bluuebunny/crossref_metadata_2025 huggingface dataset:
EGenBio: A Data Management System for Evolutionary Genomics and Biodiversity
Authors: Nahum Laila A , Reynolds Matthew T , Wang Zhengyuan O , Faith Jeremiah J , Jonna Rahul , Jiang Zhi J , Meyer Thomas J , Pollock David D
Published: September 2006

Background

Evolutionary genomics requires management and filtering of large numbers of diverse genomic sequences for accurate analysis and inference on evolutionary processes of genomic and functional change. We developed E volutionary Gen omics and Bio diversity (EGenBio; http://egenbio.lsu.edu) to begin to address this.

Description

EGenBio is a system for manipulation and filtering of large numbers of sequences, integrating curated sequence alignments and phylogenetic trees, managing evolutionary analyses, and visualizing their output. EGenBio is organized into three conceptual divisions, Evolution, Genomics, and Biodiversity. The Genomics division includes tools for selecting pre-aligned sequences from different genes and species, and for modifying and filtering these alignments for further analysis. Species searches are handled through queries that can be modified based on a tree-based navigation system and saved. The Biodiversity division contains tools for analyzing individual sequences or sequence alignments, whereas the Evolution division contains tools involving phylogenetic trees. Alignments are annotated with analytical results and modification history using our PRAED format. A miscellaneous Tools section and Help framework are also available. EGenBio was developed around our comparative genomic research and a prototype database of mtDNA genomes. It utilizes MySQL-relational databases and dynamic page generation, and calls numerous custom programs.

Conclusion

EGenBio was designed to serve as a platform for tools and resources to ease combined analysis in evolution, genomics, and biodiversity.
Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins
Authors: Tenenbaum Alexander , Fisman Enrique Z , Motro Michael , Adler Yehuda
Published: September 2006

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B) – emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP – Bezafibrate Infarction Prevention study, HHS – Helsinki Heart Study, VAHIT – Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD – Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy – selected on the basis of their safety and effectiveness – may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.
Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheumatoid arthritis
Authors: Jarvis James N , Petty Howard R , Tang Yuhong , Frank Mark Barton , Tessier Philippe A , Dozmorov Igor , Jiang Kaiyu , Kindzelski Andrei , Chen Yanmin , Cadwell Craig , Turner Mary , Szodoray Peter , McGhee Julie L , Centola Michael
Published: September 2006

Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects of the disease that suggest equally important contributions of the innate immune system. We used gene expression arrays and computer modeling to examine the function in neutrophils of 25 children with polyarticular JRA. Computer analysis identified 712 genes that were differentially expressed between patients and healthy controls. Computer-assisted analysis of the differentially expressed genes demonstrated functional connections linked to both interleukin (IL)-8- and interferon-γ (IFN-γ)-regulated processes. Of special note is that the gene expression fingerprint of children with active JRA remained essentially unchanged even after they had responded to therapy. This result differed markedly from our previously reported work, in which gene expression profiles in buffy coats of children with polyarticular JRA reverted to normal after disease control was achieved pharmacologically. These findings suggest that JRA neutrophils remain in an activated state even during disease quiescence. Computer modeling of array data further demonstrated disruption of gene regulatory networks in clusters of genes modulated by IFN-γ and IL-8. These cytokines have previously been shown to independently regulate the frequency (IFN-γ) and amplitude (IL-8) of the oscillations of key metabolites in neutrophils, including nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high-speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to induce only frequency fluctuations of NAD(P)H and superoxide ion induced both frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding that was observed in children with both active (n = 4) and inactive (n = 2) JRA. A subpopulation of polyarticular JRA neutrophils are in a chronic, activated state, a state that persists when the disease is well controlled pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an intrinsic defect in the regulation of metabolic oscillations and superoxide ion production. Our data are consistent with the hypothesis that neutrophils play an essential role in the pathogenesis of polyarticular JRA.
On stochastic recursive equations of sum and max type
Authors: Rüschendorf Ludger
Published: September 2006

In this paper we consider stochastic recursive equations of sum type, , and of max type, , where Ai, bi, and b are random, (Xi) are independent, identically distributed copies of X, and denotes equality in distribution. Equations of these types typically characterize limits in the probabilistic analysis of algorithms, in combinatorial optimization problems, and in many other problems having a recursive structure. We develop some new contraction properties of minimal Ls-metrics which allow us to establish general existence and uniqueness results for solutions without imposing any moment conditions. As an application we obtain a one-to-one relationship between the set of solutions to the homogeneous equation and the set of solutions to the inhomogeneous equation, for sum- and max-type equations. We also give a stochastic interpretation of a recent transfer principle of Rösler from nonnegative solutions of sum type to those of max type, by means of random scaled Weibull distributions.
Stochastic orders and majorization of mean order statistics
Authors: de la Cal Jesús , Cárcamo Javier
Published: September 2006

