bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature dependent efficiency droop in GaInN light-emitting diodes with different current densities
Authors: Meyaard David S. , Shan Qifeng , Cho Jaehee , Fred Schubert E. , Han Sang-Heon , Kim Min-Ho , Sone Cheolsoo , Jae Oh Seung , Kyu Kim Jong
Published: February 2012

The effect of chip area on the temperature-dependent light-output power (LOP) in GaInN-based light-emitting diodes (LEDs) is investigated. The larger the chip size, the faster the reduction in LOP with increasing temperature becomes, indicating that increasing the size of LED chips, a technology trend for reducing the efficiency droop at high currents, is detrimental for high temperature-tolerant LEDs. In addition, it is found that regardless of chip size, the temperature-dependent LOP is identical for the LEDs operating at the same current density.
Impact of the misfit dislocations on two-dimensional electron gas mobility in semi-polar AlGaN/GaN heterostructures
Authors: Liu Guipeng , Wu Ju , Zhao Guijuan , Liu Shuman , Mao Wei , Hao Yue , Liu Changbo , Yang Shaoyan , Liu Xianglin , Zhu Qinsheng , Wang Zhanguo
Published: February 2012

The mobility of two-dimensional electron gas as influenced by the charged misfit dislocations located at the interface of the semi-polar AlGaN/GaN heterostructure is quantitatively analyzed. The results indicate that the strength of the scattering due to the misfit dislocations in the semi-polar AlGaN/GaN heterointerface is comparable to the well-known scattering associated with the threading dislocations in the well-known polar c-plane AlGaN/GaN heterostructures.
Structure and magnetotransport properties of epitaxial nanocomposite La0.67Ca0.33MnO3:SrTiO3 thin films grown by a chemical solution approach
Authors: Fei Ling , Zhu Leyi , Cheng Xuemei , Wang Haiyan , Baber Stacy M. , Hill Joshua , Lin Qianglu , Xu Yun , Deng Shuguang , Luo Hongmei
Published: February 2012

Epitaxial La0.67Ca0.33MnO3:SrTiO3 (LCMO:STO) composite thin films have been grown on single crystal LaAlO3(001) substrates by a cost effective polymer-assisted deposition method. Both x-ray diffraction and high-resolution transmission electron microscopy confirm the growth of epitaxial films with an epitaxial relationship between the films and the substrates as (002)film||(002)sub and [202]film||[202]sub. The transport property measurement shows that the STO phase significantly increases the resistivity and enhances the magnetoresistance (MR) effect of LCMO and moves the metal-insulator transition to lower temperatures. For example, the MR values measured at magnetic fields of 0 and 3 T are −44.6% at 255 K for LCMO, −94.2% at 125 K for LCMO:3% STO, and −99.4% at 100 K for LCMO:5% STO, respectively.
Enhanced electrical stability of organic thin-film transistors with polymer semiconductor-insulator blended active layers
Authors: Lee Jiyoul , Young Jung Ji , Hwan Kim Do , Kim Joo-Young , Lee Bang-Lin , Park Jeong-Il , Won Chung Jong , Seok Park Joon , Koo Bonwon , Wan Jin Yong , Lee Sangyoon
Published: February 2012

We report on an enhanced electrical stability of organic thin-film transistors (OTFTs), where an organic semiconductor (poly(didodecylquaterthiophene-alt-didodecylbithiazole) (PQTBTz-C12)) and a polymer insulator (poly(methyl methacrylate) (PMMA)) blended film were used as the active layer, in comparison with a single PQTBTz-C12 OTFT. While both devices exhibit similar electrical performance in terms of mobility and ON/OFF ratios, the blended device is less susceptible to OFF-bias stress. It is suggested that the carboxyl groups of PMMA in the blend may act as suppressors with regards to hole accumulation in the channel, and thus, the PQTBTz-C12/PMMA blend based OTFTs exhibit delayed threshold voltage shifts under OFF-bias stress.
Communication: Translational Brownian motion for particles of arbitrary shape
Authors: Cichocki Bogdan , Ekiel-Jeżewska Maria L. , Wajnryb Eligiusz
Published: February 2012

A single Brownian particle of arbitrary shape is considered. The time-dependent translational mean square displacement W(t) of a reference point at this particle is evaluated from the Smoluchowski equation. It is shown that at times larger than the characteristic time scale of the rotational Brownian relaxation, the slope of W(t) becomes independent of the choice of a reference point. Moreover, it is proved that in the long-time limit, the slope of W(t) is determined uniquely by the trace of the translational-translational mobility matrix \documentclass[12pt]{minimal}\begin{document}$\bm {\mu }^{tt}$\end{document}μtt evaluated with respect to the hydrodynamic center of mobility. The result is applicable to dynamic light scattering measurements, which indeed are performed in the long-time limit.
Significant population genetic structure detected for a new and highly restricted species of Atriplex (Chenopodiaceae) from Western Australia, and implications for conservation management
Authors: Clarke Laurence J. , Jardine Duncan I. , Byrne Margaret , Shepherd Kelly , Lowe Andrew J.
Published: February 2012

