bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement in multiple sclerosis: its role in disease and potential as a biomarker
Authors: Ingram G , Hakobyan S , Robertson N P , Morgan B P
Published: November 2008

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system with a poorly defined and complex immunopathogenesis. Although initiated by reactive T cells, persistent inflammation is evident throughout the disease course. A contribution from complement has long been suspected, based on the results of pathological and functional studies which have demonstrated complement activation products in MS brain and biological fluids. However, the extent and nature of complement activation and its contribution to disease phenotype and long-term outcome remain unclear. Furthermore, functional polymorphisms in components and regulators of the complement system which cause dysregulation, and are known to contribute to other autoimmune inflammatory disorders, have not been investigated to date in MS in any detail. In this paper we review evidence from pathological, animal model and human functional and genetic studies, implicating activation of complement in MS. We also evaluate the potential of complement components and regulators and their polymorphic variants as biomarkers of disease, and suggest appropriate directions for future research.
Individualized programme to promote self‐care among older adults with asthma: randomized controlled trial
Authors: Huang Tzu‐Ting , Li Yu‐Tsui , Wang Chun‐Hua
Published: November 2008

Title.  Individualized programme to promote self‐care among older adults with asthma: randomized controlled trial.

Aim.  This paper is a report of a trial to examine the effectiveness of individualized self‐care education programmes in older adults with moderate‐to‐severe asthma.

Background.  Asthma is a common chronic disease in adults and a major cause of frequent work absences, emergency room visits, and hospitalization. The results of studies of self‐care education programmes have been largely supportive and suggest that they have positive outcomes for people with asthma. However, for older people with asthma, the effectiveness of computer‐aided, self‐learning video programmes has been controversial.

Methods.  Older adult patients with asthma (N = 148) were randomly assigned to one of three groups: usual care, individualized education, or individualized education with peak flow monitoring, and followed for 6 months. Data were collected from January to December 2006. The variables studied included demographic data, asthma self‐care competence, asthma self‐efficacy, and asthma self‐care behaviour.

Findings.  Patients in both individualized education groups reported higher asthma self‐care competence scores (F = 334·06 and 481·37, P < 0·001) and asthma self‐care and self‐efficacy scores (F = 104·08 and 68·42, P < 0·001) than patients in the usual care group. In addition, patients who received individualized education with peak flow monitoring had statistically significantly higher asthma self‐care behaviour and self‐efficacy scores (P < 0·001) and asthma control indicators (P = 0·025) than the education alone group. No differences were found among the three groups in unscheduled health service usage.

Conclusion.  Our results suggest that individualized education helps older people with asthma to enhance their self‐care behaviours, manage their disease, and increase their quality of life.
Comparison of single‐particle analysis and electron tomography approaches: an overview
Authors: JONIĆ S. , SORZANO C.O.S. , BOISSET N.
Published: November 2008

Three‐dimensional structure of a wide range of biological specimens can be computed from images collected by transmission electron microscopy. This information integrated with structural data obtained with other techniques (e.g., X‐ray crystallography) helps structural biologists to understand the function of macromolecular complexes and organelles within cells. In this paper, we compare two three‐dimensional transmission electron microscopy techniques that are becoming more and more related (at the image acquisition level as well as the image processing one): electron tomography and single‐particle analysis. The first one is currently used to elucidate the three‐dimensional structure of cellular components or smaller entire cells, whereas the second one has been traditionally applied to structural studies of macromolecules and macromolecular complexes. Also, we discuss possibilities for their integration with other structural biology techniques for an integrative study of living matter from proteins to whole cells.
Identification and characterization of a new zirconium hydride
Authors: ZHAO Z. , MORNIROLI J.‐P. , LEGRIS A. , AMBARD A. , KHIN Y. , LEGRAS L. , BLAT‐YRIEIX M.
Published: November 2008

Zirconium alloys are currently used in nuclear power plants where they are susceptible to hydrogen pick‐up. Hydride precipitation may occur when the hydrogen solubility limit is reached. Various Zr hydride phases, γ, δ and ɛ have been identified since the 1950s. Combining electron precession microdiffraction, electron energy loss spectroscopy and ab initio electronic calculations, a new Zr hydride named ζ has been identified and characterized. It belongs to the trigonal crystal system with space group P3 m1 and it is fully coherent with the αZr matrix.
Use of atomic force microscopy (AFM) for microfabric study of cohesive soils
Authors: SACHAN A.
Published: November 2008

