bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct image of a molecular orientation of a liquid crystal using directional polymerization of photoreactive mesogen
Authors: Lee You-Jin , Yu Chang-Jae , Kim Young-Ki , Jo Soo In , Kim Jae-Hoon
Published: January 2011

We present a method for visualizing the geometrical distribution of a liquid crystal (LC) arrangement using the replication of the molecular orientation by a mixture of alignment layers. We found that the anisotropic diffusion of the reactive mesogen (RM) monomers, mixed with an alignment layer, in contact with the LC was governed by the LC director through application of external voltage and allowed the directional polymerization under ultraviolet light illumination. The directional polymerization of a RM transferred and visualized the LC arrangement even at optically indistinct LC distributions.
Cut homeobox 1 causes chromosomal instability by promoting bipolar division after cytokinesis failure
Authors: Sansregret Laurent , Vadnais Charles , Livingstone Julie , Kwiatkowski Nicholas , Awan Arif , Cadieux Chantal , Leduy Lam , Hallett Michael T. , Nepveu Alain
Published: January 2011

Cell populations able to generate a large repertoire of genetic variants have increased potential to generate tumor cells that survive through the multiple selection steps involved in tumor progression. A mechanism for the generation of aneuploid cancer cells involves passage through a tetraploid stage. Supernumerary centrosomes, however, can lead to multipolar mitosis and cell death. Using tissue culture and transgenic mouse models of breast cancer, we report that Cut homeobox 1 (CUX1) causes chromosomal instability by activating a transcriptional program that prevents multipolar divisions and enables the survival of tetraploid cells that evolve to become genetically unstable and tumorigenic. Transcriptional targets of CUX1 involved in DNA replication and bipolar mitosis defined a gene expression signature that, across 12 breast cancer gene expression datasets, was associated with poor clinical outcome. The signature not only was higher in breast tumor subtypes of worse prognosis, like the basal-like and HER2
+
subtypes, but also identified poor outcome among estrogen receptor-positive/node-negative tumors, a subgroup considered to be at lower risk. The CUX1 signature therefore represents a unique criterion to stratify patients and provides insight into the molecular determinants of poor clinical outcome.
Tension-dependent structural deformation alters single-molecule transition kinetics
Authors: Sudhanshu B. , Mihardja S. , Koslover E. F. , Mehraeen S. , Bustamante C. , Spakowitz A. J.
Published: January 2011

We analyze the response of a single nucleosome to tension, which serves as a prototypical biophysical measurement where tension-dependent deformation alters transition kinetics. We develop a statistical-mechanics model of a nucleosome as a wormlike chain bound to a spool, incorporating fluctuations in the number of bases bound, the spool orientation, and the conformations of the unbound polymer segments. With the resulting free-energy surface, we perform dynamic simulations that permit a direct comparison with experiments. This simple approach demonstrates that the experimentally observed structural states at nonzero tension are a consequence of the tension and that these tension-induced states cease to exist at zero tension. The transitions between states exhibit substantial deformation of the unbound polymer segments. The associated deformation energy increases with tension; thus, the application of tension alters the kinetics due to tension-induced deformation of the transition states. This mechanism would arise in any system where the tether molecule is deformed in the transition state under the influence of tension.
Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying
Authors: Janssen Sara , Laermans Jorien , Verhulst Pieter-Jan , Thijs Theo , Tack Jan , Depoortere Inge
Published: January 2011

Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (
i
) ghrelin release via α-gustducin and (
ii
) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust
−/−
mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust
−/−
and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust
−/−
mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.
Blockade of TNF-α rapidly inhibits pain responses in the central nervous system
Authors: Hess Andreas , Axmann Roland , Rech Juergen , Finzel Stefanie , Heindl Cornelia , Kreitz Silke , Sergeeva Marina , Saake Marc , Garcia Meritxell , Kollias George , Straub Rainer H. , Sporns Olaf , Doerfler Arnd , Brune Kay , Schett Georg
Published: January 2011

There has been a consistent gap in understanding how TNF-α neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-α acts through the CNS before directly affecting joint inflammation. Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-α, nociceptive CNS activity in the thalamus and somatosensoric cortex, but also the activation of the limbic system, is blocked. Brain areas showing blood-oxygen level-dependent signals, a validated method to assess neuronal activity elicited by pain, were significantly reduced as early as 24 h after an infusion of a monoclonal antibody to TNF-α. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-α at these early time points. Moreover, arthritic mice overexpressing human TNF-α showed an altered pain behavior and a more intensive, widespread, and prolonged brain activity upon nociceptive stimuli compared with wild-type mice. Similar to humans, these changes, as well as the rewiring of CNS activity resulting in tight clustering in the thalamus, were rapidly reversed after neutralization of TNF-α. These results suggest that neutralization of TNF-α affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints.
Funneling of gibberellin signaling by the GRAS transcription regulator SCARECROW-LIKE 3 in the
Arabidopsis
root
Authors: Heo Jung-Ok , Chang Kwang Suk , Kim In A , Lee Mi-Hyun , Lee Shin Ae , Song Sang-Kee , Lee Myeong Min , Lim Jun
Published: January 2011