Atriplex sp. Yeelirrie Station (L. Trotter & A. Douglas LCH 25025) is a highly restricted, potentially new species of saltbush, known from only two sites ~30 km apart in central Western Australia. Knowledge of genetic structure within the species is required to inform conservation strategies as both populations occur within a palaeovalley that contains significant near-surface uranium mineralisation. We investigate the structure of genetic variation within populations and subpopulations of this taxon using nuclear microsatellites. Internal transcribed spacer sequence data places this new taxon within a clade of polyploid Atriplex species, and the maximum number of alleles per locus suggests it is hexaploid. The two populations possessed similar levels of genetic diversity, but exhibited a surprising level of genetic differentiation given their proximity. Significant isolation by distance over scales of less than 5 km suggests dispersal is highly restricted. In addition, the proportion of variation between the populations (12%) is similar to that among A. nummularia populations sampled at a continent-wide scale (several thousand kilometres), and only marginally less than that between distinct A. nummularia subspecies. Additional work is required to further clarify the exact taxonomic status of the two populations. We propose management recommendations for this potentially new species in light of its highly structured genetic variation.
Full regeneration of the tribasal
Polypterus
fin
Authors: Cuervo Rodrigo , Hernández-Martínez Rocío , Chimal-Monroy Jesús , Merchant-Larios Horacio , Covarrubias Luis
Published: February 2012

Full limb regeneration is a property that seems to be restricted to urodele amphibians. Here we found that
Polypterus
, the most basal living ray-finned fish, regenerates its pectoral lobed fins with a remarkable accuracy. Pectoral
Polypterus
fins are complex, formed by a well-organized endoskeleton to which the exoskeleton rays are connected. Regeneration initiates with the formation of a blastema similar to that observed in regenerating amphibian limbs. Retinoic acid induces dose-dependent phenotypes ranging from inhibition of regeneration to apparent anterior–posterior duplications. As in all developing tetrapod limbs and regenerating amphibian blastema, Sonic hedgehog is expressed in the posterior mesenchyme during fin regeneration. Hedgehog signaling plays a role in the regeneration and patterning processes: an increase or reduction of fin bony elements results when this signaling is activated or disrupted, respectively. The tail fin also regenerates but, in contrast with pectoral fins, regeneration can resume after release from the arrest caused by hedgehog inhibition. A comparative analysis of fin phenotypes obtained after retinoic acid treatment or altering the hedgehog signaling levels during regeneration allowed us to assign a limb tetrapod equivalent segment to
Polypterus
fin skeletal structures, thus providing clues to the origin of the autopod. We propose that appendage regeneration was a common property of vertebrates during the fin to limb transition.
CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells
Authors: Poppensieker Karola , Otte David-Marian , Schürmann Britta , Limmer Andreas , Dresing Philipp , Drews Eva , Schumak Beatrix , Klotz Luisa , Raasch Jennifer , Mildner Alexander , Waisman Ari , Scheu Stefanie , Knolle Percy , Förster Irmgard , Prinz Marco , Maier Wolfgang , Zimmer Andreas , Alferink Judith
Published: February 2012

Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4
−/−
mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4
−/−
mice, indicating that CCR4
+
DCs are cellular mediators of EAE development. Mechanistically, CCR4
−/−
DCs were less efficient in GM-CSF and IL-23 production and also T
H
-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4
−/−
mice, whereas intracerebral inoculation using IL-23
−/−
DCs or GM-CSF
−/−
DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type.
Lithium enhances remyelination of peripheral nerves
Authors: Makoukji Joelle , Belle Martin , Meffre Delphine , Stassart Ruth , Grenier Julien , Shackleford Ghjuvan'Ghjacumu , Fledrich Robert , Fonte Cosima , Branchu Julien , Goulard Marie , de Waele Catherine , Charbonnier Frédéric , Sereda Michael W. , Baulieu Etienne-Emile , Schumacher Michael , Bernard Sophie , Massaad Charbel
Published: February 2012

Glycogen synthase kinase 3β (GSK3β) inhibitors, especially the mood stabilizer lithium chloride, are also used as neuroprotective or anti-inflammatory agents. We studied the influence of LiCl on the remyelination of peripheral nerves. We showed that the treatment of adult mice with LiCl after facial nerve crush injury stimulated the expression of myelin genes, restored the myelin structure, and accelerated the recovery of whisker movements. LiCl treatment also promoted remyelination of the sciatic nerve after crush. We also demonstrated that peripheral myelin gene MPZ and PMP22 promoter activities, transcripts, and protein levels are stimulated by GSK3β inhibitors (LiCl and SB216763) in Schwann cells as well as in sciatic and facial nerves. LiCl exerts its action in Schwann cells by increasing the amount of β-catenin and provoking its nuclear localization. We showed by ChIP experiments that LiCl treatment drives β-catenin to bind to T-cell factor/lymphoid-enhancer factor response elements identified in myelin genes. Taken together, our findings open perspectives in the treatment of nerve demyelination by administering GSK3β inhibitors such as lithium.
The manifestation of transference during early psychotherapy sessions: Exploring an alternate data source for therapist narratives in transference research
Authors: Jaffee Catherine Tellides , Fitzpatrick Marilyn , Drapeau Martin , Bracewell Robert , Chamodraka Martha , Marini Nadia
Published: February 2012