We characterize the (continuous) majorization of integrable functions introduced by Hardy, Littlewood, and Pólya in terms of the (discrete) majorization of finite-dimensional vectors, introduced by the same authors. The most interesting version of this result is the characterization of the (increasing) convex order for integrable random variables in terms of majorization of vectors of expected order statistics. Such a result includes, as particular cases, previous results by Barlow and Proschan and by Alzaid and Proschan, and, in a sense, completes the picture of known results on order statistics. Applications to other stochastic orders are also briefly considered.
A matrix-analytic approach to the N-player ruin problem
Authors: Swan Yvik C. , Bruss F. Thomas
Published: September 2006

Consider N players, respectively owning x1, x2, …, xN monetary units, who play a sequence of games, winning from and losing to each other integer amounts according to fixed rules. The sequence stops as soon as (at least) one player is ruined. We are interested in the ruin process of these N players, i.e. in the probability that a given player is ruined first, and also in the expected ruin time. This problem is called the N-player ruin problem. In this paper, the problem is set up as a multivariate absorbing Markov chain with an absorbing state corresponding to the ruin of each player. This is then discussed in the context of phase-type distributions where each phase is represented by a vector of size N and the distribution has as many absorbing points as there are ruin events. We use this modified phase-type distribution to obtain an explicit solution to the N-player problem. We define a partition of the set of transient states into different levels, and on it give an extension of the folding algorithm (see Ye and Li (1994)). This provides an efficient computational procedure for calculating some of the key measures.
Ergodic properties and ergodic decompositions of continuous-time Markov processes
Authors: Costa O. L. V. , Dufour F.
Published: September 2006

In this paper we obtain some ergodic properties and ergodic decompositions of a continuous-time, Borel right Markov process taking values in a locally compact and separable metric space. Initially, we assume that an invariant probability measure (IPM) μ exists for the process and, without making any further assumptions on the transition kernel, obtain some characterization results for the convergence of the expected occupation measure to a limit kernel. Under the same assumption, we present the so-called Yosida decomposition. Next, instead of assuming the existence of an IPM, we assume that the Markov process satisfies a certain condition, named the T'-condition. Under this condition it is shown that the Foster-Lyapunov criterion is necessary and sufficient for the existence of an IPM and that the process admits a Doeblin decomposition. Furthermore, it is shown that in this case the set of ergodic probability measures is countable and that every probability measure for the Markov process is nonsingular with respect to the transition kernel.
Nonexponential asymptotics for the solutions of renewal equations, with applications
Authors: Yin Chuancun , Zhao Junsheng
Published: September 2006

Nonexponential asymptotics for solutions of two specific defective renewal equations are obtained. These include the special cases of asymptotics for a compound geometric distribution and the convolution of a compound geometric distribution with a distribution function. As applications of these results, we study the asymptotic behavior of the demographic birth rate of females, the perpetual put option in mathematics of finance, and the renewal function for terminating renewal processes.
Imperfect maintenance in a generalized competing risks framework
Authors: Doyen Laurent , Gaudoin Olivier
Published: September 2006

In this paper we present a general framework for the modelling of the process of corrective and condition-based preventive maintenance actions for complex repairable systems. A new class of models is proposed, the generalized virtual age models. On the one hand, these models generalize Kijima's virtual age models to the case where both preventive and corrective maintenances are present. On the other hand, they generalize the usual competing risks models to imperfect maintenance actions which do not renew the system. A generalized virtual age model is defined by both a sequence of effective ages which characterizes the effects of both types of maintenance according to a classical virtual age model, and a usual competing risks model which characterizes the dependency between the two types of maintenance. Several particular cases of the general model are derived.
Maximal avalanches in the Bak-Sneppen model
Authors: Gillett Alexis , Meester Ronald , van der Wal Peter
Published: September 2006

We study the durations of the avalanches in the maximal avalanche decomposition of the Bak-Sneppen evolution model. We show that all the avalanches in this maximal decomposition have infinite expectation, but only ‘barely’, in the sense that if we made the appropriate threshold a tiny amount smaller (in a certain sense), then the avalanches would have finite expectation. The first of these results is somewhat surprising, since simulations suggest finite expectations.
The correlation of the maxima of correlated Brownian motions
Authors: Rogers L. C. G. , Shepp Larry
Published: September 2006