During plant development, because no cell movement takes place, control of the timing and extent of cell division and coordination of the direction and extent of cell expansion are particularly important for growth and development. The plant hormone gibberellins (GAs) play key roles in the control of these developmental processes. However, little is known about the molecular components that integrate the generic GA signaling into a specific cell/tissue to coordinate cell division and cell expansion. Here we report that SCARECROW-LIKE 3 (SCL3), a GRAS protein, acts as a positive regulator to integrate and maintain a functional GA pathway by attenuating the DELLA repressors in the root endodermis. The tissue-specific maintenance of GA signaling in the root endodermis plays distinct roles along the longitudinal root axis. While in the elongation/differentiation zone (EDZ), the endodermis-confined GA pathway by SCL3 controls primarily coordination of root cell elongation; in the meristem zone (MZ) SCL3 in conjunction with the SHORT-ROOT/SCARECROW (SHR/SCR) pathway controls GA-modulated ground tissue maturation. Our findings highlight the regulatory network of the GRAS transcription regulators (SCL3, DELLAs, and SHR/SCR) in the root endodermis, shedding light on how GA homeostasis is achieved and how the maintenance of GA signaling controls developmental processes in roots.
Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation
Authors: Gapud Eric J. , Dorsett Yair , Yin Bu , Callen Elsa , Bredemeyer Andrea , Mahowald Grace K. , Omi Kazuo Q. , Walker Laura M. , Bednarski Jeffrey J. , McKinnon Peter J. , Bassing Craig H. , Nussenzweig Andre , Sleckman Barry P.
Published: January 2011

Lymphocyte antigen receptor gene assembly occurs through the process of V(D)J recombination, which is initiated when the RAG endonuclease introduces DNA DSBs at two recombining gene segments to form broken DNA coding end pairs and signal end pairs. These paired DNA ends are joined by proteins of the nonhomologous end-joining (NHEJ) pathway of DSB repair to form a coding joint and signal joint, respectively. RAG DSBs are generated in G1-phase developing lymphocytes, where they activate the ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases to orchestrate diverse cellular DNA damage responses including DSB repair. Paradoxically, although Atm and DNA-PKcs both function during coding joint formation, Atm appears to be dispensible for signal joint formation; and although some studies have revealed an activity for DNA-PKcs during signal joint formation, others have not. Here we show that Atm and DNA-PKcs have overlapping catalytic activities that are required for chromosomal signal joint formation and for preventing the aberrant resolution of signal ends as potentially oncogenic chromosomal translocations.
A multiply convergent platform for the synthesis of trioxacarcins
Authors: Švenda Jakub , Hill Nicholas , Myers Andrew G.
Published: January 2011

Many first-line cancer drugs are natural products or are derived from them by chemical modification. The trioxacarcins are an emerging class of molecules of microbial origin with potent antiproliferative effects, which may derive from their ability to covalently modify duplex DNA. All trioxacarcins appear to be derivatives of a nonglycosylated natural product known as DC-45-A2. To explore the potential of the trioxacarcins for the development of small-molecule drugs and probes, we have designed a synthetic strategy toward the trioxacarcin scaffold that enables access to both the natural trioxacarcins and nonnatural structural variants. Here, we report a synthetic route to DC-45-A2 from a differentially protected precursor, which in turn is assembled in just six steps from three components of similar structural complexity. The brevity of the sequence arises from strict adherence to a plan in which strategic bond-pair constructions are staged at or near the end of the synthetic route.
Design, synthesis, and biological evaluation of a biyouyanagin compound library
Authors: Nicolaou K. C. , Sanchini Silvano , Sarlah David , Lu Gang , Wu T. Robert , Nomura Daniel K. , Cravatt Benjamin F. , Cubitt Beatrice , de la Torre Juan C. , Hessell Ann J. , Burton Dennis R.
Published: January 2011

Modern drug discovery efforts rely, to a large extent, on lead compounds from two classes of small organic molecules; namely, natural products (i.e., secondary metabolites) and designed compounds (i.e., synthetic molecules). In this article, we demonstrate how these two domains of lead compounds can be merged through total synthesis and molecular design of analogs patterned after the targeted natural products, whose promising biological properties provide the motivation. Specifically, the present study targeted the naturally occurring biyouyanagins A and B and their analogs through modular chemical synthesis and led to the discovery of small organic molecules possessing anti-HIV and anti-arenavirus properties.
Climate change induces demographic resistance to disease in novel coral assemblages
Authors: Yakob Laith , Mumby Peter J.
Published: January 2011

