bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood Obesity in Developing Countries: Epidemiology, Determinants, and Prevention
Authors: Gupta Nidhi , Goel Kashish , Shah Priyali , Misra Anoop
Published: February 2012

Rapidly changing dietary practices and a sedentary lifestyle have led to increasing prevalence of childhood obesity (5–19 yr) in developing countries recently: 41.8% in Mexico, 22.1% in Brazil, 22.0% in India, and 19.3% in Argentina. Moreover, secular trends indicate increasing prevalence rates in these countries: 4.1 to 13.9% in Brazil during 1974–1997, 12.2 to 15.6% in Thailand during 1991–1993, and 9.8 to 11.7% in India during 2006–2009. Important determinants of childhood obesity include high socioeconomic status, residence in metropolitan cities, female gender, unawareness and false beliefs about nutrition, marketing by transnational food companies, increasing academic stress, and poor facilities for physical activity. Childhood obesity has been associated with type 2 diabetes mellitus, the early-onset metabolic syndrome, subclinical inflammation, dyslipidemia, coronary artery diseases, and adulthood obesity. Therapeutic lifestyle changes and maintenance of regular physical activity through parental initiative and social support interventions are the most important strategies in managing childhood obesity. Also, high-risk screening and effective health educational programs are urgently needed in developing countries.
Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in immature murine small intestine
Authors: Zhang Chunxian , Sherman Michael P. , Prince Lawrence S. , Bader David , Weitkamp Jörn-Hendrik , Slaughter James C. , McElroy Steven J.
Published: February 2012

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer causing subsequent inflammation and tissue necrosis. Normally the Paneth cells appear in the intestinal crypts during the first trimester of human pregnancy. Paneth cells constitute a major component of the innate immune system by producing multiple antimicrobial peptides and pro-inflammatory mediators. To better understand the possible role of Paneth cell disruption in NEC, we quantified the number of Paneth cells present in infants with NEC and found they were significantly decreased compared to age matched controls. We were able to model this loss in the intestine of P14-16 day old mice by treating them with the zinc chelator dithizone. Intestines from dithizone treated animals retained approximately half the number of Paneth cells as controls. Furthermore, by combining dithizone treatment with exposure to Klebsiella pneumoniae we were able to induce intestinal injury and inflammatory induction that resembles human NEC. Additionally, this novel Paneth cell ablation model produces NEC-like pathology consistent with other currently used animal models, but is simpler to use, can be used in older animals that have been dam fed, and represents a novel line of investigation to study NEC pathogenesis and treatment.
Chromatin mobility is increased at sites of DNA double-strand breaks
Authors: Krawczyk P. M. , Borovski T. , Stap J. , Cijsouw A. , ten Cate R. , Medema J. P. , Kanaar R. , Franken N. A. P. , Aten J. A.
Published: February 2012

DNA double-strand breaks (DSBs) can efficiently kill cancer cells, but they can also produce unwanted chromosome rearrangements (CRs) when DNA ends from different DSBs are erroneously joined. Movement of DSB-containing chromatin domains might facilitate these DSB interactions and promote formation of CRs. We, therefore, analyzed the mobility of DSB-containing chromatin domains in living mammalian cells and compared it to the mobility of non-damaged chromatin on a time-scale relevant for DSB repair. We found that DSB-containing chromatin domains are significantly more mobile than intact chromatin and capable of roaming a more than 2-fold larger area of the cell nucleus. Moreover, this increased DSB mobility, but not mobility of undamaged chromatin, can be reduced by agents that affect higher-order chromatin organization.
HMGB1/RAGE regulates muscle satellite cell homeostasis via p38 MAPK/myogenin-dependent repression of Pax7 transcription
Authors: Riuzzi Francesca , Sorci Guglielmo , Sagheddu Roberta , Donato Rosario
Published: February 2012

Expression of the paired-box (Pax) 7 transcription factor needs to be regulated during myoblast proliferation and differentiation: high Pax7 levels compromise myogenic differentiation due to excess and prolonged proliferation whereas low Pax7 levels result in precocious differentiation. We show that myogenin represses Pax7 transcription in differentiating myoblasts by binding to specific recognition sites in the Pax7 promoter, and that high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE) signaling is required for myogenin induction and myogenin-dependent repression of Pax7 transcription. Also, Pax7 negatively and myogenin positively regulate RAGE expression. RAGE, a multiligand receptor of the immunoglobulin superfamily, is not expressed in adult skeletal muscles, and is transiently expressed in activated, proliferating and differentiating satellite cells (SCs) in injured muscles. Compared with wild-type muscles, Rage-/- muscles exhibit higher basal SC numbers that increase further in injured Rage-/- muscles consequent to elevated myoblast asymmetric division, and completion of regeneration of injured Rage-/- muscles is ∼1-week delayed. Thus, RAGE signaling physiologically represses Pax7 transcription in SCs by upregulating myogenin, thereby accelerating muscle regeneration and limiting SC self-renewal.
SOHLH1 and SOHLH2 control Kit expression during postnatal male germ cell development.
Authors: Barrios Florencia , Filipponi Doria , Campolo Federica , Gori Manuele , Bramucci Federica , Pellegrini Manuela , Ottolenghi Sergio , Rossi Pellegrino , Jannini Emmanuele A. , Dolci Susanna
Published: February 2012