We obtain an expression for the correlation of the maxima of two correlated Brownian motions.
Limiting crossing probabilities of random fields
Authors: Pereira L. , Ferreira H.
Published: September 2006

Random fields on , with long-range weak dependence for each coordinate individually, usually present clustering of high values. For each one of the eight directions in , we formulate restriction conditions on local occurrence of two or more crossings of high levels. These smooth oscillation conditions enable computation of the extremal index as a clustering measure from the limiting mean number of crossings. In fact, only four directions must be inspected since for opposite directions we find the same local path crossing behaviour and the same limiting mean number of crossings. The general theory is illustrated with several 1-dependent nonstationary random fields.
Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium
Authors: Fairbank Pamela D. , Lee Chanjae , Ellis Avegiyel , Hildebrand Jeffrey D. , Gross Jeffrey M. , Wallingford John B.
Published: September 2006

Shroom family proteins have been implicated in the control of the actin cytoskeleton, but so far only a single family member has been studied in the context of developing embryos. Here, we show that the Shroom-family protein,Shroom2 (previously known as APXL) is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. In Xenopus embryos that lack Shroom2 function, we observed defects in pigmentation of the eye that stem from failure of melanosomes to mature and to associate with the apical cell surface. Ectopic expression of Shroom2 in naïve epithelial cells facilitates apical pigment accumulation, and this activity specifically requires the Rab27a GTPase. Most interestingly, we find that Shroom2, like Shroom3 (previously called Shroom),is sufficient to induce a dramatic apical accumulation of the microtubule-nucleating protein γ-tubulin at the apical surfaces of naïve epithelial cells. Together, our data identify Shroom2 as a central regulator of RPE pigmentation, and suggest that, despite their diverse biological roles, Shroom family proteins share a common activity. Finally,because the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2mutations may be a contributing factor in these human visual system disorders.
A new method for the classification of invasive cervical cancer screening histories
Authors: Bagnall Helen , Pearmain Philippa , Clare Joanne , Lawrence Gill
Published: September 2006

Objectives: To examine the ability of existing classification systems to provide screening histories for invasive cervical cancers which can be used in the evaluation of the NHS Cervical Screening Programme (NHSCSP), and to provide the diagnostic route data item required for the National Cancer Data Set (NCDS).

Methods: The ability of existing classification systems to derive unique, consistent screening histories for a cohort of invasive cervical cancers diagnosed in the West Midlands region in the period 2000–03 was tested using two separate timelines for women on normal routine recall (usually 3 or 5 years) and those on early recall having had an inadequate, low-grade abnormal or negative smear.

Results: Neither of the existing classification systems was capable of adequately categorizing all invasive cervical cancers. An original classification system incorporating features from the existing systems was therefore developed. This system includes both a 'screening status' component that essentially describes the status of a woman's interaction with the NHSCSP at the time her cancer was diagnosed, and a 'screening history' component that describes the results of previous screening tests.

Conclusions: National adoption of this new screening histories classification system would provide a detailed, consistent, nationally comparable screening history for all invasive cervical cancers which can be used in the national and regional evaluation of the NHSCSP and in local audit by clinical teams supplemented by histology and colposcopy data. The classification categories could be collapsed down to provide the diagnostic route data item required for the NCDS.
Diabetes retinopathy screening: audit of equity in participation and selected outcomes in South East London
Authors: Millett Christopher , Dodhia Hiten
Published: September 2006

Objectives: To assess uptake of the diabetes retinopathy screening programme in South East London and examine variation in attendance and screening outcomes.

Methods: Cross-sectional study of patients on a centralized disease register invited for retinal screening during 2003. The influence of age, gender, deprivation, region of birth and type of diabetes on screening attendance and outcomes was assessed.

Results: An estimated 46% of residents with known diabetes (9750/21,104) were offered digital retinopathy screening during 2003. In all, 88.9% of patients who were invited for screening attended. Attendance rates were significantly lower in younger patients (≤40 years), in those with type 1 diabetes and in patients residing in areas with the highest levels of deprivation. A total of 28.9% of patients had background retinopathy or worse during 2003. Retinopathy was more common in older patients (>40 years) and in individuals with type 1 diabetes after adjusting for other factors. Patients born outside the United Kingdom and the Republic of Ireland were significantly more likely to present with retinopathy.

