bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive–behavioural therapy for persistent and recurrent psychosis in people with schizophrenia-spectrum disorder: cost-effectiveness analysis
Authors: van der Gaag Mark , Stant A. Dennis , Wolters Kerstin J. K. , Buskens Erik , Wiersma Durk
Published: January 2011

Background

Evidence on cost-effectiveness is important to make well-informed decisions regarding care delivery.

Aims

To determine the balance between costs and health outcomes of cognitive–behavioural therapy (CBT) compared with treatment as usual (TAU) in people with schizophrenia who have persistent and recurrent symptoms of psychosis. Trial number: ISRCTN57292778.

Method

A total of 216 people were randomised and followed up for 18 months. The primary clinical outcome measure was time functioning within the normal range. Normal functioning was defined as social functioning within the 95% range of the general population and no or minimal suffering and/or no or minimal affect on daily life of persistent psychotic symptoms. The difference in number of days was estimated. Using a societal perspective, cost differences were estimated and combined with clinical outcome to yield an incremental cost-effectiveness ratio (ICER). Uncertainty was accessed using bootstrapping and displayed by means of a cost-effectiveness acceptability curve.

Results

In the CBT group, participants experienced 183 days of normal social functioning, whereas the TAU group experienced 106 days. The ICER was e47 per day of normal functioning gained. Cognitive–behavioural therapy implies higher costs, yet results in better health outcomes. Sensitivity analyses showed that targeting individuals who have not been hospitalised before receiving CBT results in an ICER of e14 per day normal functioning gained.

Conclusions

Days of normal functioning improved in the CBT condition compared with TAU, but this gain in health was associated with additional societal costs.
Social network media exposure and adolescent eating pathology in Fiji
Authors: Becker Anne E. , Fay Kristen E. , Agnew-Blais Jessica , Khan A. Nisha , Striegel-Moore Ruth H. , Gilman Stephen E.
Published: January 2011

Background

Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure – such as the proliferation of media exposure in an individual's social network – is also associated with eating disorders.

Aims

To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji.

Method

We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n= 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE–Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors.

Results

Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% CI 1.15–2.23 relating social network media exposure to upper-quartile EDE–Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association.

Conclusions

Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations.
Prospective cohort study of mental health during imprisonment
Authors: Hassan Lamiece , Birmingham Luke , Harty Mari A. , Jarrett Manuela , Jones Peter , King Carlene , Lathlean Judith , Lowthian Carrie , Mills Alice , Senior Jane , Thornicroft Graham , Webb Roger , Shaw Jenny
Published: January 2011

Background

Mental illness is common among prisoners, but little evidence exists regarding changes in symptoms in custody over time.

Aims

To investigate the prevalence and predictors of psychiatric symptoms among prisoners during early custody.

Method

In a prospective cohort study, 3079 prisoners were screened for mental illness within 3 days of reception. To establish baseline diagnoses and symptoms, 980 prisoners were interviewed; all remaining in custody were followed up 1 month and 2 months later.

Results

Symptom prevalence was highest during the first week of custody. Prevalence showed a linear decline among men and convicted prisoners, but not women or remand prisoners. It decreased among prisoners with depression, but not among prisoners with other mental illnesses.

Conclusions

Overall, imprisonment did not exacerbate psychiatric symptoms, although differences in group responses were observed. Continued discussion regarding non-custodial alternatives for vulnerable groups and increased support for all during early custody are recommended.
Personality disorder: challenges in service development in the light of the new NICE guidelines
Authors: Garrett Christopher , Lee Tennyson , Blackburn Samantha , Priestly Leanne , Bhui Kamaldeep
Published: January 2011

Aims and method

Using the National Institute for Health and Clinical Excellence (NICE) guidelines on borderline personality disorder as a framework, we describe the profile of the first 100 individuals referred to a personality disorder service in London, captured through the use of record review and case study.

Results

The referral population ethnic profile does not match the wider population of the borough; a third of the borough is Bangladeshi, but only 9% of those referred to the service are. Of those diagnosed with borderline personality disorder and on psychotropic medications, only one person had a clear current indication based on NICE guidelines. Of the 100 individuals who were referred to the service, a quarter were accepted to the programme; a third either did not want to proceed with the assessment or were unprepared for an intensive programme.