Microfabric reflects the imprints of the geologic and stress history of the soil deposit, the depositional environment and weathering history. Many investigators have been concerned with the fundamental problem of how the engineering properties of clay depend on the microfabric, which can be defined as geometric arrangement of particles within the soil mass. It is believed that scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are the only techniques that can reveal particle arrangements of clayey soils directly; however, current research introduces a novel and more advanced technique, atomic force microscopy, to evaluate the microfabric of cohesive materials. The atomic force microscopy has several advantages over SEM/TEM for characterizing cohesive particles at the sub‐micrometre range by providing 3D images and 2D images with Z‐information used in quantitative measurements of soil microfabric using SPIP software, and having the capability of obtaining images in all environments (ambient air, liquids and vacuums). This paper focuses on the use of atomic force microscopy technique to quantify the microfabric of clayey soils by developing the criteria for average and maximum values of angle of particle orientation within the soil mass using proposed empirical equations for intermediate and extreme microfabrics (dispersed, flocculated).
Salivary cortisol and IgA levels in patients with myofascial pain treated with occlusal appliances in the short term
Authors: DOEPEL M. , SÖDERLING E. , EKBERG E. L. , NILNER M. , LE BELL Y.
Published: November 2008

Summary  In many studies, the endocrinological response of individuals to different kinds of stresses has been tested. There seems to be widespread agreement that stress, depression, disability and dysfunctional illness behaviors are critical aspects of patients suffering from symptoms like pain, arising out of temporomandibular disorders (TMD). We aimed to explore treatment‐induced changes in salivary cortisol, IgA and flow rate values in TMD patients suffering from myofascial pain. Temporomandibular disorders patients (n = 39) were randomized into two groups and treated with two different occlusal appliances. Perceived stress regarding family, work, economy, relationships, general health and stress in general was evaluated at baseline according to a verbal scale. Paraffin‐stimulated saliva samples were collected before treatment and during follow‐up at 6 and 10 weeks. Flow rate was measured immediately after the saliva collection while salivary cortisol and IgA were determined from samples stored at −70 °C. No clear association between reported stress and cortisol or IgA values could be observed at baseline. At 10 weeks follow‐up, 92% of the patients felt ‘better, much better, symptom‐free’ and no difference was found between the two appliance groups. Cortisol, IgA and flow rate values showed no systematic between appliance groups’ differences. All salivary parameters showed interindividual differences but stayed intra‐individually on a similar level throughout the study and no statistically significant changes could be observed when comparing before and after treatment levels. To conclude, there were no treatment‐induced changes in saliva parameters despite successful appliance therapy in myofascial pain patients.
Molecular processes underlying the floral transition in the soybean shoot apical meristem
Authors: Wong Chui E. , Singh Mohan B. , Bhalla Prem L.
Published: November 2008

The transition to flowering is characterized by a shift of the shoot apical meristem (SAM) from leaf production to the initiation of a floral meristem. The flowering process is of vital importance for agriculture, but the associated events or regulatory pathways in the SAM are not well understood, especially at a system level. To address this issue, we have used a GeneChip® containing 37 744 probe sets to generate a temporal profile of gene expression during the floral initiation process in the SAM of the crop legume, soybean (Glycine max). A total of 331 transcripts displayed significant changes in their expression profiles. The in silico and RT‐PCR analysis on differentially regulated transcripts implies the intriguing involvement of sugar, auxin or abscisic acid (ABA) in events prior to the induction of floral homeotic transcripts. The novel involvement of ABA in the floral transition is further implicated by immunoassay, suggesting an increase in ABA levels in the SAM during this developmental transition. Furthermore, in situ localization, together with in silico data demonstrating a marked enhancement of abiotic stress‐related transcripts, such as trehalose metabolism genes in SAMs, points to an overlap of abiotic stress and floral signalling pathways.
Identification of novel meristem factors involved in shoot regeneration through the analysis of temperature‐sensitive mutants of Arabidopsis
Authors: Tamaki Hiroaki , Konishi Mineko , Daimon Yasufumi , Aida Mitsuhiro , Tasaka Masao , Sugiyama Munetaka
Published: November 2008

Adventitious organogenesis in plant tissue culture involves de novo formation of apical meristems and should therefore provide important information about the fundamentals of meristem gene networks. We identified novel factors required for neoformation of the shoot apical meristem (SAM) through an analysis of shoot regeneration in root initiation defective3 (rid3) and root growth defective3 (rgd3) temperature‐sensitive mutants of Arabidopsis. After induction of callus to regenerate shoots, cell division soon ceased and was then reactivated locally in the surface region, resulting in formation of mounds of dense cells in which adventitious‐bud SAMs were eventually constructed. The rgd3 mutation inhibited reactivation of cell division and suppressed expression of CUP‐SHAPED COTYLEDON1 (CUC1), CUC2 and SHOOT MERISTEMLESS (STM). In contrast, the rid3 mutation caused excess ill‐controlled cell division on the callus surface. This was intimately related to enhanced and broadened expression of CUC1. Positional cloning revealed that the RGD3 and RID3 genes encode BTAF1 (a kind of TATA‐binding protein‐associated factor) and an uncharacterized WD‐40 repeat protein, respectively. In the early stages of shoot regeneration, RGD3 was expressed (as was CUC1) in the developing cell mounds, whereas RID3 was expressed outside the cell mounds. When RID3 was over‐expressed artificially, the expression levels of CUC1 and STM were significantly reduced. Taken together, these findings show that both negative regulation by RID3 and positive regulation by RGD3 of the CUC–STM pathway participate in proper control of cell division as a prerequisite for SAM neoformation.
Pilot study of oxygen transport rate of banked red blood cells
Authors: Buchwald H. , Menchaca H. J. , Michalek V. N. , Rudser K. D. , Rohde T. D. , O'Dea T. , Connett J. E. , Gorlin J.
Published: November 2008

