3‐mm diamond burr producing a highest equivalent noise level of 102 dB SPL eq. The energy of the noise increased at the higher end of the frequency spectrum, with a 2.3‐mm cutting burr producing a noise level of 105 dB SPL eq at 1 kHz and 125 dB SPL eq at 8 kHz. In contrast, the same sized diamond burr produced 96 dB SPL eq at 1 kHz and 99 dB at 8 kHz.

Conclusion: This study suggests that drilling on the ossicular chain can produce vibratory force that is analogous with noise levels known to produce acoustic trauma. For the same type of burr, the larger the diameter, the greater the vibratory force, and for the same size of burr, the cutting burr creates more vibratory force than the diamond burr. The cutting burr produces greater high‐frequency than lower‐frequency vibratory energy.
Selective Activation of Cat Primary Auditory Cortex by way of Direct Intraneural Auditory Nerve Stimulation
Authors: Kim Seung‐Jae , Badi Arunkumar N. , Normann Richard A.
Published: May 2007

Objectives/Hypothesis: Although cochlear implants have been successfully used by many individuals with profound hearing impairment, limitations still remain with this approach to hearing restoration, including poor stimulation selectivity because of cross‐talk between electrodes and poor low‐frequency percepts. These limitations may be mitigated by direct intraneural stimulation of the auditory nerve by way of an array of penetrating microelectrodes. Such an approach should provide focal stimulation and selective activation of the nerve fibers, thereby minimizing cross‐talk among implanted stimulating electrodes and evoking narrow‐band frequency percepts.

Study Design: We investigated the activation of primary auditory cortex evoked by such direct intraneural electrical stimulation of the auditory nerve.

Methods: We implanted 11 penetrating microelectrodes in the cat auditory nerve, simulated the nerve by way of these electrodes, and recorded the evoked neuronal activity patterns in cat primary auditory cortex. We compared these activation patterns with acoustically evoked cortical activity patterns obtained in a different animal.

Results: Our results showed that direct stimulation of the auditory nerve evoked localized activity patterns in primary auditory cortex similar in spatial extent to those evoked by acoustic stimulation and that the extent of cortical activation by both acoustic and electrical stimuli was graded with stimulus intensity. These results suggest that the implanted electrodes can excite independent and small populations of nerve fibers.

Conclusion: This study demonstrates the functional feasibility of direct intraneural auditory nerve stimulation with an array of penetrating microelectrodes and that such an approach could form the foundation for an auditory prosthesis with improved frequency coding.
Cochlear Implantation in the Neurofibromatosis Type 2 Patient: Long‐Term Follow‐up
Authors: Neff Brian A. , Wiet R Mark , Lasak John M. , Cohen Noel L. , Pillsbury Harold C. , Ramsden Richard T. , Welling D Bradley
Published: May 2007

Objective: To evaluate the long‐term hearing outcomes of neurofibromatosis type 2 (NF2) patients with cochlear implants.

Methods: Retrospective analysis of cochlear implant performance in NF2 patients using open‐ and closed‐set speech perception testing.

Results: Patients with NF2‐associated bilateral vestibular schwannomas frequently become profoundly deaf. The aim of surgical resection should be to preserve serviceable hearing in at least one ear; however, this goal can be difficult to achieve. Frequently, tumor size or poor preoperative hearing status can require a surgical approach that leaves the patient with a profound, bilateral sensorineural hearing loss. If the cochlear nerve is preserved anatomically after vestibular schwannoma surgery, and if promontory stimulation confirms the functionality of the cochlear nerve, then cochlear implantation is an excellent option to restore hearing. We present six cochlear implant patients with NF2 who attained a significant improvement in open‐ and closed‐set speech understanding with a mean follow‐up of 7.9 (range: 5–13) years after surgery. In all but one case, the hearing results did not deteriorate over the follow‐up period.

Conclusion: Early surgical intervention for vestibular schwannomas in NF2 patients when the cochlear nerve can be spared is an important consideration to allow for possible cochlear implantation. A 6‐ to 8‐week recovery period for the anatomically intact cochlear nerve may be necessary to obtain a positive promontory stimulation response following tumor resection and should be performed prior to cochlear implantation.
Does Suture Material and Technique Really Matter? Lessons Learned From 800 Consecutive Blepharoplasties
Authors: Joshi Arjun S. , Janjanin Sasa , Tanna Neil , Geist Craig , Lindsey Charlie
Published: May 2007

Objectives: The purpose of this study was to evaluate established suture materials and techniques for blepharoplasty closure and evaluate for any differences in rates of complications between these groups.