Conclusions: This study identified considerable inequity in the delivery of a local diabetic retinopathy screening programme. Equity audits should form an integral component of ongoing quality assurance monitoring of retinopathy screening programmes.
Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes
Authors: Marks D , Thorogood M , Neil S M , Humphries S E , Neil H A W
Published: September 2006

Objectives: To determine what proportion of cases of heterozygous familial hypercholesterolaemia would be identified by cascade screening conducted by a specialist hospital clinic, and by how much this would increase the prevalence of diagnosed cases.

Setting: Hospital clinic serving a population of 605,900 in Oxfordshire, UK

Methods: A specialist nurse obtained details of living first-degree relatives from 227 adult patients with heterozygous familial hypercholesterolaemia currently or previously attending Oxford lipid clinic after excluding 79 adults without relatives living in Oxfordshire and 48 children. Index cases were asked to invite relatives resident in Oxfordshire for testing.

Results: A total of 227 index cases had 1075 first-degree relatives, including 442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded 171 previously screened adults and 46 for other reasons. Among 225 eligible adult relatives, 28 responders (12%) planned to consult their general practitioner and 52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted them tested. The positive diagnostic rate was 29% (15/52) in adults and 32% (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000 (95% confidence intervals [CI] 0.52–0.65) to 0.67/1000 (95% CI 0.60–0.73), representing 33.5% of predicted cases.

Conclusions: Cascade screening conducted by a specialist hospital clinic within its population catchment area did not substantially increase the prevalence of diagnosed familial hypercholesterolaemia. To maximize response rates, clinic staff need to approach relatives directly. Validated age, sex and country-specific diagnostic criteria should be defined, possibly with access to DNA-based tests, to help resolve diagnostic uncertainty.
Screening for sickle cell disease on dried blood: a new approach evaluated on 27,000 Belgian newborns
Authors: Boemer François , Vanbellinghen Jean-François , Bours Vincent , Schoos Roland
Published: September 2006

Setting: Early diagnosis of sickle cell disease decreases morbidity. However, cost-effective screening programmes are not yet available.

Methods: We explored the feasibility of systematic screening performed on dried blood harvested from five-day-old newborns.

Results: A total of 27,010 samples were collected in Belgian maternity units between June 2003 and February 2005, and the presence of haemoglobin (Hb) C or S in the eluted blood was examined by an enzyme-linked immunosorbent assay (ELISA) test performed with a monoclonal antibody detecting both mutated forms. As this antibody slightly cross-reacts with Hb A, better specificity is achieved if the test is performed not later than day 5. Among the 27,010 samples, 132 (0.49%) were positive. Molecular biology tests performed on dried blood from positive samples showed that 106 of these babies were heterozygotes for the Hb S mutation and three were heterozygotes for the Hb C mutation, while three newborns were SS homozygotes (0.011%). Seventeen samples (0.063%) were false-positives as we could not detect any mutation.

Conclusions: We have developed a new immunological approach in the field of haemoglobinopathy neonatal screening. This ELISA test is cheap (€0.2/test or €1800/detected SS homozygote) and could be centralized. Its cost-effectiveness in the whole Belgian population is comparable with that of screening for phenylketonuria or congenital adrenal hyperplasia. Further improvements should obviously be achieved in order to better discriminate heterozygotes and homozygotes, but the accessibility and the low cost of the test are relevant arguments for the screening extension in a wide range of countries, especially in Central Africa.
The effect of screening programmes on the treatment of benign breast neoplasms: observations from current practice in Italy
Authors: Rossi Paolo Giorgi , Federici Antonio , Farchi Sara , Chini Francesco , Barca Alessandra , Guasticchi Gabriella , Borgia Piero
Published: September 2006

Purpose: In the Lazio region, Italy, mammographic screening programmes were gradually activated from 1999 to 2003, providing an opportunity to compare two unselected populations in the same time period: women who were contacted in writing, and those who had not been contacted. In this study, we compare the incidences of treatments for benign and malignant neoplasms in the two groups.

Methods: The target population was women aged 50–69 years. We linked all incident cases of surgery for benign and malignant breast neoplasms, from the Hospital Information System (1999–2003) to the Mammographic Screening Information System (1999–2001). We calculated incidence, adjusted for age and standardized breast cancer mortality ratio in each area of residence, for benign and malignant neoplasms surgery in non-yet-contacted and contacted woman. Incidence for contacted women was calculated for the two years following initial contact.