Background and Objectives Dynamic oximetry provides a new way to assess the effect of blood storage on the oxygen transport rate (OTR).

Materials and Methods In dynamic oximetry, the rate at which oxyhemoglobin becomes deoxyhemoglobin is measured optically, thereby, indirectly measuring the rate at which oxygen leaves the red blood cell (RBC) making it available for transfer to tissues. Extending the physiologic diffusion time in an in vitro apparatus, consisting of a diffusion system and gas exchanger capable of controlling the surface area and the time of exposure for oxygenation and deoxygenation, makes OTR measurement feasible. Eight normal blood donor units, collected in adenine, dextrose, sorbitol, sodium chloride and mannitol , were stored for 8 weeks under standard conditions and serially sampled for OTR.

Results We report that the OTR at the time of blood bank donation appears to be singular for each donor, that the interdonor differences are maintained over time, and that the individual OTR increased 1·72‐fold (95% CI 1·51, 1·95) over 8 weeks, adjusting for sex, age and plasma cholesterol level.

Conclusion Oxygen transport rate increases during storage; blood units with similar haemoglobin content may have significant differences in OTR. Studies examining blood parameters at the time of donation and blood storage on patient outcomes should consider measuring OTR, as it may contribute to differences in observed efficacy of tissue oxygenation.
Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association
Authors: Hinotsu Shiro , Akaza Hideyuki , Miki Tsuneharu , Fujimoto Hiroyuki , Shinohara Nobuo , Kikuchi Eiji , Mizutani Yoichi , Koga Hirofumi , Okajima Eijiro , Okuyama Akihiko ,   The Japanese Urological Association
Published: November 2008

Objectives:  It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.

Methods:  The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non‐smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed

Results:  In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non‐smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size.

Conclusions:  The finding of 6‐year‐earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.
Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: Multi‐institutional dataset from three European centers
Authors: Novara Giacomo , De Marco Vincenzo , Dalpiaz Orietta , Galfano Antonio , Bouygues Vianney , Gardiman Marina , Martignoni Guido , Patard Jean Jacques , Artibani Walter , Ficarra Vincenzo
Published: November 2008

Objectives:  To identify the variables predictive of contralateral metachronous upper urinary tract transitional cell carcinoma (UUT‐TCC) after nephroureterectomy (NFU) for non‐metastatic UUT‐TCC.

Methods:  Clinical and pathological data of 234 patients who had undergone NFU for UUT‐TCC from 1989 to 2005 in three European urological centers were retrospectively collected and analyzed.

Results:  The median follow‐up duration for the whole cohort was 34 months. Contralateral metachronous UUT‐TCC was detected in 14 patients (6%). Three patients were treated by NFU, while seven patients underwent ureterectomy and reimplantation and four patients were treated by endoscopic resection plus bacillus Calmette–Guérin instillations within the UUT through a nephrostomic tube. On univariate analysis, a prior history of bladder TCC before NFU was the only factor predictive of the occurrence of contralateral UUT‐TCC. Specifically, the 5‐year probabilities of being free from contralateral UUT‐TCC were 96.6% for the patients with de novo UUT‐TCC, and 91.1% and 55.3% for those having non‐muscle‐invasive and muscle invasive bladder TCC before the UUT cancer, respectively. All survival differences were statistically significant (no history of bladder TCC vs history of non‐muscle‐invasive bladder TCC, log rank P value 0.015; history of non‐muscle‐invasive bladder TCC vs history of muscle‐invasive bladder TCC, log rank P value 0.035).

