bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution dielectric spectroscopy and electric-field dependence of carbon allotropes including multiwall and single-wall nanotubes
Authors: Basu Rajratan , Iannacchione Germano S.
Published: February 2008

High-resolution isothermal dielectric spectroscopy is reported as a function of frequency up to 105Hz and electric field Erot on four carbon allotropes; amorphous glass, diamond, multiwall nanotubes (MWNTs), and single-wall nanotubes (SWNTs). The diamond spectra are featureless while the glass, MWNT, and SWNT samples exhibit two modes. A common low-frequency mode, likely due to surface space charges, is observed at ∼16Hz that decreases in dispersion strength and increases in frequency linearly with increasing Erot. A higher-frequency mode, different for each sample, is also observed having a dispersion strength and frequency independent of Erot.
Identification of Ciliary Localization Sequences within the Third Intracellular Loop of G Protein-coupled Receptors
Authors: Berbari Nicolas F. , Johnson Andrew D. , Lewis Jacqueline S. , Askwith Candice C. , Mykytyn Kirk
Published: February 2008

Primary cilia are sensory organelles present on most mammalian cells. The functions of cilia are defined by the signaling proteins localized to the ciliary membrane. Certain G protein–coupled receptors (GPCRs), including somatostatin receptor 3 (Sstr3) and serotonin receptor 6 (Htr6), localize to cilia. As Sstr3 and Htr6 are the only somatostatin and serotonin receptor subtypes that localize to cilia, we hypothesized they contain ciliary localization sequences. To test this hypothesis we expressed chimeric receptors containing fragments of Sstr3 and Htr6 in the nonciliary receptors Sstr5 and Htr7, respectively, in ciliated cells. We found the third intracellular loop of Sstr3 or Htr6 is sufficient for ciliary localization. Comparison of these loops revealed a loose consensus sequence. To determine whether this consensus sequence predicts ciliary localization of other GPCRs, we compared it with the third intracellular loop of all human GPCRs. We identified the consensus sequence in melanin-concentrating hormone receptor 1 (Mchr1) and confirmed Mchr1 localizes to primary cilia in vitro and in vivo. Thus, we have identified a putative GPCR ciliary localization sequence and used this sequence to identify a novel ciliary GPCR. As Mchr1 mediates feeding behavior and metabolism, our results implicate ciliary signaling in the regulation of body weight.
A survey of allelic imbalance in F1 mice
Authors: Campbell Catarina D. , Kirby Andrew , Nemesh James , Daly Mark J. , Hirschhorn Joel N.
Published: February 2008

There are widespread, genetically determined differences in gene expression. However, methods that compare transcript levels between individuals are subject totrans-acting effects and environmental differences. By looking at allele-specific expression in the F1 progeny of inbred mice, we can directly test for allelic imbalance (AI), which must be due tocis-acting variants in the parental strains. We tested over one hundred genes for AI between C57Bl/6J and A/J alleles in F1 mice, including a validation set of 23 genes enriched forcis-acting variants and a second set of 92 genes whose orthologs were previously examined for AI in humans. We assayed an average of two transcribed SNPs per gene in liver, spleen, and brain from three male and three female F1 mice. In the set of 92 genes, we observed 33 genes (36%) with significant AI including genes with AI that was specific to certain tissues or transcripts. We also observed extensive tissue-specific AI, with 11 out of 92 genes (12%) having differences in AI between tissues. Interestingly, several genes with alternate transcripts have transcript-specific AI. Finally, we observed that the presence of AI in human genes was correlated to the presence of AI in the mouse orthologs (one-tailedP= 0.003), suggesting that certain genes may be more tolerant ofcis-acting variation across species.
Chromodomains direct integration of retrotransposons to heterochromatin
Authors: Gao Xiang , Hou Yi , Ebina Hirotaka , Levin Henry L. , Voytas Daniel F.
Published: February 2008

The enrichment of mobile genetic elements in heterochromatin may be due, in part, to targeted integration. The chromoviruses are Ty3/gypsy retrotransposons with chromodomains at their integrase C termini. Chromodomains are logical determinants for targeting to heterochromatin, because the chromodomain of heterochromatin protein 1 (HP1) typically recognizes histone H3 K9 methylation, an epigenetic mark characteristic of heterochromatin. We describe three groups of chromoviruses based on amino acid sequence relationships of their integrase C termini. Genome sequence analysis indicates that representative chromoviruses from each group are enriched in gene-poor regions of the genome relative to other retrotransposons, and when fused to fluorescent marker proteins, the chromodomains target proteins to specific subnuclear foci coincident with heterochromatin. The chromodomain of the fungal element, MAGGY, interacts with histone H3 dimethyl- and trimethyl-K9, and when the MAGGY chromodomain is fused to integrase of the Schizosaccharomyces pombe Tf1 retrotransposon, new Tf1 insertions are directed to sites of H3 K9 methylation. Repetitive sequences such as transposable elements trigger the RNAi pathway resulting in their epigenetic modification. Our results suggest a dynamic interplay between retrotransposons and heterochromatin, wherein mobile elements recognize heterochromatin at the time of integration and then perpetuate the heterochromatic mark by triggering epigenetic modification.
ALCOHOL AND THE MOTORIST*
Authors: BLENCH T. H.
Published: February 2008