Study Design and Methods: This was a prospective study of a large sequential series of patients undergoing upper blepharoplasty who were treated by the same senior author over a 5‐year period. Patients were assigned one of four techniques for closure of the incision based on the senior author's experience. After 6 weeks, rates of complications and revisions were noted and addressed. Satisfaction rates were noted at 3 months.

Results: In the group whose incisions were closed with running subcuticular polypropylene (Prolene), 5 (2.5%) presented with milia, and 11 (5.5%) had a standing cone deformity (SCD). Use of running cutaneous locked Prolene resulted in 8 patients (17%) with milia and 2 patients (4.4%) requiring revision of a SCD. Use of a running 6‐0 plain gut suture resulted in 12 patients (6.7%) with milia and 5 patients (2.8%) with unsightly scarring. In the group whose incisions were closed with running 6‐0 fast‐absorbing gut, 10 patients (2%) presented with milia, and there were no scar revisions. There were statistically significant differences between the groups with respect to formation of milia, scarring, and persistent erythema (P < .008).

Conclusions: Blepharoplasty is a safe and effective procedure that can be performed successfully with several established techniques. In our experience, closure with two interrupted 6‐0 Prolene sutures and a running 6‐0 fast‐absorbing gut resulted in the lowest rates of complications and revisions.
The Ductal Stretching Technique: An Endoscopic‐Assisted Technique for Removal of Submandibular Stones
Authors: Nahlieli Oded , Shacham Rachel , Zagury Ami , Bar Tal , Yoffe Boris
Published: May 2007

Objective: The purpose of this study was to describe an innovative surgical technique for the removal of posterior and hilar stones of the submandibular salivary duct.

Methods: Between 1999 and 2005, 172 patients who had sialolithiasis of the submandibular duct were treated primarily by transoral incision and marsupialization of the duct and salivary gland. The ductal stretching technique involved endoscopic location of the stone, incision of the oral mucosa above the duct, isolation of the duct from the surrounding tissues, stretching of the duct, ductal incision above the calculus, sialolithotomy, and insertion of a drain.

Results: Forty‐one patients with stones located in the posterior aspect of the duct were symptom‐free and stone free after the procedure. One hundred and five patients with stones located in the hilum were treated with a success rate of 98%. Twenty‐six patients with multiple stones in the hilar region were treated with a success rate of 81%. The overall success rate of the procedure was 96%. In 48 patients (28%), an additional undetected stone was diagnosed by endoscopy after the removal of the stone in the hilum. In 62 patients (36%), strictures were diagnosed endoscopically posterior to the stone. Lingual nerve paresthesia occurred in one patient, who recovered completely.

Conclusion: The ductal stretching technique is recommended as the procedure of choice in cases with posterior and hilar stones more than 5 mm in diameter to avoid surgical removal of the salivary gland.
Outcome of Endoscopic Treatment of Adult Postintubation Tracheal Stenosis
Authors: Nouraei S A. Reza , Ghufoor Khalid , Patel Anil , Ferguson Tina , Howard David J. , Sandhu Guri S.
Published: May 2007

Objectives/Hypothesis: To assess the results of primary endoscopic treatment of adult postintubation tracheal stenosis, to identify predictors of a successful outcome, and better define the scope and limitations of minimally‐invasive surgery for this condition.

Methods: Sixty‐two consecutive patients treated between April 2003 and 2006 with initial endoscopic surgery were prospectively studied. Patient and lesion characteristics, treatment details, complications, decannulation, and open surgery rates were recorded. Actuarial analysis and Cox regression were used to identify predictors of decannulation and freedom from external surgery.

Results: There were 34 male patients and the average age was 45 ± 16 years. The average stenosis height was 18 mm (range: 5–55 mm), and 82% of lesions were Myer‐Cotton grades III or IV. Lesion height and intubation‐to‐treatment latency independently predicted success of endoscopic surgery. Ninety‐six percent of patients with lesions <30 mm in height were treated endoscopically, but the success rate fell to 20% for lesions longer than 30 mm. Patients with recalcitrant lesions underwent airway augmentation (n = 11) or resection (n = 3), with a 79% success rate. All patients were decannulated, but some, predominantly morbidly obese patients, required long‐term stents for dynamic airway compromise. Ninety‐eight percent of re‐interventions occurred within 6 months.