Introduction: Previous transference studies have compared in‐session client narratives about significant others to in‐session client narratives about the therapist, limiting data to the information that clients are willing to share with the therapist. Method: The first three sessions of 30 therapies with high‐functioning individuals were examined using the Core Conflictual Relationship Theme (CCRT) method. Client narratives about others were drawn from the psychotherapy sessions and client narratives about the therapist were drawn from a Participant Critical Event (PCE) interview conducted after the third session of therapy. Results: Factor analyses of the CCRT components indicated several relational patterns: a complementary pattern of relating characterised by a devaluation of the therapist and idealisation of others; a concordant relational transfer where clients feel bad with both the therapist and others; and as clients experience control issues with significant others, they wish to adopt a submissive stance toward the therapist. The results suggest that the source of therapist narratives may influence the results of transference research.
Photo-induced currents in CdZnTe crystals as a function of illumination wavelength
Authors: Teague L C , A L Washington , Duff M C , Groza M , Buliga V , Burger A
Published: February 2012

We report variations in the currents of CdZnTe semiconductor crystals during exposure to a series of light emitting diodes of various wavelengths ranging from 470 to 950 nm. The changes in the steady-state current of one CdZnTe crystal with and without illumination along with the time dependence of the illumination effects are discussed. Analysis of the de-trapping and transient bulk currents during and after optical excitation yield insight into the behaviour of charge traps within the crystal. Similar behaviour is observed for illumination of a second CdZnTe crystal suggesting that the overall illumination effects are not crystal dependent.
A new approach for improving the silicon texturing process using gas-lift effect
Authors: Amouzgar M , Kahrizi M
Published: February 2012

A new cost-effective and efficient approach is proposed for texturing the crystalline silicon using the gas-lift effect (GLE). The advantages of this approach over the conventional ones are that significantly lower amounts of IPA is used and much shorter etching time is required to achieve the same reflectivity. GLE is generated by taking advantage of the hydrogen bubbles evolved between the silicon wafer being etched and a glass plate, placed in parallel, creating a gap of 1–2 mm. This effect then acts as a pumping mechanism detaching more bubbles from the silicon surface, accelerating them to the top and out of the system, as quickly as they are generated. Experiments were carried out with various combinations of TMAH/IPA concentrations for two different GLE conditions to analyse and determine their influence on etching time, etching rate, surface morphology and reflectivity of the textured silicon surface. The use of this new approach in surface texturing, allowed the reduction of the required IPA by 50% and etching time by more than 60% to achieve the same reflectivity. This can ultimately lead to a significant reduction in cost by increasing the efficiency of the texturing process. A combination of 3.5% IPA and 2 mm GLE resulted in a textured silicon surface having a low specular solar-weighted reflectivity of 0.15%.
TiO2 coatings with Au nanoparticles analysed by photothermal IR radiometry
Authors: Macedo F , Vaz F , Torrell M , Faria R T , Cavaleiro A , Barradas N P , Alves E , Junge K H , Bein B K
Published: February 2012

Optically active Au : TiO2 nanocomposite thin films with an amount of gold of about 15 at% were prepared by dc reactive magnetron sputtering. After the deposition, the samples were annealed in vacuum at different constant temperatures between 200 and 800 °C. Depending on the annealing temperature, considerable changes have been found in the films' crystalline structure and for the number, the shape and the dimensions of the Au clusters. Modulated IR Radiometry (MIRR), a non-contact, non-destructive modulation-frequency-dependent photothermal measurement technique, was used for the characterization of the thermo-optical depth profiles of the as-deposited and annealed samples. Based on the results of MIRR, it was possible to establish correlations of the measured thermo-optical depth profiles with various effects: the heat treatment induced progress of crystallization of the TiO2 matrix, the evolution of Au nanoparticles and strong subsurface heat sources related to the surface plasmon resonance (SPR) effect. For the annealing temperature of 800 °C, a diffusion and accumulation of gold just at the surface was found, which contributes to limit the subsurface heat sources and the SPR effect.
Changes and trends in the demersal fish community of the Flemish Cap, Northwest Atlantic, in the period 1988–2008
Authors: Pérez-Rodríguez Alfonso , Koen-Alonso Mariano , Saborido-Rey Fran
Published: February 2012

Pérez-Rodríguez, A., Koen-Alonso, M., and Saborido-Rey, F. 2012. Changes and trends in the demersal fish community of the Flemish Cap, Northwest Atlantic, in the period 1988–2008. – ICES Journal of Marine Science, 69: 902–912. The Flemish Cap fish community (NAFO Division 3M) has been fished since the 1950s, and major changes in the biomass and abundance of its most important commercial species have been reported since the late 1980s. Variations in oceanographic conditions at the Cap, with alternating periods of cold and warm weather, have also been described. This work examines the existence of common trends in the biomass levels of the main demersal species over time using dynamic factor analysis, and the occurrence of “occasional species” was explored in relation to temperature conditions. Overall, there have been significant changes in community structure involving both commercial and non-commercial species. Common trends among species were identified and overall fishing pressure, environmental conditions (represented by a moving average of the North Atlantic Oscillation, NAO), and predation pressure (represented by the abundance of piscivorous fish) emerged as important drivers of the temporal dynamics. The NAO influence in the dynamics of most species was in agreement with their temperature preference. For occasional species, their pattern of occurrence appears also to be linked to changes in temperature regimes.
Muscle-Specific Kinase-Antibody-Positive Myasthenia Gravis After Autologous Bone Marrow Transplantation
Authors: Grover Kavita Mohindra , Sripathi Naganand , Elias Stanton Bernard
Published: February 2012