Results: The target population in Lazio is 681,000; 116,000 women were contacted during the study period and 3252 malignant and 1566 benign neoplasms were surgically treated. Annual incidence was, respectively, 2.0/1000 and 1.1/1000 for malignant and benign neoplasms in women not contacted, and, respectively, 2.9/1000 and 1.1/1000 in the contacted population. Among the contacted group, annual incidence was 4.3/1000 and 1.5/1000 in compliant women, and 2.0/1000 and 0.9/1000 in non-compliant women. About one-half of the surgeries for benign neoplasms in compliant women were treated against the recommendation of the screening programme.

Conclusions: The implementation of the screening programme did not increase the incidence of treatment for benign neoplasms, and detected 50% more malignant neoplasms.
Overpaid CEOs and Underpaid Managers: Fairness and Executive Compensation
Authors: Wade James B. , O'Reilly Charles A. , Pollock Timothy G.
Published: September 2006

In this study we propose that norms of fairness are salient to top decision makers and show that over- or underpayment of the CEO cascades down to lower organizational levels. Moreover, it appears that CEOs use their own power not only to increase their own salaries, but also those of their subordinates. One implication of such a process may be that the overpayment of a top executive has higher costs than have previously been realized. We also find evidence suggesting that CEOs serve as a key referent for employees in determining whether their own situation is “fair,” and this influences their reactions to their own compensation. More specifically, we find that when lower-level managers are underpaid relative to the CEO—that is, underpaid more than the CEO or overpaid less—they are more likely to leave the organization. Results obtained from testing our hypotheses on a sample of more than 120 firms over a five-year period demonstrates the importance of considering fairness in the setting of CEO pay. Implications for the design of executive compensation packages are discussed.
A method of meatoplasty
Authors: Anthony Walter P.
Published: September 2006

An adequate external auditory meatus is necessary to prevent accumulation of debris in cases of atresia and stenosis and to facilitate good postoperative care following tympanoplasty and mastoidectomy. A method of enlarging the meatus which has been used in almost 400 operations is presented.

An endaural incision is made which is extended superiorly above the pinna. The upper half of the auricular cartilage is mobilized. In closing this incision the relationship of the superior edge of the tragus is advanced superiorly and the crus of the helix is moved inferiorly, thus opening the meatus.

This method results in an adequate external meatus without the removal of conchal cartilage and eliminates the possibility of perichondritis.
Eversion of the lining membrane of the vestibule
Authors: Shea John J.
Published: September 2006

The pressure gradient of nearly 1,000 mm of water that can develop between the perilymph and the middle ear makes the choice of material used to seal the oval window after the stapes is removed of great importance.

This potential pressure gradient is the sum of the 350 mm of water positive pressure that can develop in the perilymph when the head is down and the 600 mm of water negative pressure that can develop in the middle ear when the Eustachian tube is blocked, and the air is absorbed.

As a result of this potential pressure gradient after the stapes is removed, there is a definite tendency for the oval window to remain open or reopen later. The lining membrane of the vestibule that does form in time has a tendency to evert and displace or otherwise inactivate the prosthesis.

A full report will be made of how these pressures develop and the resulting hearing loss due to perilymph fistula and eversion of the lining membrane of the vestibule that have been observed.
Facial nerve and stapes anomaly: A case report
Authors: Mcclerkin William W. , Schuknecht Harold F.
Published: September 2006

A 17‐year‐old white female presented with a unilateral conductive hearing loss which had been present since birth. The external auditory canal and tympanic membrane appeared to be normal, and the manubrium was mobile.

Exploratory tympanotomy revealed the horizontal segment of the facial nerve to be dehiscent and displaced inferiorly, thus occupying the oval window niche. The nerve was interposed between a rudimentary crural arch and a fixed stapes footplate. The malleus and incus were normal. A burr hole was made into the vestibule at the superior edge of the oval window; however the utricular macula was encountered, and further attempts at reconstruction were discarded. Other procedures, such as rerouting the facial nerve in association with stapedectomy or fenestration of the lateral semicircular canal, were considered to be inappropriate for this case of unilateral deafness.
The electron transport system in the cochlear hair cell: The ultrastructural cytochemistry of respiratory enzymes in hair cell mitochondria of the Guinea pig.
Authors: Spector Gershon J. , Carr Charles
Published: September 2006

A systematic analysis of the electron transport system in hair cell mitochondria of the guinea pig is presented. This is the first such attempt to explain the underlying oxido‐reduction mechanisms for the aerobic metabolism of the hair cell. The study is based on recent developments in ultrastructural cytochemical techniques. These techniques have been modified, expanded, and applied to the study of the inner ear.