Conclusions: Minimally invasive treatment is effective in postintubation airway stenosis and obviates the need for open cervicomediastinal surgery in most patients. Patients with old and long lesions are less likely to be cured endoscopically. For most patients in this subgroup, endoscopic surgery makes airway augmentation a viable, less invasive alternative to resection. Patients were unlikely to require further therapy after 6 months of symptom‐free follow‐up.
Oropharyngeal Foreign Body After Attempted Nasal Intubation: A Case of Traumatic Middle Turbinectomy
Authors: Scott Andrew R. , Gray Stacey T.
Published: May 2007

A nasopharyngeal airway, or nasal trumpet, is an adjunctive airway device used to bypass upper airway obstruction at the level of the oral cavity or oropharynx. Although nasal trumpet placement on an awake patient may be uncomfortable, there are no reports of significant trauma from insertion. We present an unusual case of middle turbinate avulsion presenting as a foreign body in the oropharynx after several attempts at placement of a nasopharyngeal airway in an unconscious patient. We hope to raise awareness that nasal intubation in patients with altered consciousness can result in significant nasal trauma, especially after multiple attempts have failed.
Trace gas emissions from the marine biosphere
Authors: Liss Peter S
Published: May 2007

A wide variety of trace gases (e.g. dimethyl sulphide, organohalogens, ammonia, non-methane and oxygenated hydrocarbons, volatile oxygenated organics and nitrous oxide) are formed in marine waters by biological and photochemical processes. This leads in many, but not all, cases to supersaturation of the water relative to marine air concentrations and a net flux of trace gas to the atmosphere. Since the gases are often in their reduced forms in the water, once in the atmosphere they are subject to oxidation by photolysis or radical attack to form chemically reactive species that can affect the oxidizing capacity of the air. They can also lead to the formation of new particles or the growth of existing ones that can then contribute to both direct and indirect (via the formation of cloud condensation nuclei) aerosol effects on climate. These cycles are discussed with respect to their impacts on the chemistry of the atmosphere, climate and human health.

This whole topic was the subject of an extensive review (Nightingale & Liss 2003 In
Treatise in geochemistry
(eds H. D. Holland & K. K. Turekian), pp. 49–81) and what will be attempted here is a brief update of the earlier paper. There is no attempt to be comprehensive either in terms of gases covered or to give a complete review of all the recent literature. It is a personal view of recent advances both from my own research group as well as significant work from others. Questions raised at the meeting ‘Trace gas biogeochemistry and global change’ are dealt with at appropriate places in the text (rather than at the end of the piece). Discussion of each of the gases or group of gases is given in the following separate sections.
Interpreting satellite column observations of formaldehyde over tropical South America
Authors: Palmer Paul I , Barkley Michael P , Kurosu Thomas P , Lewis Alastair C , Saxton Julie E , Chance Kelly , Gatti Luciana V
Published: May 2007

Space-borne column measurements of formaldehyde (HCHO), a high-yield oxidation product of volatile organic compounds (VOCs), represent important constraints for quantifying net regional fluxes of VOCs. Here, we interpret observed distributions of HCHO columns from the Global Ozone Monitoring Experiment (GOME) over tropical South America during 1997–2001. We present the first comparison of year-long
in situ
isoprene concentrations and fire-free GOME HCHO columns over a tropical ecosystem. GOME HCHO columns and
in situ
isoprene concentrations are elevated in the wet and dry seasons, with the highest values in the dry season. Previous analysis of the
in situ
data highlighted the possible role of drought in determining the elevated concentrations during the dry season, inferring the potential of HCHO columns to provide regional-scale constraints for estimating the role of drought on isoprene emissions. The agreement between the observed annual cycles of GOME HCHO columns and Along-Track Scanning Radiometer firecount data over the Amazon basin (correlations typically greater than 0.75 for a particular year) illustrates the potential of HCHO column to provide quantitative information about biomass burning emissions.
Methane and nitrous oxide in the ice core record
Authors: Wolff Eric , Spahni Renato
Published: May 2007