It was with rather more than a show of reluctance that I yielded to the persuasions of your President, my old friend and colleague, Professor Macdonald, to speak to you on this subject which for many years had been brought with increasing frequency to my notice. I felt, however, the signal honour he and your Society were doing me, it seemed rather churlish not to do what I could. I made it clear to your President that in doing so, and knowing the diversity of opinions, the many facets of the problem and the varying emotions involved, I could express only my views, and that certainly with no desire to prove myself right and others wrong. “The fool,” said Blake, “sees not the same tree as the wise man.” When he wrote that the word “fool” meant uninstructed and I suppose we can be compared with trees. The swaying poplar, the sturdy oak, the weeping willow, as well as the trembling aspen and the monkey puzzle.
INTERIM REPORT TO SOCIETY FOR THE STUDY OF ADDICTION, MARCH 1960
Authors: MacLeod L. D. , Ashby W. R.
Published: February 2008

Some progress has been made in studying the relationship between phenylethanol and the alcohol dehydrogenase of mammalian liver. We have now found that under conditions similar to those in which dehydrogenation of ethanol can be observed, phenylethanol also undergoes dehydrogenation by this enzyme.
Studies in the History of Alcoholism—II. Acute Alcoholism in Ancient Greek and Roman Medicine
Authors: LEIBOWITZ J. O.
Published: February 2008

Descriptions of acute alcoholic psychosis go back to Hippocrates, Galen, and Cassius Felix. While the term “frenesis” was chiefly applied to mental disorientation accompanying febrile diseases, it was also used with regard to acute alcoholism. The syndrome of Delirium tremens, first described in 1813 at some length, has been traced to Cassius Felix of the fifth century A.D., whose account was based on ancient Greek sources.

Les descriptions de psychoses aigues alcooliques remontent à Hippocrate, Galen et Cassius Felix. Quoique le terme “frénésie”était principalement appliquéà une désorientation mentale accompagnée de maladies fébriles, il était employéégalement en ce qui concerne l'alcoolisme aigu. Le syndrome du Delirium tremens, décrit pour la première fois en quelque longeur en 1813 a été remontéà Cassius Felix au Cinquième siècle A.D., dont le récit se base d'anciennes sources grecques.

Beschreibungen von akut alkoholischer Psychose wurden bereits von Hippokrates, Galen und Cassius Felix gegeben. Obwohl sich der Ausdruck “Frenese” hauptsächlich auf geitige Desorientiertheit, eine Begleiterscheinung von Fiebererkrankungen bezog, wurde er auch in Bezug auf akuten Alkoholismus verwendet. Die erste, einigermassen ausführliche Beschreibung des Syndroms von Delirium tremens in 1813 wurde auf den im fünften Jahrhundert A.D. lebenden Cassius Felix zurückgeführt, dessen Bericht sich auf altertümliche, griechische Quellen stützte.
Treatment of Compulsorily Detained Alcoholics*
Authors: BEWLEY THOMAS
Published: February 2008

Résumé Les problèmes du traitement d'alcooliques retenus par contrainte sont décrits. Des efforts antérieurs pour résoudre ces problèmes en Grande‐Bretagne et aux Etats‐Unis sont compareés. Les différentes façons au moyen desquelles un alcoolique peut être détenu selon les lois sur la santé mentale sont discutées. Des méthodes de traitement en prison sont mentionées brièvement. Le implications pour un traitement futur couronné de succès sont esquissées.

Es wird das Problem der Behandlung von zwangsweise internierten Alkoholikern beschrieben. Frühere Lösungsversuche für dieses Problem in Großbritannien und in den Vereinigten Staaten werden verglichen. Es werden die verschiedenen Weisen diskutiert, laut welchen ein Alkoholiker unter dem Mental Health Act (Gesetz betreffend geistige Gesundheit) interniert werden kann. Behandlungsmethoden in Gefängnissen werden kurz gestreift. Die Folgerungen für erfolgreiche Behandlung in der Zukunft werden ausgeführt.
Alcoholism and Drug Addiction in Israel
Authors: WISLICKI L.
Published: February 2008

Résumé L'alcoolisme aigu est rare et l'alcoolisme forcé est presque inconnu en Israel quoique la consommation ait augmenté considérablement ces quelques dernières années. Le hashish est fumé principalement par la génération plus avancée en âge venant de pays où il est d'un usage courant.

Comme drogues auxquelles on s'adonne, la morphine principalement et, à un degré croissant, l'opium sont “utilisés tandis que l'héroine, la cocaine, le LSD et I'amphétamine jouent un rôle mineur ou aucun rôle.

L'incidence, les facteurs sociologiques et juridiques, et le traitement de ces conditions sont discutées et des preuves statistiques sont présentées.

In Israel ist schwere Trunksucht selten und chronisches Säufertum beinahe unbekannt, obwohl der Alkohol‐Konsum in den letzten Jahren beträchtlich zugenommen hat. Haschisch wird hauptsächlich von der älteren Generation geraucht, die aus Ländern stammt wo das gang und gäbe ist. Als Rauschgift wird hauptsächlich Morphium und, in steigendem Maβe, Opium verwendet, während Heroin, Kokain, LSD und Amphetamin eine untergeordnete oder gar keine Rolle spielen.