The use of distyryl ditetrazolium salt (DS‐NBT) for dehydrogenase experiments and 3,31 diaminobenzidine (DAB) for cytochrome experiments allows precise localization of enzyme activities due to the amorphous electron opaque reaction products which do not obliterate ultrastructural detail. Rigorous morphologic and cytochemical controls are employed to confirm the specificity of the reactions studied.

Enzyme systems from the three major classes of oxido‐reduction respiratory chain enzymes are studied: the pyridine‐linked dehydrogenases — lactic acid dehydrogenase, flavin‐linked dehydrogenases — succinic dehydrogenase and NADH2‐diaphorase, and cytochromes — cytochrome oxidase. Our results indicate that the respiratory oxido‐reduction reactions, from NADH to cytochrome oxidase are located on the inner mitochondrial membrane, in the outer compartment and the intracristate space. This electron transport system has direction (vectorial metabolism) and anisotropy (spatial orientation). Its properties are best explained by the chemiosmotic hypothesis.

The hair cell mitochondria are cytochemically indistinguishable (with regard to these four reactions) from free liver mitochondria. A cursory review of mitochondria of the stria vascularis, supporting cells of the organ of Corti, and the vestibular system reveals a similar, ultrastructural cytochemical picture. The results of these experiments are in close agreement with the studies on rat heart, liver, and muscle mitochondria, and with the accepted biochemical fractionation data.

The question of whether the mitochondria can perform mechanical work, in terms of conformational changes, is open to debate. Our results demonstrate that it is hazardous to interpret the morphologic mitochondrial alterations in terms of functional activity. This is due to the inherent artifacts in all morphologic experiments which are dependent on prefixation and osmolarity alterations.
The changes in phase lag during sinusoidal angular rotation following labyrinthectomy in the cat.
Authors: Moran Willard B.
Published: September 2006

The purpose of this study was to evaluate the cat following unilateral labyrinthectomy to see if changes in the phase lag occurred during sinusoidal angular rotation. The phase lag is felt to occur because the action of the cupla and endolymph are heavily damped causing the reversal of a nystagmus direction to lag behind the actual change of the direction of the rotational force. Fourteen cats were used as normal control and four unilateral labyrinthectomized cats were evaluated. The results indicate that unilateral labyrinthectomy does have an effect on the phase lag when sinusoidal angular rotation is used.
A study of tumors of the parapharyngeal space.
Authors: Work Walter P. , Hybels Roger L.
Published: September 2006

A retrospective study of patients with parapharyngeal tumors has been completed, and this report concerns 40 patients cared for during the years 1962–1973. The parapharyngeal space is a potential anatomical space with three rigid walls so that growth of a tumor proceeds either medially or inferiorly or both. This pattern of growth accounts for the distinct clinical appearance of a displaced palate and pharynx. As noted in this series of cases, Table I depicts the types of tumors which involved the parapharyngeal space. Eighty‐two percent of the cases presented with benign tumors. On the other hand, 18 percent of the patients had malignant tumors.

Benign mixed cell tumors and schwannomas are the most commonly noted benign tumors. Several cases presented with unusual tumors.

In most patients the tumor was discovered on routine physical examination. Arteriography has become a valuable and safe diagnostic study. These procedures often help the surgeon to determine the extent of tumor, vessel displacement and the possibility of chemodectoma and even malignancy in some patients.

An external surgical approach is recommended for surgical excision of the benign parapharyngeal tumor in most patients. Intraoral incisional biopsy in patients with benign tumors is to be avoided because of dangers of vessel and nerve injury as well as “seeding” of the biopsy site. On the other hand, malignancy may be diagnosed with incisional biopsy either performed externally or intraorally, depending on the judgment of the surgeon as to the anatomical location and site of the neoplasm. In final analysis the external surgical approach allows the surgeon systematically to identify tumor, important cranial nerves including the facial nerve and the great vessels. Every effort should be made by the surgeon not to violate the capsule of a benign mixed tumor during its removal. Removal of tumor is enhanced frequently by preliminary excision of the submandibular gland, vessel ligation and mandibulotomy. In the latter instance the patient must undergo tracheostomy. Postoperative cranial nerve palsies occurred for the most part in those patients who underwent surgical excision of schwannomas. These tumors originated from the vagus nerve or cervical sympathetic chain. Sacrifice of these nerves during removal caused little morbidity.