Clinical implications

The under-representation of Black and minority ethnic individuals in referrals in the peresonality disorder service needs to be actively addressed. Interventions are required to support psychiatrists in reviewing their prescribing practice regarding individuals with borderline personality disorder. Access to the service needs to be improved.
A Role for Nuclear Factor Interleukin-3 (NFIL3), a Critical Transcriptional Repressor, in Down-Regulation of Periovulatory Gene Expression
Authors: Li Feixue , Liu Jing , Jo Misung , Curry Thomas E.
Published: January 2011

The LH surge triggers dramatic transcriptional changes in genes associated with ovulation and luteinization. The present study investigated the spatiotemporal expression of nuclear factor IL-3 (NFIL3), a transcriptional regulator of the basic leucine zipper transcription factor superfamily, and its potential role in the ovary during the periovulatory period. Immature female rats were injected with pregnant mare's serum gonadotropin, treated with human chorionic gonadotropin (hCG), and ovaries or granulosa cells were collected at various times after hCG. Nfil3 mRNA was highly induced both in intact ovaries and granulosa cells after hCG treatment. In situ hybridization demonstrated that Nfil3 mRNA was highly induced in theca-interstitial cells at 4–8 h after hCG, localized to granulosa cells at 12 h, and decreased at 24 h. Overexpression of NFIL3 in granulosa cells inhibited the induction of prostaglandin-endoperoxide synthase 2 (Ptgs2), progesterone receptor (Pgr), epiregulin (Ereg), and amphiregulin (Areg) and down-regulated levels of prostaglandin E2. The inhibitory effect on Ptgs2 induction was reversed by NFIL3 small interfering RNA treatment. In theca-interstitial cells the expression of hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (Hpgd) was also inhibited by NFIL3 overexpression. Data from luciferase assays demonstrated that NFIL3 overexpression decreased the induction of the Ptgs2 and Areg promoter activity. EMSA and chromatin immunoprecipitation analyses indicated that NFIL3 binds to the promoter region containing the DNA-binding sites of cAMP response element binding protein and CCAAT enhancer binding protein-β. In summary, hCG induction of NFIL3 expression may modulate the process of ovulation and theca-interstitial and granulosa cell differentiation by regulating expression of PTGS2, PGR, AREG, EREG, and HPGD, potentially through interactions with cAMP response element binding protein and CCAAT enhancer binding protein-β on their target gene promoters.
Wiener-Hopf Factorization for a Family of Lévy Processes Related to Theta Functions
Authors: Kuznetsov A.
Published: January 2011

In this paper we study the Wiener-Hopf factorization for a class of Lévy processes with double-sided jumps, characterized by the fact that the density of the Lévy measure is given by an infinite series of exponential functions with positive coefficients. We express the Wiener-Hopf factors as infinite products over roots of a certain transcendental equation, and provide a series representation for the distribution of the supremum/infimum process evaluated at an independent exponential time. We also introduce five eight-parameter families of Lévy processes, defined by the fact that the density of the Lévy measure is a (fractional) derivative of the theta function, and we show that these processes can have a wide range of behavior of small jumps. These families of processes are of particular interest for applications, since the characteristic exponent has a simple expression, which allows efficient numerical computation of the Wiener-Hopf factors and distributions of various functionals of the process.
First Passage of a Markov Additive Process and Generalized Jordan Chains
Authors: D‘Auria Bernardo , Ivanovs Jevgenijs , Kella Offer , Mandjes Michel
Published: January 2011

In this paper we consider the first passage process of a spectrally negative Markov additive process (MAP). The law of this process is uniquely characterized by a certain matrix function, which plays a crucial role in fluctuation theory. We show how to identify this matrix using the theory of Jordan chains associated with analytic matrix functions. This result provides us with a technique that can be used to derive various further identities.
Discrete Scan Statistics Generated by Exchangeable Binary Trials
Authors: Eryilmaz Serkan
Published: January 2011

Let {Xi}i=1n be a sequence of random variables with two possible outcomes, denoted 0 and 1. Define a random variable Sn,m to be the maximum number of 1s within any m consecutive trials in {Xi}i=1n. The random variable Sn,m is called a discrete scan statistic and has applications in many areas. In this paper we evaluate the distribution of discrete scan statistics when {Xi}i=1n consists of exchangeable binary trials. We provide simple closed-form expressions for both conditional and unconditional distributions of Sn,m for 2m ≥ n. These results are also new for independent, identically distributed Bernoulli trials, which are a special case of exchangeable trials.
Regulation of cofilin phosphorylation and asymmetry in collective cell migration during morphogenesis
Authors: Zhang Lijun , Luo Jun , Wan Ping , Wu Jing , Laski Frank , Chen Jiong
Published: January 2011