Das Vorkommen, soziologische und juristische Faktoren, sowie die Behandlung dieser Zustände wird besprochen, unter Anführung von statistichen Unterlagen.
Lilliputian Hallucination Complicating Dexamphetamine‐Amylobarbitone Addiction
Authors: TODD JOHN
Published: February 2008

Two cases of drug abuse have been described, the persons concerned being adolescent youths. In the first case, separate episodes of formication and Lilliputian hallucination occurred; in the second case, an episode of Lilliputian hallucination occurred. Although both these youths took other drugs, amphetamine‐drugs appeared to be the dominant drugs and therefore the probable cause of the hallucinatory phenomena described. Attention has been drawn to the marked similarity which obtains between the effect of cocaine—on the one hand, and amphetamine‐drugs—on the other. The writer has suggested that in future, addicts may substitute intravenous methylamphetamine for intravenous cocaine.
The Yin–Yang of thrombin and activated protein C
Authors: Dutt Tina , Toh Cheng Hock
Published: February 2008

The concepts of Yin and Yang provided the intellectual framework of much of Chinese scientific thinking, especially in the fields of biology and medicine. The organs of the body were seen to be inter‐related and their functions could be best appreciated through understanding connections and correlations, in the same way as in other naturally occurring phenomena. Although this principle is recognizable within our current understanding of pro‐ and anti‐coagulant mechanisms, the literature in this field seldom conveys the unifying nature of its overall structure. Considering the coagulation cascade and the anticoagulant system as opposing but complementary forces would be central to the concept of Yin and Yang. This article is presented along such lines with a focus on thrombin and activated protein C (APC) as key examples of that balancing axis in maintaining haemostatic harmony. The emphasis will be on how understanding this relationship at the molecular and cellular level holds promise in the translation to improved clinical care.
Sex Hormones and Excitation–Contraction Coupling in the Uterus: The Effects of Oestrous and Hormones
Authors: Wray S. , Noble K.
Published: February 2008

In this review, we examine how far the increased understanding that we have of the events in excitation contraction can explain the effects of the oestrous cycle and sex hormones on uterine function. Observational studies of electrical and mechanical activity in the rat myometrium have shown a relative quiescence during pro‐oestrous, with little propagation of any electrical events. Thus, uterine activity can be said to approximately inversely reflect plasma 17β‐oestradiol concentrations. We show that Ca2+signalling and mechanical activity are greatest in metoestrous and dioestrous compared to pro‐oestrous and oestrous. These data are discussed in terms of hormonal effects on Ca2+and K+channels. Finally, the influence of sex hormones on lipid rafts and caveolae are considered and discussed in relation to recent findings on their role in uterine signalling and contractility, and cholesterol levels and obesity.
Facing up to the challenge: a view of the capacity of services to meet the needs of people with challenging behaviour
Authors: TURNBULL J.
Published: February 2008

Challenging behaviour is a descriptive rather than a diagnostic term. It is applied to various types of behaviour shown by people with learning disabilities, to which caregivers react strongly. Caregivers respond in this way because these types of behaviour are either proscribed by law or contravene a general perception of what is normal behaviour. Recently, services have responded to the challenge presented by certain clients by seeking to relocate them in less institutional settings and by employing staff with the necessary skills to modify their behaviour. However, there is considerable disagreement about what forms of intervention are effective and ethically acceptable, and consequently, confidence in the ability of caregivers to bring about change has been reduced. More recent work has emphasized the importance of an organizational response to the challenge, focusing on the need for service managers to be more explicit about what staff are required to do and to provide consequences for appropriate staff performance. The health service reforms are considered to provide sufficient incentives for organizations to change.
Attitude to treatment and direction of interest of forensic mental health nurses: a comparison with nurses working in other specialties
Authors: KINSELLA C. , CHALONER C.
Published: February 2008

Attitude to treatment and direction of interest of forensic mental health nurses: a comparison with nurses working in other specialties

The attitudes of nurses working within forensic psychiatry are often perceived as being custodially oriented. Working on this commonly held assumption the authors hypothesized that nurses working within a physically controlled environment such as a Regional Secure Unit would hold more conservative/biological attitudes toward treatment, and would be more ‘object’‐oriented (as opposed to ‘psychologically’ oriented) than those working in less physically controlled clinical areas. [For the purpose of this paper the term ‘Regional Secure Unit’ is used to describe the medium secure facilities that were included in this study, although one of the units did not serve a wholly regional function.]

This paper outlines a study that attempted to examine this hypothesis. A total of 84 nurses from three clinical specialties (Regional Secure Units, Acute Admission Wards and Drug Dependence Units) completed the Attitude to Treatment Questionnaire (ATQ) and the Direction of Interest Questionnaire (DIQ) (Caine et al. 1981). Each nurse also completed a demographic information questionnaire, supplying details of age, professional experience and educational attainment. The results indicate no significant differences on measures used between speciality groups. Significant positive correlations were found between age and conservatism on the ATQ, and between ATQ conservatism and DIQ object centredness. Implications of these results are discussed and suggestions for future research are made.
The self‐management of psychiatric medications: a pilot study
Authors: DUBYNA J. , QUINN C.
Published: February 2008

The self‐management of psychiatric medications: a pilot study

This paper reports on a pilot study where a scheme for the self‐management of medication has been devised as an intervention strategy, where the mental health nurse and the mentally ill client work together to improve the client's knowledge of prescribed medication and medication‐related issues.