Conclusions:  In our multicenter dataset of patients who had undergone NFU for UUT‐TCC, contralateral metachronous UUT‐TCC occurred in 6% of the patients. A prior history of bladder TCC before NFU was the only variable predictive of UUT recurrence at univariate analysis.
Determination of SIF for patched crack in aluminum plates by the combined finite element and genetic algorithm approach
Authors: ERGUN E. , TASGETIREN S. , TOPCU M.
Published: November 2008

In this paper, the finite element method is used to analyze the behaviour of repaired cracks in 2024‐T3 aluminum with bonded patches made of unidirectional composite plates. The problem is considered in Mode I condition. First the KI stress intensity factor (SIF) is calculated by the finite element method using displacement correlation technique. Different plate and patch thicknesses and crack lengths are considered in the analyses. Then an equation is determined by using genetic algorithms for the calculation of stress intensity factor without any further finite element analysis. The equation gives reasonably accurate results.
An efficient stress intensity factor solution scheme for corner cracks at holes under bivariant stressing
Authors: LEE Y. D. , McCLUNG R. C. , CHELL G. G.
Published: November 2008

This paper summarizes the development of an efficient stress intensity factor (SIF) solution scheme applicable to a corner crack (CC) in a rectangular section subjected to arbitrary stressing on the crack plane. A general bivariant weight function (WF) formulation developed previously for a CC in a plate was extended to address a CC at a hole. Two supplemental algorithms were developed to achieve a substantial reduction in the computational time necessary for practical application. The new SIF solution scheme was validated by comparison with more than 180 three‐dimensional (3D) boundary element (BE) solutions.
The World Federation of Societies of Anaesthesiologists and Pediatric Anesthesia
Authors: ENRIGHT ANGELA
Published: November 2008

The World Federation of Societies of Anaesthesiologists (WFSA) is an organization whose principal goal is to improve the standard of anesthesia worldwide. The education and pediatric committees focus on the needs of pediatric patients in developing countries. Subspecialty training in pediatric anesthesia is supported in several regions. The publications committee supports the distribution of textbooks in pediatric anesthesia.
The role of systemic cytotoxic therapy for prostate cancer
Authors: Chang Sam S. , Kibel Adam S.
Published: November 2008

Prostate cancer is among the most common types of cancer and cause of cancer‐related deaths among men in the USA and Europe. Despite improvements in early detection and treatment for localized disease, many patients still present with advanced disease, or attempted curative local therapy fails. Although hormone therapy is successful initially in the vast majority of patients, most develop hormone‐refractory prostate cancer (HRPC) after 18–24 months. In the past, the use of chemotherapy in the management of prostate cancer has been limited, but recent evidence of its efficacy in HRPC has prompted further research to determine if it could have a more extensive role in the treatment of this disease. Data from several studies have highlighted the possible beneficial effects of incorporating chemotherapeutic agents in treatment regimens for HRPC, showing evidence of a survival advantage. One of the goals of research now is to determine optimal management strategies for different patient populations with prostate cancer. Preliminary data suggest that further improvements in efficacy might be achieved with multi‐agent chemotherapy or by treating patients earlier in the disease process.
Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes
Authors: Rizzo M. , Berneis K. , Altinova A. E. , Toruner F. B. , Akturk M. , Ayvaz G. , Rini G. B. , Spinas G. A. , Arslan M.
Published: November 2008

Aims  Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low‐density lipoprotein (LDL) size and all seven subclasses, as well as the ‘atherogenic–lipoprotein phenotype’[ALP, e.g. concomitant presence of elevated triglycerides, reduced high‐density lipoprotein (HDL)‐cholesterol and increased small, dense LDL].

Methods  In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation.

Results  Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL‐I (P = 0.0074) and increased LDL‐IVA (P = 0.0146) and ‐IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL‐I and positively with LDL‐IVA and ‐IVB (all P < 0.05). ALP due to high HDL‐cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107).

Conclusions  Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end‐points in these women remains to be determined by future prospective studies.
Algorithm for Accurate Three‐Dimensional Scene Graph Updates in High‐Speed Animations of Previously Simulated Construction Operations
Authors: Rekapalli Prasant V. , Martínez Julio C. , Kamat Vineet R.
Published: November 2008

Abstract: Visualization of construction operations is an important technique to communicate the logic of simulation models in detail. Early efforts resulted in a scene graph and frame update algorithm that was capable of converting discrete information from simulation models into smooth and continuous 3D animations. That algorithm did not account for high speed or concurrent animation because the need to do so was not anticipated. Recent advances in computing power and an interest in using the technology for next generation applications now demand accurate high speed and concurrent animations. This article presents the design of the original algorithm at a previously undocumented level of detail and specificity, and that allows for the analysis of its shortcomings when used at high speeds or concurrently with simulation. Two subsequent but still inadequate designs of the algorithm are also presented and analyzed in detail so that they can serve as an illustration of the path toward the final design and place it in proper context. The article concludes with the final design and evaluation of the algorithm, which is accurate at very high animation speeds and supports concurrent animation of simulation models.
Gentlemanly capitalism revisited: a case study of the underpricing of initial public offerings on the London Stock Exchange, 1946–861
Authors: CHAMBERS DAVID
Published: November 2008