During Drosophila oogenesis, two actin dynamics regulators, cofilin and Rac, are required for the collective migration of a coherent cluster of cells called border cells. Cell culture data have shown that Rac and cofilin are both essential for lamellipodium formation, but Rac signaling results in phosphorylation and hence inactivation of cofilin. So it remains unclear whether cofilin phosphorylation plays a promoting or inhibitory role during cell migration. We show here that cofilin is required for F-actin turnover and lamellipodial protrusion in the border cells. Interestingly, reducing the dosage of cofilin by half or expressing a phospho-mimetic mutant form, S3E, partially rescues the migration and protrusion defects of Rac-deficient border cells. Moreover, cofilin exhibits moderate accumulation in border cells at the migratory front of the cluster, whereas phospho-cofilin has a robust and uniform distribution pattern in all the outer border cells. Blocking or overactivating Rac signaling in border cells greatly reduces or increases cofilin phosphorylation, respectively, and each abolishes cell migration. Furthermore, Rac may signal through Pak and LIMK to result in uniform phosphorylation of cofilin in all the outer border cells, whereas the guidance receptor Pvr (PDGF/VEGF receptor) mediates the asymmetric localization of cofilin in the cluster but does not affect its phosphorylation. Our study provides one of the first models of how cofilin functions and is regulated in the collective migration of a group of cells in vivo.
Coordination of mitosis and morphogenesis: role of a prolonged G2 phase during chordate neurulation
Authors: Ogura Yosuke , Sakaue-Sawano Asako , Nakagawa Masashi , Satoh Nori , Miyawaki Atsushi , Sasakura Yasunori
Published: January 2011

Chordates undergo a characteristic morphogenetic process during neurulation to form a dorsal hollow neural tube. Neurulation begins with the formation of the neural plate and ends when the left epidermis and right epidermis overlying the neural tube fuse to close the neural fold. During these processes, mitosis and the various morphogenetic movements need to be coordinated. In this study, we investigated the epidermal cell cycle in Ciona intestinalis embryos in vivo using a fluorescent ubiquitination-based cell cycle indicator (Fucci). Epidermal cells of Ciona undergo 11 divisions as the embryos progress from fertilization to the tadpole larval stage. We detected a long G2 phase between the tenth and eleventh cell divisions, during which fusion of the left and right epidermis occurred. Characteristic cell shape change and actin filament regulation were observed during the G2 phase. CDC25 is probably a key regulator of the cell cycle progression of epidermal cells. Artificially shortening this G2 phase by overexpressing CDC25 caused precocious cell division before or during neural tube closure, thereby disrupting the characteristic morphogenetic movement. Delaying the precocious cell division by prolonging the S phase with aphidicolin ameliorated the effects of CDC25. These results suggest that the long interphase during the eleventh epidermal cell cycle is required for neurulation.
Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas
Authors: Kopinke Daniel , Brailsford Marisa , Shea Jill E. , Leavitt Rebecca , Scaife Courtney L. , Murtaugh L. Charles
Published: January 2011

Notch signaling regulates numerous developmental processes, often acting either to promote one cell fate over another or else to inhibit differentiation altogether. In the embryonic pancreas, Notch and its target gene Hes1 are thought to inhibit endocrine and exocrine specification. Although differentiated cells appear to downregulate Hes1, it is unknown whether Hes1 expression marks multipotent progenitors, or else lineage-restricted precursors. Moreover, although rare cells of the adult pancreas express Hes1, it is unknown whether these represent a specialized progenitor-like population. To address these issues, we developed a mouse Hes1CreERT2 knock-in allele to inducibly mark Hes1+ cells and their descendants. We find that Hes1 expression in the early embryonic pancreas identifies multipotent, Notch-responsive progenitors, differentiation of which is blocked by activated Notch. In later embryogenesis, Hes1 marks exocrine-restricted progenitors, in which activated Notch promotes ductal differentiation. In the adult pancreas, Hes1 expression persists in rare differentiated cells, particularly terminal duct or centroacinar cells. Although we find that Hes1+ cells in the resting or injured pancreas do not behave as adult stem cells for insulin-producing beta (β)-cells, Hes1 expression does identify stem cells throughout the small and large intestine. Together, these studies clarify the roles of Notch and Hes1 in the developing and adult pancreas, and open new avenues to study Notch signaling in this and other tissues.
Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6
Authors: Matsushima Danielle , Heavner Whitney , Pevny Larysa H.
Published: January 2011

In humans, haploinsufficiency of either SOX2 or PAX6 is associated with microphthalmia, anophthalmia or aniridia. In this study, through the genetic spatiotemporal specific ablation of SOX2 on both wild-type and Pax6-haploinsufficent backgrounds in the mouse, we have uncovered a transcriptionally distinct and developmentally transient stage of eye development. We show that genetic ablation of SOX2 in the optic cup results in complete loss of neural competence and eventual cell fate conversion to non-neurogenic ciliary epithelium. This cell fate conversion is associated with a striking increase in PAX6, and genetically ablating SOX2 on a Pax6-haploinsufficient background partially rescues the Sox2-mutant phenotype. Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina.
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling
Authors: Weber Silvio , Niessen Michaela T. , Prox Johannes , Lüllmann-Rauch Renate , Schmitz Annika , Schwanbeck Ralf , Blobel Carl P. , Jorissen Ellen , de Strooper Bart , Niessen Carien M. , Saftig Paul
Published: January 2011