Aspects of non‐compliance and the various factors involved in the non‐compliance of psychiatric medications by the person who is severely mentally ill are discussed. When noncompliance to psychiatric medication is briefly examined, the complexity of the phenomena becomes increasingly apparent, confounding single intervention strategies, therefore as the phenomena is multidimensional, so must be any response.

A review of the literature, and from the past clinical experience of the authors, suggests that when there is an involved therapeutic alliance, and the active participation of both the client and the mental health nurse in a rehabilitation orientated self‐medication management scheme, a difference can occur for the client where their understanding of, and compliance with, psychiatric medication can improve. This could possibly improve the overall quality of life for the mentally ill person.

Within a psychosocial rehabilitation setting, a self‐medication management scheme has been developed that gradually facilitates the client's responsibility for managing their own prescribed medication, and in conjunction with this increased awareness of their medication and related issues, the focus eventually leads to the client having complete responsibility for managing their own medication.

This self‐medication management scheme consists of several graded stages that are contractual in nature, in which the clients and nurses are active participants. A rating and self‐reporting scale has been developed within the scheme and is used by both the nurse and the client to assist in gauging the client's understanding and knowledge of issues related to their medication use. This self‐medication management scheme has demonstrated that when severely mentally ill persons are given the opportunity to practice and manage their own medication as a component of the rehabilitative process, a self‐medication management scheme does make a difference.
Suicide in Northern Ireland: a comparison of two quinquennia (1982–1986 and 1987–1991)
Authors: McLAUGHLIN C. , WHITTINGTON D.
Published: February 2008

This study compares government records of death by suicide, in Northern Ireland, during two quinquennia in the decade 1982–1991. Specifically these quinquennia are 1982–1986 l 1987–1991. During the latter quinquennium there was an increse m rate for males in most age groups, except the 45–54 and the over 65 years age groups. However, females had an increased rate in the 15–24 and 35–54 years age groups, but have a decreased rate in the other age groups. There has been a decrease in the rate of suicides by poisoning with solids and liquids for both sexes. However, male suicide rates by more violent methods have increased substantially during the latter quinquennium. Three cohorts of males, those in the 15–24, 25–34, and 55–64 age groups, have shown substantial increases during the latter quinquennium. Suggestions for psychiatric intervention strategies are made.
Responses of individual stomata in Ipomoea pes‐caprae to various CO2 concentrations
Authors: Kamakura Mai , Furukawa Akio
Published: February 2008

The responses of individual stomata to CO2 concentrations ranging from 0 to 900 μmol mol−1 air were analysed in Ipomoea pes‐caprae L. Sweet (Convolvulaceae). The stomata were directly observed using a measurement system that permitted continuous observation of stomatal movement under controlled light and CO2 conditions. A CO2 concentration of 350 μmol mol−1 or higher induced stomatal closure, whereas concentrations below 350 μmol mol−1 did not. The time lag before stomatal closure decreased with increasing CO2 concentration, as did the steady‐state aperture of the stomata after a change in CO2 concentration. However, the rate of stomatal closure increased with increasing CO2 concentration. Therefore, not only the stomatal closure rate but also the time from the CO2 concentration change to the beginning of stomatal closure changed with increasing CO2 concentration. These results suggest that atmospheric CO2 may be the stimulus for the closure of guard cells. No significant differences were observed between adaxial and abaxial stomata in terms of their responses to CO2. However, heterogeneous responses were detected between neighbouring stomata on each leaf surface.
Cav1 L‐type Ca2+ channel signaling complexes in neurons
Authors: Calin‐Jageman Irina , Lee Amy
Published: February 2008

Cav1 L‐type Ca2+ channels play crucial and diverse roles in the nervous system. The pre‐ and post‐synaptic functions of Cav1 channels not only depend on their intrinsic biophysical properties but also their dynamic regulation by a host of cellular influences. These include protein kinases and phosphatases, G‐protein coupled receptors, scaffolding proteins, and Ca2+‐binding proteins. The cytoplasmic domains of the main pore forming α1 subunit of Cav1 offer a number of binding sites for these modulators, permitting fast and localized regulation of Ca2+ entry. Through effects on Cav1 gating, localization, and coupling to effectors, protein modulators are efficiently positioned to adjust Cav1 Ca2+ signals that control neuronal excitability, synaptic plasticity, and gene expression.
A test of a winter farm management option for mitigating nitrous oxide emissions from a dairy farm
Authors: Luo J. , Ledgard S. F. , Lindsey S. B.
Published: February 2008