How Kit expression is regulated in the germline is still an open question. SOHLH1 and SOHLH2, two bHLH transcription factors specifically expressed in germ cells, have been recently involved in the differentiation of spermatogonia and oocytes. In the male, deletion of each transcription factor leads to the disappearance of Kit-expressing spermatogonia in the prepuberal testis. In the female, both SOHLH1 and SOHLH2 ablations are responsible of oocyte loss in the neonatal ovary. To investigate if Kit expression might be regulated by these two transcription factors in male germ cells, we have first performed an expression study of SOHLH1 and SOHLH2 during fetal and postnatal development. In these experiments we found a strong positive correlation between Kit and the two transcription factors only in postnatal spermatogonia. SOHLH2 was found enriched in undifferentiated spermatogonia, whereas SOHLH1 expression was maximal in Kit-dependent stages. Expression of SOHLH1, but not SOHLH2, was increased in postnatal mitotic germ cells by treatment with All-trans Retinoic Acid (AtRA), an analog of retinoic acid. We also found that E-box sequences contained within the Kit promoter and its first intron can be transactivated in transfection experiments overexpressing either Sohlh1or Sohlh2. Co-transfection of both factors showed a cooperative effect. EMSA experiments further showed that SOHLH1 and SOHLH2 can independently and cooperatively bind an E-box containing probe. In vivo, co-immunoprecipitation results evidenced that the two proteins interact and overexpression of both factors increases endogenous Kit expression in ES cells. Finally, by ChIP analysis, SOHLH1 was found to occupy an E-box containing region within kit promoter in spermatogonia chromatin. Altogether, our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signalling involved in spermatogonia differentiation and spermatogenetic progression.
Uncovering functional differences between kindlin-1 and kindlin-2 in keratinocytes
Authors: Bandyopadhyay Aditi , Rothschild Gerson , Kim Sean , Calderwood David A. , Raghavan Srikala
Published: February 2012

Integrin β1-null keratinocytes can adhere to fibronectin via αvβ6, but form large peripheral focal adhesions and exhibit defective cell spreading. Here we report that, in addition to the reduced avidity of αvβ6 to fibronectin, the inability of integrin β6 to efficiently bind and recruit kindlin-2 to focal adhesions directly contributes to these phenotypes. Kindlins regulate integrins through direct interactions with the integrin β cytoplasmic tail and keratinocytes express kindlin-1 and kindlin-2. Notably, while both localize to focal adhesions in wild-type cells, only kindlin-1 localizes to the β6-rich adhesions of β1-null cells. Rescue of β1-null cells with wild-type and chimeric integrin constructs revealed a correlation between kindlin-2 recruitment and cell spreading. Furthermore, despite the presence of kindlin-1, kindlin-2 knockdown in wild-type keratinocytes impaired cell spreading. Our data reveal unexpected functional consequences of differences in the association of two homologous kindlin isoforms with two closely related integrins and suggest that despite their similarities different kindlins are likely to have specific unique functions.
Prolonged seizure activity impairs mitochondrial bioenergetics and induces cell death
Authors: Kovac Stjepana , Domijan Ana-Marija , Walker Matthew C. , Abramov Andrey Y.
Published: February 2012

The mechanisms underlying neuronal death following excessive activity such as occurs during prolonged seizures are unclear, but mitochondrial dysfunction has been hypothesized to play a role. Here, we tested this with fluorescence imaging techniques in rat glio-neuronal neocortical co-cultures using low magnesium to induce seizure-like activity. Glutamate activation of NMDA receptors resulted in calcium oscillations in neurons and a sustained depolarization of the mitochondrial membrane potential, which was cyclosporine A sensitive indicating mitochondrial permeability transition pore opening and dependent on glutamate release and NMDA receptor activation, as it was not observed after depleting vesicular glutamate with vacuolar-type H+ ATPase concanamycin A or blocking NMDA receptors with APV. Neuronal ATP levels in soma and dendrites decreased significantly during prolonged seizures and correlated with the frequency of the oscillatory calcium signal, indicative of activity-dependent ATP consumption. Blocking mitochondrial complex I, complex V or uncoupling mitochondrial oxidative phosphorylation under low magnesium conditions accelerated activity-dependent neuronal ATP consumption. Neuronal death increased after two and twenty-four hours of low magnesium, compared to control treatment and was reduced by supplementation with the mitochondrial complex I substrate pyruvate. These findings demonstrate a critical role for mitochondrial dysfunction in seizure activity induced neuronal death, and that strategies aimed at redressing this are neuroprotective.
Metastasis gene NEDD9 acts through integrin β3 and Src to promote mesenchymal motility and inhibit amoeboid motility.
Authors: Ahn Jessica , Sanz-Moreno Victoria , Marshall Christopher J.
Published: February 2012