A 44-year-old man presented with oculobulbar weakness approximately 5 years after autologous bone marrow transplantation (BMT). His workup led to the diagnosis of muscle-specific kinase-antibody-related myasthenia gravis (MG). There has been only one case report of muscle-specific kinase-antibody-positive MG after BMT, which was allogeneic. We report the first case of autologous BMT-associated MG with muscle-specific kinase antibody. The pathogenic mechanisms of immune dysregulation leading to MG after BMT are discussed.
Outcome Prediction Value of Nerve Conduction Studies for Endoscopic Carpal Tunnel Surgery
Authors: Lo Yew-Long , Lim Shu-Han , Fook-Chong Stephanie , Lum Sau-Ying , Teoh Lam-Chuan , Yong Fook-Chuan
Published: February 2012

Objective

Carpal tunnel syndrome is the most common entrapment neuropathy. We explore the clinical use of nerve conduction study in the outcome prediction and preoperative selection for endoscopic carpal tunnel syndrome surgery.

Methods

Sixty-seven patients with carpal tunnel syndrome were prospectively enrolled. Each patient's clinical symptomatic score at baseline and 3 months postsurgery was compared with nerve conduction study parameters of distal motor latency, motor amplitude, motor conduction velocity, distal sensory latency, sensory amplitude, and sensory conduction velocity. A statistical logistic regression model was used to ascertain outcomes.

Results

Endoscopic surgery resulted in significant improvement for all four major symptoms pain, numbness, paresthesia, and weakness. From multivariate logistic regression, a shorter distal sensory latency is associated with a higher likelihood of a good outcome (P = 0.058; odds ratio, 0.912; 95% confidence interval, 0.828–1.0) only for paresthesia. The other factors were not found to be significant (all P > 0.10). The area under the curve (AUC) was 0.69 (95% confidence interval for AUC, 0.50–0.88). A cutoff of 6.0 ms or lower for sensory latency predicts for good outcome (in terms of paresthesia score) with the sensitivity/certainty of 84.6% and positive predictive value of 86.8%. A receiver operating characteristic analysis of baseline paresthesia score for good outcome of the paraesthesia domain showed that the AUC was 0.967 (95% confidence interval for AUC, 0–1.0). At a cutoff of baseline paraesthesia score of 4 or above, prediction for good outcome achieved a sensitivity of 87.2% and positive predictive value of 97.1%.

Conclusions

A shorter distal sensory latency is associated with a higher likelihood of a good outcome for paraesthesia. In addition, patients with baseline of 4 or above had correlated with better surgical outcome than those with less severe symptoms. Our data thus suggest that surgical benefit is best seen in patients with moderate symptoms, in combination with electrophysiological evidence of early demyelination, as a possible therapeutic window.
Muscle Restricted Vasculitis Causing Dropped Head Syndrome
Authors: Nielsen Amy Almaraz , Smith Benn E. , Engel Andrew G. , Bosch Erich Peter
Published: February 2012

A 52-year-old man presented with a severe head drop and proximal extremity weakness. Magnetic resonance imaging of the cervical spine showed T2 hyperintensity in cervical paraspinal muscles. Electrodiagnostic studies revealed an axial myopathy isolated to paraspinal muscles. A splenius capitis muscle biopsy confirmed an acute myopathy associated with nonsystemic vasculitis. The patient improved on steroids, intravenous immunoglobulin, and monthly pulse doses of cyclophosphamide. Our case emphasizes that a subgroup of patients with dropped head syndrome have treatable conditions.
It is optimal to be optimistic about survival
Authors: McNamara John M. , Trimmer Pete C. , Houston Alasdair I.
Published: February 2012

We investigate the optimal behaviour of an organism that is unable to obtain a reliable estimate of its mortality risk. In this case, natural selection will shape behaviour to be approximately optimal given the probability distribution of mortality risks in possible environments that the organism and its ancestors encountered. The mean of this distribution is the average mortality risk experienced by a randomly selected member of the species. We show that if an organism does not know the exact mortality risk, it should act as if the risk is less than the mean risk. This can be viewed as being optimistic. We argue that this effect is likely to be general.
Biting off more than you can chew: sexual selection on the free amino acid composition of the spermatophylax in decorated crickets
Authors: Gershman Susan N. , Mitchell Christopher , Sakaluk Scott K. , Hunt John
Published: February 2012