A trial was conducted in 2004 and 2005 to evaluate the effect of a stand‐off winter stock management system on nitrous oxide (N2O) emissions from a dairy farm in New Zealand. The management system consisted of removing cows from pasture after grazing for 6 h per day and keeping them on a stand‐off pad for the rest of the day during the late autumn/winter seasons in order to reduce soil physical damage because of grazing on wet soils. The N2O emissions were measured on pasture that was grazed either for all day or for 6 h. The N2O emissions from the stand‐off pad were also measured. A closed chamber technique was used for measuring N2O fluxes. The New Zealand International Panel for Climate Change inventory methodology was used to calculate annual N2O emissions from land application of farm effluent, leached and volatilized N. Significantly lower (P < 0.05) N2O emission rates were found when the stand‐off grazed pasture was compared to the control in the winter seasons when soil was wet. Total N2O emission rates measured over one grazing interval in the late autumn/winter (May–August) in 2004 were 2.72 and 1.21 kg N2O‐N/ha for the control and the stand‐off grazed pastures, respectively. The respective emissions in 2005 were 0.97 and 0.22 kg N2O‐N/ha. When all possible sources contributing to emissions of N2O (both measured and calculated from the non‐measured sources) were included, total annual emissions of 7.7 and 7.0 kg N2O‐N per hectare of grazed pasture in the control and stand‐off treatments, respectively, were estimated. These results suggest that the use of stand‐off pads as a management practice during the wet seasons can be effective at reducing N2O emissions from dairy farm systems.
Epilepsy surgery in patients with normal or nonfocal MRI scans: Integrative strategies offer long‐term seizure relief
Authors: Jayakar Prasanna , Dunoyer Catalina , Dean Pat , Ragheb John , Resnick Trevor , Morrison Glenn , Bhatia Sanjiv , Duchowny Michael
Published: February 2008

Summary

Purpose:Excisional surgery achieves seizure freedom in a large proportion of children with intractable lesional epilepsy, but the outcome for children without a focal lesion on MRI is less clear. We report the outcome of a cohort predominantly of children with nonlesional intractable partial epilepsy undergoing resective surgery.

Methods:We studied 102 patients with nonlesional intractable partial epilepsy who underwent excisional surgery. The epileptogenic region was identified by integrating clinical exam and video‐EEG data complemented by ictal SPECT (n = 40), PET (n = 10), extraoperative subdural monitoring (n = 80), and electrocorticography (n = 22). All patients had follow‐up greater than 2 years, 76 patients had 5‐year follow‐up, and 43 patients had 10‐year follow‐up.

Results:A total of 66 resections were unilobar; 36 were multilobar. One patient died of causes unrelated to seizures or surgery. At 2‐year follow‐up, 44 of 101 patients were seizure‐free, 15 experienced >90% reduction, 17 had >50% reduction, and 25 were unchanged. At 5‐year follow‐up, 35 of 76 patients were seizure‐free, 12 experienced >90% reduction, 12 had >50% reduction, and 17 were unchanged. At 10‐year follow‐up, 16 of 43 patients were seizure‐free, 13 experienced >90% reduction, 7 had >50% reduction, and 7 were unchanged.

Outcomes correlated with the presence of convergent focal interictal spikes (p < 0.005) on the scalp EEG and completeness of resection (p < 0.0005).

Conclusions:Our findings demonstrate that excisional surgery is successful in the majority of children with nonlesional partial epilepsy. A multimodal integrative approach can minimize the size of resection and alleviate the need for invasive EEG monitoring. Focal interictal spikes and completeness of resection predict good outcome. The benefits of surgery are long‐lasting.
When Predictions Fail: The Case of Unexpected Pathways Toward High School Dropout
Authors: Pagani Linda S. , Vitaro Frank , Tremblay Richard E. , McDuff Pierre , Japel Christa , Larose Simon
Published: February 2008

This study examines childhood variables that tend to deflect life‐course trajectories away from finishing high school. We examined unexpectedly graduating in the presence of three empirical risk factors (having a mother that did not finish high school, being from a single‐parent family in early childhood, and having repeated a grade in primary school) and unexpectedly not graduating in the absence these same factors (low risk). The comparison groups comprised individuals who expectedly did not graduate (first case) and expectedly graduated (second case). We found that having experienced all three factors practically guaranteed not finishing high school, thus defining a crystal clear target group for policy. Without screening, intervention, and follow‐up, individuals facing such cumulative risk are most unlikely to graduate. We also found a group of males and females that did not finish high school despite not having these three risk factors. These missed estimates become nontrivial once they are translated into a population‐level statistic of lost human capital investments. Specific family and individual factors helped explain the unexpected life course toward not finishing high school, especially for low‐risk males and females. Our results suggest policies that support childhood screening for attention‐related difficulties and helping parents better understand supervision during adolescence.
Varying Coefficient Model with Unknown Within‐Subject Covariance for Analysis of Tumor Growth Curves
Authors: Krafty Robert T. , Gimotty Phyllis A. , Holtz David , Coukos George , Guo Wensheng
Published: February 2008