The disintegrin and metalloproteinase Adam10 has been implicated in the regulation of key signaling pathways that determine skin morphogenesis and homeostasis. To address the in vivo relevance of Adam10 in the epidermis, we have selectively disrupted Adam10 during skin morphogenesis and in adult skin. K14-Cre driven epidermal Adam10 deletion leads to perinatal lethality, barrier impairment and absence of sebaceous glands. A reduction of spinous layers, not associated with differences in either proliferation or apoptosis, indicates that loss of Adam10 triggers a premature differentiation of spinous keratinocytes. The few surviving K14-Adam10-deleted mice and mice in which Adam10 was deleted postnatally showed loss of hair, malformed vibrissae, epidermal hyperproliferation, cyst formation, thymic atrophy and upregulation of the cytokine thymic stromal lymphopoetin (TSLP), thus indicating non cell-autonomous multi-organ disease resulting from a compromised barrier. Together, these phenotypes closely resemble skin specific Notch pathway loss-of-function phenotypes. Notch processing is indeed strongly reduced resulting in decreased levels of Notch intracellular domain fragment and functional Notch signaling. The data identify Adam10 as the major Site-2 processing enzyme for Notch in the epidermis in vivo, and thus as a central regulator of skin development and maintenance.
Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry inXenopus
Authors: Marjoram Lindsay , Wright Christopher
Published: January 2011

The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty proproteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry.
Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear
Authors: Radosevic Marija , Robert-Moreno Àlex , Coolen Marion , Bally-Cuif Laure , Alsina Berta
Published: January 2011

Proper spatial control of neurogenesis in the inner ear ensures the precise innervation of mechanotransducing cells and the propagation of auditory and equilibrium stimuli to the brain. Members of the Hairy and enhancer of split (Hes) gene family regulate neurogenesis by inhibiting neuronal differentiation and maintaining neural stem cell pools in non-neurogenic zones. Remarkably, their role in the spatial control of neurogenesis in the ear is unknown. In this study, we identify her9, a zebrafish ortholog of Hes1, as a key gene in regulating otic neurogenesis through the definition of the posterolateral non-neurogenic field. First, her9 emerges as a novel otic patterning gene that represses proneural function and regulates the extent of the neurogenic domain. Second, we place Her9 downstream of Tbx1, linking these two families of transcription factors for the first time in the inner ear and suggesting that the reported role of Tbx1 in repressing neurogenesis is in part mediated by the bHLH transcriptional repressor Her9. Third, we have identified retinoic acid (RA) signaling as the upstream patterning signal of otic posterolateral genes such as tbx1 and her9. Finally, we show that at the level of the cranial otic field, opposing RA and Hedgehog signaling position the boundary between the neurogenic and non-neurogenic compartments. These findings permit modeling of the complex genetic cascade that underlies neural patterning of the otic vesicle.
Cilia-driven fluid flow as an epigenetic cue for otolith biomineralization on sensory hair cells of the inner ear
Authors: Yu Xianwen , Lau Doreen , Ng Chee Peng , Roy Sudipto
Published: January 2011

Ciliary motility is necessary for many developmental and physiological processes in animals. In zebrafish, motile cilia are thought to be required for the deposition of otoliths, which comprise crystals of protein and calcium carbonate, on hair cells of the inner ear. The identity of the motile cilia and their role in otolith biogenesis, however, remain controversial. Here, we show that the ear vesicle differentiates numerous motile cilia, the spatial distribution of which changes as a function of the expression pattern of the ciliogenic gene foxj1b. By contrast, the hair cells develop immotile kinocilia that serve as static tethers for otolith crystallization. In ears devoid of all cilia, otoliths can form but they are of irregular shapes and sizes and appear to attach instead to the hair cell apical membranes. Moreover, overproduction of motile cilia also disrupts otolith deposition through sustained agitation of the precursor particles. Therefore, the correct spatial and temporal distribution of the motile cilia is crucial for proper otolith formation. Our findings support the view that the hair cells express a binding factor for the otolith precursors, while the motile cilia ensure that the precursors do not sediment prematurely and are efficiently directed towards the hair cells. We also provide evidence that the kinocilia are modified motile cilia that depend on Foxj1b for their differentiation. We propose that in hair cells, a Foxj1b-dependent motile ciliogenic program is altered by the proneural Atoh proteins to promote the differentiation of immotile kinocilia.
Spatial and temporal requirements for sonic hedgehog in the regulation of thalamic interneuron identity
Authors: Jeong Yongsu , Dolson Diane K. , Waclaw Ronald R. , Matise Michael P. , Sussel Lori , Campbell Kenneth , Kaestner Klaus H. , Epstein Douglas J.
Published: January 2011