Allegations of British capital market failure are numerous, but frequently contentious. This paper revisits the literature by highlighting the post‐1945 market for initial public offerings (IPOs) as a clear instance of capital market failure. Despite the tender method delivering substantially lower underpricing than the traditional fixed‐price offer method, it was adopted by only one in 10 firms going public. This missed opportunity cost issuing firms between £1.7 billion and £3.5 billion in real proceeds forgone between 1960 and 1986, excluding privatizations, and was symptomatic of a lack of competition in equity underwriting before Big Bang.
Ex‐Dividend Day Behavior in the Absence of Taxes and Price Discreteness*
Authors: AL YAHYAEE KHAMIS , PHAM TOAN , WALTER TERRY
Published: November 2008

We examine the ex‐dividend day behavior in a unique setting where (1) there are neither taxes on dividends nor on capital gains, (2) stock prices have been decimalized, (3) dividends are distributed annually, and (4) we have data that enable us to examine bid–ask bounce effects. In this economy, any price decline that is smaller than the dividends cannot be attributed to taxes and price discreteness. Like previous studies, we find that the stock price drops by less than the amount of dividends and there is a significant positive ex‐day return. By examining abnormal volumes around the ex‐dividend day, we find no evidence of short‐term trading. We are able to account for our results using market microstructure models. When the impact of market microstructure is taken into account, the ex‐dividend drop is not significantly different from the value of the dividend paid.
Behavioural environments and niche construction: the evolution of dim‐light foraging in bees
Authors: Wcislo William T. , Tierney Simon M.
Published: November 2008

Most bees forage for floral resources during the day, but temporal patterns of foraging activity vary extensively, and foraging in dim‐light environments has evolved repeatedly. Facultative dim‐light foraging behaviour is known in five of nine families of bees, while obligate behaviour is known in four families and evolved independently at least 19 times. The light intensity under which bees forage varies by a factor of 108, and therefore the evolution of dim‐light foraging represents the invasion of a new, extreme niche. The repeated evolution of dim‐light foraging behaviour in bees allows tests of the hypothesis that behaviour acts as an evolutionary pacemaker. With the exception of one species ofApis, facultative dim‐light foragers show no external structural traits that are thought to enable visually mediated flight behaviour in low‐light environments. By contrast, most obligate dim‐light foragers show a suite of convergent optical traits such as enlarged ocelli and compound eyes. In one intensively studied species (Megalopta genalis) these optical changes are associated with neurobiological changes to enhance photon capture. The available ecological evidence suggests that an escape from competition for pollen and nectar resources and avoidance of natural enemies are driving factors in the evolution of obligate dim‐light foraging.
MPTP and MPP+ target specific aminergic cell populations in larval zebrafish
Authors: Sallinen V , Torkko V , Sundvik M , Reenilä I , Khrustalyov D , Kaslin J , Panula P
Published: November 2008

Larval zebrafish offers a good model to approach brain disease mechanisms, as structural abnormalities of their small brains can be correlated to quantifiable behavior. In this study, the structural alterations in one diencephalic dopaminergic nucleus induced by 1‐methyl‐4‐phenylpyridinium (MPP+), a toxin inducing Parkinson’s disease in humans, and those found in several neuronal groups after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), the pretoxin, were associated with decreased swimming speed. Detailed cell counts of dopaminergic groups indicated a transient decline of tyrosine hydroxylase expressing neurons up to about 50% after MPTP. The MPTP effect was partly sensitive to monoamine oxidase inhibitor deprenyl. Detailed analysis of the developing catecholaminergic cell groups suggests that the cell groups emerged at their final positions and no obvious significant migration from the original positions was seen. One 5‐HT neuron group was also affected by MPTP treatment, whereas other groups remained intact, suggesting that the effect is selective. New nomenclature for developing catecholaminergic cell groups corresponding to adult groups is introduced. The diencephalic cell population consisting of groups 5,6 and 11 was sensitive to both MPTP and MPP+ and in this respect resembles mammalian substantia nigra. The results suggest that MPTP and MPP+ induce a transient functional deficit and motility disorder in larval zebrafish.
Average Probability that a “Cold Hit” in a DNA Database Search Results in an Erroneous Attribution
Authors: Song Yun S. , Patil Anand , Murphy Erin E. , Slatkin Montgomery
Published: November 2008

Abstract:  We consider a hypothetical series of cases in which the DNA profile of a crime‐scene sample is found to match a known profile in a DNA database (i.e., a “cold hit”), resulting in the identification of a suspect based only on genetic evidence. We show that the average probability that there is another person in the population whose profile matches the crime‐scene sample but who is not in the database is approximately 2(N − d)pA, where N is the number of individuals in the population, d is the number of profiles in the database, and pA is the average match probability (AMP) for the population. The AMP is estimated by computing the average of the probabilities that two individuals in the population have the same profile. We show further that if a priori each individual in the population is equally likely to have left the crime‐scene sample, then the average probability that the database search attributes the crime‐scene sample to a wrong person is (N − d)pA.
Outcome of late‐life depression after 3 years of sequential treatment
Authors: Kok R. M. , Nolen W. A. , Heeren T. J.
Published: November 2008

Objective:  To study the outcome of a sequential treatment protocol in elderly, severely depressed in‐patients.