SummaryIn this article we develop a nonparametric estimation procedure for the varying coefficient model when the within‐subject covariance is unknown. Extending the idea of iterative reweighted least squares to the functional setting, we iterate between estimating the coefficients conditional on the covariance and estimating the functional covariance conditional on the coefficients. Smoothing splines for correlated errors are used to estimate the functional coefficients with smoothing parameters selected via the generalized maximum likelihood. The covariance is nonparametrically estimated using a penalized estimator with smoothing parameters chosen via a Kullback–Leibler criterion. Empirical properties of the proposed method are demonstrated in simulations and the method is applied to the data collected from an ovarian tumor study in mice to analyze the effects of different chemotherapy treatments on the volumes of two classes of tumors.
Hospital and Demographic Influences on the Disposition of Transient Ischemic Attack
Authors: Coben Jeffrey H. , Owens Pamela L. , Steiner Claudia A. , Crocco Todd J.
Published: February 2008

Objectives:  There is substantial variation in the emergency department (ED) disposition of patients with transient ischemic attack (TIA), and the factors responsible for this variation have not been determined. In this study, the authors examined the influence of clinical, sociodemographic, and hospital characteristics on ED disposition.

Methods:  All ED‐treated TIA cases from community hospitals in 11 states were identified from the 2002 Healthcare Cost and Utilization Project (HCUP). Using the aggregate data, descriptive analyses compared admitted and discharged cases. Pearson’s chi‐square test was used to determine the statistical significance of these comparisons. Based on the results of the bivariate analyses, logistic regression models of the likelihood of hospital admission were derived, using a stepwise selection process. Adjusted risk ratios and 95% confidence intervals (CI) were calculated from the logistic regression models.

Results:  A total of 34,843 cases were identified in the 11 states, with 53% of cases admitted to the hospital. In logistic regression models, differences in admission status were found to be strongly associated with clinical characteristics such as age and comorbidities. After controlling for comorbidities, differences in admission status were also found to be associated to hospital type and with sociodemographic characteristics, including county of residence and insurance status.

Conclusions:  While clinical factors predictably and appropriately impact the ED disposition of patients diagnosed with TIA, several nonclinical factors are also associated with differences in disposition. Additional research is needed to better understand the basis for these disparities and their potential impact on patient outcomes.
Nurse‐led prostate assessment clinics – are they fit for purpose?
Authors: Pisipati Sailaja , Bromage Stephen J , Fraser Kate , Dickens Joanne , Ladds Thomas , Pearce Ian
Published: February 2008

Nurse‐led prostate assessment clinics (PACs) have been shown to be both cost‐effective and reduce the workload of urologists. We set out to determine how closely guidelines were adhered to in our PAC and whether the outcomes of these clinics, as determined by set protocols, were producing effective management strategies. The notes of 100 consecutive patients who attended the PAC at a single institution were retrospectively analysed. The presenting symptoms, examination findings, investigations performed and their results were documented, and the consultation outcome was recorded. In particular, we assessed whether the guidelines for investigations and management were followed and whether there were any changes in these following consultant review. Of the 100 patients (mean age 67 years), 79 were referred from primary care. The most common presenting symptoms were frequency and nocturia. Ninety‐two per cent of patients were appropriately assigned to the PAC. Eighty‐two per cent had a complete assessment according to the clinic guidelines. Patient management was appropriate and based on clinic guidelines in 81%. Following consultant review, 78% had no change in their management, while 26% were discharged. Nurse‐led PACs are fit for purpose. Guidelines for assessment and management are closely followed with minimal changes to treatment at consultant review.
A Simple Technique for Determining Slug Frequency Using Differential Pressure
Authors: Wilkens R. J. , Thomas D. K.
Published: February 2008

An experiment was performed to study air∕water slug frequency in a horizontal clear pipe by means of visual inspection and differential pressure measurement in the range of 0–1∕s. Results showed that a simplified model for slug pressure drop allowed the differential pressure data to compare favorably with visual observations for slug frequency. It was concluded that this technique gives a proper estimation of slug frequency, given only basic flow information. It is recommended that this technique be used when constrained to differential pressure or used to analyze existing differential pressure data.
Experienced Saxophonists Learn to Tune Their Vocal Tracts
Authors: Chen Jer Ming , Smith John , Wolfe Joe
Published: February 2008

Acousticians have long debated whether and how the resonances of the vocal tract are involved in the playing of clarinet and saxophone. We measured the resonances of saxophonists' vocal tracts directly while they played. Over most of the instrument's range, there is no simple relation between tract resonances and the note played, and the tract resonances varied among players. In the high (altissimo) range, a strong resonance of the tracts of professional saxophonists was systematically tuned slightly above the desired note. Amateurs, who did not tune a strong resonance, were unable to play notes in the altissimo range.
Similar Cytokine Responses and Degrees of Anemia in Patients withPlasmodium falciparumandPlasmodium vivaxInfections in the Brazilian Amazon Region
Authors: Fernandes Andréa Aparecida Morais , de Moura Carvalho Leonardo José , Zanini Graziela Maria , da Silva Ventura Ana Maria Revorêdo , Souza José Maria , Cotias Paulo Marcelo , Silva-Filho Isaac Lima , Daniel-Ribeiro Cláudio Tadeu
Published: February 2008