In caudal regions of the diencephalon, sonic hedgehog (Shh) is expressed in the ventral midline of prosomeres 1-3 (p1-p3), which underlie the pretectum, thalamus and prethalamus, respectively. Shh is also expressed in the zona limitans intrathalamica (zli), a dorsally projecting spike that forms at the p2-p3 boundary. The presence of two Shh signaling centers in the thalamus has made it difficult to determine the specific roles of either one in regional patterning and neuronal fate specification. To investigate the requirement of Shh from a focal source of expression in the ventral midline of the diencephalon, we used a newly generated mouse line carrying a targeted deletion of the 525 bp intronic sequence mediating Shh brain enhancer-1 (SBE1) activity. In SBE1 mutant mice, Shh transcription was initiated but not maintained in the ventral midline of the rostral midbrain and caudal diencephalon, yet expression in the zli was unaffected. In the absence of ventral midline Shh, rostral thalamic progenitors (pTH-R) adopted the molecular profile of a more caudal thalamic subtype (pTH-C). Surprisingly, despite their early mis-specification, neurons derived from the pTH-R domain continued to migrate to their proper thalamic nucleus, extended axons along their normal trajectory and expressed some, but not all, of their terminal differentiation markers. Our results, and those of others, suggest a model whereby Shh signaling from distinct spatial and temporal domains in the diencephalon exhibits unique and overlapping functions in the development of discrete classes of thalamic interneurons.
The Labor Market Returns to Cognitive and Noncognitive Ability: Evidence from the Swedish Enlistment
Authors: Lindqvist Erik , Vestman Roine
Published: January 2011

We use data from the Swedish military enlistment to assess the importance of cognitive and noncognitive ability for labor market outcomes. The measure of noncognitive ability is based on a personal interview conducted by a psychologist. We find strong evidence that men who fare poorly in the labor market—in the sense of unemployment or low annual earnings—lack noncognitive rather than cognitive ability. However, cognitive ability is a stronger predictor of wages for skilled workers and of earnings above the median. (JEL J24, J31, J45)
Are Restaurants Really Supersizing America?
Authors: Anderson Michael L , Matsa David A
Published: January 2011

While many researchers and policymakers infer from correlations between eating out and body weight that restaurants are a leading cause of obesity, a basic identification problem challenges these conclusions. We exploit the placement of Interstate Highways in rural areas to obtain exogenous variation in the effective price of restaurants and examine the impact on body mass. We find no causal link between restaurant consumption and obesity. Analysis of food-intake micro-data suggests that consumers offset calories from restaurant meals by eating less at other times. We conclude that regulation targeting restaurants is unlikely to reduce obesity but could decrease consumer welfare. (JEL I12, I18, L51, L66)
Bank Integration and Transmission of Financial Shocks: Evidence from Japan
Authors: Imai Masami , Takarabe Seitaro
Published: January 2011

This paper investigates whether banking integration plays an important role in transmitting financial shocks across geographical boundaries by using a dataset on the branch network of nationwide city banks and a prefecture-level dataset on the formation and collapse of the real estate bubble in Japan. The results show that the credit and economic cycle of financially integrated prefectures exhibits higher sensitivity to fluctuation in land prices in cities relative to financially isolated ones. These results suggest nationwide banks can be a source of economic volatility when they pass on the impacts of financial shocks to host economies. (JEL E44, G21, R30)
Pricing-to-Market and the Failure of Absolute PPP
Authors: Alessandria George , Kaboski Joseph P
Published: January 2011

We show that deviations from the law of one price in tradable goods are an important source of violations of absolute purchasing power parity. Using highly disaggregated export data, we document systematic international price discrimination: at the US dock, low-income countries pay lower prices. This pricing-to-market is about twice as important as local nontraded inputs for differences in tradable prices. We propose a model of consumer search and pricing-to-market in which consumers in low-income countries have a comparative advantage in nontraded, nonmarket search activities. Evidence from cross-country time-use studies and US export prices supports the model. (JEL E31, F14)
Fatigue and Dizziness during Corticosteroid Infusion; Sertraline-Induced Anisocoria; Bupropion-Associated Mixed-Type Dyskinesia; Hypereosinophilia Associated with Echinacea Use; Hepatotoxicity Associated with Metformin Therapy; Neutropenia as a Class Effect of Antipsychotic Agents; Poppers-Associated Retinal Toxicity
Authors: Shuster Joel
Published: January 2011

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
An Evaluation of Alvimopan Use as Part of Perioperative Management of Patients Undergoing Laparoscopic Small and Large Bowel Resections
Authors: Whelpley Robin , Pierce Marshall , Collins Rebeccah , Timmerman William
Published: January 2011

Objective

Delayed gastrointestinal (GI) recovery (postoperative ileus) is a risk for patients undergoing bowel resection (BR) and presents clinical challenges including prolonged hospital length of stay (LOS) and increased postoperative morbidity. Alvimopan, an oral, peripherally acting mu-opioid receptor antagonist, is the first therapy approved to accelerate GI recovery after BR. Published data have described alvimopan use in open BR. In contrast, this study focused on laparoscopic BR.