Method:  All 81 patients from a 12‐week double‐blind randomized controlled trial (RCT) comparing venlafaxine with nortriptyline were asked to participate in a 3 year follow‐up study. Thirty‐two patients who did not achieve remission during the RCT, entered an open sequential treatment protocol and were treated with augmentation with lithium, switch to a monoamine oxidase inhibitor or ECT.

Results:  Seventy‐eight of the 81 patients (96.3%) achieved a response [≥50% reduction in Montgomery Åsberg Depression Rating Scale score) and 68 patients (84%) a complete remission (final MADRS score ≤ 10) within 3 years of treatment. Greater severity and longer duration of the depressive episode at baseline predicted poor recovery. Augmentation with lithium may be the best treatment option in treatment resistant depressed elderly. Only few patients dropped‐out due to side‐effects.

Conclusion:  Our study demonstrates the importance of persisting with antidepressant treatment in elderly patients who do not respond to the first or second treatment.
Developing a user‐generated measure of continuity of care: brief report
Authors: Rose D. , Sweeney A. , Leese M. , Clement S. , Jones I. R. , Burns T. , Catty J. , Wykes T.
Published: November 2008

Objective:  This paper describes a measure of continuity of care, establishes its reliability and tests it in a field trial sample for evidence of its validity. In contrast to others, this measure has been generated from the perspectives of service users. As continuity of care is a concern particularly for those with severe mental illness, we have confined our work to this population group.

Method:  Service users in focus groups and expert panels generated the measure. The researchers were themselves service users. Test–retest reliability was assessed with an independent sample. The measure was administered to a final independent field trial sample to determine their experiences of continuity of care and for further psychometric testing.

Results:  The measure generated by service users has satisfactory psychometric properties. Service users in the field trial sample were more satisfied when continuity, as assessed by this measure, was in place.

Conclusion:  It is possible and valid to construct outcome measures in mental health entirely from the user perspective. This has not been done before.
Process from pattern in the distribution of an endangered leaf beetle
Authors: Chapman Daniel S. , Oxford Geoff S. , Dytham Calvin
Published: November 2008

We investigated whether signals of known dispersal processes and habitat patch turnover could be detected in a snapshot of the distribution of the tansy leaf beetleChrysolina graminisamong patches of its host plant tansyTanacetum vulgare. Beetle occupancy in 1305 patches was analysed using autologistic generalised additive models (GAMs). These model spatial autocorrelation with an autocovariate calculated as the distance‐weighted rate of occupancy among neighbouring patches. The autocovariate that best explained beetle occupancy was one which represented the active search for patches during beetle dispersal, included a distance weight that closely matched a previously fitted dispersal kernel and had neighbourhood sizes encompassing ∼95% of known dispersal distances. Autocovariates distinguishing between neighbours on the same and opposite riverbanks outperformed those that did not, revealing the river as a barrier to dispersal. Differentiating between up and downstream autocorrelation did not improve model fit, as is consistent with the beetle's lack of directional bias in dispersal. Habitat connectivity (the extent to which it was surrounded by other patches) did not appear to affect beetle occupancy in the field, while positive effects were found for distributions simulated from the GAM. We argue that this reflects a non‐equilibrium distribution driven by slow responses to high rates of habitat patch turnover due to limited dispersal ability. Our findings suggest that presence/absence snapshots can reveal patterns of dispersal and be used to test whether species’ ranges are at equilibrium. Such information is important for effective conservation so the possibility of inferring these patterns from distribution data is an appealing one.
Density‐dependent linkage of scale‐dependent feedbacks: a flume study on the intertidal macrophyte Spartina anglica
Authors: Bouma T. J. , Friedrichs M. , Van Wesenbeeck B. K. , Temmerman S. , Graf G. , Herman P. M. J.
Published: November 2008