The mechanisms of malarial anemia induction are poorly understood, but cytokines and autoantibodies are considered to play important roles. This work aimed at evaluating the degree of anemia and the plasmatic profile of the cytokines tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), interleukin-12 (IL-12), migration inhibitory factor (MIF), and IL-10 and the monocyte chemotactic protein-1 (MCP-1) chemokine, as well as evaluating the presence of antibodies directed to components of the normal erythrocyte membrane and to cardiolipin in individuals with malaria from the Brazilian Amazon. No difference was observed in the frequency of anemia between patients infected byPlasmodium vivaxand those infected byPlasmodium falciparum, and there was no relationship between the levels of parasitemia and the manifestations of anemia inP. vivaxandP. falciparumpatients. Significant increases in the concentrations of TNF-α, IFN-γ, MIF, and MCP-1 were observed in patients withP. falciparumandP. vivaxmalaria, whereas the concentrations of IL-10 was increased only in patients withP. vivaxinfection. Higher concentrations of IL-12 and IL-10 were observed in theP. falciparumanemic patients, while for TNF-α this profile was observed in the nonanemic ones.P. vivax-infected andP. falciparum-infected patients with positive immunoglobulin M (IgM) or IgM and IgG responses, respectively, against blood-stage forms of the parasites had significantly lower hemoglobin levels than did those with negative responses. There was no correlation between the presence of anti-erythrocyte and anti-cardiolipin antibodies and the presence or intensity of the anemia. Our data suggest that in areas of low endemicity and unstable transmission of malaria,P. vivaxandP. falciparuminfections present similar characteristics in terms of the induction of anemia and cytokine responses.
Sitka alder, a candidate for mixed stands
Authors: Harrington Constance A. , Deal Robert L.
Published: February 2008

Juvenile height growth of Sitka alder (Alnussinuata (Regel) Rydb.), a nitrogen-fixing shrub, was examined on eight sites. The potential compatibility of mixed stands of Sitka alder and Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco) was then assessed by comparing height-growth curves of the two species at early ages. Based on Sitka alder's low height and early slowdown in height growth, it appears to be a reasonable candidate for mixed stands on sites where additions of nitrogen or organic matter are desirable. On poor quality Douglas-fir sites, however, Douglas-fir should be given a head start to insure that it is not suppressed.
Seed Storage Oil Mobilization
Authors: Graham Ian A.
Published: February 2008

Storage oil mobilization starts with the onset of seed germination. Oil bodies packed with triacylglycerol (TAG) exist in close proximity with glyoxysomes, the single membrane–bound organelles that house most of the biochemical machinery required to convert fatty acids derived from TAG to 4-carbon compounds. The 4-carbon compounds in turn are converted to soluble sugars that are used to fuel seedling growth. Biochemical analysis over the last 50 years has identified the main pathways involved in this process, including β-oxidation, the glyoxylate cycle, and gluconeogenesis. In the last few years molecular genetic dissection of the overall process in the model oilseed species Arabidopsis has provided new insight into its complexity, particularly with respect to the specific role played by individual enzymatic steps and the subcellular compartmentalization of the glyoxylate cycle. Both abscisic acid (ABA) and sugars inhibit storage oil mobilization and a substantial degree of the control appears to operate at the transcriptional level.
Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells
Authors: Yang Cheng , Kaushal Varsha , Shah Sudhir V. , Kaushal Gur P.
Published: February 2008

Autophagy has emerged as another major “programmed” mechanism to control life and death much like “programmed cell death” is for apoptosis in eukaryotes. We examined the expression of autophagic proteins and formation of autophagosomes during progression of cisplatin injury to renal tubular epithelial cells (RTEC). Autophagy was detected as early as 2–4 h after cisplatin exposure as indicated by induction of LC3-I, conversion of LC3-I to LC3-II protein, and upregulation of Beclin 1 and Atg5, essential markers of autophagy. The appearance of cisplatin-induced punctated staining of autophagosome-associated LC3-II upon GFP-LC3 transfection in RTEC provided further evidence for autophagy. The autophagy inhibitor 3-methyladenine blocked punctated staining of autophagosomes. The staining of normal cells with acridine orange displayed green fluorescence with cytoplasmic and nuclear components in normal cells but displayed considerable red fluorescence in cisplatin-treated cells, suggesting formation of numerous acidic autophagolysosomal vacuoles. Autophagy inhibitors LY294002 or 3-methyladenine or wortmannin inhibited the formation of autophagosomes but induced apoptosis after 2–4 h of cisplatin treatment as indicated by caspase-3/7 and -6 activation, nuclear fragmentation, and cell death. This switch from autophagy to apoptosis by autophagic inhibitors further suggests that the preapoptotic lag phase after treatment with cisplatin is mediated by autophagy. At later stages of cisplatin injury, apoptosis was also found to be associated with autophagy, as autophagic inhibitors and inactivation of autophagy proteins Beclin 1 and Atg5 enhanced activation of caspases and apoptosis. Our results demonstrate that induction of autophagy mounts an adaptive response, suppresses cisplatin-induced apoptosis, and prolongs survival of RTEC.
The Pool of Fast Releasing Vesicles Is Augmented by Myosin Light Chain Kinase Inhibition at the Calyx of Held Synapse
Authors: Srinivasan Geetha , Kim Jun Hee , von Gersdorff Henrique
Published: February 2008

Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca2+currents or action potential waveform. Moreover, Ca2+imaging experiments showed that [Ca2+]itransients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca2+buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.
Rostral Versus Caudal Differences in Mechanical Entrainment of the Lamprey Central Pattern Generator for Locomotion
Authors: Tytell Eric D. , Cohen Avis H.
Published: February 2008

In fishes, undulatory swimming is produced by sets of spinal interneurons constituting a central pattern generator (CPG). The CPG generates waves of muscle activity that travel from head to tail, which then bend the body into wave shapes that also travel from head to tail. In many fishes, the wavelengths of the neural and mechanical waves are different, resulting in a rostral-to-caudal gradient in phase lag between muscle activity and bending. The neural basis of this phase gradient was investigated in the lamprey spinal cord using an isolated in vitro preparation. Fictive swimming was induced using d-glutamate and the output of the CPG was measured using suction electrodes placed on the ventral roots. The spinal cord was bent sinusoidally at various points along its length. First, the ranges of entrainment were estimated. Middle segments were able to entrain to frequencies approximately twice as high as those at end segments. Next, phase lags between centers of ventral root bursts and the stimulus were determined. Two halves of the cycle were identified: stretching and shortening of the edge of spinal cord on the same side as the electrode. Stimuli at rostral segments tended to entrain segmental bursting at the beginning of the stretch phase, almost 50% out of phase with previously measured in vivo electromyography data. Stimuli at caudal segments, in contrast, entrained segments at the end of stretch and the beginning of shortening, approximately the same phase as in vivo data.
Genetic and Clinical Features of P450 Oxidoreductase Deficiency
Authors: Scott Rachel R. , Miller Walter L.
Published: February 2008

P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder of steroidogenesis with multiple clinical manifestations. POR is the electron donor for all microsomal P450 enzymes, including the three steroidogenic enzymes P450c17 (17α-hydroxylase/17,20-lyase), P450c21 (21-hydroxylase), and P450aro (aromatase). Since the first description of POR mutations in 2004, about 50 patients have been reported. Serum steroid profiles indicate partial deficiencies in 21-hydroxylase, 17α-hydroxylase and 17,20-lyase. The 17-OH progesterone levels are elevated, as in 21-hydroxylase deficiency, while androgen levels are low; cortisol may be normal but is poorly responsive to adrenocorticotropic hormone. Most patients also have associated skeletal malfor- mations (craniosynostosis, radio-ulnar synostosis, midface hypoplasia, bowed femora) termed Antley-Bixler syndrome. Antley-Bixler syndrome with normal steroidogenesis is caused by autosomal dominant gain-of-function mutations in fibroblast growth factor receptor 2. Males with POR deficiency are often undervirilized, while females can be virilized. The prognosis for patients with POR deficiency appears to depend on the severity of the bony malformations and their timely treatment. The potential impact of POR mutations on drug metabolism by other hepatic P450 enzymes requires further investigation. Given the varied physical and biochemical phenotype of POR deficiency and the risk of adrenal insufficiency, clinicians should be alert to this potential diagnosis.
Testicular Expressed Genes Are Missing in Familial X-Linked Kallmann Syndrome due to Two Large Different Deletions in Daughter’s X Chromosomes
Authors: Hershkovitz Eli , Loewenthal Neta , Peretz Asaf , Parvari Ruti
Published: February 2008

Background: X-linked Kallmann syndrome (KS) is caused mainly by point mutations, in the KAL1 gene. Large deletions >1 Mb are rare events in the human population and commonly result in contiguous gene syndromes. Methods: A search for the mutation causing KS carried out on two pairs of first-degree cousins of 2 sisters. Results: Two different apparently independent deletions were found. The deleted sequences encompass the KAL1 gene and four known additional genes exclusively expressed in testis. Two of these genes belong to the FAM9 gene family, which shares some homology with the SCYP3 gene, previously implicated in azoospermia. One of the events causing the deletion may have been mediated by an L1 transposition, the other by a non-homologous end joining. Such non-homologous recombinations have not yet been reported in the KAL genomic region and thus this area may be more prone to deletions than previously expected. Conclusions: This is the first report on genetic characterization of KS with a deletion of solely testis-expressed genes. The absence of these genes may have unfavorable implications for the patients regarding future fertility.
Variation in Growth Hormone Immunoassays in Clinical Practice in Canada
Authors: Amed Shazhan , Delvin Edgard , Hamilton Jill
Published: February 2008

Background/Aims: The diagnosis of growth hormone (GH) deficiency in children in Canada is based on clinical, auxological, radiographic and biochemical criteria which include response to provocative GH testing. The objective of this study was to determine the variability of GH assays used at Canadian pediatric hospitals. Methods: Pooled samples of patient sera were generated at a single center and tested at 15 laboratories across Canada using local GH assays. Additional samples were analyzed using the most commonly employed assays. Results: DSL and AutoDelfia© assays measured lower for all samples. Linear regression analysis demonstrated excellent correlation between Access 2©, AutoDelfia, and Immulite 2000©, however, Bland-Altman plots revealed bias when comparing these assays. Conclusions: Adequate comparison and standardization of commercially available GH immunoassays is necessary to ensure consistent interpretation of results.