Nuptial food gifts function to enhance male fertilization success, but their consumption is not always beneficial to females. In decorated crickets, the spermatophore transferred at mating includes a gelatinous mass, the spermatophylax, which is consumed by females after mating. However, females often discard spermatophylaxes shortly after mating, whereupon they terminate sperm transfer. We hypothesized that females discard gifts based on their assessment of the gift itself, and specifically the composition of free amino acids. We tested this hypothesis by comparing spermatophylaxes discarded by females after mating with those that were destined to be fully consumed, and employed multivariate selection analysis to quantify the strength and form of multivariate sexual selection operating on the free amino acid composition of gifts. The analysis yielded a saddle-shaped fitness surface with two local peaks. Different amino acid profiles appear to elicit continued feeding on the spermatophylax either because they offer the same level of gustatory appeal, or because they differentially affect both the gustatory appeal and texture of the spermatophylax. We conclude that the gustatory response of females to males' nuptial food gifts represents an important avenue of post-copulatory mate choice, imposing significant sexual selection on the free amino acid composition of the spermatophylax.
Current understanding of human genetics and genetic analysis of psoriasis
Authors: OKA Akira , MABUCHI Tomotaka , OZAWA Akira , INOKO Hidetoshi
Published: February 2012

During the past 5 years, genome‐wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. These studies appeared to provide strong evidence because the susceptibility genes are involved in the interleukin‐23/T‐helper 17 axis of psoriasis immunopathogenesis and/or skin barrier functions. However, the “identified” genes only explained a small proportion of psoriasis heritability, although it is known to be comparatively higher than that of other common diseases. GWAS are based on the hypothesis that disease‐causing variants are high frequency variants within populations. However, this hypothesis is problematic because deleterious variants such as those predisposing to specific diseases will generally not be maintained by selection pressure throughout human evolution. This issue also affects psoriasis studies. Here, we review the current paradigm shift in human genetic analyses and its implications for detection of psoriasis‐causing variants based on linkage analysis and GWAS, except the well‐known psoriasis susceptibility locus HLA‐C.
Association of adiponectin with blood pressure in healthy people
Authors: Baden Megu Y. , Yamada Yuya , Takahi Yasumitsu , Obata Yoshinari , Saisho Kenji , Tamba Sachiko , Yamamoto Koji , Umeda Miyuki , Furubayashi Aiko , Tsukamoto Yoshifumi , Sakaguchi Katsuhiko , Matsuzawa Yuji
Published: February 2012

Objective

With the increasing prevalence of diseases related to obesity, metabolic syndrome and its key player adiponectin are now attracting considerable attention. Hypoadiponectinaemia is reported to be a risk factor for hypertension and associated with endothelial dysfunction, which is closely related to complications of obesity such as hypertension. As there is limited information regarding serum adiponectin levels in normotensive people, we undertook the large‐scale study to determine the association of adiponectin with blood pressure (BP) in mainly normotensive people.

Design, patients and measurements

In 21 100 Japanese adults (12 363 men and 8737 women) who had no apparent diseases, we examined the relationship between the serum adiponectin concentration and BP by performing a questionnaire survey, physical measurements and measurement of laboratory parameters including the serum adiponectin level.

Results

Subjects with hypoadiponectinaemia had higher systolic and diastolic BPs as already reported. And interestingly, subjects with higher adiponectin had lower systolic and diastolic BP. According to linear regression analysis, adiponectin showed a significant negative correlation with systolic and diastolic BP independently of the other variables. Analysis of covariance according to adiponectin quintiles showed that systolic and diastolic BP in highest adiponectin quintile was significantly lower than in other quintiles.

Conclusions

This study revealed that there were significant trends toward lower systolic and diastolic BP with higher adiponectin not only in hypertensive people but also in normotensive people.
Emerging therapeutic strategies for Epstein–Barr virus+ post‐transplant lymphoproliferative disorder
Authors: Hatton Olivia , Martinez Olivia M. , Esquivel Carlos O.
Published: February 2012

Hatton O, Martinez OM, Esquivel CO. Emerging therapeutic strategies for Epstein–Barr virus+ post‐transplant lymphoproliferative disorder.

Abstract:  De novo malignancies represent an increasing concern in the transplant population, particularly as long‐term graft and patient survival improves. EBV‐associated B‐cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell‐based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B‐cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV‐associated malignancies.
System for integrated adherence monitoring: Real‐time non‐adherence risk assessment in pediatric kidney transplantation
Authors: Pai Ahna L. H. , Rausch Joseph , Tackett Alayna , Marsolo Keith , Drotar Dennis , Goebel Jens
Published: February 2012

Pai ALH, Rausch J, Tackett A, Marsolo K, Drotar D, Goebel J. System for integrated adherence monitoring: Real‐time non‐adherence risk assessment in pediatric kidney transplantation.

Abstract:  This study reports initial results of the development of the SIAM, a non‐adherence risk assessment system for tacrolimus and sirolimus for the pediatric kidney transplant population. Forty‐eight youths between 10 and 25 yr of age diagnosed with chronic kidney disease or a kidney transplant used an electronic pill bottle (EM; time stamps each bottle opening) to dispense their medication for at least 30 days or until their next clinic appointment. Youth also completed a self‐report adherence measure, and standard deviations were calculated for the last four medication serum trough levels obtained for each patient. Estimation models were developed for each medication (i.e., SIAMTACRO and SIAMSIRO) to assign weights to these clinically available adherence measures (self‐report and trough levels) for the calculation of a non‐adherence risk composite score. SIAMTACRO models included both self‐report and tacrolimus trough levels and significantly predicted EM. For sirolimus, the model predictive of adherence as measured by EM consisted of the standard deviation of sirolimus trough levels only (SIAMSIRO). Non‐adherence risk can be effectively assessed using clinically available assessment tools. However, the best methods for using self‐report and trough levels to predict non‐adherence likely differ based on the medication for which adherence is being assessed.
Can evolution of sexual dimorphism be triggered by developmental temperatures?
Authors: KETOLA T. , KRISTENSEN T. N. , KELLERMANN V. M. , LOESCHCKE V.
Published: February 2012