NEDD9, a member of the Cas family of signal transduction molecules, is amplified at the genetic level in melanoma and elevated expression levels have been shown to correlate with melanoma progression and metastasis. While NEDD9 interacts with the guanine nucleotide exchange factor DOCK3 to promote Rac activation and the elongated, mesenchymal-type of tumor cell invasion, the molecular mechanisms through which NEDD9 promotes melanoma metastasis are not fully understood. We show that signalling through increased NEDD9 levels requires integrin β3 signalling, leads to elevated phosphorylation of integrin β3 resulting in increased Src and FAK but decreased ROCK signalling to drive elongated, mesenchymal-type invasion in environments that contain vitronectin. NEDD9 over-expression does not affect ROCK signalling through activation of RhoA but decreases ROCKII signalling through Src dependent phosphorylation of a negative regulatory site Tyr 722. In NEDD9 over-expressing melanoma cells, inhibition of Src with dasatinib results in a switch from Rac driven elongated, mesenchymal-type invasion to ROCK dependent rounded, amoeboid invasion. These findings brings into question whether dasatinib would work as a therapeutic agent to block melanoma invasion and metastasis; a combination treatment of dasatinib and a ROCK inhibitor may be a better alternative based on the in vitro data presented here in order to inhibit both elongated, mesenchymal-type and rounded, amoeboid motility.
The hydrodynamic function of shark skin and two biomimetic applications
Authors: Oeffner Johannes , Lauder George V.
Published: February 2012

It has long been suspected that the denticles on shark skin reduce hydrodynamic drag during locomotion, and a number of man-made materials have been produced that purport to use shark-skin-like surface roughness to reduce drag during swimming. But no studies to date have tested these claims of drag reduction under dynamic and controlled conditions in which the swimming speed and hydrodynamics of shark skin and skin-like materials can be quantitatively compared with those of controls lacking surface ornamentation or with surfaces in different orientations. We use a flapping foil robotic device that allows accurate determination of the self-propelled swimming (SPS) speed of both rigid and flexible membrane-like foils made of shark skin and two biomimetic models of shark skin to measure locomotor performance. We studied the SPS speed of real shark skin, a silicone riblet material with evenly spaced ridges and a Speedo® ‘shark skin-like’ swimsuit fabric attached to rigid flat-plate foils and when made into flexible membrane-like foils. We found no consistent increase in swimming speed with Speedo® fabric, a 7.2% increase with riblet material, whereas shark skin membranes (but not rigid shark skin plates) showed a mean 12.3% increase in swimming speed compared with the same skin foils after removing the denticles. Deformation of the shark skin membrane is thus crucial to the drag-reducing effect of surface denticles. Digital particle image velocimetry (DPIV) of the flow field surrounding moving shark skin foils shows that skin denticles promote enhanced leading-edge suction, which might have contributed to the observed increase in swimming speed. Shark skin denticles might thus enhance thrust, as well as reduce drag.
Mechanisms underlying parallel reductions in aerobic capacity in non-migratory threespine stickleback (Gasterosteus aculeatus) populations
Authors: Dalziel Anne C. , Ou Michelle , Schulte Patricia M.
Published: February 2012

Non-migratory, stream-resident populations of threespine stickleback, Gasterosteus aculeatus, have a lower maximum oxygen consumption (ṀO2,max) than ancestral migratory marine populations. Here, we examined laboratory-bred stream-resident and marine crosses from two locations (West and Bonsall Creeks) to determine which steps in the oxygen transport and utilization cascade evolved in conjunction with, and thus have the potential to contribute to, these differences in ṀO2,max. We found that West Creek stream-resident fish have larger muscle fibres (not measured in Bonsall fish), Bonsall Creek stream-resident fish have smaller ventricles, and both stream-resident populations have evolved smaller pectoral adductor and abductor muscles. However, many steps of the oxygen cascade did not evolve in stream-resident populations (gill surface area, hematocrit, mean cellular hemoglobin content and the activities of mitochondrial enzymes per gram ventricle and pectoral muscle), arguing against symmorphosis. We also studied F1 hybrids to determine which traits in the oxygen cascade have a genetic architecture similar to that of ṀO2,max. In West Creek, ṀO2,max, abductor and adductor size all showed dominance of marine alleles, whereas in Bonsall Creek, ṀO2,max and ventricle mass showed dominance of stream-resident alleles. We also found genetically based differences among marine populations in hematocrit, ventricle mass, pectoral muscle mass and pectoral muscle pyruvate kinase activity. Overall, reductions in pectoral muscle mass evolved in conjunction with reductions in ṀO2,max in both stream-resident populations, but the specific steps in the oxygen cascade that have a genetic basis similar to that of ṀO2,max, and are thus predicted to have the largest impact on ṀO2,max, differ among populations.
Effects of different substrates on the sprint performance of lizards
Authors: Tulli Maria Jose , Abdala Virginia , Cruz Felix B.
Published: February 2012