Climate change is reshaping biological communities and has already generated novel ecosystems. The functioning of novel ecosystems could depart markedly from that of existing systems and therefore obscure the impacts of climate change. We illustrate this possibility for coral reefs, which are at the forefront of climatic stress. Disease has been a principal cause of reef degradation and is expected to worsen with increased future thermal stress. However, using a field-tested epizoological model, we show that high population turnover within novel ecosystems enhances coral resistance to epizootics. Thus, disease could become a less important driver of change in the future. We emphasize the need to move away from projections based on historic trends toward predictions that account for novel behavior of ecosystems under climate change.
Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII
Authors: Hu Chuhong , Cela Racel G. , Suzuki Masataka , Lee Brendan , Lipshutz Gerald S.
Published: January 2011

Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential “cure.” Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.
Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating β-catenin
Authors: Fiedler Marc , Mendoza-Topaz Carolina , Rutherford Trevor J. , Mieszczanek Juliusz , Bienz Mariann
Published: January 2011

Wnt/β-catenin signaling controls numerous steps in normal animal development and can also cause cancer if inappropriately activated. In the absence of Wnt, β-catenin is targeted continuously for proteasomal degradation by the Axin destruction complex, whose activity is blocked upon Wnt stimulation by Dishevelled, which recruits Axin to the plasma membrane and assembles it into a signalosome. This key event during Wnt signal transduction depends on dynamic head-to-tail polymerization by the DIX domain of Dishevelled. Here, we use rescue assays in
Drosophila
tissues and functional assays in human cells to show that polymerization-blocking mutations in the DIX domain of Axin disable its effector function in down-regulating Armadillo/β-catenin and its response to Dishevelled during Wnt signaling. Intriguingly, NMR spectroscopy revealed that the purified DIX domains of the two proteins interact with each other directly through their polymerization interfaces, whereby the same residues mediate both homo- and heterotypic interactions. This result implies that Dishevelled has the potential to act as a “natural” dominant-negative, binding to the polymerization interface of Axin's DIX domain to interfere with its self-assembly, thereby blocking its effector function.
Regional rescue of spinocerebellar ataxia type 1 phenotypes by
14-3-3
ε haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration
Authors: Jafar-Nejad Paymaan , Ward Christopher S. , Richman Ronald , Orr Harry T. , Zoghbi Huda Y.
Published: January 2011

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a CAG repeat encoding a polyglutamine tract in Ataxin-1 (ATXN1). Both WT and mutant ATXN1 interact with 14-3-3 proteins, and 14-3-3 overexpression stabilizes ATXN1 levels in cells and increases ATXN1 toxicity in flies. To determine whether reducing 14-3-3 levels might mitigate SCA1 pathogenesis, we bred
Sca1
154Q/+
mice to mice lacking one allele of
14-3-3
ε.
14-3-3
ε haploinsufficiency rescued cerebellar pathology and motor phenotypes but, surprisingly, not weight loss, respiratory dysfunction, or premature lethality. Biochemical studies revealed that reducing
14-3-3
ε levels exerted different effects in two brain regions especially vulnerable in SCA1: Although diminishing levels of both WT and mutant ATXN1 in the cerebellum,
14-3-3
ε haploinsufficiency did not alter ATXN1 levels in the brainstem. Furthermore,
14-3-3
ε haploinsufficiency decreased the incorporation of expanded ATXN1 into its large toxic complexes in the cerebellum but not in the brainstem, and the distribution of ATXN1’s small and large native complexes differed significantly between the two regions. These data suggest that distinct pathogenic mechanisms operate in different vulnerable brain regions, adding another level of complexity to SCA1 pathogenesis.
A modest decrease in endothelial NOS in mice comparable to that associated with human
NOS3
variants exacerbates diabetic nephropathy
Authors: Wang Chih-Hong , Li Feng , Hiller Sylvia , Kim Hyung-Suk , Maeda Nobuyo , Smithies Oliver , Takahashi Nobuyuki
Published: January 2011

Polymorphisms in the human endothelial nitric oxide synthase (eNOS) gene (
NOS3
) have been associated with advanced nephropathy in diabetic patients and with decreased expression in tissue culture. However, direct proof that modest genetic decreases in
eNOS
expression worsen diabetic nephropathy is lacking. To investigate this effect, we took advantage of the hybrid vigor and genetic uniformity of the F1 progeny (eNOS
+/+
, eNOS
+/−
, or eNOS
−/−
with or without diabetes) of a cross between heterozygous 129S6/SvEvTac eNOS
+/−
inbred females and heterozygous C57BL/6J eNOS
+/−
inbred males carrying the dominant Akita diabetogenic mutation
Ins2
C96Y/+
. Whereas all C57BL/6J inbred eNOS
−/−
and eNOS
+/−
diabetic mice died before 5 mo, almost half of the F1 hybrid eNOS
−/−
and eNOS
+/−
diabetic mice lived until killed at 7 mo. Heterozygous eNOS
+/−
diabetic mice expressed ∼35%
eNOS
mRNA in the kidney and ∼25% glomerular eNOS protein relative to their eNOS
+/+
diabetic littermates. These decreases in eNOS elevated blood pressure (BP) but not blood glucose. Urinary albumin excretion, mesangial expansion, glomerulosclerosis, mesangiolysis, and glomerular filtration rate increased in the order: eNOS
+/+
Akita < eNOS
+/−
Akita < eNOS
−/−
Akita, independently of BP. Glomerular basement membrane thickening depended on increased BP. Renal expression of tissue factor and other inflammatory factors increased with the nephropathy;
Nos2
also increased. Surprisingly, however, decreased
eNOS
expression ameliorated the increases in oxidative stress and tubulointerstitial fibrosis caused by diabetes. Our data demonstrate that a modest decrease in eNOS, comparable to that associated with human
NOS3
variants, is sufficient to enhance diabetic nephropathy independently of its effects on BP.
SPK-1, an SR protein kinase, inhibits programmed cell death in
Caenorhabditis elegans
Authors: Galvin Brendan D. , Denning Daniel P. , Horvitz H. Robert
Published: January 2011