Spartina anglica is an autogenic ecosystem engineer. At a local (within‐vegetation) scale, it improves plant growth by enhancing sediment accretion through attenuation of hydrodynamic energy with its shoots. This constitutes a short‐range positive feedback. The vegetation also shows a long‐distance negative feedback through formation of erosion troughs around the tussock, which are restricting lateral expansion. There is a growing recognition of the important role of such scale‐dependent feedbacks for landscape structuring and ecosystem stability. By a series of flume studies, we provide direct experimental evidence that 1) both the local positive and the long‐distance negative feedback are strongly density‐dependent with clear thresholds, and 2) that both feedbacks are inherently linked via their density dependence, partly as the result of conservation laws. The observed thresholds occurred at vegetation densities commonly found in the field. We demonstrate that threshold densities are affected by external hydrodynamic forcing for the long‐distance negative feedback. We expect the same to be true for the local positive feedback (sediment accretion), so that under mild hydrodynamic forcing, this local positive feedback may occur in the absence of a long‐distance negative feedback (formation of erosion troughs). The density dependence of nearby positive and the long‐distance negative feedback and how external conditions affect the linkage of both feedbacks are important factors shaping the vegetated salt‐marsh landscape.
Correlation of dystrophin–glycoprotein complex and focal adhesion complex with myosin heavy chain isoforms in rat skeletal muscle
Authors: Masuda S. , Hayashi T. , Hashimoto T. , Taguchi S.
Published: November 2008

Aim:  The dystrophin–glycoprotein complex (DGC) and focal adhesion complex (FAC) are transmembrane structures in muscle fibres that link the intracellular cytoskeleton to the extracellular matrix. DGC and FAC proteins are abundant in slow‐type muscles, indicating the structural reinforcement which play a pivotal role in continuous force output to maintain posture for long periods. The aim of the present study was to examine the expression of these structures across fast‐type muscles containing different myosin heavy chain (MHC) isoform patterns which reflect the fatigue‐resistant characteristics of skeletal muscle.

Methods:  We measured the expression of dystrophin and β1 integrin (representative proteins of DGC and FAC respectively) in plantaris, extensor digitorum longus, tibialis anterior, red and white portions of gastrocnemius, superficial portion of vastus lateralis and diaphragm, in comparison with soleus (SOL) and cardiac muscle from rats.

Results:  The expression of dystrophin and β1 integrin correlated positively with the percentage of type I, IIa and IIx MHC isoforms and negatively with that of type IIb MHC isoform in fast‐type skeletal muscles, and their expression was abundant in SOL and cardiac muscle.

Conclusion:  Our results support the idea that DGC and FAC are among the factors that explain the fatigue‐resistant property not only of slow‐type but also of fast‐type skeletal muscles.
Uncertainty as a Predictor of Adjustment to an Implantable Cardioverter Defibrillator
Authors: Mauro Ann Marie P.
Published: November 2008

Although the implantable cardioverter defibrillator (ICD) has reduced the risk of sudden cardiac death, some recipients experience uncertainty and adjustment problems related to the device. The study's purpose was to test hypotheses that predicted defibrillator recipients with greater uncertainty would have less psychosocial adjustment overall; less adjustment in the domestic, social, and vocational environments and in sexual relationships; and have more psychological distress at 1 and 8 weeks following hospital discharge. A repeated measures, correlational survey design was used with 94 adult defibrillator recipients from 4 hospitals. The Mishel Uncertainty in Illness Scale, Psychosocial Adjustment to Illness Scale Self‐Report, and demographics were completed at both time points. The sample was predominantly white, male, and married. There were no gender differences and younger adults had more adjustment problems than older adults. Results supported all but 2 hypotheses as participants had less psychosocial adjustment overall, less adjustment in all domains except vocational environment, and more psychological distress at 1 and 8 weeks after discharge. In conclusion, ICD recipients with greater uncertainty were at greater risk for psychosocial adjustment problems during the first 2 months and may require interventions, particularly younger adults.
Empathy: A Social Cognitive Neuroscience Approach
Authors: Rameson Lian T. , Lieberman Matthew D.
Published: November 2008

There has been recent widespread interest in the neural underpinnings of the experience of empathy. In this review, we take a social cognitive neuroscience approach to understanding the existing literature on the neuroscience of empathy. A growing body of work suggests that we come to understand and share in the experiences of others by commonly recruiting the same neural structures both during our own experience and while observing others undergoing the same experience. This literature supports a simulation theory of empathy, which proposes that we understand the thoughts and feelings of others by using our own mind as a model. In contrast, theory of mind research suggests that medial prefrontal regions are critical for understanding the minds of others. In this review, we offer ideas about how to integrate these two perspectives, point out unresolved issues in the literature, and suggest avenues for future research.
A Genetic Framework for the Control of Cell Division and Differentiation in the Root Meristem
Authors: Ioio Raffaele Dello , Nakamura Kinu , Moubayidin Laila , Perilli Serena , Taniguchi Masatoshi , Morita Miyo T. , Aoyama Takashi , Costantino Paolo , Sabatini Sabrina
Published: November 2008