The variation in substrate structure is one of the most important determinants of the locomotor abilities of lizards. Lizards are found across a range of habitats, from large rocks to loose sand, each of them with conflicting mechanical demands on locomotion. We examined the relationships among sprint speed, morphology and different types of substrate surfaces in species of lizards that exploit different structural habitats (arboreal, saxicolous, terrestrial and arenicolous) in a phylogenetic context. Our main goals were to assess which processes drive variability in morphology (i.e. phylogeny or adaptation to habitat) in order to understand how substrate structure affects sprint speed in species occupying different habitats and to determine the relationship between morphology and performance. Liolaemini lizards show that most morphological traits are constrained by phylogeny, particularly toe 3, the femur and foot. All ecological groups showed significant differences on rocky surfaces. Surprisingly, no ecological group performed better on the surface resembling its own habitat. Moreover, all groups exhibited significant differences in sprint speed among the three different types of experimental substrates and showed the best performance on sand, with the exception of the arboreal group. Despite the fact that species use different types of habitats, the highly conservative morphology of Liolaemini species and the similar levels of performance on different types of substrates suggest that they confer to the ‘jack of all trades and master of none’ principle.
Polarotactic tabanids find striped patterns with brightness and/or polarization modulation least attractive: an advantage of zebra stripes
Authors: Egri Ádám , Blahó Miklós , Kriska György , Farkas Róbert , Gyurkovszky Mónika , Åkesson Susanne , Horváth Gábor
Published: February 2012

The characteristic striped appearance of zebras has provoked much speculation about its function and why the pattern has evolved, but experimental evidence is scarce. Here, we demonstrate that a zebra-striped horse model attracts far fewer horseflies (tabanids) than either homogeneous black, brown, grey or white equivalents. Such biting flies are prevalent across Africa and have considerable fitness impact on potential mammalian hosts. Besides brightness, one of the likely mechanisms underlying this protection is the polarization of reflected light from the host animal. We show that the attractiveness of striped patterns to tabanids is also reduced if only polarization modulations (parallel stripes with alternating orthogonal directions of polarization) occur in horizontal or vertical homogeneous grey surfaces. Tabanids have been shown to respond strongly to linearly polarized light, and we demonstrate here that the light and dark stripes of a zebra’s coat reflect very different polarizations of light in a way that disrupts the attractiveness to tabanids. We show that the attractiveness to tabanids decreases with decreasing stripe width, and that stripes below a certain size are effective in not attracting tabanids. Further, we demonstrate that the stripe widths of zebra coats fall in a range where the striped pattern is most disruptive to tabanids. The striped coat patterns of several other large mammals may also function in reducing exposure to tabanids by similar mechanisms of differential brightness and polarization of reflected light. This work provides an experimentally supported explanation for the underlying mechanism leading to the selective advantage of a black-and-white striped coat pattern.
Geometry of compensatory feeding and water consumption inDrosophila melanogaster
Authors: Fanson Benjamin G. , Yap Sarsha , Taylor Phillip W.
Published: February 2012

Feeding behaviour is an expression of an animal’s underlying nutritional strategy. The study of feeding decisions can hence delineate nutritional strategies. Studies of Drosophila melanogaster feeding behaviour have yielded conflicting accounts, and little is known about how nutrients affect feeding patterns in this important model species. Here, we conducted two experiments to characterize nutrient prioritization and regulation. In a choice experiment, we allowed female flies to self-regulate their intake of yeast, sucrose and water by supplying individual flies with three microcapillary tubes: one containing only yeast of varying concentrations, another with just sucrose of varying concentrations, and the last with just water. Flies tightly regulated yeast and sucrose to a constant ratio at the expense of excess water intake, indicating that flies prioritize macronutrient regulation over excess water consumption. To determine the relative importance of yeast and sucrose, in a no-choice experiment, we provided flies with two microcapillary tubes: the first with one of the 28 diets varying in yeast and sucrose content and the other with only water. Flies increased total water intake in relation to yeast consumption but not sucrose consumption. Additionally, flies increased diet intake as diet concentration decreased and as the ratio of sugar to yeast equalized. Using a geometric scaling approach, we found that the patterns of diet intake can be explained by flies prioritizing protein and carbohydrates equally and by the lack of substitutability between the nutrients. We conclude by illustrating how our results harmonize conflicting results in the literature once viewed in a two-dimensional diet landscape.
The Value of Information in the Court: Get it Right, Keep it Tight
Authors: Iaryczower Matias , Shum Matthew
Published: February 2012

We estimate an equilibrium model of decision making in the US Supreme Court that takes into account both private information and ideological differences between justices. We measure the value of information in the court by the probability that a justice votes differently from how she would have voted without case-specific information. Our results suggest a sizable value of information: in 44 percent of cases, justices' initial leanings are changed by their personal assessments of the case. Our results also confirm the increased politicization of the Supreme Court in the last quarter century. Counterfactual simulations provide implications for institutional design. (JEL D72, D82, D83, K10)
Standard Setting Committees: Consensus Governance for Shared Technology Platforms
Authors: Simcoe Timothy
Published: February 2012