To identify genes involved in protecting cells from programmed cell death in
Caenorhabditis elegans
, we performed a genetic screen to isolate mutations that cause an increase in the number of programmed cell deaths. We screened for suppressors of the cell-death defect caused by a partial loss-of-function mutation in
ced-4
, which encodes an Apaf-1 homolog that promotes programmed cell death by activating the caspase CED-3. We identified one extragenic
ced-4
suppressor, which has a mutation in the gene
spk-1
. The
spk-1
gene encodes a protein homologous to serine-arginine-rich (SR) protein kinases, which are thought to regulate splicing. Previous work suggests that
ced-4
can be alternatively spliced and that the splice variants function oppositely, with the longer transcript (
ced-4L
) inhibiting programmed cell death.
spk-1
might promote cell survival by increasing the amount of the protective
ced-4L
splice variant. We conclude that programmed cell death in
C. elegans
is regulated by an alternative splicing event controlled by the SR protein kinase SPK-1.
Killer cell Ig-like receptor (KIR) 3DL1 down-regulation enhances inhibition of type 1 diabetes by autoantigen-specific regulatory T cells
Authors: Qin Hanjun , Wang Zunde , Du Weiting , Lee Wen-Hui , Wu Xiwei , Riggs Arthur D. , Liu Chih-Pin
Published: January 2011

Both Foxp3+regulatory T cells (Tregs) and antigen-expanded Foxp3−Tregs play an important role in regulating immune responses as well as in preventing autoimmune diseases and graft rejection. Molecular mechanisms modulating Treg function remain largely unclear, however. We report here on the expression and function of an inhibitory killer cell Ig-like receptor, KIR3DL1, in a nonobese diabetic (NOD) mouse-derived autoantigen-specific Treg (2D2), which protects from type 1 diabetes (T1D) in adoptive transfer experiments. This gene is not expressed in T1D pathogenic T cells (Tpaths) or non-Tpath T cells. KIR genes are known to play an important role in regulating natural killer (NK) cell function, but their role in Tregs and T1D is unknown. To examine whether KIR3DL1 expression may modulate Treg function, we used shRNA to down-regulate KIR3DL1 expression (2D2-shKIR). We find that KIR3DL1 down-regulation enhances in vitro function, as measured by improved suppression of target cell proliferation. Antibody blockade of IL-10 but not IL-4 partially abrogated suppressive function. In vivo function is also improved. Adoptive transfer of 2D2-shKIR into 10-wk-old NOD mice prevented spontaneous insulitis and T1D, and the inhibitory effect was further improved if the cells were transferred earlier into 6-wk-old NOD mice. These studies indicate that KIR3DL1 expression may negatively regulate Treg function and suggest a previously undescribed target for improving immune tolerance for potential treatment of autoimmune diseases like T1D.
Senile and Arteriosclerotic Dementia—A Study of Personal, Social and Family Data
Authors: Davies G. Vernon , Teltscher Betty , Davies Brian
Published: January 2011

40 patients with senile dementia, 40 with arteriosclerotic dementia, and 40 people attending an elderly citizens' club have been compared with respect to certain social and personal data. The senile dementia group showed significant tendencies to positive family history, unusual personality characteristics and greater duration of widowhood.
Parental Deprivation and Psychiatric Illness in Old Age
Authors: McDonald Carrick
Published: January 2011

Early parental deprivation was identified from coded information in 1,103 case histories of psychiatric patients over the age of 60. Associations were sought between maternal, paternal or combined deprivation and any diagnostic category in this geriatric group.
Ethology and Psychiatry
Authors: Jones Ivor H.
Published: January 2011

Some of the principles underlying the science of ethology are described. Analogies are drawn between ethological and psychiatric observations in the psychiatric areas of reactions to separation, bereavement, depression, anxiety, sexual disorders and hysteria. It is suggested that in other areas also, notably obsessional states and schizophrenia, ethological concepts may be relevant. The implications and limitations of these analogies are briefly explored.
The Racially Different Psychiatrist—Implications for Psychotherapy
Authors: Varghese Frank T. N.
Published: January 2011