Polar ice cores contain, in trapped air bubbles, an archive of the concentrations of stable atmospheric gases. Of the major non-CO
2
greenhouse gases, methane is measured quite routinely, while nitrous oxide is more challenging, with some artefacts occurring in the ice and so far limited interpretation. In the recent past, the ice cores provide the only direct measure of the changes that have occurred during the industrial period; they show that the current concentration of methane in the atmosphere is far outside the range experienced in the last 650 000 years; nitrous oxide is also elevated above its natural levels. There is controversy about whether changes in the pre-industrial Holocene are natural or anthropogenic in origin. Changes in wetland emissions are generally cited as the main cause of the large glacial–interglacial change in methane. However, changing sinks must also be considered, and the impact of possible newly described sources evaluated. Recent isotopic data appear to finally rule out any major impact of clathrate releases on methane at these time-scales. Any explanation must take into account that, at the rapid Dansgaard–Oeschger warmings of the last glacial period, methane rose by around half its glacial–interglacial range in only a few decades. The recent EPICA Dome C (Antarctica) record shows that methane tracked climate over the last 650 000 years, with lower methane concentrations in glacials than interglacials, and lower concentrations in cooler interglacials than in warmer ones. Nitrous oxide also shows Dansgaard–Oeschger and glacial–interglacial periodicity, but the pattern is less clear.
Comparing the climate effect of emissions of short- and long-lived climate agents
Authors: Shine Keith P , Berntsen Terje K , Fuglestvedt Jan S , Skeie Ragnhild Bieltvedt , Stuber Nicola
Published: May 2007

Multi-gas climate agreements require a metric by which emissions of gases with different lifetimes and radiative properties can be placed on a common scale. The Kyoto Protocol to the United Nations Framework Convention on Climate Change uses the global warming potential (GWP) as such a metric. The GWP has attracted particular criticism as being inappropriate in the context of climate policy which seeks to restrict warming below a given target, because it gives equal weight to emissions irrespective of the target and the proximity to the target. The use of an alternative metric, the time-dependent global temperature change potential (GTP), is examined for its suitability and the prospects for it including very short-lived species. It retains the transparency and relative ease of use, which are attractive features of the GWP, but explicitly includes a dependence on the target of climate policy. The weighting of emissions using the GTP is found to be significantly dependent on the scenarios of future emissions and the sensitivity of the climate system. This may indicate that the use of any GTP-based weighting in future policymaking would necessitate regular revisions, as the global-mean temperature moves towards a specified target.
Atmospheric aerosols versus greenhouse gases in the twenty-first century
Authors: Andreae Meinrat O
Published: May 2007

Looked at in a simplistic way, aerosols have counteracted the warming effects of greenhouse gases (GHG) over the past century. This has not only provided some ‘climate protection’, but also prevented the true magnitude of the problem from becoming evident. In particular, it may have resulted in an underestimation of the sensitivity of the climate system to the effect of GHG. Over the present century, the role of aerosols in opposing global warming will wane, as there are powerful policy reasons to reduce their emissions and their atmospheric lifetimes are short in contrast to those of the GHG. On the other hand, aerosols will continue to play a role in regional climate change, especially with regard to the water cycle. The end of significant climate protection by atmospheric aerosols, combined with the potentially very high sensitivity of the climate system, makes sharp and prompt reductions in greenhouse gas emissions, especially CO2, very urgent.
Thermal limits and adaptation in marine Antarctic ectotherms: an integrative view
Authors: Pörtner Hans O , Peck Lloyd , Somero George
Published: May 2007

A cause and effect understanding of thermal limitation and adaptation at various levels of biological organization is crucial in the elaboration of how the Antarctic climate has shaped the functional properties of extant Antarctic fauna. At the same time, this understanding requires an integrative view of how the various levels of biological organization may be intertwined. At all levels analysed, the functional specialization to permanently low temperatures implies reduced tolerance of high temperatures, as a trade-off. Maintenance of membrane fluidity, enzyme kinetic properties (Kmandkcat) and protein structural flexibility in the cold supports metabolic flux and regulation as well as cellular functioning overall. Gene expression patterns and, even more so, loss of genetic information, especially for myoglobin (Mb) and haemoglobin (Hb) in notothenioid fishes, reflect the specialization of Antarctic organisms to a narrow range of low temperatures. The loss of Mb and Hb in icefish, together with enhanced lipid membrane densities (e.g. higher concentrations of mitochondria), becomes explicable by the exploitation of high oxygen solubility at low metabolic rates in the cold, where an enhanced fraction of oxygen supply occurs through diffusive oxygen flux. Conversely, limited oxygen supply to tissues upon warming is an early cause of functional limitation. Low standard metabolic rates may be linked to extreme stenothermy. The evolutionary forces causing low metabolic rates as a uniform character of life in Antarctic ectothermal animals may be linked to the requirement for high energetic efficiency as required to support higher organismic functioning in the cold. This requirement may result from partial compensation for the thermal limitation of growth, while other functions like hatching, development, reproduction and ageing are largely delayed. As a perspective, the integrative approach suggests that the patterns of oxygen- and capacity-limited thermal tolerance are linked, on one hand, with the capacity and design of molecules and membranes, and, on the other hand, with life-history consequences and lifestyles typically seen in the permanent cold. Future research needs to address the detailed aspects of these interrelationships.
Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO‐406
Authors: Pan Jingxuan , Quintás‐Cardama Alfonso , Manshouri Taghi , Cortes Jorge , Kantarjian Hagop , Verstovsek Srdan
Published: May 2007