Follow‐up examinations in this series of patients revealed that if benign tumors are removed from the parapharyngeal space in a deliberately planned manner, recurrence rates are extremely low. In patients who are treated for malignant lesions, prognosis must be guarded, as mortality rates are high regardless of the type of therapy.
The use of proplasttm in otologic surgery.
Authors: Shea John J. , Homsy Charles A.
Published: September 2006

The use of alloplastic implants in otolaryngologic and maxillofacial surgery has a long history. In recent years, collaborative efforts among materials scientists, surgeons, and dentists have elucidated biological and functional criteria for implant materials.

Using these criteria, a new alloplastic material, ProplastTM was developed, the first of a new generation of materials for implantation, which is a composite of Teflon polymer and elemental carbon. It is very well tolerated as an interphase between metal and plastic implants and tissue.

The gross physical appearance is that of a resilient black felt sponge. Because of the ingredients from which ProplastTM is made it exhibits extraordinary chemical and thermal resistance, permitting firm fusion of pieces 0.5 mm to 5 mm in thickness to metallic and rigid plastic implant materials. The resultant lamination may be sterilized by routine steam autoclave techniques used for metals.

Like the elemental carbon with which it is covered, ProplastTM has the least reaction of any material known when tested in simulated biochemical exposure to pseudoextracellular fluid.

The elemental carbon surface renders ProplastTM extremely wettable to body fluid, permitting precipitation of host proteins in a relatively undenatured form, camouflaging the implant from the body's immunologic rejection mechanism. Since it is 70 to 90 percent porous, ProplastTM is malleable and easily handled. It can be shaped with a knife or scissors and even shaved to a sheet 1/50th of an inch in thickness with a dermatome. Teflon and other plastics and metals suitable for implantation can be laminated to ProplastTM to form a composite alloplast with unlimited structural properties and shapes. Even though ProplastTM is relatively new to otolaryngology, it has been used extensively for the past three years in orthopedic and oral surgery as an interphase material between metal implants and surrounding tissue. These uses have demonstrated that fibrous ingrowth into the ProplastTM is rapid and acts to stabilize metal and plastic prostheses mechanically.

Bound to a Teflon columella it has been successful as a Total Ossicular Replacement Prosthesis, to prevent necrosis of the drum over the malleus with a prosthesis around it, to reconstruct an atrophic retracted drum and to reconstruct the posterior canal wall. Animal experiments are now underway to determine the effect of ProplastTM on the inner ear as an oval window seal. If these are satisfactory, ProplastTM will be tried as an oval window seal around a Teflon piston inserted into a small hole in the footplate for otosclerosis.
Zinc therapy in otology
Authors: Ruggles Richard L. , Linquist Philip A.
Published: September 2006

At a recent panel on Otology, I asked the audience for a show of hands of those using Zinc for delayed healing and granulations. It was surprising to note that not more than 4 physicians out of 100 had tried Zinc. The need to report our encouraging results was apparent. From 1971 to 1975, 544 tympanoplasties and 122 mastoidectomies were studied for delayed healing due to granulations. Forty‐six patients were found to have resistant granulations. Thirty‐three of these healed within two weeks of therapy, 10 more required a total of four weeks for healing, and three did not respond well. Sixteen patients had recurrence when the medication was terminated as soon as healing had occurred but responded well when the medication was continued for four weeks after healing was complete. Five patients had nausea, which subsided when the dosage was reduced from the usual 200 mg. of Zinc Sulfate, three times daily with meals to 100 mg., t.i.d. or b.i.d. One patient developed mild urticaria.

Zinc therapy is apparently indicated in granulomata of the ear when healing does not occur with conventional therapy, especially in the postoperative patient; however, it will not suffice when there is massive involvement of the mastoid or middle ear, where surgical removal is indicated.
Rhomboid flap principles and common variations
Authors: Fee Willard E. , Gunter Jack P. , Carder Henry M.
Published: September 2006

The rhomboid flap was initially popularized by a Russian, Alexander Limberg, and modified by Claude Dufourmentel of Paris. Numerous variations on the flap have been proposed more recently by Webster and Gunter. This flap has found its way into the practice of most surgeons doing head and neck surgery, with its primary advantage being that it is an extremely simple flap operation to learn, with great versatility. The general principles and their clinical application are presented in order to increase proper utilization of the flap.
Targeted Gene-Expression Analysis by Genome-Controlled Reverse Transcription-PCR
Authors: Stenman Jakob , Paju Annukka , Rissanen Oso , Tenkanen Tuomas , Haglund Caj , Räsänen Jari , Salo Jarmo , Stenman Ulf-Håkan , Orpana Arto
Published: September 2006

Background: For gene-expression analysis, which is anticipated to play an important role in classification of tumors and premalignant conditions, PCR-based quantitative assays must have increased diagnostic quantitative accuracy and reproducibility and enable analysis of gene expression in formalin-fixed paraffin-embedded (FFPE) tissue samples.