Voluntary Standard Setting Organizations (SSOs) use a consensus process to create new compatibility standards. Practitioners have suggested that SSOs are increasingly politicized and perhaps incapable of producing timely standards. This article develops a simple model of standard setting committees and tests its predictions using data from the Internet Engineering Task Force, an SSO that produces many of the standards used to run the Internet. The results show that an observed slowdown in standards production between 1993 and 2003 can be linked to distributional conflicts created by the rapid commercialization of the Internet. (JEL C78, L15, L86)
New Trade Models, Same Old Gains?
Authors: Arkolakis Costas , Costinot Arnaud , Rodríguez-Clare Andrés
Published: February 2012

Micro-level data have had a profound influence on research in international trade over the last ten years. In many regards, this research agenda has been very successful. New stylized facts have been uncovered and new trade models have been developed to explain these facts. In this paper we investigate to what extent answers to new micro-level questions have affected answers to an old and central question in the field: how large are the welfare gains from trade? A crude summary of our results is: “So far, not much.” (JEL F11, F12)
Henry Ingersoll Bowditch (1808–82): American physician, public health advocate and social reformer
Authors: Butler Paul M
Published: February 2012

Henry Ingersoll Bowditch, a Bostonian physician from the mid-19th century, lived a passionate life full of commitment and devotion to various noble causes – he was a champion of public health, an advocate for inclusion of women in medicine and a staunch abolitionist, all unpopular social perspectives at that time in medical and political history. Seemingly difficult personality traits including his stubbornness and moralistic outlook were likely ‘adaptive’ as he confronted the political reality of major institutional change. His interest in statistical trends and environmental influences and his inductive reasoning led to a deeper understanding of consumption (tuberculosis), the widespread diagnostic use of the stethoscope and thoracocentesis.
Arthur Neve (1859–1919) and a Mission Hospital in Srinagar, Kashmir
Authors: Akhtar Rais
Published: February 2012

Mark Harrison has said that hospitals occupy a central place within health-care systems, not only on account of their curative functions but also as centres of teaching and research. The indigenous system of medicine practised by Hakims in Kashmir is the Unani. The Mission Hospital in Srinagar, Kashmir became the most important hospital attracting patients, not only within Kashmir but also in the surrounding countries and not only because of the curative facilities provided at the hospital but also because of the humane approach of its physicians, outstanding among them being Arthur Neve. The patients represented every class of society. Patients come from villages scattered throughout Kashmir and the Plains of India, and a few from Tibet, Afghanistan, Yarkand and Khostan. According to Neve, in 1912 there were 23,642 new outpatients and 1979 inpatients. Physical, socio-cultural and political conditions hinder access to the Mission Hospital. Neve's younger brother Ernest F Neve (1861–1946) made significant contributions when an earthquake struck and during cholera outbreaks in Kashmir at the end of the 19th century.
Johns Hopkins Hospital notables portrayed on philatelic material
Authors: Guaraldi Federica , Gori Davide , Hruban Ralph , Caturegli Patrizio
Published: February 2012

The philatelic medium is an extensive repository of the portraits of doctors of many nations. Using an electronic matching system to identify links between the lists of alumni and faculties register of Johns Hopkins Hospital in Baltimore and that of three stamp catalogues, 14 notable persons have been identified in the philatelic record. The Johns Hopkins Hospital was established in Baltimore in 1889 and instituted the revolutionary concept of combining patient care with research and teaching. Its founder Johns Hopkins (1795–1873) and 13 among alumni and faculties have been portrayed on postage stamps and first day covers of USA, Canada, Antigua, Barbuda, Palau, Maldives, Canada and Sweden. Five of them – du Vigneaud (1901–78), Smith (b. 1931), Nathans (1928–99), Hubel (b. 1926) and Wiesel (b. 1924) – were awarded the Nobel Prize for Medicine or Physiology. By means of the philatelic medium, portraits of Hopkins scientists and doctors, including Sir William Osler (1849–1919) and Dr Virgina Apgar (1909–74), are distributed in their many tens of thousands on envelopes sent not only to recipients in the USA but to the wider world.
Pulmonary nocardiosis: a comparative analysis of Nocardia asteroides and non-asteroides species
Authors: Amin Assad , Mahmood Syed Faisal , Anis Mariam , Adhi Fatima , Ahmad Saira , Ali Farheen , Khan Erum
Published: February 2012

Our study compares the risk factors, clinical presentations and outcomes of pulmonary infections caused by Nocardia asteroides and non- asteroides species. We performed a retrospective cohort study comparing pulmonary infections by both species in patients presenting to a tertiary care hospital in Karachi, Pakistan. Forty-one patients were identified with pulmonary nocardiosis, with 58.5% belonging to the N. asteroids complex. The most common clinical findings were fever and a cough for both groups, with lobar infiltrates being the most common finding on chest radiographs. In vitro testing showed a sensitivity of all species to trimethoprim-sulfamethoxazole (TMP-SMZ), aminoglycosides, ceftriaxone and imipenem. The majority of the patients were treated with TMP-SMZ in combination with other drugs. The results of our study suggest that there is no significant difference in the risk factors, presentations and outcomes of pulmonary infections by N. asteroides and non- asteroides species. Immunocompromised patients are more likely to have unfavorable outcomes.
A comparison of specimen adequacy in fine needle aspiration biopsies performed by pathologists, trained nursing staff and clinicians
Authors: Nteene Litheba M , Wright Colleen A
Published: February 2012