The activity of the novel tyrosine kinase inhibitor INNO‐406 against human cells with mutated KIT was investigated. Human mast cell (HMC)‐1.1 cells with juxtamembrane domain mutation V560G, and HMC‐1.2 cells with both V560G and the kinase domain mutation D816V, were treated with INNO‐406 (0.02–5.00 µM) or imatinib for 72 h. INNO‐406 and imatinib were equipotent against HMC‐1 cells regarding cell proliferation (IC50 51 nM and 75 nM, respectively), inhibition of KIT phosphorylation, and induction of apoptosis. In contrast, neither drug was effective against HMC‐1.2 cells at the dose range tested. The present results suggest clinical potential for INNO‐406 in KIT V560G‐expressing malignancies. (Cancer Sci 2007; 98: 1223–1225)
Rate of detoxification service use and its impact among a cohort of supervised injecting facility users
Authors: Wood Evan , Tyndall Mark W. , Zhang Ruth , Montaner Julio S. G. , Kerr Thomas
Published: May 2007

Background  Vancouver, Canada recently opened a medically supervised injecting facility (SIF) where injection drug users (IDU) can inject pre‐obtained illicit drugs. Critics suggest that the facility does not help IDU to reduce their drug use.

Methods  We conducted retrospective and prospective database linkages with residential detoxification facilities and used generalized estimating equation (GEE) methods to examine the rate of detoxification service use among SIF participants in the year before versus the year after the SIF opened. In secondary analyses, we used Cox regression to examine if having been enrolled in detoxification was associated with enrolling in methadone or other forms of addiction treatment. We also evaluated the impact of detoxification use on the frequency of SIF use.

Results  Among 1031 IDU, there was a statistically significant increase in the uptake of detoxification services the year after the SIF opened. [odds ratio: 1.32 (95% CI, 1.11–1.58); P = 0.002]. In turn, detoxification was associated independently with elevated rates of methadone initiation [relative hazard = 1.56 (95% CI, 1.04–2.34); P = 0.031] and elevated initiation of other addiction treatment [relative hazard = 3.73 (95% CI, 2.57–5.39); P < 0.001]. Use of the SIF declined when the rate of SIF use in the month before enrolment into detoxification was compared to the rate of SIF use in the month after discharge (24 visits versus 19 visits; P = 0.002).

Conclusions  The SIF's opening was associated independently with a 30% increase in detoxification service use, and this behaviour was associated with increased rates of long‐term addiction treatment initiation and reduced injecting at the SIF.
Genetic and environmental influences on the relationship between peer alcohol use and own alcohol use in adolescents
Authors: Fowler Tom , Shelton Katherine , Lifford Kate , Rice Frances , McBride Andrew , Nikolov Ivan , Neale Michael C. , Harold Gordon , Thapar Anita , Van Den Bree Marianne B. M.
Published: May 2007

Aims  Genetically influenced aspects of adolescent behaviour can play a role in alcohol use and peer affiliation. We explored the correlations between friends' alcohol use and adolescent own use with a genetically sensitive design.

Design  Genetic and environmental factors were estimated on adolescent reports of their friends' alcohol use and their own use and problem use of alcohol. The correlations between the genetic and environmental factors that influence friends' alcohol use and adolescent own alcohol use and problem use were also estimated.

Participants  A total of 862 twin pairs aged 11–17 years sampled from the UK population‐based Cardiff Study of All Wales and North‐west of England Twins (CaStANET).

Measurements  Data on adolescent own alcohol use and problem use and the alcohol use of their three best friends were obtained using self‐report questionnaires.

Findings  A significant genetic influence was found on adolescent friends' alcohol use (about 30%). Significant correlations of 0.60 and 0.70 were found between the genetic influences on friends' alcohol use and adolescents' own use and problem use of alcohol. Common environmental influences were almost completely correlated for friends' alcohol use and adolescents' own alcohol use and problem use (0.91 and 0.94).