Methods: We developed a reverse transcription–PCR-based quantitative assay that modifies the cDNA sequence to increase the melting temperature of short (56–64 bp) PCR amplicons, enabling their quantification in-tube by homogeneous melting-curve analysis. We used this method to analyze the expression of 8 genes, 7 potential colon cancer markers, and 1 control in samples obtained from 3 colon carcinoma cell lines, endoscopic biopsy from 8 patients undergoing gastroscopy for Barrett esophagus, and archival FFPE and frozen tissue from 20 patients who underwent surgery for colon carcinoma.

Results: The detection limit of the assay, when optimized for FFPE samples, was 100 copies of cDNA, and the dynamic range was 3 orders of magnitude. A prototype assay containing a panel of 8 genes displayed good reproducibility compared with the commercially available TaqMan® assay (interassay CVs, 5%–20% vs 7%–43%, respectively). Gene-expression analysis was performed successfully in 26 (96%) of 27 endoscopic biopsy specimens, 30 (86%) of 35 archival FFPE samples, and 20 (100%) of 20 archival frozen samples.

Conclusions: This new technology combines the reproducibility of competitive PCR with accurate quantitative detection by in-tube melting-curve analysis, enabling efficient analysis of mRNA profiles in samples with small numbers of cells or small amounts of tissue, as well as in archival FFPE tissues.
Health Outcomes Categorized by Current and Previous Definitions of Acute Myocardial Infarction in an Unselected Cohort of Troponin-Naïve Emergency Department Patients
Authors: Kavsak Peter A , MacRae Andrew R , Palomaki Glenn E , Newman Alice M , Ko Dennis T , Lustig Viliam , Tu Jack V , Jaffe Allan S
Published: September 2006

Background: In a population originally classified for acute myocardial infarction (AMI) by the World Health Organization (WHO) definition, we compared the health outcomes after retrospectively reclassifying with the European Society of Cardiology and the American College of Cardiology (ESC/ACC) AMI definition, using the peak cardiac troponin I (cTnI) concentrations. The health outcomes were based on the WHO definition and occurred in an era that preceded the use of cardiac troponin biomarkers.

Methods: For 448 patients who presented to the emergency department with symptoms suggestive of cardiac ischemia in 1996, we obtained data for all-cause mortality and recurrent AMI for up to 1 year after the initial presentation. We performed retrospective analysis of the patients’ frozen plasma samples to measure cTnI (AccuTnI®, Beckman Coulter).

Results: At 30, 120, and 360 days, the risk for AMI/death in patients positive for AMI by only the ESC/ACC criteria was significantly lower than the risk in patients positive by both ESC/ACC and WHO criteria, and significantly higher than in patients negative according to both criteria. In a separate analysis, patients with a peak cTnI >0.10 μg/L were at greater risk for AMI/death than patients with cTnI concentrations of 0.04–0.10 μg/L. Patients negative by both definitions or with peak cTnI concentrations <0.04 μg/L had the highest event-free survival rates (92% and 94%, respectively) at 1 year.

Conclusion: In a troponin-naïve population, patients classified as positive for AMI by only the ESC/ACC criteria have a prognosis that appears to be intermediate between those classified positive by both the WHO and ESC/ACC definitions and those who meet neither criteria.
Nanopositioniertechnik für große Bewegungsbereiche (Nanopositioning over Large Travel Ranges)
Authors: Hesse Steffen , Schäffel Christoph
Published: September 2006

Auf Basis des Konzepts integrierter Mehrkoordinatenantriebe werden Nanopositioniersysteme für große Verfahrbereiche entwickelt. Dabei ist die Umsetzung einer hochpräzisen Abbe-Fehler-freien Positionsmessung eine wesentliche Voraussetzung. Durch gezielte Untersuchungen der Funktionsgruppen für Antrieb und Führung werden Störquellen und genauigkeitsbegrenzende Faktoren identifiziert und so die kritischen Stellen für eine Reduzierung der Positionierunsicherheit lokalisiert.
Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1–4, and IGFBPs-1–3 protease activity in obese subjects
Authors: Rasmussen Michael Højby , Juul Anders , Kjems Lise Lund , Hilsted Jannik
Published: September 2006

Objective: Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1–4, and IGFBPs-1–3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD).

Design: Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ).

Methods: Free IGF-I was determined by a non-competitive immunoradiometric assay.

Results: Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1–3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups.

Conclusions: We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.