Fine needle aspiration biopsies (FNAB) performed by trained professional nurses and pathology registrars in an FNAB clinic were compared with aspirates by clinicians from regional clinics and hospitals. Of the 7709 reports retrieved from the archives, the highest number of unsatisfactory aspirates came from clinicians (42%), followed by registrars (20.09%) while the nurses had the lowest overall unsatisfactory rate (14.32%). We conclude that, in countries experiencing a shortage of adequately qualified and experienced medical personnel, it is essential to train nurses to perform and manage FNAB clinics.
The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme protein p65 induces multiple structural changes in telomerase RNA
Authors: Akiyama Benjamin M. , Loper John , Najarro Kevin , Stone Michael D.
Published: February 2012

The unique cellular activity of the telomerase reverse transcriptase ribonucleoprotein (RNP) requires proper assembly of protein and RNA components into a functional complex. In the ciliate model organism Tetrahymena thermophila, the La-domain protein p65 is required for in vivo assembly of telomerase. Single-molecule and biochemical studies have shown that p65 promotes efficient RNA assembly with the telomerase reverse transcriptase (TERT) protein, in part by inducing a bend in the conserved stem IV region of telomerase RNA (TER). The domain architecture of p65 consists of an N-terminal domain, a La-RRM motif, and a C-terminal domain (CTD). Using single-molecule Förster resonance energy transfer (smFRET), we demonstrate the p65CTD is necessary for the RNA remodeling activity of the protein and is sufficient to induce a substantial conformational change in stem IV of TER. Moreover, nuclease protection assays directly map the site of p65CTD interaction to stem IV and reveal that, in addition to bending stem IV, p65 binding reorganizes nucleotides that comprise the low-affinity TERT binding site within stem–loop IV.
Impact of Performance-Based Contracting on Product Reliability: An Empirical Analysis
Authors: Guajardo Jose A. , Cohen Morris A. , Kim Sang-Hyun , Netessine Serguei
Published: February 2012

Using a proprietary data set provided by a major manufacturer of aircraft engines, we empirically investigate how product reliability is impacted by the use of two different types of after-sales maintenance support contracts: time and material contracts (T&MC) and performance-based contracts (PBC). We offer a number of competing arguments based on the theory of incentives that establish why product reliability may increase or decrease under PBC. We build a two-stage econometric model that explicitly accounts for the endogeneity of contract choices, and find evidence of a positive and significant effect of PBC on product reliability. The estimation of our model indicates that product reliability is higher by 25%–40% under PBC compared to under T&MC, once the endogeneity of contract choice is taken into account. Our results are consistent with two mechanisms for reliability improvement under PBC: more frequent scheduled maintenance and better care performed in each maintenance event.

This paper was accepted by Martin Lariviere, operations management.
Network Progeny? Prefounding Social Ties and the Success of New Entrants
Authors: Roberts Peter W. , Sterling Adina D.
Published: February 2012

Entrepreneurs that were employed by successful industry incumbents prior to founding tend to confer advantages on their new organizations. We propose and then demonstrate a similar “network progeny” effect rooted in the social relationships that form among entrepreneurs. Our analysis of new entrants into the Ontario wine industry shows that prefounding friendship ties of the founders of one especially prominent entrepreneurial firm led to significantly higher ice wine prices. This attests to the promise of a network progeny extension of the parent–progeny account of new firm success. Follow-on analysis indicates that this effect is not attributable to an entrant's ability to make ice wines of superior quality or to it having access to better distribution knowledge. We therefore conclude that having a social tie to this prominent entrepreneurial firm generated reflected prominence that enhanced the valuations and therefore prices of wines made by connected market entrants.

This paper was accepted by Jesper Sørensen, organizations.
The Planning of Guaranteed Targeted Display Advertising
Authors: Turner John
Published: February 2012

As targeted advertising becomes prevalent in a wide variety of media vehicles, planning models become increasingly important to ad networks that need to match ads to appropriate audience segments, provide a high quality of service (meet advertisers' goals), and ensure that ad serving opportunities are not wasted. We define Guaranteed Targeted Display Advertising (GTDA) as a class of media vehicles that include webpage banner ads, video games, electronic outdoor billboards, and the next generation of digital TV, and formulate the GTDA planning problem as a transportation problem with quadratic objective. By modeling audience uncertainty, forecast errors, and the ad server's execution of the plan, we derive sufficient conditions that state when our quadratic objective is a good surrogate for several ad delivery performance metrics. Moreover, our quadratic objective allows us to construct duality-based bounds for evaluating aggregations of the audience space, leading to two efficient algorithms for solving large problems: the first intelligently refines the audience space into successively smaller blocks, and the second uses scaling to find a feasible solution given a fixed audience space partition. Near-optimal schedules can often be produced despite significant aggregation.
Factors affecting the incidence of deep wound infection after hip fracture surgery
Authors: Harrison T. , Robinson P. , Cook A. , Parker M. J.
Published: February 2012

Prospective data on 6905 consecutive hip fracture patients at a district general hospital were analysed to identify the risk factors for the development of deep infection post-operatively. The main outcome measure was infection beneath the fascia lata.