Methods

Historic data were retrospectively collected and alvimopan data were prospectively collected from 1 surgeon at our facility. Adults undergoing laparoscopic partial small or large BR with primary anastamosis scheduled to receive intravenous, opioid-based, patient-controlled analgesia were eligible. Pregnancy, opioid analgesic on the home medication reconciliation form, complete bowel obstruction, colostomy or ileostomy creation, and unplanned surgery were exclusion criteria. All patients were uniformly managed with a standardized accelerated postoperative care pathway to facilitate GI recovery. LOS, time to first bowel movement (BM), 30-day readmission rate, and the cost were evaluated. Data were analyzed using Pearson chi-square and independent samples t tests.

Results

Thirty-nine alvimopan and 56 historic cohort patients were included. Time to first BM was reduced by 1.2 days and LOS was reduced by 1.1 days (both P < .001) in the alvimopan cohort compared with control. Overall variable cost data were reduced by $1,368 in the alvimopan cohort. Readmission rates were low and comparable.

Conclusions

Laparoscopic surgery can decrease LOS compared with open BR; however, alvimopan use at our facility reduced LOS and time to BM while remaining cost-effective in this patient population.
Supporting Adolescent Learning and Development Using Applied Learning Pedagogies in a Regional Secondary School: An Evaluation of a Pilot Program
Authors: Campbell Chris , Faulkner Michael , Pridham Bruce
Published: January 2011

Pedagogies to develop autonomy and social responsibility in early adolescent learners persist as an ongoing agenda for schools. This paper reports on one Australian regional secondary college’s pilot program to improve learner engagement in one year 8 class using applied learning principles across the curriculum. In late 2006, participating students in this applied learning initiative were interviewed in small groups, their parents surveyed, and their home group teacher interviewed. Overwhelmingly, student perspectives strongly endorsed the pilot program and were consistent with parent and teacher observations of these same students’ feelings toward engagement within the program. This article details adolescents’ self-reported significant learning, locating them within a wider discourse of secondary school curriculum and current knowledge about early adolescent learners. This article also provides particular reference to the applied learning principles around which the pilot program was conceived and framed.
Spherical projections and liftings in geometric tomography
Authors: Goodey Paul , Kiderlen Markus , Weil Wolfgang
Published: January 2011

We use spherical projection and lifting operators in Euclidean d-space to describe a general framework for a variety of integral transforms arising in geometric tomography. These operators will be applied to support functions and surface area measures of convex bodies and to radial functions of star bodies. We then investigate averages of lifted projections and show that they correspond to self-adjoint intertwining operators. We obtain formulas for the eigenvalues of these operators and use them to ascertain circumstances under which tomographic measurements determine the original bodies. This approach via mean lifted projections leads us to some unexpected relationships between seemingly disparate geometric constructions.
Contact deformations of closed 1-forms on -bundles over
Authors: Dathe Hamidou , Rukimbira Philippe
Published: January 2011

If a closed 3-manifold M supports a closed, nonsingular, irrational 1-form which linearly deforms into contact forms, then M supports a K-contact form. On the 3-torus, a closed nonsingular 1-form deforms linearly into contact forms if and only if it is a fibration 1-form. On any other 2-dimensional torus bundle over the circle, every closed, nonsingular 1-form deforms linearly into contact forms.
Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
Authors: Matheeussen Veerle , Baerts Lesley , De Meyer Guido , De Keulenaer Gilles , Van der Veken Pieter , Augustyns Koen , Dubois Véronique , Scharpé Simon , De Meester Ingrid
Published: January 2011

Dipeptidyl peptidase IV (DPPIV)/CD26 is by far the most extensively studied member of the prolyl oligopeptidase family of serine proteases. The discovery of the related enzymes DPP8 and DPP9 necessitates a (re-)evaluation of the DPPIV-like enzymatic activity in cells and organs. In this study, we aimed (1) to investigate the expression of the individual dipeptidyl peptidases in different types of endothelial cells (ECs) and (2) to reconsider published data in relation to our findings. Examination of DPP expression in rat primary ECs of aortic, endocardial and cardiac microvascular origin revealed the presence of DPPIV-like activity in all cell lysates. More than half of this activity could be attributed to DPP8/9. Western blot analysis revealed an abundance of the DPP8 protein as compared to DPP9. The expression of DPPIV and DPP8 was significantly higher in the cardiac microvascular endothelium than in the other ECs, suggesting a more pronounced role of these DPPs in the microvasculature.In situ, DPP activity in ventricular microvasculature was completely inhibited by sitagliptin, indicating that DPPIV is the predominant DPPIV-like enzyme in this organ. By contrast, immunohistochemical studies indicated DPP9 as the predominant DPP in human carotid artery ECs. In conclusion, our results support a highly regulated expression of individual DPPs in ECs, with a spatial heterogeneity in the cardiovascular tree.
Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
Authors: Grouzmann Eric , Bigliardi Paul , Appenzeller Monique , Pannatier André , Buclin Thierry
Published: January 2011