The race of the therapist can play a significant role in the manifestation of transference and counter-transference phenomena in inter-racial psychotherapy. References to the race of therapist may be the first sign of a developing transference relationship. Failure to appreciate the impact of racial difference can impede therapeutic progress while sensitive confrontation may be a valuable tool in the recognition and communication of emotionally charged feelings in therapy. Dream material is influenced by the race of the therapist who may be less easy to disguise in dreams, and the therapist may avoid certain dream interpretations because of unacknowledged discomfort about race. These observations have implications for the supervisory process in training and for the general issue of the influence of the person of the therapist on the process of psychotherapy.
The Utility of a Multivariate Normal Model for Studying Familial Patterns in Medical and Psychiatric Data
Authors: Hopper John L.
Published: January 2011

Quantitative traits (such as blood pressure, height or anxiety level) are usually more similar in related than in unrelated individuals. A positive correlation between two family members indicates that there are common factors (genetic and/or environmental) which predispose to the trait values in this pair of individuals. A negative correlation can indicate that there is (environmental) competition or some other cause for negative interaction between the pair of relatives. Using a flexible method for the analysis of quantitative data measured over pedigrees, it is possible to estimate the magnitude of the correlations between family members as a function of both their genetic relationship and their cohabitation history. This computer-based method can distinguish the effects of shared genes from some of the effects of shared family environment, and can identify negative interactions between family members which are likely to be of particular interest in studies of behavioural and psychiatric traits. The utility of this method is illustrated with pedigree data on blood lead levels, blood pressure levels and psychological traits.
Relaxation Training for Chronic Pain Patients Using Emg Feedback: An Analysis of Process and Outcome Effects
Authors: Spence N. D.
Published: January 2011

The purpose of the present study was to clarify the role of EMG-based relaxation training for a diverse group of chronic pain patients by examining in detail both process and outcome changes. Eighteen pain clinic patients were each given 10 sessions of relaxation training using frontalis feedback. The results of the study do not support the use of relaxation training as a standard procedure for chronic pain patients. Psychophysiological assessment carried out before and after training indicated some reduction in EMG levels, with less change in GSR and HR activity. No significant alteration occurred in mean pain and medication measures after training, although there was a trend for sedative/hypnotic usage to be smaller. Most important, individual differences in outcome were not consistently related to process variables monitored during training. This lack of association supports the view that physiological change is not necessary for clinical benefit after relaxation training.
The Search for Intimacy in Mid-Life: An Exploration of Several Myths
Authors: Parker Gordon
Published: January 2011

The mid-life phase, with its component features (e.g., solitude, detachment and self-doubt), its tasks (e.g., the search for self and reattachment) and several outcomes (e.g., rapprochement, chronic depression), is reviewed. A novella by John Fowles, The Ebony Tower, is presented as an allegorical account of the mid-life crisis, and its inherent myths examined. Key clinical issues, including the attributional distorting effect of mood on the protagonist's search for self and induced states of learned helplessness, are explored with reference to literary myths and clinical vignettes.
The Effects of Stressful Life Events and Disasters: Research and Theoretical Issues
Authors: McFarlane Alexander C.
Published: January 2011

The study of the relationship between adversity and physical and psychiatric illness can be researched by examining either the effect of multiple random events or the impact of a single event, such as a disaster. There has, however, been little cross-fertilisation of theory or methodology between these two areas of investigation. Disaster research has much to learn from the methodological rigour of life events research. Equally the study of disaster victims can help define the similarities and differences between distress and illness, an issue central to the validity of the concept of ‘caseness’ in the study of non-patient samples. In the past, the failure to separate these phenomena may have led to exaggerated estimates of the prevalence of morbidity among disaster victims. It is also important to examine the intervening role played by distress generated by an event in causing physical and psychiatric disorder.
Health Consequences of Youth Unemployment
Authors: Sanford Mark N. , Mullen Paul E.
Published: January 2011

The impact of unemployment on the physical and mental health of adolescents is one of the critical medical and social issues of our age. This paper reviews recent studies examining the link between youth unemployment and physical and mental ill-health. The evidence suggests that youth unemployment is associated with an increased vulnerability to psychiatric disorder. It is more firmly established that unemployment influences the course and prognosis of those with preexisting psychiatric disorders. Psychiatric disorder itself can also lead to reduced employability, particularly during periods of economic adversity. Fruitful areas of further study are identified.
The Detection of Alcohol Use in Psychiatric Casualty Patients
Authors: Anaf G. M. , Rosenman S. J.
Published: January 2011

This study assessed the extent of alcohol use among casualty attenders at a metropolitan psychiatric hospital. Seventeen of 97 patients showed measurable alcohol levels at the time of presentation. Patients with functional psychoses used alcohol excessively, but the heaviest and most frequent use was among women, especially those with personality disorders. It is suggested that routine alcohol testing is worthwhile and inexpensive, and it may lead to earlier detection and treatment of alcohol abuse.
The Sick Child's Predicament
Authors: Taylor David C.
Published: January 2011