A total of 50 patients (0.7%) had deep infection. Operations by consultants or a specialist hip fracture surgeon had half the rate of deep infection compared with junior grades (p = 0.01). Increased duration of anaesthesia was significantly associated with deep infection (p = 0.01). The method of fracture fixation was also significant. Intracapsular fractures treated with a hemiarthroplasty had seven times the rate of deep infection compared with those treated by internal fixation (p = 0.001). Extracapsular fractures treated with an extramedullary device had a deep infection rate of 0.78% compared with 0% for those treated with intramedullary devices (p = 0.02).

The management of hip fracture patients by a specialist hip fracture surgeon using appropriate fixation could significantly reduce the rate of deep infection and associated morbidity, along with extended hospitalisation and associated costs.
Conservative management of patients with an osteoporotic vertebral fracture
Authors: Longo U. G. , Loppini M. , Denaro L. , Maffulli N. , Denaro V.
Published: February 2012

Osteoporotic vertebral compression fractures (VCFs) are an increasing public health problem. Recently, randomised controlled trials on the use of kyphoplasty and vertebroplasty in the treatment of these fractures have been published, but no definitive conclusions have been reached on the role of these interventions. The major problem encountered when trying to perform a meta-analysis of the available studies for the use of cementoplasty in patients with a VCF is that conservative management has not been standardised. Forms of conservative treatment commonly used in these patients include bed rest, analgesic medication, physiotherapy and bracing.

In this review, we report the best evidence available on the conservative care of patients with osteoporotic VCFs and associated back pain, focusing on the role of the most commonly used spinal orthoses. Although orthoses are used for the management of these patients, to date, there has been only one randomised controlled trial published evaluating their value. Until the best conservative management for patients with VCFs is defined and standardised, no conclusions can be drawn on the superiority or otherwise of cementoplasty techniques over conservative management.
Long-term results of arthroscopic excision of unstable osteochondral lesions of the lateral femoral condyle
Authors: Lim H-C. , Bae J-H. , Park Y-E. , Park Y-H. , Park J-H. , Park J-W. , Suh D-H.
Published: February 2012

The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (sd 3.5) pre-operatively to a mean of 87.3 (sd 5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover’s classification and when compared with the pre-operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston’s rating scale, where 19 knees were rated as good, four as fair and five as poor.

We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory.
The use of femoral struts and impacted cancellous bone allograft in patients with severe femoral bone loss who undergo revision total hip replacement
Authors: Buttaro M. A. , Costantini J. , Comba F. , Piccaluga F.
Published: February 2012

We determined the midterm survival, incidence of peri-prosthetic fracture and the enhancement of the width of the femur when combining struts and impacted bone allografts in 24 patients (25 hips) with severe femoral bone loss who underwent revision hip surgery. The pre-operative diagnosis was aseptic loosening in 16 hips, second-stage reconstruction in seven, peri-prosthetic fracture in one and stem fracture in one hip. A total of 14 hips presented with an Endoklinik grade 4 defect and 11 hips a grade 3 defect. The mean pre-operative Merle D’Aubigné and Postel score was 5.5 points (1 to 8).

The survivorship was 96% (95% confidence interval 72 to 98) at a mean of 54.5 months (36 to 109). The mean functional score was 17.3 points (16 to 18). One patient in which the strut did not completely bypass the femoral defect was further revised using a long cemented stem due to peri-prosthetic fracture at six months post-operatively. The mean subsidence of the stem was 1.6 mm (1 to 3). There was no evidence of osteolysis, resorption or radiolucencies during follow-up in any hip. Femoral width was enhanced by a mean of 41% (19% to 82%). A total of 24 hips had partial or complete bridging of the strut allografts.

This combined biological method was associated with a favourable survivorship, a low incidence of peri-prosthetic fracture and enhancement of the width of the femur in revision total hip replacement in patients with severe proximal femoral bone loss.
Predictors of the accuracy of quotation of references in peer-reviewed orthopaedic literature in relation to publications on the scaphoid
Authors: Buijze G. A. , Weening A. A. , Poolman R. W. , Bhandari M. , Ring D.
Published: February 2012

Using inaccurate quotations can propagate misleading information, which might affect the management of patients. The aim of this study was to determine the predictors of quotation inaccuracy in the peer-reviewed orthopaedic literature related to the scaphoid. We randomly selected 100 papers from ten orthopaedic journals. All references were retrieved in full text when available or otherwise excluded. Two observers independently rated all quotations from the selected papers by comparing the claims made by the authors with the data and expressed opinions of the reference source. A statistical analysis determined which article-related factors were predictors of quotation inaccuracy. The mean total inaccuracy rate of the 3840 verified quotes was 7.6%. There was no correlation between the rate of inaccuracy and the impact factor of the journal. Multivariable analysis identified the journal and the type of study (clinical, biomechanical, methodological, case report or review) as important predictors of the total quotation inaccuracy rate.