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.
Structure determination of channel and transport proteins by high-resolution microscopy techniques
Authors: Meury Marcel , Harder Daniel , Ucurum Zöhre , Boggavarapu Rajendra , Jeckelmann Jean-Marc , Fotiadis Dimitrios
Published: January 2011

High-resolution microscopy techniques provide a plethora of information on biological structures from the cellular level down to the molecular level. In this review, we present the unique capabilities of transmission electron and atomic force microscopy to assess the structure, oligomeric state, function and dynamics of channel and transport proteins in their native environment, the lipid bilayer. Most importantly, membrane proteins can be visualized in the frozen-hydrated state and in buffer solution by cryo-transmission electron and atomic force microscopy, respectively. We also illustrate the potential of the scintillation proximity assay to study substrate binding of detergent-solubilized transporters prior to crystallization and structural characterization.
Omp85 in eukaryotic systems: one protein family with distinct functions
Authors: Schleiff Enrico , Maier Uwe G. , Becker Thomas
Published: January 2011

Omp85-like proteins are evolutionary ancient components of bacterial outer membranes and their evolutionary offspring. As a consequence, proteins of this family can be found in the outer membrane systems of Gram-negative bacteria and endosymbiotically derived organelles. In the different membranes, they perform distinct functions such as catalyzing protein insertion into or protein transport across the bilayer. Here, the knowledge on the Omp85-like proteins in the eukaryotic system with regard to structural properties and physiological behavior is summarized.
Evolution of ABC transporters by gene duplication and their role in human disease
Authors: Moitra Karobi , Dean Michael
Published: January 2011

The ATP-binding cassette (ABC) transporter genes represent the largest family of transporters and these genes are abundant in the genome of all vertebrates. Through analysis of the genome sequence databases we have characterized the full complement of ABC genes from several mammals and other vertebrates. Multiple gene duplication and deletion events were identified in ABC genes in different lineages indicating that the process of gene evolution is still ongoing. Gene duplication resulting in either gene birth or gene death plays a major role in the evolution of the vertebrate ABC genes. The understanding of this mechanism is important in the context of human health because these ABC genes are associated with human disease, involving nearly all organ systems of the body. In addition, ABC genes play an important role in the development of drug resistance in cancer cells. Future genetic, functional, and evolutionary studies of ABC transporters will provide important insight into human and animal biology.
The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?
Authors: Bangert Irina , Tumulka Franz , Abele Rupert
Published: January 2011

The transporter associated with antigen processing-like (TAPL) is a polypeptide transporter translocating cytosolic peptides into the lumen of lysosomes driven by ATP hydrolysis. TAPL belongs to the family of ABC transporters and forms a homodimer. This ABC transporter not only shows a broad tissue but also a wide phylogenetic distribution, because orthologs are still found in nematodes and insects. Here, we present the topology, substrate specificity, and distribution of this intracellular polypeptide transporter. Additionally, we will discuss its proposed physiological functions such as housekeeping together with a specialized factor for metabolite storage as well as for the adaptive immunity.
Novel aspects of cellular action of dipeptidyl peptidase IV/CD26
Authors: Ansorge Siegfried , Nordhoff Karsten , Bank Ute , Heimburg Anke , Julius Heiko , Breyer Doreen , Thielitz Anja , Reinhold Dirk , Täger Michael
Published: January 2011

The cellular dipeptidyl peptidase IV (DPIV, E.C.3.4.14.5, CD26) is a type II membrane peptidase with various physio-logical functions. Our main knowledge on DPIV comes from studies of soluble DPIV which plays a role in regulation of glucose homeostasis by inactivation of the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic poly-peptide. It has been reported that membrane-bound DPIV plays a crucial role in the immune system and in other tissues and cells, but the knowledge on the action of cellular DPIV and its regulation is limited. In this study, we show particularly for immune cells that DPIV and not DP8 or DP9 is the most potent member of the DPIV family in regulating cellular immune functions. Moreover, we provide evidence that soluble and cellular DPIV differ in functions and hand-ling of substrates and inhibitors owing to the different accessibility of peptide substrates to the two access paths of DPIV. The different functions are based on the favored access path of the central pore of cellular DPIV and a special central pore binding site which assists substrate access to the active site of the enzyme. The newly discovered central pore binding site mediates an autosterical regulation of cellular DPIV and is its most crucial target site to regulate cellular functions such as growth and cytokine production. Neuropeptide Y (NPY) processing by cellular DPIV was found to be inhibited by ligands which interact with the central pore binding site. This finding suggests a crucial role of the immunosuppressive cytokine NPY in the function of DPIV in growth regulation.
Substrate recognition and translocation by polyspecific organic cation transporters
Authors: Koepsell Hermann
Published: January 2011