There is widespread criticism of medicine which contrasts with its manifest success in biotechnology. Medicine's failure to convince stems partly from the fact that its successful biotechnology distracts it from the mundane task of responding appropriately to components of commonplace sicknesses which do not stem from disease (things) or illness (symptoms) but from predicaments. Predicaments are painful social situations or circumstances, complex, unstable, morally charged and varying in their import in time and place, which are readily discernible from a good history. Predicaments are distinguished from environmental agents by being an aspect of social organisation rather than structures. Dangerous and excruciating predicaments are described as well as the predicaments of being sick, and being in hospital. Child psychiatrists are often presented with problems where diagnosis of disease or illness in the child is inappropriate and resolution of its predicament alleviates the distress that had been presented in the language of sickness. The model is capable of broader application in psychiatry and medicine. Doctors should be more concerned to know about the context and background of their patients' sickness, as patients give this information very freely if asked. If patients' complaints are misunderstood then medical responses, made in good faith, may be seen as dangerous intrusions leading to a loss of trust, anger, and litigiousness.
Imaginal Desensitization: A Cost-Effective Treatment in Two Shop-Lifters and a Binge-Eater Resistant to Previous Therapy
Authors: McConaghy Nathaniel , Blaszczynski Alex
Published: January 2011

Case reports are given of three patients, two suffering from compulsive shop-lifting and one from binge-eating, who responded to a week's treatment with imaginal desensitization after having failed to respond to prolonged interpretative psychotherapy. Expectancy of improvement did not appear to play a major role in their response, but it appears impossible to disprove that expectancy determines the response to this or any form of psychotherapy. Whether or not imaginal desensitization acted specifically in the present study, in view of its cost-efficacy it is suggested it is worthy of trial in impulse disorders which have persisted despite treatment.
L-Tryptophan: A Rational Anti-Depressant and a Natural Hypnotic?
Authors: Boman Bruce
Published: January 2011

L-tryptophan is an essential amino acid which is the metabolic precursor of serotonin. Because of the evidence that serotonin deficiency may be an aetiological factor in some sorts of affective disorder and that serotonin is important in the biochemistry of sleep, L-tryptophan has been suggested as a “rational” anti-depressant and as a “natural” hypnotic. This paper reviews the biochemistry and pharmacology of L-tryptophan as well as the literature of the clinical trials that have been conducted with it and suggests that, by itself, L-tryptophan may be useful in mild cases of depression accompanied by endogenous features and cases of bipolar disorder resistant to standard treatments. It also potentiates the monoamine oxidase inhibitors and possibly the serotonergic tricyclic drugs. L-tryptophan may improve the depressed mood of Parkinsonian patients and has a clinically useful hypnotic action. There is evidence it may be useful in organic mental disorders induced by levodopa. Dosage schedules, contraindications and complications are discussed.
Pseudodementia in Schizophrenia and Mania
Authors: Wright J. Murray , Silove Derrick
Published: January 2011

The importance of differentiating depressive pseudodementia from true dementia seems to be well recognized by psychiatrists, yet there seems less recognition that other functional psychoses in the elderly can present with symptoms of cognitive impairment. In this report, we describe two patients - one suffering from late onset schizophrenia and one from a manic illness - who were diagnosed as suffering from dementia in the early stages of their illnesses. We discuss some of the difficulties in making diagnoses in these cases which include an historical tendency for clinicians, including psychiatrists, to assume an organic aetiology for first presentation psychoses in old age. Although the concept of pseudodementia has been criticised in recent years, we conclude that it retains its clinical utility in that it orientates the clinician to the importance of recognizing treatable functional psychoses in the elderly.
Psychotic Depression: A Review and Clinical Experience
Authors: Parker G. , Hadzi-Pavlovic D. , Hickie I. , Mitchell P. , Wilhelm K. , Brodaty H. , Boyce P. , Eyers K. , Pedic F.
Published: January 2011

We review research literature on psychotic (delusional) depression, including demographic, illness pattern, clinical, biological marker and treatment issues. Secondly, we report a study of a consecutive sample of 137 patients meeting criteria for DSM-III melancholia, RDC definite endogenous depression and our “clinical” criteria for endogenous depression, of whom there were 35 “psychotic depressives” (PDs). The PDs were contrasted with the remaining 76 depressives (EDs) and with an age and sex-matched subset (MEDs). The PDs were distinctly older than the EDs at assessment and at initial onset of any affective disorder. Compared to the MEDs, they tended to have longer illnesses, were more likely to be hospitalised (and to have longer stays), to receive (in the past and for the current episode) combination antipsychotic/antidepressant medication and/or ECT, and to have a poorer course over the following year. They were no more likely to have a bipolar pattern, a family history of depressive disorder, schizophrenia or alcoholism, or vegetative depressive features. Developmental psychosocial stressors and antecedent life event stressors were not over-represented. Most of the PDs had delusions, one-fifth reported hallucinations and psychomotor disturbance was marked. Other differential clinical findings were sustained mood disturbance, constipation, and the absence of a diurnal variation in mood and energy.
An Examination of Recent Suicides in Remote Australia: Further Information from the Kimberley
Authors: Hunter Ernest M.
Published: January 2011