Genetic prerequisites for the evolution of sexual dimorphism, sex‐specific heritabilities and low or negative genetic correlations between homologous traits in males and females are rarely found. However, sexual dimorphism is evolving rapidly following environmental change, suggesting that sexual dimorphism and its genetic background could be environmentally sensitive. Yet few studies have explored the sensitivity of the genetic background of sexual dimorphism on environmental variation. In this study, onDrosophila melanogaster, we used a large nested full‐sib–half‐sib breeding design where families were split into four different developmental temperatures: two constant temperature treatments of 25 and 30 °C and two cycling temperatures with means of 25 and 30 °C, respectively. After emergence, we tested heat shock tolerance of adult flies. We found that sexual dimorphism was strongly affected by temperature during development. Moreover, we found that female heritability was significantly lower in flies developing at hot temperature and more so under hot and cycling temperatures. Interestingly, most of the genetic variation for heat shock tolerance was orthogonal (i.e. noncorrelated) between sexes, allowing independent evolution of heat shock tolerance in males and females. These findings give support to the hypothesis that the evolution of sexual dimorphism can be influenced by the environments experienced during development.
Do different disparity proxies converge on a common signal? Insights from the cranial morphometrics and evolutionary history of Pterosauria (Diapsida: Archosauria)
Authors: FOTH C. , BRUSATTE S. L. , BUTLER R. J.
Published: February 2012

Disparity, or morphological diversity, is often quantified by evolutionary biologists investigating the macroevolutionary history of clades over geological timescales. Disparity is typically quantified using proxies for morphology, such as measurements, discrete anatomical characters, or geometric morphometrics. If different proxies produce differing results, then the accurate quantification of disparity in deep time may be problematic. However, despite this, few studies have attempted to examine disparity of a single clade using multiple morphological proxies. Here, as a case study for this question, we examine the disparity of the volant Mesozoic fossil reptile clade Pterosauria, an intensively studied group that achieved substantial morphological, ecological and taxonomic diversity during their 145+ million‐year evolutionary history. We characterize broadscale patterns of cranial morphological disparity for pterosaurs for the first time using landmark‐based geometric morphometrics and make comparisons to calculations of pterosaur disparity based on alternative metrics. Landmark‐based disparity calculations suggest that monofenestratan pterosaurs were more diverse cranially than basal non‐monofenestratan pterosaurs (at least when the aberrant anurognathids are excluded), and that peak cranial disparity may have occurred in the Early Cretaceous, relatively late in pterosaur evolution. Significantly, our cranial disparity results are broadly congruent with those based on whole skeleton discrete character and limb proportion data sets, indicating that these divergent approaches document a consistent pattern of pterosaur morphological evolution. Therefore, pterosaurs provide an exemplar case demonstrating that different proxies for morphological form can converge on the same disparity signal, which is encouraging because often only one such proxy is available for extinct clades represented by fossils. Furthermore, mapping phylogeny into cranial morphospace demonstrates that pterosaur cranial morphology is significantly correlated with, and potentially constrained by, phylogenetic relationships.
A functional screen for recovery of 4′‐phosphopantetheinyl transferase and associated natural product biosynthesis genes from metagenome libraries
Authors: Owen J. G. , Robins K. J. , Parachin N. S. , Ackerley D. F.
Published: February 2012

The single‐module non‐ribosomal peptide synthetase BpsA from Streptomyces lavendulae has the unique ability to autonomously synthesize a coloured product (indigoidine) from a single substrate (l‐glutamine), conditional upon activation by a 4′‐phosphopantetheinyl transferase (PPTase) partner. We show that bpsA can be expressed in an entD PPTase gene deleted mutant of Escherichia coli to yield a sensitive reporter strain for recovery of PPTase genes from metagenome libraries. We also show that recombinant bpsA constructs, generated by substitution of the native peptidyl carrier protein domain followed by directed evolution to restore function, can be used to increase the diversity of PPTase genes recovered from a sample. As PPTases are essential for activation of non‐ribosomal peptide synthetase and polyketide synthase enzymes, they are frequently associated with secondary metabolite gene clusters. Nearly half of the PPTases recovered in our screening of two small‐insert soil metagenome libraries were genetically linked to recognizable secondary metabolite biosynthetic genes, demonstrating that PPTase‐targeting functional screens can be used for efficient recovery of natural product gene clusters from metagenome libraries. The plasticity and portability of bpsA reporter genes can potentially be exploited to maximize recovery and expression of PPTase‐bearing clones in a wide range of hosts.
Meta‐analysis of survival based on resection margin status following surgery for recurrent rectal cancer
Authors: Bhangu A. , Ali S. M. , Darzi A. , Brown G. , Tekkis P.
Published: February 2012

Aim  To determine the presence and duration of survival advantages was investigated for resection margin status (R0, R1 or R2) following surgery for locally recurrent rectal cancer (LRRC).