Organic cation transporters (OCTs) of the SLC22 family play a pivotal role in distribution and excretion of cationic drugs. They mediate electrogenic translocation of cations in both directions. OCTs are polyspecific transporters. During substrate translocation they perform a series of conformational changes involving an outward-facing conformation, an occluded state and an inward-facing conformation. Mutagenesis of OCT1 in combination with homology modeling showed that identical amino acids form the innermost parts of the outward-open and inward-open binding clefts. In addition to low affinity substrate binding sites, OCT1 contains high affinity substrate binding sites that can mediate inhibition via non-transported compounds.
Role of the Ca2+-activated Cl- channels bestrophin and anoctamin in epithelial cells
Authors: Kunzelmann Karl , Kongsuphol Patthara , Chootip Krongkarn , Toledo Caio , Martins Joana R. , Almaca Joana , Tian Yuemin , Witzgall Ralph , Ousingsawat Jiraporn , Schreiber Rainer
Published: January 2011

Two families of proteins, the bestrophins (Best) and the recently cloned TMEM16 proteins (anoctamin, Ano), recapitulate properties of Ca2+-activated Cl- currents. Best1 is strongly expressed in the retinal pigment epithelium and could have a function as a Ca2+-activated Cl- channel as well as a regulator of Ca2+ signaling. It is also present at much lower levels in other cell types including epithelial cells, where it regulates plasma membrane localized Cl- channels by controlling intracellular Ca2+ levels. Best1 interacts with important Ca2+-signaling proteins such as STIM1 and can interact directly with other Ca2+-activated Cl- channels such as TMEM16A. Best1 is detected in the endoplasmic reticulum (ER) where it shapes the dynamic ER structure and regulates cell proliferation, which could be important for renal cystogenesis. Ca2+-activated Cl- channels of the anoctamin family (TMEM16A) show biophysical and pharmacological properties that are typical for endogenous Ca2+-dependent Cl- channels. TMEM16 proteins are abundantly expressed and many reports demonstrate their physiological importance in epithelial as well as non-epithelial cells. These channels are also activated by cell swelling and can therefore control cell volume, proliferation and apoptosis. To fully understand the function and regulation of Ca2+-activated Cl- currents, it is necessary to appreciate that Best1 and TMEM16A are embedded in a protein network and that they probably operate in functional microdomains.
The multidrug transporter Pdr5: a molecular diode?
Authors: Gupta Rakeshkumar P. , Kueppers Petra , Schmitt Lutz , Ernst Robert
Published: January 2011

A subset of the family of ATP-binding cassette (ABC) transporters has been in focus owing to their involvement in conferring multidrug resistance in cancer cells and among immune compromised individuals. Saccharomyces cerevisiae is protected against xenobiotics by similar machineries that are part of the pleitropic drug resistance (PDR) network. The ABC transporter Pdr5 is an important member of this PDR network in yeast and is involved in cellular detoxification by the efflux of a wide variety of drugs and substrates. In this review, we focus on the aspects of detergent effects and the degeneracy in conserved sequences that is observed in the nucleotide binding domains of Pdr5 and discuss their functional relevance.
A structural and functional analysis of type III periplasmic and substrate binding proteins: their role in bacterial siderophore and heme transport
Authors: Chu Byron C.H. , Vogel Hans J.
Published: January 2011

InEscherichia colithe Fhu, Fep and Fec transport systems are involved in the uptake of chelated ferric iron-siderophore complexes, whereas in pathogenic strains heme can also be used as an iron source. An essential step in these pathways is the movement of the ferric-siderophore complex or heme from the outer membrane transporter across the periplasm to the cognate cytoplasmic membrane ATP-dependent transporter. This is accomplished in each case by a dedicated periplasmic binding protein (PBP). Ferric-siderophore binding PBPs belong to the PBP protein superfamily and adopt a bilobal type III structural fold in which the two independently folded amino and carboxy terminal domains are linked together by a single long α-helix of approximately 20 amino acids. Recent structural studies reveal how the PBPs of the Fhu, Fep, Fec and Chu systems are able to bind their corresponding ligands. These complex structures will be discussed and placed in the context of our current understanding of the entire type III family of Gram-negative periplasmic binding proteins and related Gram-positive substrate binding proteins.