Conclusions  There is considerable overlap in the common environmental and genetic factors that contribute to the relationship between adolescents' own alcohol use and that of their friends. These findings contribute to understanding of the mechanisms by which friends' alcohol use influences adolescent drinking behaviour.
Effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self‐help materials: randomized controlled trial
Authors: Sutton Stephen , Gilbert Hazel
Published: May 2007

Objective  To evaluate the effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self‐help materials.

Design  Randomized controlled trial.

Setting  The UK Quitline.

Participants  A total of 1508 current smokers and recent ex‐smokers.

Interventions  The control group received usual care (telephone counselling and an information pack sent through the post). The intervention group received in addition a computer‐generated individually tailored advice letter.

Main outcome measures  All outcomes were assessed at 6‐month follow‐up. The primary outcome measure was self‐reported prolonged abstinence for at least 3 months. Secondary outcomes were self‐reported prolonged abstinence for at least 1 month and 7‐day and 24‐hour point‐prevalence abstinence.

Results  For the sample as a whole, quit rates did not differ significantly between the two conditions. However, among the majority (n = 1164) who were smokers at baseline, quit rates were consistently higher in the intervention group: prolonged abstinence for 3 months, 12.2% versus 9.0% [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 0.96–2.04, P = 0.080); prolonged abstinence for 1 month, 16.4% versus 11.3% (OR = 1.53, 95% CI = 1.09–2.15, P = 0.013); 7‐day point‐prevalence abstinence, 18.9% versus 12.7% (OR = 1.59, 95% CI = 1.15–2.19, P = 0.004); 24‐hour point‐prevalence abstinence, 20.9% versus 15.4% (OR = 1.45, 95% CI = 1.07–1.96, P = 0.015).

Conclusions  The results for the smokers are encouraging in showing a small but useful effect of the tailored letter on quit rate. Versions of the tailoring program could be used on the web and in general practices, pharmacies and primary care trusts.
Stability of subtypes of natural recovery from alcohol dependence after two years
Authors: Bischof Gallus , Rumpf Hans‐Jürgen , Meyer Christian , Hapke Ulfert , John Ulrich
Published: May 2007

Aims  The lack of consistent findings in studies on natural recovery from alcohol dependence may reflect heterogeneous subgroups according to social support and problem severity. In a previous report, we identified the following groups: high severity of dependence, low alcohol‐related problems and low social support (low problems–low support: LPLS), high severity of dependence, high alcohol‐related problems and medium social support (high problems–medium support: HPMS) and high social support, late age of onset, low severity of dependence and low alcohol‐related problems (low problems–high support: LPHS). However, little is known about the trajectories of these groups. The aim of the present study is to analyse the stability of these three groups report on longer‐term outcomes.

Design and participants  A cohort of initially untreated remitters recruited through media solicitation (n = 178) was followed‐up after 24 months.

Measurements  Personal interviews using standardized instruments including social support together with interview data from collaterals.

Results  Differences between the cluster groups in social support diminished over time; however, even at follow‐up, LPLS revealed less social support by friends when compared to LPHS and showed significant higher rates of relapse and utilization of formal help than did HPHS and LPHS.

Conclusions  Data show that the interplay between psychosocial resources and substance‐related problems may still account for differences in trajectories of naturally remitted individuals in a 2‐year follow‐up.
Equity of access to treatment, and barriers to treatment for illicit drug use in Australia
Authors: Digiusto Erol , Treloar Carla
Published: May 2007

Aims and design  This study investigated equity of access to treatment and barriers to treatment for illicit drug use, using Andersen's behavioural model of health service utilization.

Setting and participants  The study involved 492 drug users who had received treatment and 193 who had not.

Measurements  Participants were interviewed to gather data relating to 19 predisposing, need and enabling variables.

Findings  Never‐treated participants exhibited less need for treatment than those who had received treatment. They experienced less negative emotion, used their main drug less often, had fewer drug‐related health problems and fewer drug‐using friends, were less likely to have blood‐borne virus infections and were more likely to be using drugs for ‘fun’. They also had more negative attitudes towards drug treatment staff, were less likely to believe that appropriate treatment was available and less likely to believe that professional help was necessary to get off drugs. Prevalence of physical and mental health problems was high in both groups.