Aboriginal suicide has emerged as an issue of public concern only within the recent past. Within the last decade there has been a substantial increase from levels that were previously low. Under the shadow of the Royal Commission into Aboriginal Deaths in Custody these increases, involving primarily young adult males, raise serious questions. Two years ago the author examined a series of suicides that had occurred in one area of remote Aboriginal Australia, the Kimberley region of Western Australia. This paper examines suicides that have occurred in the following two years, with comparisons both with the previous suicides, and with a group of age-matched Aborigines from the general Kimberley population drawn from a random sample survey.
A 13 Year Follow-Up of Child Psychiatry Training
Authors: Marriage Keith , Halasz George
Published: January 2011

The graduates from two child psychiatry training programmes over a 13 year period responded to a questionnaire designed to elicit their retrospective evaluations of various aspects of their educational experience. Information is presented about areas of knowledge judged important, specific experiences which were helpful and unhelpful, and current patterns of practice of these graduates. Their attitudes toward supervision and supervisors are discussed, as are implications for recruitment of future trainees and teachers/faculty.
On the Perception of Madness
Authors: James Norman McI.
Published: January 2011

Since the beginning of recorded history, mental illness has been recognised as being primarily in the province of the healing profession. This view has continued, despite the fact that psychiatry left the mainstream of medicine with the development of asylums during the 19th century. With the advent of deinstitutionalisation however, psychiatrists, particularly in Australia, have increasingly left public practice. As result, the treatment of the severely and chronically mentally ill, especially those with behavioural disorder, has become neglected. It is argued that moves toward the mainstreaming of acute psychiatry to general hospitals offer new opportunity for the profession to reassert itself in this essential but difficult area of psychiatric practice.
Eye-Movement Desensitisation: A Simple Treatment for Post-Traumatic Stress Disorder?
Authors: Page Andrew C. , Crino Rocco D.
Published: January 2011

Eye-movement desensitisation has been identified in a number of case studies to be an effective treatment for post-traumatic stress disorder (PTSD). A further case study reporting success is presented. The treatment appears rapid and may represent a potentially cost-effective treatment for PTSD. However, no treatment study to date has conformed to the ideal methodology of a double-blind placebo controlled trial and therefore its efficacy remains to be demonstrated. A minimal but stringent set of criteria for identification of treatment efficacy are outlined. The implications of eye-movement desensitisation being identified as an effective treatment for PTSD are discussed.
Factors Associated with the Prevalence of Antibiotic Use for the Treatment of Hospital-Acquired Infections at 393 French Hospitals: A Regional Variation Analysis
Authors: Amadeo B. , Dumartin C. , Venier A. G. , Fourrier-Réglat A. , Coignard B. , Rogues A. M.
Published: January 2011

Objective.

The present study investigated regional variations in antibiotic use for the treatment of hospital-acquired infections (HAIs) in France by means of a multilevel analysis, to identify targets for quality improvement.

Methods.

Data were obtained from the 2001 and 2006 French national point-prevalence surveys of HAIs and antibiotic use. The present study was conducted using data from 393 nonteaching public hospitals. Data included patient characteristics calculated at the hospital level (mean age and proportion of patients with the following: HAI, presence of a vascular catheter, presence of a urinary catheter, surgical procedure, and immunodeficiency) and hospital characteristics (size and presence of an intensive care unit). The regional effect was measured using a random intercept on a regional variable.

Results.

Overall, the prevalence of antibiotic use was 5.35% for both study years. The most commonly used antibiotics for HAIs were fluoroquinolones (2001, 1.33%; 2006, 1.35%) and combinations of penicillins with a β-lactamase inhibitor (2001, 0.92%; 2006, 1.02%). Mapping of antibiotic use showed wide variation between regions. The regional effect explained 3% of antibiotic variation in the unadjusted analysis. In the multivariable analysis, hospital size, high prevalence of patients with immunodeficiency, and infection characteristics explained 45% of the variability in antibiotic use. The regional effect was not retained in the final model.

Conclusion.

The pattern of antibiotic use for HAIs differed over time, and regional variations were mostly explained by patient characteristics; there was no regional effect. Models that take data hierarchy into account are essential to better approach antibiotic use and develop relevant strategies for improvement.
ControllingLegionellain Hospital Drinking Water: An Evidence-Based Review of Disinfection Methods
Authors: Lin Yusen E. , Stout Janet E. , Yu Victor L.
Published: January 2011

Hospital-acquired Legionnaires' disease is directly linked to the presence ofLegionellain hospital drinking water. Disinfecting the drinking water system is an effective preventive measure. The efficacy of any disinfection measures should be validated in a stepwise fashion from laboratory assessment to a controlled multiple-hospital evaluation over a prolonged period of time. In this review, we evaluate systemic disinfection methods (copper-silver ionization, chlorine dioxide, monochloramine, ultraviolet light, and hyperchlorination), a focal disinfection method (point-of-use filtration), and short-term disinfection methods in outbreak situations (superheat-and-flush with or without hyperchlorination). The infection control practitioner should take the lead in selection of the disinfection system and the vendor. Formal appraisals by other hospitals with experience of the system under consideration is indicated. Routine performance of surveillance cultures of drinking water to detectLegionellaand monitoring of disinfectant concentrations are necessary to ensure long-term efficacy.
History of SHEA-Sponsored Research: Time to Pass the Torch
Authors: Simmons Bryan , Braun Barbara I. , Steinberg James P. , Kritchevsky Stephen B.
Published: January 2011