Plant growth and development are sustained by meristems. Meristem activity is controlled by auxin and cytokinin, two hormones whose interactions in determining a specific developmental output are still poorly understood. By means of a comprehensive genetic and molecular analysis in
Arabidopsis
, we show that a primary cytokinin-response transcription factor, ARR1, activates the gene
SHY2/IAA3
(
SHY2
), a repressor of auxin signaling that negatively regulates the
PIN
auxin transport facilitator genes: thereby, cytokinin causes auxin redistribution, prompting cell differentiation. Conversely, auxin mediates degradation of the SHY2 protein, sustaining PIN activities and cell division. Thus, the cell differentiation and division balance necessary for controlling root meristem size and root growth is the result of the interaction between cytokinin and auxin through a simple regulatory circuit converging on the
SHY2
gene.
PA-824 Kills Nonreplicating
Mycobacterium tuberculosis
by Intracellular NO Release
Authors: Singh Ramandeep , Manjunatha Ujjini , Boshoff Helena I. M. , Ha Young Hwan , Niyomrattanakit Pornwaratt , Ledwidge Richard , Dowd Cynthia S. , Lee Ill Young , Kim Pilho , Zhang Liang , Kang Sunhee , Keller Thomas H. , Jiricek Jan , Barry Clifton E.
Published: November 2008

Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of
Mycobacterium tuberculosis
(Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system.
Difference between the Abilities of Human Fcγ Receptor-Expressing CV-1 Cells To Neutralize American and Asian Genotypes of Dengue Virus 2
Authors: Rodrigo W. W. I. S. , Alcena D. C. , Kou Z. , Kochel T. J. , Porter K. R. , Comach G. , Rose R. C. , Jin X. , Schlesinger J. J.
Published: November 2008

Sera from patients involved in a Peruvian outbreak of dengue virus serotype 1 infection cross-neutralized the American genotype of dengue virus serotype 2 up to 100-fold more efficiently than they did the virulent Asian genotype of dengue virus serotype 2, as determined by a plaque reduction neutralization test (PRNT) with CV-1 fibroblasts modified to express human Fcγ receptor CD32. The concordant preferential immune enhancement of the Asian genotype of dengue virus serotype 2 in human monocytes suggests that such a modification might strengthen the correlation between the PRNT titer and protection.
Protective HLA Class I Alleles That Restrict Acute-Phase CD8+T-Cell Responses Are Associated with Viral Escape Mutations Located in Highly Conserved Regions of Human Immunodeficiency Virus Type 1
Authors: Wang Yaoyu E. , Li Bin , Carlson Jonathan M. , Streeck Hendrik , Gladden Adrianne D. , Goodman Robert , Schneidewind Arne , Power Karen A. , Toth Ildiko , Frahm Nicole , Alter Galit , Brander Christian , Carrington Mary , Walker Bruce D. , Altfeld Marcus , Heckerman David , Allen Todd M.
Published: November 2008

The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8+T-cell responses may be more effective than others at containing HIV-1. Unfortunately, substantial diversities in the breadth, magnitude, and function of these responses have impaired our ability to identify responses most critical to this control. It has been proposed that CD8 responses targeting conserved regions of the virus may be particularly effective, since the development of cytotoxic T-lymphocyte (CTL) escape mutations in these regions may significantly impair viral replication. To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution. The majority of HLA-associated mutations were found in p24 Gag, Pol, and Nef. Reversion of HLA-associated mutations in the absence of the selecting HLA allele was also commonly observed, suggesting an impact of most CTL escape mutations on viral replication. Although no correlations were observed between the number or location of HLA-associated mutations and protective HLA alleles, limiting the analysis to mutations selected by acute-phase immunodominant responses revealed a strong positive correlation between mutations at conserved residues and protective HLA alleles. These data suggest that control of HIV-1 may be associated with acute-phase CD8 responses capable of selecting for viral escape mutations in highly conserved regions of the virus, supporting the inclusion of these regions in the design of an effective vaccine.
DNA Genome Size Affects the Stability of the Adenovirus Virion
Authors: Smith Adam C. , Poulin Kathy L. , Parks Robin J.
Published: November 2008

Replication-defective adenovirus (Ad) vectors can vary considerably in genome length, but whether this affects virion stability has not been investigated. Helper-dependent Ad vectors with a genome size of ∼30 kb were 100-fold more sensitive to heat inactivation than their parental helper virus (>36 kb), and increasing the genome size of the vector significantly improved heat stability. A similar relationship between genome size and stability existed for Ad with early region 1 deleted. Loss of infectivity was due to release of vertex proteins, followed by disintegration of the capsid. Thus, not only does the viral DNA encode all of the heritable information essential for virus replication, it also plays a critical role in maintaining capsid strength and integrity.