Conclusions  The study documented significant unmet treatment need and identified several sources of inequity and barriers to treatment that would be amenable to policy and service development. Drug user organizations and peer educators and motivational interventions in primary care settings should be utilized to market the nature and benefits of treatment effectively, and to address the causes of drug users' negative attitudes towards treatment.
Identification of the human cytochromes P450 catalysing the rate‐limiting pathways of gliclazide elimination
Authors: Elliot David J. , Suharjono  , Lewis Benjamin C. , Gillam Elizabeth M. J. , Birkett Donald J. , Gross Annette S. , Miners John O.
Published: May 2007

What is already known about this subject

• Gliclazide is a widely used oral hypoglycaemic agent.

• The major metabolites of gliclazide formedin vivohave been identified.

• However, the cytochrome P450 enzymes catalysing the rate‐limiting pathways of gliclazide elimination are unknown.

What this study adds

• CYP2C9 is the major enzyme involved in the various hydroxylation pathways of gliclazide, although a contribution of CYP2C19 to tolymethylhydroxylation, the major metabolic route, cannot be discounted.

• Factors known to influence CYP2C9 activity will provide the main source of variability in gliclazide pharmacokinetics.

Aims

To identify the human cytochrome P450 (CYP) enzymes responsible for the formation of the 6β‐hydroxy (6β‐OHGz), 7β‐hydroxy (7β‐OHGz) and hydroxymethyl (MeOH‐Gz) metabolites of gliclizide (Gz).

Methods

6β‐OHGz, 7β‐OHGz and MeOH‐Gz formation by human liver microsomes and a panel of recombinant human P450s was measured using a high‐performance liquid chromatography procedure, and the kinetics of metabolite formation was determined for each pathway. Effects of prototypic CYP enzyme selective inhibitors were characterized for each of the microsomal metabolic pathways.

Results

Microsomes from six human livers converted Gz to its 6β‐OHGz, 7β‐OHGz, and MeOH‐Gz metabolites, with respective mean (± SD)Kmvalues of 461 ± 139, 404 ± 143 and 334 ± 75 µmand meanVmaxvalues of 130 ± 55, 82 ± 31 and 268 ± 115 pmol min−1 mg−1, respectively.Vmax/Kmratios for the microsomal reactions parallelled relative metabolite formationin vivo. Sulfaphenazole inhibited microsomal 6β‐OHGz, 7β‐OHGz and MeOH‐Gz formation by 87, 83 and 64%, respectively, whereas S‐mephenytoin caused significant inhibition (48%) of only MeOH‐Gz formation. Recombinant CYP2C9, CYP2C18 and CYP2C19 catalysed all hydroxylation pathways, whereas CYP2C8 formed only 6β‐OHGz and 7β‐OHGz.

Conclusion

Taken together, the results indicate that CYP2C9 is the major contributor to Gz metabolic clearance, although CYP2C19 may also be involved in MeOH‐Gz formation (the major metabolic pathway). Factors known to influence CYP2C9 activity will provide the main source of variability in Gz pharmacokinetics.
Directed engineering of umbilical cord blood stem cells to produce C‐peptide and insulin
Authors: Denner L. , Bodenburg Y. , Zhao J. G. , Howe M. , Cappo J. , Tilton R. G. , Copland J. A. , Forraz N. , McGuckin C. , Urban R.
Published: May 2007

Abstract.  Objectives: In this study, we investigated the potential of umbilical cord blood stem cell lineages to produce C‐peptide and insulin. Materials and methods: Lineage negative, CD133+ and CD34+ cells were analyzed by flow cytometry to assess expression of cell division antigens. These lineages were expanded in culture and subjected to an established protocol to differentiate mouse embryonic stem cells (ESCs) toward the pancreatic phenotype. Phase contrast and fluorescence immunocytochemistry were used to characterize differentiation markers with particular emphasis on insulin and C‐peptide. Results: All 3 lineages expressed SSEA‐4, a marker previously reported to be restricted to the ESC compartment. Phase contrast microscopy showed all three lineages recapitulated the treatment‐dependent morphological changes of ESCs as well as the temporally restricted expression of nestin and vimentin during differentiation. After engineering, each isolate contained both C‐peptide and insulin, a result also obtained following a much shorter protocol for ESCs. Conclusions: Since C‐peptide can only be derived from de novo synthesis and processing of pre‐proinsulin mRNA and protein, we conclude that these results are the first demonstration that human umbilical cord blood‐derived stem cells can be engineered to engage in de novo synthesis of insulin.
A study of enamel matrix proteins on differentiation of porcine bone marrow stromal cells into cementoblasts
Authors: Song A. M. , Shu R. , Xie Y. F. , Song Z. C. , Li H. Y. , Liu X. F. , Zhang X. L.
Published: May 2007