Since its inception, the Society for Healthcare Epidemiology of America (SHEA) has promoted research into prevention of adverse events in hospitals. In 1995, SHEA made this mission concrete by initiating a collaborative research project with the Joint Commission on the Accreditation of Health Care Organization (now known as the Joint Commission). In the early 1990s, the Joint Commission was implementing its “Agenda for Change” and associated Indicator Monitoring System. At the time, there were numerous competing measurement systems that used different definitions, all aimed at measuring the quality of patient care, and many had indicators measuring the incidence of hospital-acquired infections. Some of these indicators used administrative data, such as International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, to measure adverse events.
Pillars and towers of quadratic transformations
Authors: Abhyankar Shreeram
Published: January 2011

Infinite pillars of quadratic transformations are used to describe residue fields of subrings of finitely generated ring extensions of the ring of integers. Towers whose underlying quadratic transformations are finite pillars or nonpillars are employed for the construction of basic dicritical divisors.
Apollonian circle packings and closed horospheres on hyperbolic 3-manifolds
Authors: Kontorovich Alex , Oh Hee
Published: January 2011

We show that for a given bounded Apollonian circle packing

P

\mathcal P

, there exists a constant

c
>
0

c>0

such that the number of circles of curvature at most

T
T

is asymptotic to

c
⋅

T
α

c\cdot T^\alpha

as

T
→
∞

T\to \infty

. Here

α
≈
1.30568
(
8
)

\alpha \approx 1.30568(8)

is the residual dimension of the packing. For

P

\mathcal P

integral, let

π

P

(
T
)

\pi ^{\mathcal {P}}(T)

denote the number of circles with prime curvature less than

T
T

. Similarly let

π
2

P

(
T
)

\pi _2^{\mathcal {P}}(T)

be the number of pairs of tangent circles with prime curvatures less than

T
T

. We obtain the upper bounds

π

P

(
T
)
≪

T
α

/

log
⁡
T

\pi ^{\mathcal {P}}(T)\ll T^\alpha /\log T

and

π
2

P

(
T
)
≪

T
α

/

(
log
⁡
T

)
2

\pi _2^{\mathcal {P}}(T)\ll T^\alpha /(\log T)^2

, which are sharp up to a constant multiple. The main ingredient of our proof is the effective equidistribution of expanding closed horospheres in the unit tangent bundle of a geometrically finite hyperbolic

3
3

-manifold

Γ
∖

H

3

\Gamma \backslash \mathbb {H}^3

under the assumption that the critical exponent of

Γ
\Gamma

exceeds one.
Fluctuation exponent of the KPZ/stochastic Burgers equation
Authors: Balázs M. , Quastel J. , Seppäläinen T.
Published: January 2011

We consider the stochastic heat equation
\[

∂
t

Z
=

∂
x
2

Z
−
Z

W
˙

\partial _tZ= \partial _x^2 Z - Z \dot W

\]
on the real line, where

W
˙

\dot W

is space-time white noise.

h
(
t
,
x
)
=
−
log
⁡
Z
(
t
,
x
)

h(t,x)=-\operatorname {log} Z(t,x)

is interpreted as a solution of the KPZ equation, and

u
(
t
,
x
)
=

∂
x

h
(
t
,
x
)

u(t,x)=\partial _x h(t,x)

as a solution of the stochastic Burgers equation. We take

Z
(
0
,
x
)
=
exp
⁡
{
B
(
x
)
}

Z(0,x)=\exp \{B(x)\}

, where

B
(
x
)

B(x)

is a two-sided Brownian motion, corresponding to the stationary solution of the stochastic Burgers equation. We show that there exist

0
>

c
1

≤

c
2

>
∞

0> c_1\le c_2 >\infty

such that
\[

c
1

t

2

/

3

≤
Var
⁡
(
log
⁡
Z
(
t
,
x
)
)
≤

c
2

t

2

/

3

.

c_1t^{2/3}\le \operatorname {Var}(\operatorname {log} Z(t,x) )\le c_2 t^{2/3}.

\]
Analogous results are obtained for some moments of the correlation functions of

u
(
t
,
x
)

u(t,x)

. In particular, it is shown there that the bulk diffusivity satisfies
\[

c
1

t

1

/

3

≤

D

bulk

(
t
)
≤

c
2

t

1

/

3

.

c_1t^{1/3}\le D_\textrm {bulk}(t) \le c_2 t^{1/3}.

\]
The proof uses approximation by weakly asymmetric simple exclusion processes, for which we obtain the microscopic analogies of the results by coupling.