We concluded that inaccurate quotations in the peer-reviewed orthopaedic literature related to the scaphoid were common and slightly more so for certain journals and certain study types. Authors, reviewers and editorial staff play an important role in reducing this inaccuracy.
Clinical and radiological results following radial osteotomy in patients with Kienböck’s disease
Authors: Rodrigues-Pinto R. , Freitas D. , Costa L. D. , Sousa R. , Trigueiros M. , Lemos R. , Silva C. , Oliveira A.
Published: February 2012

Radial osteotomy is currently advocated for patients with Lichtman’s stages II and IIIA of Kienböck’s disease; its place in the treatment of patients with stage IIIB disease remains controversial. The purpose of this study was to evaluate the medium-term results of this procedure and to compare the outcome in patients with stage IIIB disease and those with earlier stages (II and IIIA). A total of 18 patients (18 osteotomies) were evaluated both clinically and radiologically at a mean follow-up of 10.3 years (4 to 18). Range of movement, grip strength and pain improved significantly in all patients; the functional score (Nakamura Scoring System (NSSK)) was high and self-reported disability (Disabilities of Arm, Shoulder and Hand questionnaire) was low at the final follow-up in all patients evaluated. Patients with stage IIIB disease, however, had a significantly lower grip strength, lower NSSK scores and higher disability than those in less advanced stages. Radiological progression of the disease was not noted in either group, despite the stage. Radial osteotomy seems effective in halting the progression of disease and improving symptoms in stages II, IIIA and IIIB. Patients with less advanced disease should be expected to have better clinical results.
Porous metal revision shells for management of contained acetabular bone defects at a mean follow-up of six years
Authors: Sternheim A. , Backstein D. , Kuzyk P. R. T. , Goshua G. , Berkovich Y. , Safir O. , Gross A. E.
Published: February 2012

We report the use of porous metal acetabular revision shells in the treatment of contained bone loss. The outcomes of 53 patients with ≤ 50% acetabular bleeding host bone contact were compared with a control group of 49 patients with > 50% to 85% bleeding host bone contact. All patients were treated with the same type of trabecular metal acetabular revision shell. The mean age at revision was 62.4 years (42 to 80) and the mean follow-up of both groups was 72.4 months (60 to 102). Clinical, radiological and functional outcomes were assessed. There were four (7.5%) mechanical failures in the ≤ 50% host bone contact group and no failures in the > 50% host bone contact group (p = 0.068). Out of both groups combined there were four infections (3.9%) and five recurrent dislocations (4.9%) with a stable acetabular component construct that were revised to a constrained liner. Given the complexity of the reconstructive challenge, porous metal revision acetabular shells show acceptable failure rates at five to ten years’ follow-up in the setting of significant contained bone defects. This favourable outcome might be due to the improved initial stability achieved by a high coefficient of friction between the acetabular implant and the host bone, and the high porosity, which affords good bone ingrowth.
Institutionalization as a Risk Factor for Inappropriate Drug Use in the Elderly: A Swedish Nationwide Register-Based Study
Authors: Haasum Ylva , Fastbom Johan , Johnell Kristina
Published: February 2012

Background:

Few studies have investigated institutionalization as a potential risk factor for potentially inappropriate drug use (PIDU), Sweden now has unique possibilities for comparisons of drug use in large populations of institutionalized and home-dwelling elderly through linkage of the Swedish Prescribed Drug Register (SPDR) with the Swedish Social Services Register.

Objective:

To compare PIDU in institutionalized versus home-dwelling elderly persons in Sweden.

Methods:

We conducted a cross-sectional retrospective study of 1,260,843 home-dwelling and 86,721 institutionalized elderly individuals. We analyzed data on age, sex, and dispensed drugs for individuals aged 65 years or older registered in the SPDR from July to September 2008. Data on type of housing wore retrieved from the Social Services Register. The main outcome measures of PIDU were use of anticholinergic drugs, long-acting benzodiazepines, concurrent use of 3 or more psychotropics, and potentially serious drug-drug interactions (DDIs).

Results:

Thirty percent of the institutionalized and 12% of the home-dwelling elderly were exposed to PIDU. Living in an institution was strongly associated with overall PIDU (OR 2.36; 95% CI 2.29 to 2.44), use of anticholinergic drugs (OR 2.58; 95% CI 2.48 to 2.68), long-acting benzodiazepines (OR 1.50; 95% CI 1.41 to 1.60), and concurrent use of 3 or more psychotropics (OR 7.26; 95% CI 6.96 to 7.59), after controlling for age, sex, and number of drugs (used as proxy for comorbidity). However, institutionalization was associated with a lower probability of potentially serious DDIs (OR 0.60; 95% CI 0.55 to 0.65).

Conclusions:

Our results indicate that institutionalization is a potential risk factor for PIDU. This implies that more cautious prescribing is warranted in institutions, where the frailest and most vulnerable elderly individuals reside. Research is needed to identify underlying risk factors for PIDU within these settings.