Abstract.  Objective: To further explore the role of enamel matrix proteins (EMPs) in periodontal regeneration, we have used porcine bone marrow‐derived stromal cells (BMSCs) to observe whether the EMPs could have an effect on their differentiation into cementoblasts. Materials and methods: In this study, EMPs were extracted from porcine tooth germs by the use of acetic acid. BMSCs obtained from porcine iliac marrow aspiration were inoculated onto the surface of autologous root slices treated with or without EMPs. Following 7‐day co‐culture, all the BMSC‐seeded root slices, with their respective non‐cell‐inoculated control specimens, were pocketed with expanded polytetrafluoroethylene membrane and were transplanted subcutaneously into 11 nude mice. The animals were sacrificed after 3 and 8 weeks, and the new specimens were processed for haematoxylin and eosin staining. Results: Histological analysis demonstrated new cellular cementum‐like tissue formed along EMP‐treated root slices. Conclusion: Our work has indicated for the first time, differentiation of BMSCs into cementoblasts using an EMP‐based protocol.
Soil and human health: an epidemiological review
Authors: Hough R. L.
Published: May 2007

Two different approaches have been used to study relationships between soil and human health: aggregate‐ and individual‐level. Aggregate‐level is the primary approach used in the geosciences and broadly relates spatial soil characteristics to geographic incidence of disease. However, this may not be appropriate for a wide range of exposures and disease outcomes. For example, many diseases with long latency periods are associated with early life or cumulative exposure to the causative agent, rather than an individual’s current geographical location. Public health scientists and epidemiologists often refer to aggregate‐level studies as being ‘hypothesis forming’, and consider individual‐level approaches as the ‘gold standard’ for investigating causes of human health outcomes. This paper investigates the appropriateness of individual‐level study for disease outcomes associated with soil by reviewing the weight of evidence from individual‐level studies that have included exposure to soil as a risk‐factor for disease. The majority of these studies are very specific, inspired by explicit case reports and medical records. The review showed that exposure to soil was implicated mainly in the spread of enteric parasites, but also in the incidence of certain cancers, bacterial infections, and mycoses. There was little evidence for specific soil contaminants as causative agents of disease at an individual level but there was also little evidence contrary to this. Further individual‐level studies into soil:human health scenarios are required in order to derive more appropriate dose‐effect relationships for regulatory science and risk assessment.
Mannose‐binding lectin without the aid of its associated serine proteases alters lipopolysaccharide‐mediated cytokine/chemokine secretion from human endothelial cells
Authors: Kang Hee Jung , Lee Sun‐Mi , Lee Hyeon‐Hwa , Kim Ji Yeon , Lee Byung‐Chul , Yum Jung‐Sun , Moon Hong Mo , Lee Bok Luel
Published: May 2007

Coupling between certain pathogen‐associated molecular patterns and corresponding pattern recognition receptors of endothelial cells is important for the mediation of vascular inflammatory responses. Mannose‐binding lectin (MBL) recognizes certain carbohydrate structures of microbes and subsequently activates the complement system as well as facilitates the phagocytosis of targets. We investigated whether MBL can intervene in the interaction between bacterial lipopolysaccharide (LPS) and endothelial cells to modulate subsequent inflammatory responses. In response to LPS, human umbilical vein endothelial cells (HUVEC) produced various cytokines/chemokines. Addition of the purified human MBL/MBL‐associated serine proteases (MASP) complex or recombinant human MBL enhanced LPS‐mediated cytokine/chemokine secretion by HUVEC, including interleukin‐8 (IL‐8), IL‐6 and monocyte chemoattractant protein‐1 in a dose‐dependent manner. This enhancing effect was ameliorated by the addition of anti‐MBL antibody or mannan. Among the cytokines/chemokines we analysed, IL‐6 showed the greatest increase of secretion in the presence of native MBL/MASP complex or recombinant MBL. MBL, regardless of its association with MASP, alters LPS‐mediated cytokine/chemokine secretion of HUVEC. Besides the well‐known functions of MBL, to activate the lectin–complement pathway and to facilitate clearance of targets, alteration of cytokine/chemokine secretion may provide an additional role for MBL in modulating vascular inflammation.