Method  A systematic review of the literature was performed for studies comparing resection margin status for LRRC. Weighted mean differences and meta‐analysis of hazard ratios were used as a measure of median and overall cumulative survival.

Results  Twenty‐two studies were included, providing outcome for 1460 patients undergoing surgery for LRRC. 57% underwent an R0 resection, 25% an R1 resection and 11% an R2 resection. The most commonly performed operations were abdominoperineal excision (35%), exenteration (23%) and anterior resection (21%). The range of median survival per resection margin was R0 28–92 months, R1 12–50 months, R2 6–17 months. Patients undergoing an R0 resection survived on average for 37.6 (95% confidence interval: 23.5–51.7) months longer than those undergoing R1 resection and 53.0 (31.2–74.8) months longer than those undergoing R2 resection. This correlated to a hazard ratio of 2.03 (1.73–2.38) for R0 vs R1 and 3.41 (2.21–5.25) for R0 vs R2. Patients undergoing R1 resection survived on average 13.3 (7.23–19.4) months longer than those undergoing R2 resection [hazard ratio of 1.68 (1.33–2.12)].

Conclusion  Patients undergoing R0 resection have the greatest survival advantage following surgery for recurrent rectal cancer. There is a survival advantage for R1 over R2 resection, but there may be no benefit of R2 resection over palliative treatment.
Formalin dab, the effective way of treating haemorrhagic radiation proctitis: a randomized trial from a tertiary care hospital in South India
Authors: Nelamangala Ramakrishnaiah V. P. , Javali T. D. , Dharanipragada K. , Reddy K. S. , Krishnamachari S.
Published: February 2012

Aim  Chronic radiation proctitis with bleeding is a common problem encountered following radiotherapy for pelvic malignancy. Sucralfate‐steroid enema and formalin dab are two common nonsurgical treatments. A randomized trial was conducted to compare the efficacy of these two methods.

Method  This was a prospective randomized controlled trial conducted in the Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) from August 2005 to May 2007. One‐hundred and two patients with chronic radiation proctitis, presenting as rectal bleeding after radiotherapy for carcinoma of the cervix, were recruited and randomly allocated into two treatment groups: Group 1, formalin dab; and Group 2, sucralfate‐steroid retention enema. The mean age of the patients was 51.3 ± 5.1 years. The mean interval between the end of radiotherapy and the onset of bleeding was 12.3  ± 3.5 months. Symptom score and sigmoidoscopic grade were assessed before, and at 1 month after, treatment.

Results  Ninety per cent of patients in Group 1 and 74.5% of patients in Group 2 responded to treatment (P = 0.038). In spite of having a higher median symptom score before treatment, patients in Group 1 demonstrated a marked decrease in symptom score after treatment compared with patients in Group 2 and the difference once again was statistically significant (P = 0.000). Similarly, the median sigmoidoscopic grade was significantly lower for patients in Group 1 compared with patients in Group 2 after treatment (P = 0.000). There were no specific treatment‐related complications in either group.

Conclusions  Formalin (4%) dab is superior to sucralfate‐steroid retention enema for treatment of chronic haemorrhagic radiation proctitis.
Insulinoma may mask the existence of Type 1 diabetes
Authors: Oikawa Y. , Katsuki T. , Kawasaki M. , Hashiguchi A. , Mukai K. , Handa K. , Tomita M. , Kabeya Y. , Asai Y. , Iwase K. , Hirose S. , Koyama K. , Atsumi Y. , Shimada A.
Published: February 2012

Diabet. Med. 29, e138–e141 (2012)

Background  Insulinoma is a tumour of insulin‐producing cells of the pancreas and is known to be one of the causes of hypoglycaemia. Usually, appropriate removal of the insulinoma results in normalization of blood glucose levels. However, we found novel cases of insulinoma, in which hyperglycaemia developed soon after resection of the insulinoma.

Case report  We encountered two patients with repeated hypoglycaemia caused by insulinoma. Following removal of the insulinoma, unanticipated hyperglycaemia was observed in both patients. Thereafter, their blood tests revealed low levels of serum C‐peptide and high titres of anti‐glutamic acid decarboxylase antibody, indicating concomitant Type 1 diabetes. Indeed, histological examination of the resected specimen revealed that one patient showed insulitis in non‐tumorous pancreatic tissue in which β‐cells had already disappeared. Moreover, inflammatory cells infiltrated the insulinoma, as if it were insulitis of Type 1 diabetes, suggesting the existence of anti‐islet autoimmunity.

Conclusion  These are first cases of insulinoma associated with underlying Type 1 diabetes. Physicians should be aware of the possibility that insulinoma may mask Type 1 diabetes, and measurement of anti‐islet autoantibodies may be helpful to find underlying Type 1 diabetes, such as in these cases. It is pathologically interesting that the immune cell infiltration into insulinoma may be suggestive of anti‐islet autoimmunity.
Trends in the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds metropolitan area, 2005–2010
Authors: Arora S. , Kolb S. , Goyder E. , McKibbin M.
Published: February 2012

Diabet. Med. 29, e112–e116 (2012)

Aim  This study reports the incidence of visual impairment certification due to diabetic retinopathy in Leeds between 2008 and 2010 and makes a comparison with data from 2005, immediately before the introduction of a comprehensive screening service.

Methods  The primary causes of visual impairment certification between 2008 and 2010 were collected and reviewed. Mid‐year population estimates and a diabetes prevalence model were used to determine the incidence of certification secondary to diabetic retinopathy.

Results  Diabetic retinopathy was the primary cause of visual impairment certification in 33 of 446 (7.4%) certificates in 2008, 34 of 410 (8.3%) certificates in 2009 and 24 of 392 (6.1%) in 2010. For the total population in 2008, 2009 and 2010, the combined incidence of either sight impairment or severe sight impairment due to diabetic retinopathy was 42.3, 43.2 and 30 per million per year, respectively. For the population with diagnosed diabetes mellitus, the combined incidence of either sight impairment or severe sight impairment secondary to diabetic retinopathy was 1227, 1192 and 796 per million per year, respectively. For each year, the incidence of visual impairment was lower than the corresponding figure for 2005.

Conclusion  Following the introduction of a comprehensive retinal screening service, the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds Metropolitan area appears to be decreasing. However, a multifaceted approach, addressing all the avoidable risk factors, may be required to maintain this trend in view of the increasing prevalence of Type 2 diabetes.
Would sickle cell trait influence the metabolic control in sub‐Saharan individuals with type 2 diabetes?
Authors: Ama V. , Kengne A. P. , Nansseu N. J. R. , Nouthe B. , Sobngwi E.
Published: February 2012

Diabet. Med. 29, e334–e337 (2012)

Aims  To determine the prevalence and effects of sickle cell trait on metabolic control in a Cameroonian diabetic population in a tertiary care setup.

Methods  This was a cross‐sectional study involving 73 consecutive outpatients with Type 2 diabetes recruited from the Yaounde National Diabetes and Obesity Centre. Sickle cell trait status was based on haemoglobin electrophoresis. Metabolic control was assessed by plasma glucose and HbA1c, and comparisons made between participants with and without sickle cell trait, with adjustment for confounders through linear regressions models

Results  The prevalence of sickle cell trait was 19%, without sex difference, and comparable with figures in individuals without diabetes in this setting. Participants with diabetes and sickle cell trait were older than the non‐trait participants (66 vs. 58 years, P = 0.02). Otherwise, clinical and biological profile including indicators of metabolic control were similarly distributed between trait and non‐trait participants (all P >0.08). After adjustment for confounders, sickle cell trait was unrelated to fasting glucose (β = 0.02; 95% confidence interval −37.68–43.30) and HbA1c (β = −0.03, 95% confidence interval −1.18–0.93), and did not affect the relationship between the two markers of diabetes control (β = −0.03, 95% confidence interval −1.18–0.89).

Conclusions  Sickle cell trait was as frequent in this subgroup of patients with Type 2 diabetes as in the general population, suggesting no specific association with diabetes. It does not affect the metabolic control of diabetes. However, how this translates into long‐term outcome needs to be fully elucidated in this setting, with an increasing population with both sickle cell trait and diabetes mellitus.
Time needed to evacuate the Netherlands in the event of large‐scale flooding: strategies and consequences
Authors: Kolen Bas , Helsloot Ira
Published: February 2012

On 30 May 2008, the Government of the Netherlands informed the national parliament about the effectiveness of preventive evacuation of coastal and river areas in case of flooding. Analysis of a case study showed that it is impossible to evacuate coastal areas preventively within a 48‐hour time span preceding a worst credible scenario flood caused by a storm surge. This fact illustrates the need for alternative evacuation strategies, such as vertical evacuation (evacuating to safe havens, inside the flood zone) or shelter‐in‐place (hiding), to reduce loss of life and the impact of the evacuation. This paper defines these strategies and demonstrates, by returning to the case study used by the Dutch government, that they require different measures, methods of approach, and crisis management processes. In addition, it addresses the need for flexible and scalable preparation so that after detecting and understanding the threat, authorities and citizens can make decisions about different evacuation strategies.
The academic medical centre and nongovernmental organisation partnership following a natural disaster
Authors: Sarani Babak , Mehta Samir , Ashburn Michael , Nakashima Koji , Gupta Rajan , Dombroski Derek , Schwab C. William
Published: February 2012

The global response to the 12 January 2010 earthquake in Haiti revealed the ability to mobilise medical teams quickly and effectively when academic medical centres partner non‐governmental organisations (NGO) that already have a presence in a zone of devastation. Most established NGOs based in a certain region are accustomed to managing the medical conditions that are common to that area and will need additional and specialised support to treat the flux of myriad injured persons. Furthermore, an NGO with an established presence in a region prior to a disaster appears better positioned to provide sustained recovery and rehabilitation relief. Academic medical centres can supply these essential specialised resources for a prolonged time. This relationship between NGOs and academic medical centres should be further developed prior to another disaster response. This model has great potential with regard to the rapid preparation and worldwide deployment of skilled medical and surgical teams when needed following a disaster, as well as to the subsequent critical recovery phase.